Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

ADVANCED POLYMER NANOPARTICLES Synthesis and Surface Modifications

ADVANCED POLYMER NANOPARTICLES Synthesis and Surface Modifications

Edited by

Vikas Mittal

Boca Raton London New York

CRC Press is an imprint of the Taylor & Francis Group, an informa business

CRC Press Taylor & Francis Group 6000 Broken Sound Parkway NW, Suite 300 Boca Raton, FL 33487-2742 © 2011 by Taylor and Francis Group, LLC CRC Press is an imprint of Taylor & Francis Group, an Informa business No claim to original U.S. Government works Printed in the United States of America on acid-free paper 10 9 8 7 6 5 4 3 2 1 International Standard Book Number: 978-1-4398-1443-7 (Hardback) This book contains information obtained from authentic and highly regarded sources. Reasonable efforts have been made to publish reliable data and information, but the author and publisher cannot assume responsibility for the validity of all materials or the consequences of their use. The authors and publishers have attempted to trace the copyright holders of all material reproduced in this publication and apologize to copyright holders if permission to publish in this form has not been obtained. If any copyright material has not been acknowledged please write and let us know so we may rectify in any future reprint. Except as permitted under U.S. Copyright Law, no part of this book may be reprinted, reproduced, transmitted, or utilized in any form by any electronic, mechanical, or other means, now known or hereafter invented, including photocopying, microfilming, and recording, or in any information storage or retrieval system, without written permission from the publishers. For permission to photocopy or use material electronically from this work, please access www.copyright. com (http://www.copyright.com/) or contact the Copyright Clearance Center, Inc. (CCC), 222 Rosewood Drive, Danvers, MA 01923, 978-750-8400. CCC is a not-for-profit organization that provides licenses and registration for a variety of users. For organizations that have been granted a photocopy license by the CCC, a separate system of payment has been arranged. Trademark Notice: Product or corporate names may be trademarks or registered trademarks, and are used only for identification and explanation without intent to infringe. Library of Congress Cataloging-in-Publication Data Advanced polymer nanoparticles : synthesis and surface modifications / [edited by] Vikas Mittal. p. cm. “A CRC title.” Includes bibliographical references and index. ISBN 978-1-4398-1443-7 (hardcover : alk. paper) 1. Polymerization. 2. Nanoparticles. 3. Polymers--Surfaces. I. Mittal, Vikas. II. Title. TP156.P6A38 2011 620.1’92--dc22 Visit the Taylor & Francis Web site at http://www.taylorandfrancis.com and the CRC Press Web site at http://www.crcpress.com

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Contents Preface..................................................................................................................... vii Editor........................................................................................................................ix Contributors.............................................................................................................xi 1. Polymer Latex Technology: An Overview..................................................1 V. Mittal 2. Synthesis of Polymer Particles with Core-Shell Morphologies........... 29 Claudia Sayer and Pedro Henrique Hermes de Araújo 3. Advanced Polymer Nanoparticles with Nonspherical Morphologies.................................................................................................. 61 Yongxing Hu, Jianping Ge, James Goebl, and Yadong Yin 4. Block, Graft, Star, and Gradient Copolymer Particles........................... 97 H. Matahwa, E. T. A. van den Dungen, J. B. McLeary, and B. Klumperman 5. Polymer Nanoparticles by Reversible Addition-Fragmentation Chain Transfer Microemulsion Polymerization................................... 133 J. O’Donnell and E. Kaler 6. pH-Responsive Polymer Nanoparticles.................................................. 169 Jonathan V. M. Weaver 7. Smart Thermo-Responsive Nanoparticles............................................. 197 Peng Tian and Qinglin Wu 8. Surface Tailoring of Polymer Nanoparticles with Living Polymerization Methods............................................................................ 223 Koji Ishizu and Dong Hoon Lee 9. Effects of Nano-Sized Polymerization Locus on the Kinetics of Controlled/Living Radical Polymerization............................................ 263 Hidetaka Tobita 10. Functional Polymer Particles by Emulsifier-Free Polymerization.... 307 V. Mittal

v

vi

Contents

11. Polymer Nanoparticles with Surface Active Initiators and Polymer Initiators........................................................................................ 329 Klaus Tauer Index...................................................................................................................... 361

Preface Polymer latex particles are a very important class of polymeric materials, which are used for a large number of commercial applications. These particles are synthesized in the aqueous dispersion phase by numerous synthesis methodologies such as emulsion, miniemulsion, microemulsion, dispersion, suspension, inverse emulsion (in organic phase), polymerization, etc. Over the years, significant enhancement in the techniques dealing with the synthesis and surface tailoring of polymer particles has been achieved, which has also resulted in the widening of the application spectrum of these particles. These advances include use of advanced controlled polymerization means such as nitroxide-mediated polymerization, atom transfer radical polymerization, radical addition fragmentation transfer polymerization, etc., as well as use of advanced stabilizers, surface modifiers, etc. These advances have made it possible to achieve polymer particles with specific sizes consisting of polymer chains of specific molecular weights and tailorable chemical compositions or properties according to the requirement. Because the advanced synthesis techniques are the key to achieve new functional properties in the polymer nanoparticles, and the surface modifications of these particles are required to ensure their use for specific applications, it is of immense importance to bring readers up-to-date on recent advances in these fields. This information will enable readers to design the required particle systems. This book thus serves the purpose of summarizing the developments in the synthesis and surface modification techniques to generate advanced polymer particles, and the contents have been accordingly organized. Chapter 1 introduces polymer latex technology with an overview of the various conventional and recent synthesis methodologies. Synthesis and characterization of particles with core-shell morphol­ogies have been focused on in Chapter 2. Chapter 3 reports the generation of nonspherical polymer particles by following different synthetic routes. The generation of specific architectures such as block, star, graft, and gradient copolymer particles has been detailed in Chapter 4. Microemulsion polymerization using reversible addition-fragmentation chain transfer controlled radical polymerization is the subject of Chapter 5. In Chapter 6, pH-responsive nanoparticles have been described, whereas the synthesis of smart thermally responsive particles has been reported in Chapter 7. Surface tailoring of various organic and inorganic nanoparticles by polymers is the subject of Chapter 8. Theoretical studies on the kinetics of controlled radical polymerization techniques have been explained in Chapter 9. Chapter 10 reports the synthesis of functional nanoparticles by using the ­surfactant-free emulsion polymerization vii

viii

Preface

approach. Chapter 11 describes various surface-active initiators as well as polymeric stabilizers developed for polymer nanoparticles in recent years. At this juncture, I would like to express my heartfelt thanks to Taylor & Francis Group for their kind support during the project. I am equally thankful to Professor Massimo Morbidelli at the Swiss Federal Institute of Technology, Zurich, Switzerland, who has been my guide in polymer latex technology. I am indebted to my family, especially my mother, whose continuous support and motivation have made this work feasible. I dedicate this book to my dear wife Preeti, for her valuable help in coediting the book as well as for her efforts in improving the quality of the book. Vikas Mittal Ludwigshafen, Germany

Editor Dr. Vikas Mittal studied chemical engineering at Punjab Technical Univer­ sity in Punjab, India. He later obtained his master of technology in polymer science and engineering from the Indian Institute of Technology, Delhi, India. Subsequently, he joined Professor U. W. Suter’s polymer chemistry group at the Department of Materials at the Swiss Federal Institute of Technology, Zurich, Switzerland, where he worked for his doctoral degree with a focus on the subjects of surface chemistry and polymer nanocomposites. He also jointly worked with Professor M. Morbidelli at the Department of Chemistry and Applied Biosciences on the synthesis of functional polymer latex particles with thermally reversible behaviors. After completion of his doctoral research, Dr. Mittal joined the Active and Intelligent Coatings section of Sun Chemical Group Europe in London. He worked for the development of water- and solvent-based coatings for food-packaging applications. He later joined BASF Polymer Research in Ludwigshafen, Germany, as a polymer engineer, where he is currently working as a laboratory manager responsible for the physical analysis of organic and inorganic colloids. His research interests include organic–inorganic nanocomposites, novel filler surface modifications, thermal stability enhancements, polymer latexes with functionalized surfaces, etc. He has authored more than 40 scientific publications, book chapters, and patents on these subjects.

ix

Contributors

Pedro Henrique Hermes de Araújo Department of Chemical Engineering Federal University of Santa Catarina Florianópolis, Brazil

Dong Hoon Lee Department of Organic Materials and Macromolecules Tokyo Institute of Technology Tokyo, Japan

Jianping Ge Department of Chemistry University of California–Riverside Riverside, California

H. Matahwa Department of Chemistry and Polymer Science University of Stellenbosch Matieland, South Africa

James Goebl Department of Chemistry University of California–Riverside Riverside, California Yongxing Hu Department of Chemistry University of California–Riverside Riverside, California Koji Ishizu Department of Organic Materials and Macromolecules Tokyo Institute of Technology Tokyo, Japan E. Kaler Stony Brook University Stony Brook, New York B. Klumperman Department of Chemistry and Polymer Science University of Stellenbosch Matieland, South Africa and Lab of Polymer Chemistry Eindhoven University of Technology Eindhoven, the Netherlands

J. B. McLeary Plascon Research Centre University of Stellenbosch Matieland, South Africa V. Mittal Polymer Research BASF SE Ludwigshafen, Germany and Department of Chemistry and Applied Biosciences Institute of Chemical and Bioengineering ETH Zurich Zurich, Switzerland J. O’Donnell Iowa State University Ames, Iowa Claudia Sayer Department of Chemical Engineering Federal University of Santa Catarina Florianópolis, Brazil xi

xii

Contributors

Klaus Tauer Department of Colloid Chemistry Max Planck Institute of Colloids and Interfaces Golm, Germany

E. T. A. van den Dungen Department of Chemistry and Polymer Science University of Stellenbosch Matieland, South Africa

Peng Tian School of Renewable Natural Resources Louisiana State University Baton Rouge, Louisiana

Jonathan V. M. Weaver Department of Chemistry University of Liverpool Liverpool, United Kingdom

Hidetaka Tobita Department of Materials Science and Engineering University of Fukui Fukui, Japan

Qinglin Wu School of Renewable Natural Resources Louisiana State University Baton Rouge, Louisiana

Yadong Yin Department of Chemistry University of California–Riverside Riverside, California

1 Polymer Latex Technology: An Overview*

V. Mittal Contents 1.1 Introduction.....................................................................................................1 1.2 Emulsion Polymerization..............................................................................2 1.3 Controlled Polymerization and its Use in Emulsion Polymerization Processes..............................................................................9 1.4 Conventional and Controlled Miniemulsion Polymerization................ 16 1.5 Generation of Copolymer or Core-Shell Particles.................................... 20 References................................................................................................................ 25

1.1 Introduction Polymer nanoparticles find use in a number of applications like coatings, adhesives, paints, etc. The applications of these nanoparticles are significantly affected by their physical properties as well as surface morphology, which can be controlled by the synthesis process used to generate such particles. Emulsion poly­mer­i­za­tion and its modified methodologies are the most commonly used techniques to achieve poly­mer nanoparticles. These techniques also allow the generation or surface functionalization of the particles either in situ or by following separate specific steps. Polymerization of monomer by emulsion poly­mer­i­za­tion offers significant advantages in the whole poly­mer­ i­za­tion process as compared to bulk and solution poly­mer­i­za­tion methods. It allows better control of the heat and viscosity of the system, and emulsion poly­mer­i­za­tion allows the achievement of an increase in molecular weight of the poly­mer chains without negatively impacting the rate of poly­mer­i­za­tion [1]. In emulsion poly­mer­i­za­tion, most of the monomer is present as monomer droplets in the aqueous phase, which diffuses to the polymerizing particles during the course of poly­mer­i­za­tion. The diffusion of the monomer is *

The work was carried out at Institute of Chemical and Bioengineering, Department of Chemistry and Applied Biosciences, ETH Zurich, Zurich, Switzerland.

1

2

Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

possible when the monomer is partially water soluble. Thus, emulsion poly­ mer­i­za­tion is not very effective with extremely hydrophobic and extremely hydrophilic monomers. The extremely hydrophobic monomers would always stay in the monomer droplets, leading to no poly­mer­i­za­tion, whereas the hydrophilic monomers would poly­mer­ize mainly by homogenous poly­mer­ i­za­tion and not micellar poly­mer­i­za­tion. To circumvent these difficulties, miniemulsion poly­mer­i­za­tion is used [2,3]. In this technique, the diffusion of the monomer molecules through the aqueous phase is not required, as the monomer droplets are directly poly­mer­ized. Therefore, such a technique has no problem in achieving the poly­mer­i­za­tion of even extremely hydrophobic monomers. To poly­mer­ize very hydrophilic monomers, inverse miniemulsion can be used. Combination of controlled poly­mer­i­za­tion methods like nitroxide-mediated poly­mer­i­za­tion, atom transfer radical poly­mer­i­za­tion, and reversible addition fragmentation chain transfer poly­mer­i­za­tion with the emulsion and miniemulsion poly­mer­i­za­tion methods has further enhanced the possibilities of achieving functional poly­mer particles [4]. By using these techniques, synthesis of functional block copolymer or graft copolymer particles can be achieved, which is not possible by using conventional emulsion poly­mer­i­za­tion techniques owing to the very short lifetime of the radicals. The surface morphologies of the particles can also be efficiently controlled or tuned by using such controlled poly­mer­i­za­tion methods, which expands the spectrum of application of these particles. This chapter aims to provide an overview of the conventional emulsion poly­mer­i­za­tion methods and the more advanced methods of synthesizing poly­mer particles.

1.2 Emulsion Polymerization Emulsion poly­mer­i­za­tion is a heterogeneous poly­mer­i­za­tion technique that uses water as dispersion medium for the poly­mer­i­za­tion of water-insoluble monomers in the form of suspended particles. Styrene, methyl methacrylate, butyl acrylate, etc. are examples of the most commonly used monomers for the generation of polymers by emulsion poly­mer­i­za­tion. The surfactants are generally used to provide colloidal stability to the system. The surfactant can be cationic, anionic, or nonionic, and its amount exceeds the critical micelle concentration significantly. The surfactants form micelles in the system in which the poly­mer­i­za­tion takes place. Thus, this process can be visualized as a bulk poly­mer­i­za­tion in each of the suspended particles. Polymerization by this mode helps to circumvent the problems of heat and viscosity control generally associated with bulk poly­mer­i­za­tion. By changing the amount of surfactant, the molecular weight of the poly­mer chains can be increased without decreasing the poly­mer­i­za­tion rate, which is not possible in other modes of poly­mer­i­za­tion. The presence of a significant amount of surfactant

3

Polymer Latex Technology: An Overview

in the system can lead to certain disadvantages; however, many applications of particles are not affected by the presence of surfactants. Surfactant-free poly­mer­i­za­tion can also be used to generate poly­mer particles in order to circumvent the problems associated with the use of emulsifier, but in this case, the mode of poly­mer nucleation is completely different. As mentioned previously, the amount of the surfactant exceeds the critical micelle concentration in the emulsified emulsion poly­mer­i­za­tion process. The micelles formed as a result of this excess amount have a size in the range of 10 nm, and one micelle generally consists of 100–200 surfactant molecules [1]. Surface tension of the solution decreases with the addition of surfactant at critical micelle concentration. A host of other solution properties are also affected at critical micelle concentration of the surfactant, which include conductivity, turbidity, osmotic pressure, etc. [5]. However, in the emulsion poly­mer­i­za­tion process, it is the reduction in the surface tension of the aqueous phase that is of prime importance. Because surfactants are amphiphilic molecules containing one hydrophobic part and one hydrophilic part, in the micelle they orient themselves in a way so that the hydrophobic part forms the inner part of the micelle and the hydrophilic part radiates away from this inner part of the micelle into the aqueous phase. The resulting hydrophobic space inside the micelle owing to the self-assembly of the surfactant molecules is an ideal place for the hydrophobic monomer to reside and also provides an ideal environment for the radicals to enter the micelle. Figure 1.1 shows the representation of the association of the surfactant molecules after the critical micelle concentration of the surfactant is reached [6]. When the inverse emulsion poly­mer­i­za­tion is used, then the hydrophilic part of the surfactant forms the inner part of the micelles and the hydrophilic chains intermix with the organic dispersion phase.

(a)

(b)

Figure 1.1 Organization of the surfactant molecules (a) below and (b) above the critical micelle concentration of the surfactant in the aqueous solution.

4

Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

The monomers used for emulsion poly­mer­i­za­tion are water insoluble (water soluble for inverse emulsion poly­mer­i­za­tion). However, the monomer should have some extent of water solubility in order to diffuse through the aqueous phase as required during the course of poly­mer­i­za­tion. When the monomer is added to the system, a part of the monomer enters the micelles and a part is dissolved in the aqueous phase owing to partial water solubility. However, the majority of the monomer is present in the form of monomer droplets. The size of the monomer droplets is much larger than that of micelles; however, their number is much lower as compared to the micelles. Water-soluble initiators are generally used to initiate the poly­mer­i­za­tion reaction. The initiator generates the radicals in the aqueous phase owing to thermal dissociation. The generated radicals have the possibility of entering either the micelles or the monomer droplets. However, experimental evidence proves the absence of droplet poly­mer­i­za­tion. The radicals do not enter the monomer droplets, as the radical entities are hydrophilic in nature whereas the monomer droplets are hydrophobic. Also, because the number of monomer droplets is much smaller than the number of micelles, it is micelles that capture the majority of the radicals. Also, the unique architecture of the micelles provides attractive conditions for the radicals to enter. Figure 1.2a shows the mechanism of the micellar nucleation for the generation of poly­mer particles. This mode of nucleation is also termed heterogeneous nucleation. The homogenous mode of particle nucleation is also possible when (a) the amount of surfactant is below its critical micelle concentration, (b) no surfactant is used during the poly­mer­i­za­tion, or (c) the monomer is significantly water soluble. In this mode of nucleation, the generated radicals in the aqueous phase start reacting with the dissolved monomer molecules. However, after adding a few monomer units in the chains, these chains no longer remain water soluble and come out of the solution. These chains are not stable on their own and keep collapsing with each other in order to attain stability. They also adsorb a certain amount of surfactant from either the micelles or the aqueous phase itself. Partial stability is also provided by the negative charges from the initiator moieties. In the case of the surfactant-free poly­mer­i­za­tion, the initiator charges are the only source of colloidal stability of the particles. Figure 1.2b shows the process of homogenous nucleation. The emulsion poly­mer­i­za­tion process is generally divided into three intervals. The first is the particle formation interval. The radicals are generated in the aqueous phase after the thermal dissociation of the initiator. These radicals start entering the micelles and initiate poly­mer­i­za­tion. These active micelles where the poly­mer­i­za­tion starts to take place are then referred to as poly­mer particles. The number of particles in this interval keeps increasing owing to the continuous entry of the generated radicals in the micelles. This also leads to continuous increase in the rate of the poly­mer­i­za­tion. As the poly­ mer­i­za­tion of the monomer in the particles proceeds, the size of the particles keeps increasing and the amount of monomer in the particles keeps depleting. However, this depletion of the monomer is replenished by the absorption of

Polymer Latex Technology: An Overview

5

(a)

(b) Figure 1.2 (a) Representation of micellar nucleation mechanism for the generation of poly­mer particles. (b) Homogenous nucleation mechanism for the synthesis of poly­mer particles.

the monomer from the aqueous phase. The aqueous phase in turn absorbs more monomer from the monomer droplets. Therefore, a mass transfer from the monomer droplets to the poly­mer articles keeps taking place during the course of poly­mer­i­za­tion. For this diffusion process to take place, the monomer is required to be partially soluble in water. As the poly­mer particles become bigger in size and their surface area increases as a function of time or

6

Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

Figure 1.3 Schematic of various intervals of the emulsion poly­mer­i­za­t ion process.

monomer conversion, they require more amount of surfactant to remain stable. The surfactant dissolved in the aqueous phase is continuously adsorbed on the surface of the poly­mer particles, leading to the reduction of the surfactant amount in the solution to lower than the critical micelle concentration. This in turn destabilizes the remaining micelles and these micelles disappear, providing their surfactant for the stabilization of the poly­mer particles. Thus at the end of the first interval, no micelle is left and most of the surfactant is used to stabilize the poly­mer particles. It has to be noted that the final number of poly­mer particles is much lower than the original number of micelles. Also, roughly 15% of the monomer is poly­mer­ized by the end of the first interval [1]. Figure 1.3 represents the various intervals of emulsion poly­mer­i­za­tion. Once excess surfactant is no longer present in the system, no new particles nucleate. This marks the beginning of the second interval of emulsion poly­mer­i ­za­t ion. Because no new particles nucleate, the amount of the particles remains almost constant; this also leads to an almost constant poly­mer­i ­za­t ion rate in this interval. The size of the poly­mer particles, however, keeps increasing as a function of conversion. The monomer present in the monomer droplets continues to replenish the monomer in the aqueous phase as well as monomer-swollen poly­mer particles. After a certain extent of conversion, the monomer droplets also disappear. This also signals the start of the final interval of the emulsion poly­mer­i ­za­ tion process. The concentration of the monomer in the poly­mer particles keeps decreasing, and as a result the rate of poly­mer­i ­za­t ion also steadily decreases. Because the monomer is almost consumed, the poly­mer­i ­za­t ion rate virtually falls to zero. Figure 1.4 shows the evolution of the particle size as a function of conversion.

7

Polymer Latex Technology: An Overview

300 nm

200 nm (a)

(b)

400 nm (c) Figure 1.4 (a–c) Increase of the size of the particles as a function of conversion.

Emulsion poly­mer­i­za­tion can also lead to the generation of various different surface morphologies of the poly­mer particles as well as particle sizes or families. Figure 1.5 shows the examples of monomodal, bimodal, or multimodal poly­mer particles along with morphologies like planar, orange-peel, strawberry or surface craters, etc. Polymers synthesized with emulsion poly­mer­i­za­tion are not always homopolymers, but most of the time are copolymers. When more than one monomer is poly­mer­ized together, the reactivity of the monomers defines the resulting morphology of the particles. Different reactivities of the monomer lead to totally different copolymer composition in the poly­mer particles, leading to a gradient in the concentration of the monomers with radius. This occurs because of the faster poly­mer­i­za­tion of the reactive monomer thus accumulating near the center of the particles, followed by the poly­mer­i­za­tion of the lesser reactive monomer, which then is present in a majority near the

8

Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

300 nm

200 nm (a)

(b)

250 nm (c)

300 nm (d)

Figure 1.5 (a–d) Various morphologies of particles achieved with emulsion poly­mer­i­za­t ion.

outer surface of the particles. Differences in the water solubilities of the monomers can also lead to the generation of specific morphologies of the particles. As an example, in Figure 1.6 are shown the copolymer particles of styreneco-N-isopropylacrylamide synthesized by the surfactant-free approach, that is, by the homogenous nucleation method. N-isopropylacrylamide being hydrophilic in nature starts to poly­mer­ize first, followed by the poly­mer­i­ za­tion of more hydrophobic styrene. But because the poly­mer chains from styrene are also hydrophobic in nature, they push the hydrophilic chains of poly(N-isopropylacrylamide) away to the surface, leading to the morphology as shown in Figure 1.6.

9

Polymer Latex Technology: An Overview

300 nm

250 nm

(a)

(b)

300 nm (c) Figure 1.6 (a–c) Scanning electron microscopy (SEM) micrographs of copolymer particles of styrene-coN-isopropylacrylamide.

1.3 Controlled Polymerization and its Use in Emulsion Polymerization Processes The conventional radical poly­mer­i­za­tion is limited as a technique in that the control in the molecular weight or its distribution is difficult to achieve. It is also not easy to achieve well-defined morphologies in the particles like block copolymers because the life of the radical is too short, and uncontrolled termination reactions take place very fast. Controlled living poly­mer­i­za­tion techniques, on the other hand, can circumvent the aforementioned limitations in the emulsion poly­mer­i­za­tion process [4]. In these techniques, the chains

10

Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

TEMPO mediated nitroxide polymerization (NMP) Atom transfer radical polymerization (ATRP)

Activator regenerated by elecron transfer (ARGET) atom transfer radical polymerization (ATRP)

SG1 mediated nitroxide polymerization (NMP) Degenerative transfer

Living polymerization

Activator generated by elecron transfer (AGET) atom transfer radical polymerization (ATRP)

Reversible additionfragmentation chain transfer (RAFT) polymerization

Reverse atom transfer radical polymerization (ATRP)

Figure 1.7 Representation of various living poly­mer­i­za­t ion techniques. (Reprinted from V. Mittal, Advances in Polymer Latex Technology, New York: Nova Science Publishers, 2009. With permission.)

are terminated but only irreversibly, and after a short period of time become active again to propagate the poly­mer chains. In such processes, the termination reactions are effectively eliminated, and the controlled molecular weight distributions as well as advanced morphologies in the poly­mer particles can be achieved. There have been many techniques developed in the last years to achieve controlled poly­mer­i­za­tion, and these techniques are generally classified into two categories: those based on reversible termination and those based on reversible transfer. Figure 1.7 is the representation of the various controlled poly­mer­i­za­tion techniques. In the category of reversible termination, nitroxide-mediated poly­mer­i­za­tion (NMP) and atom transfer radical poly­mer­i­za­tion (ATRP) are the most studied approaches. ATRP has also been further modified into techniques like reverse atom transfer radical poly­mer­ i­za­tion, activator generated by electron transfer ATRP, etc. In the category of reversible transfer, techniques like reversible addition-­fragmentation chain transfer (RAFT) poly­mer­i­za­tion and degenerative transfer are mostly reported. During the poly­mer­i­za­tion, the concentration of dormant species continues to increase as compared to the active chains. At the end of poly­ mer­i­za­tion, the dormant species may be present in amounts six times higher than the active chains. This effectively leads to elimination of termination and allows much longer lifetimes for the radicals.

Polymer Latex Technology: An Overview

11

NMP, where nitroxides are used to irreversibly terminate the poly­mer chains, has been used in two different ways. In one case, a conventional free radical initiator and a separately added nitroxide are added to control the poly­mer­i­za­tion. The two most commonly used nitroxides for this purpose are 2,2,6,6-tetramethyl-1-piperidinoxyl (TEMPO) and N-ter-butyl-1diethylphosphono-2,2’-dimethylpropyl (SG1). The nitroxides were initially developed for the poly­mer­i­za­tion of styrene; however, a number of other nitroxides have been developed that are also suitable for the poly­mer­i­za­tion of acrylates. In the other case, an alkoxyamine is used, the decomposition of which leads to the generation of two radicals: one reactive and one stable. This radical pair then controls the poly­mer­i­za­tion and thus does not require the addition of conventional free radical initiator. Figures 1.8 and 1.9 represent the poly­mer­i­za­tion of lauryl methacrylate and styrene by using nitroxides and alkoxyamines, respectively. The only disadvantage of the nitroxide-mediated stable free radical poly­mer­i­za­tion was the requirement of a high temperature for the poly­mer­i­za­tion reaction, which is sometimes not feasible for thermally sensitive systems; however, various nitroxides have been developed that also allow use at lower reaction temperatures. The initially carried-out reactions with styrene in emulsion led to poor colloidal stability, which resulted in a large amount of coagulum generated in the poly­mer­i­za­tion reactions. It was claimed that the particle nucleation as well as poly­mer­i­za­tion in droplets were a few reasons, among others, for this behavior. The seed method has also been described for emulsion poly­mer­ i­za­tion with SG1 as nitroxide [7]. In this case, a seed is generated first with low solid content, and the seed particles are then swollen in monomer and followed by subsequent poly­mer­i­za­tion of these seed particles. This helps to avoid the generation of monomer droplets and thus poly­mer­i­za­tion in droplets. It was also possible to achieve the previously described reaction as a single step. After the synthesis of seed as before, a certain amount of monomer is added without cooling the seed latex and the reaction is run until high conversion is achieved. The formed latexes were very stable in nature and no coagulum was generated. It is also important to monitor the progress of the reaction especially at high conversion, as at very high conversions, chains start to terminate each other and the polydispersity in the chain length as well as molecular weight increases. Therefore, it is always beneficial to stop the poly­mer­i­za­tion reaction a little below the full conversion. It was also confirmed that the alkoxyamines based on SG1 are more optimally operatable for achieving controlled poly­mer­i­za­tion of a wide range of monomers as compared to TEMPO nitroxide. ATRP represents another technique based on the principle of reversible termination, and in this process, an organic halide is used to irreversibly terminate the propagating chains. This technique has been very successful for the controlled poly­mer­i­za­tion of styrenics as well as acrylates and methacrylates. It also does not require very high temperatures as compared

12

Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

O C

CH2

O O

O

CH C

+

C

O

OC12H25

O C

CH2

O

CH C

• CH

CH2 O

C

OC12H25

CH2

CH

+

O

O

C

OC12H25

OC12H25

CH3 H3C •O

OC2H5

CH3 N

CH

H3C

P CH3

OC2H5 O

CH3 CH3

O C

H3C O

CH2

CH C

CH2 O

OC12H25

CH C

O O

OC12H25

CH3 N

CH

H3C

OC2H5 P CH3

OC2H5 O

CH3

Figure 1.8 Nitroxide-mediated controlled radical poly­mer­i­za­t ion of lauryl methacrylate with SG1 nitroxide.

to NMP, and in many cases can also be undertaken at room temperature. Figure 1.10a shows the schematic of the ATRP process. Cuprous salt forms a complex with ligand, L (amines of different chemical architectures), which makes it more soluble in the solvents [1]. Initiation of the reaction takes place by the dissociation of the halide atom from the initiator and leading to the generation of a free reactive radical. The bromide atom is captured by cuprous halide ligand complex and it forms CuBr2 ligand complex. This compound is very stable and hence is called deactivator. The generation of this compound thus leads to reduction in the concentration of the free radical species in the system. The growing radical continues to add monomer units to the poly­mer chain, and at some point it comes in contact with CuBr2

13

Polymer Latex Technology: An Overview

CH H3C

H3C

• CH

• CH

N

O

• O

+

H3C

CH3

CH2

CH3

H3C

CH3

H3C

N H3C CH3

CH

+

CH2

CH

H3C

CH

H3C

H3C • O

CH3

N H3C CH3

CH3

H3C CH

CH2

CH

N

O

H3C

H3C

CH2

CH3

CH

n H3C CH H3C

CH2

CH

CH2 n

CH

O

CH3

N H3C

CH3

Figure 1.9 Nitroxide-mediated free radical poly­mer­i­za­t ion of styrene by using alkoxyamine as nitroxide as well as initiator.

ligand complex and is temporarily terminated by the formation of RMn+1-Br compound. It is also possible to carry out the reverse ATRP process similarly (Figure 1.10b). In this process, a conventional free radical initiator like AIBN or benzoyl peroxide is used to initiate the poly­mer­i­za­tion reaction, which is controlled by the addition of CuBr2 ligand complex. The radicals add few monomer units, and during this process come in contact with this complex to form the dormant species. One limitation of such a technique is the presence of transition metal in the final particles, which though possible to wash off adds another processing step in the synthesis process. Another limitation

14

Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

P

P• +

Br + CuBr/L

CuBr2/L

M PM• nM PM•n+1

RMn+1 – Br +

CuBr/L

(a) O C

O

O O

O

+

C

CuBr2/L

C

O

Br

M O C

O

M•

nM

O C

O

M•n+1

+

CuBr2/L

O C

O

M•n+1

Br

+

CuBr/L

(b) Figure 1.10 Schematic of (a) ATRP and (b) reverse ATRP processes for controlled living poly­mer­i­za­t ion. (Adapted from G. Odian, Principles of Polymerization, Hoboken, NJ: John Wiley & Sons, 2004; and V. Mittal, Advances in Polymer Latex Technology, New York: Nova Science Publishers, 2009.)

is the reaction of the copper compounds with the other constituents of the system. One example is the reaction of these compounds with the emulsifier used in the poly­mer­i­za­tion system, leading to the poisoning of the initiator, which subsequently results in no or little poly­mer­i­za­tion. Therefore, it is possible to work in the emulsion with the ATRP when there is no surfactant or surfactants with no interaction with the initiator are chosen. ATRP in emulsion processes also faced problems similar to those in NMP. In one reported study, ethyl 2-bromoisobutyrate was used as an ATRP initiator, and copper bromide was complexed with 4,4’-dinonyl-2,2’-bipyridyl to form the catalyst system [8]. Nonionic surfactant Tween 85 was used. The poly­mer­i­za­tion was achieved by first mixing together copper salts with 4,4’-dinonyl-2,2’-bipyridyl, to which the monomer was added. The solution was allowed to mix and was added with surfactant. To this solution, water was added under vigorous

15

Polymer Latex Technology: An Overview

stirring to form the emulsion. To this emulsion was then added the initiator to initiate the poly­mer­i­za­tion reaction. The reaction conditions needed to be very accurately controlled, and the reaction was overall very sensitive to minor changes in the reaction parameters. Seeded poly­mer­i­za­tion similar to that used with NMP was also used in this case. The use of cationic surfactants was also reported for the ATRP processes in emulsion. Dodecyl trimethyl ammonium bromide and myristyl trimethyl ammonium bromide were used as cationic surfactants, and their effect on the latex stability, amount of coagulum, and the polydispersity in the molecular weight was quantified. The first surfactant though gave a good control of polydispersity; however, the whole system was observed to coagulate after the initiation of poly­mer­i­ za­tion. In the case of the second surfactant, the latex stability was better, but the polydispersity in the molecular weight or chain lengths was very high. RAFT is a controlled poly­mer­i­za­tion technique based on the principle of reversible transfer. The core of this process is a RAFT agent that contains dithioester groups. The living poly­mer­i­za­tion takes place because the transferred end group in the polymeric dithioester is as labile as the dithioester group in the starting RAFT agent. The initiator for the poly­mer­i­za­tion can be the conventional initiators like AIBN or benzoyl peroxide. Figure  1.11 explains the principle of RAFT poly­mer­i­za­tion. Though it is one of the versatile techniques for the poly­mer­i­za­tion of a large number of monomers, it also has its own limitations, such as the presence of remainder RAFT agent and the commercial unavailability of the RAFT agents. Similar to NMP and ATRP, initial trials with RAFT also were faced with difficulties of coagulum generation. The RAFT agent was difficult to be transported to the poly­ mer particles through the aqueous phase. RAFT poly­mer­i­za­tion of styrene in emulsion was reported by Szkurhan et al. [9]. The process named nano­ precipitation was carried out by forming nano-sized particles by precipitation of the acetone solution of macro RAFT agent in the aqueous poly(vinyl alcohol) solution. The macro RAFT agent was prepared by conventional free R1

Mn + S

SR2

MnS

R1

M•m + S

R1

R1 •

SR2

MmS

•

S

MnS R1

R1 SMn

+ R•2

SMn

MmS

+ M•n S

Figure 1.11 Mechanism of reversible transfer processes used in reversible addition-fragmentation chain transfer processes. (Adapted from G. Odian, Principles of Polymerization, Hoboken, NJ: John Wiley & Sons, 2004; and V. Mittal, Advances in Polymer Latex Technology, New York: Nova Science Publishers, 2009.)

16

Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

radical poly­mer­i­za­tion. The formed nanoparticles were subsequently swollen with monomer and were poly­mer­ized in the living manner. This nanoprecipitation method was also named seeded poly­mer­i­za­tion because, in this case, the nano-sized particles formed by precipitation act as seeds to form poly­mer particles. Both water- and oil-soluble initiators were used. When the initiator used was oil soluble, it was premixed with the RAFT agent, whereas the water-soluble initiator was dissolved in PVA solution. With both watersoluble and oil-soluble initiators, the rate of poly­mer­i­za­tion was quite slow, and increasing the reaction temperature was not helpful in increasing the rate of poly­mer­i­za­tion. Another study reported the synthesis of poly­mer particles in emulsion by RAFT without the problems of loss of colloidal stability and the molecular weight control [10]. Trithiocarbonate RAFT agents were used in the study to form short stabilizing blocks from a hydrophilic monomer, from which diblocks were created by the subsequent poly­mer­ i­za­tion of a hydrophobic monomer. These diblocks self-assembled to form micelles, and subsequent poly­mer­i­za­tion could be carried out. Figure  1.12 demonstrates the particles generated by this technique.

1.4 Conventional and Controlled Miniemulsion Polymerization In surfactant-aided emulsion poly­mer­i­za­tion, the goal is to achieve the micellar nucleation and to avoid the droplet nucleation as much as possible. But the poly­mer­i­za­tion of extremely hydrophobic monomers by conventional emulsion poly­mer­i­za­tion is not possible because of their inability to diffuse from the monomer droplets through the aqueous phase to the poly­mer particles. To achieve poly­mer­i­za­tion of such systems, miniemulsion poly­mer­i­za­tion has proved to be a versatile method [2,3]. The mode of poly­mer­i­za­tion is based on the droplet poly­mer­i­za­tion principle. The monomer droplets are generated by shearing the system with high energy along with the addition of costabilizer (with the surfactant), which needs to be hydrophobic in order to avoid the collapse of the monomer droplets by Ostwald ripening when the shearing of the system is stopped. Thus in this mode of poly­mer­i­za­tion, it is important to avoid the micellar nucleation; therefore, the amount of surfactant is below the critical micelle concentration. The particles in the general size range of 50–500 nm can be synthesized by using miniemulsion poly­mer­i­za­tion. These are similar in size to the monomer droplets in the beginning of the poly­mer­ i­za­tion. The initiators used for the poly­mer­i­za­tion are water soluble as in the case of emulsion poly­mer­i­za­tion. The initiator on dissociation generates radicals in the aqueous phase, and these radicals enter the droplets and initiate poly­mer­i­za­tion. In conventional emulsion poly­mer­i­za­tion, also called macroemulsion poly­mer­i­za­tion, the micellar nucleation is very sensitive and is affected by a large number of factors like surfactant amount, initiator amount,

17

Polymer Latex Technology: An Overview

Conventional core-shell: different chains in the core and shell

Triblock polymer: the same chains extend from the shell into the core (a)

0.20 µm X 19000

(b) Figure 1.12 (a) Schematic representation of RAFT-based triblock copolymer chains forming the core and shell of the particles and their comparison with conventional core-shell particles. (b) TEM micrograph of poly(acrylic acid)-b-poly(butyl acrylate)-b-polystyrene particles. (Reprinted from C. J. Ferguson, R. J. Hughes, D. Nguyen, T. T. Pham, R. G. Gilbert, A. K. Serelis, C. H. Such, and B. S. Hawkett, Macromolecules 38: 2191–2204, 2005. With permission from the American Chemical Society.)

18

Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

Figure 1.13 Schematic of the miniemulsion poly­mer­i­za­t ion process. The molecules with black and gray color represent the surfactant and costabilizer, respectively.

agitation, reaction temperature, etc. However, that is not the case in miniemulsion poly­mer­i­za­tion. Figure 1.13 also represents the scheme of poly­mer­i­za­tion in miniemulsion. The monomer is added to the surfactant and costabilizer in the aqueous phase followed by homogenization under high shear to break the bigger monomer droplets into droplets with the size range of 10–500 nm [2,3,11]. The amount of the surfactants and the shearing translate into the size of the monomer droplets. As mentioned earlier, in emulsion poly­mer­i­za­tion, the poly­mer­i­za­tion is driven by the diffusion of the monomer through the aqueous phase. In this process, monomer droplets disappear and the micelles convert into the poly­mer particles, whereas in miniemulsion poly­mer­i­za­tion, the monomer droplets directly translate into poly­mer particles. As a result, the rate of poly­mer­i­za­tion is also different for these two processes. The rate of poly­mer­i­za­tion in the emulsion poly­mer­i­za­tion first increases owing to the generation of the particles and reaches a constant phase after the disappearance of the micelles. The rate then decreases owing to the depletion of the monomer in the particles. As there is no diffusion of monomer in the miniemulsion poly­mer­i­za­tion, the constant rate period is absent. The rate first increases owing to the nucleation of the particles and then decreases when the monomer is consumed in the particles. Not only hydrophobic monomers, but also extremely hydrophilic monomers can be poly­mer­ized using the miniemulsion poly­mer­i­za­tion method. In this case, one has to use the inverse miniemulsion poly­mer­i­za­tion. Also in this case, hydrophobic reaction medium is used along with a lipophobe used as costabilizer. One must be clear that the addition of costabilizer stops the conversion of a miniemulsion into a conventional emulsion; however, the addition of a costabilizer to conventional emulsion does not automatically convert it into a miniemulsion. It is only after the addition of high shearing energy that it becomes a stable miniemulsion. The costabilizers should be hydrophobic, soluble in monomer, and have a low molecular weight. However, the use of conventional costabilizers like cetyl alcohol and hexadecane pose a potential hazard owing to their volatility, and the presence of these even in the minor amounts in the poly­mer particles may not be acceptable for many applications. Therefore, a lot of research effort has been focused in the direction of generation of more compatible costabilizers. Polymeric stabilizers from the poly­mer of the monomer

Polymer Latex Technology: An Overview

19

to be poly­mer­ized have been used in some of the reported studies [3,12,13]. These polymers are soluble in their own monomers and thus allow better intermixing at the interphase. They also eliminate the use of volatile costabilizers, providing more acceptability to the system for the commercial applications. Monomeric costabilizers have also been developed in recent years that can copoly­mer­ize with the monomer under poly­mer­i­za­tion [14]. These costabilizers form copolymer chains that are bound inside the particles, and thus the possibility of the diffusion of low molecular weight components out of the particles is eliminated. The potential diffusion of the low molecular weight components, especially substances like cetyl alcohol or hexadecane, can pose health hazards when the poly­mer particles are used in application with food contact. Similarly, the other components of the poly­mer­i­za­tion system like initiator and chain transfer agent have also been used as costabilizers [15,16]. Therefore, the materials act as dual-role components. They not only perform their function as initiator or chain transfer agent, respectively, but also help to achieve the stability for the monomer droplets and poly­mer particles. Miniemulsion poly­mer­i­za­tion has also been proved to be advantageous in living poly­mer­i­za­tion systems. The various living poly­mer­i­za­tion methods like NMP, ATRP, and RAFT have been shown to be beneficial in miniemulsion poly­mer­i­za­tion to generate specialty polymers or polymers with special architecture like block copolymers. Colloidal stability and ease of poly­mer­ i­za­tion process are also better in the case of miniemulsion poly­mer­i­za­tion than conventional emulsion poly­mer­i­za­tion. For NMP, nitroxide-capped poly­mer chains have been used as initiator as well as nitroxide. The use of such nitroxide-capped poly­mer chains for the initiation and reaction control allows one to properly estimate the number of starting chains in the system, helping to achieve better control of the molecular weight. The use of nitroxide-capped poly­mer also helps to partition the nitroxide solely in the organic phase owing to the hydrophobicity. In such reported studies with polystyrene terminated with TEMPO as initiator as well as nitroxide, hexadecane as costabilizer, and DOWFAX 8390 as surfactant, it was reported that changing the amount of surfactant led to the generation of different particle sizes, but the rate of poly­mer­i­za­tion was not affected, which is different from the behavior seen in conventional emulsion poly­mer­i­za­tion [17,18]. Figure 1.14 demonstrates the transmission electron microscopy (TEM) images of the polystyrene particles generated in nitroxide-mediated miniemulsion poly­mer­i­za­tion using different amounts of TEMPO-terminated oligomers of polystyrene as macroinitiator. A great deal of process development has been reported for ATRP in miniemulsion. A number of studies have been reported that apply the direct or forward ATRP in miniemulsion, but reverse ATRP, in which conventional free radical poly­mer­i­za­tion initiator like AIBN can be used with the transition metal compound in its higher oxidation state, was observed to be more suitable for miniemulsion poly­mer­i­za­tion. This eliminates the use of air-sensitive Cu(I) species and requires only the use of Cu(II) species, which

20

Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

(a)

(b)

Figure 1.14 TEM images of the polystyrene particles prepared by nitroxide-mediated miniemulsion poly­ mer­i­za­t ion using different amounts of TEMPO-terminated oligomers of polystyrene (TTOPS) as macroinitiator. (a) 5% TTOPS and (b) 20% TTOPS (100 nm). (Reprinted from G. Pan, E. D. Sudol, V. L. Dimonie, and M. S. El-Aasser, Macromolecules 34: 481–88, 2001. With permission from the American Chemical Society.)

is more stable in air. A narrow molecular weight distribution as well as linear increase in the molecular weight as a function of conversion was reported, and the final latexes were stable over a period of time. In one such study on reverse ATRP processes [19], Brij 98 surfactant and CuBr2/dNbpy (4,4’-di[5nonyl]-4,4’-bipyridine) complex were used along with hexadecane costabilizer. Both water-soluble as well as oil-soluble initiators were used for the poly­mer­i­za­tion. It was observed that the poly­mer­i­za­tion rate was independent of the size and number of particles and the amount of surfactant. The shear forces were able to influence only the size of the particles and not the poly­mer­i­za­tion rate. In the case of oil-soluble initiator, the poly­mer­i­za­tion was observed to proceed by droplet nucleation mode because the monomersoluble initiator was already present in the droplet during the miniemulsion; whereas when water-soluble initiator was used, both micellar as well as droplet nucleation were reported to take place. Similarly RAFT has also been used successfully in miniemulsion for the poly­mer­i­za­tion of styrene as well as water-soluble monomers like acrylamide [11,20–22].

1.5 Generation of Copolymer or Core-Shell Particles The generation of well-defined copolymer morphologies like block copoly­mer particles is difficult to achieve by the use of conventional emulsion poly­mer­ i­za­tion because of the uncontrolled free radical poly­mer­i­za­tion and the short life of the radicals. To achieve certain control on the copoly­mer­i­za­tion, monomer reactivity ratios and monomer-feeding methodology must be considered.

21

Polymer Latex Technology: An Overview

300 nm

300 nm

(a)

(b)

300 nm

300 nm (c)

(d)

Figure 1.15 (a–d) Different morphologies of copolymer particles generated by conventional emulsion poly­ mer­i­za­t ion.

The monomers have different reactivity ratios; therefore, if the monomers are added together, the more reactive monomer starts to poly­mer­ize first followed by the poly­mer­i­za­tion of the less reactive monomer. This creates a gradient of concentration of the monomer units in the poly­mer particles as a function of radius. Figure 1.15 provides some examples of various copolymer particles that can be achieved by emulsion poly­mer­i­za­tion like core-shell grafted particles, core-shell particles with hydrophilic shell and hydrophobic core, copolymer particles with different surface morphologies, etc. Apart from reactivity ratios, mode of addition of the monomers during the course of poly­mer­i­za­tion is also of utmost importance to achieve control on the particle characteristics. Batch addition of the monomers does not lead to generation of the structured latexes; therefore, semibatch addition of the monomers is generally preferred. This mode of addition can be achieved by either flooded

22

Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

addition or starved addition of the monomers. In flooded addition, monomers are added at a rate higher than their rate of consumption. This mode of addition leads to buildup of the monomers in the poly­mer­i­za­tion reaction and may lead to the generation of secondary nucleation of the particles. Starved addition of the monomers, on the other hand, is the addition of monomers at a rate slower than their poly­mer­i­za­tion rate, and this allows one to retain the chemical composition of the poly­mer chains equal to the monomer ratios in the feed or according to the requirement. The starved conditions eliminate the possibility of secondary nucleation, though one has to be careful about the control of the amount of the surfactant in the system as well as charges on the surface. As an example, if copoly­mer­i­za­tion of a hydrophilic monomer and a hydrophobic monomer is considered, initially the surface may be hydrophobic, but as the chains rich in hydrophilic monomer content get pushed out to the surface of the particles during the course of poly­mer­i­za­tion, the surface becomes hydrophilic. This would lead to a change in the surface properties of the particles and would allow the release of the surfactant from the surface of the particles owing to the hydrophili­city. This also results in the nonentry of the hydrophobic monomer into the poly­mer particles, causing monomer concentration drift in particles or secondary nucleation. Interesting studies have been reported for the generation of copolymer particle latexes by emulsion poly­mer­i­za­tion. Batch poly­mer­i­za­tion of copoly­mer particles of polystyrene and poly(methyl methacrylate) were reported without the use of initiators [23]. These copolymer particles of poly(methyl methacrylateco-styrene) were prepared by thermally initiated emulsion copoly­mer­i­za­tion. It was observed that totally different particle morphologies like hemispherical, sandwich-like, core-shell, inverted core-shell particle morphologies, etc. were obtained depending on the poly­mer­i­za­tion conditions. It was reported that the incorporation of the initiator fragments to one end of the chains allows the polystyrene chains to become more hydrophilic, changing the surface nature of the poly­mer particles. In another study to generate copolymer particles, poly(methyl methacrylate) seed was used to generate the copolymer particles of poly(methyl methacrylate) with polystyrene [24]. It was observed that by using the oil-soluble initiators, an inverted core-shell morphology of the particles was obtained, in which the polystyrene chains were present in the core of the particles and the poly(methyl methacrylate) covered the particles owing to its hydrophilicity. In the case of water-soluble initiator, the morphology was less affected by the hydrophilicity of the polymers, but was more affected by the initiator concentration and poly­mer­i­za­tion temperature. Controlled living poly­mer­i­za­tion methods provide much better possibilities to generate the structured latex particles with different morphologies of chemistries owing to the prolonging of the radical age either by reversible termination or by reversible transfer. In one such study to generate triblock copolymers using emulsion poly­mer­i­za­tion, water-soluble SG1based bifunctional alkoxyamine (Figure  1.16; sodium salt of alkoxyamine was used owing to water solubility) and Dowfax 8390 surfactant were used

23

Polymer Latex Technology: An Overview

HOOC

O N

O P O O

O CH2 CH2 O 3

O

O

t-butanol T = 80 – 100°C

HOOC

O O P

COOH O CH2 CH2 O

N O

O N

3

O

O

O

O (1) NaOH (2)

R

R = Ph, COOBu

Emulsion T = 112°C

COO– +Na

Na+ –OOC R O O P O

N O

O P O

R O CH2 CH2 O

x

3

O

O

x

O N

O P O O

Figure 1.16 Synthesis and use of SG1-based water-soluble bifunctional alkoxyamine. (Reprinted from J. Nicolas, B. Charleux, O. Guerret, and S. Magnet, Macromolecules 38: 9963–73, 2005. With permission from the American Chemical Society.)

[11,25]. When a bifunctional alkoxyamine was used, two functional ends of this alkoxyamine could be used to generate triblock copolymers. Thus, in order to generate polystyrene-b-poly(butyl acrylate)-b-polystyrene triblock copolymer particles, a seed was first generated from butyl acrylate particles. The seed was further swollen with butyl acrylate to form central poly(butyl acrylate) block in the emulsion particles. The particles were then added with styrene to form two blocks of styrene around the central poly(butyl acrylate) block to form the triblock copolymer. In another study using ATRP, the seeded-poly­mer­i­za­tion approach was used to synthesize block copolymers of poly(i-butyl methacrylate) and polystyrene using ethyl 2-bromoisobutyrate as initiator and CuBr/4,4’-dinonyl-2,2’-dipyridinyl as catalyst ligand

24

Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

800 nm

300 nm (a)

(b)

100 nm (c)

250 nm (d)

Figure 1.17 (a, b) SEM and TEM micrographs of latex particles functionalized with an ATRP initiator. (c, d) The grafted brushes of thermally responsive poly­mer poly(N-isopropylacrylamide) from the surface of the ATRP initiator functionalized particles.

complex [26]. Tween 80 (polyoxyethylene sorbitan monooleate) was used as surfactant. First a seed of poly(i-butyl methacrylate) end-capped with ATRP initiator was prepared to which a batch of styrene then was added to form a block copolymer. Thermally responsive poly­mer particles were also reported by the use of ATRP [27–29]. The process included the synthesis of seed particles, functionalization of seed particles by ATRP initiator, and the grafting of the poly(N-isopropylacrylamide) chains from the surface. Figure 1.17 shows these functional particles [28]. In another study using RAFT poly­mer­i­za­ tion, core-shell functional particles were achieved by using o-­ethylxanthyl

Polymer Latex Technology: An Overview

25

pTA/RuO4 cryo

Observation at –150°C

Figure 1.18 Core-shell particles of polystyrene-b-poly(butyl acrylate)/poly(acetoacetoxy ethyl methacrylate). The black core represents polystyrene whereas the soft shell is poly(butyl acrylate)/ poly(acetoacetoxy ethyl methacrylate) component. (Reprinted from M. J. Monteiro and J. de Barbeyrac, Macromolecules 34: 4416–23, 2001. With permission from the American Chemical Society.)

ethyl propionate as RAFT agent [30]. The poly­mer­i­za­tion reactions were carried out in the presence of poly(methyl methacrylate) seed particles of predetermined number and size distribution. The seed was added first with styrene monomer to form polystyrene block, which was then added with butyl acrylate. Styrene was added in batch conditions, whereas butyl acrylate was added slowly to the emulsion system so as to avoid the buildup of high concentration of monomer in this system. Similarly, core-shell particles consisting of block copolymer of polystyrene-b-poly/butyl acrylate)/ poly(acetoacetoxy ethyl methacrylate) were also prepared by using xanthates as RAFT agents. Figure  1.18 shows the TEM image of such core-shell particles [31]. Miniemulsion poly­mer­i­za­tion has also been extensively used for the synthesis of functional latex particles [32–38].

References

1. Odian, G. 2004. Principles of poly­mer­iz­ a­tion. Hoboken, NJ: John Wiley & Sons. 2. Landfester, K. 2001. Polyreactions in miniemulsions. Macromolecular Rapid Communications 22:896–936.

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Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

3. Schork, F. J., Luo, Y., Smulders, W., Russum, J. P., Butté, A., and K. Fontenot. 2005. Miniemulsion poly­mer­i­za­tion. Advances in Polymer Science 175:129–255. 4. Matyjaszewski, K., and T. P. Davis. 2002. Handbook of radical poly­mer­i­za­tion. Hoboken, NJ: John Wiley & Sons. 5. Hiemenz, P. C., and R. Rajagopalan. 1997. Principles of colloid and surface chemis­ try. New York: Marcel Dekker. 6. Mittal, V. 2009. Advances in poly­mer latex technology. New York: Nova Science Publishers. 7. Nicolas, J., Charleux, B., and S. Magnet. 2006. Multistep and semibatch nitroxide-mediated controlled free-radical emulsion poly­mer­i­za­tion: A significant step toward conceivable industrial processes. Journal of Polymer Science, Part A: Polymer Chemistry 44:4142–53. 8. Eslami, H., and S. Zhu. 2005. Emulsion atom transfer radical poly­mer­i­za­tion of 2-ethylhexyl methacrylate. Polymer 46:5484–93. 9. Szkurhan, A. R., Kasahara, T., and M. K. Georges. 2006. Reversible-addition fragmentation chain transfer radical emulsion poly­mer­i­za­tion by a nanoprecipitation process. Journal of Polymer Science, Part A: Polymer Chemistry 44:5708–18. 10. Ferguson, C. J., Hughes, R. J., Nguyen, D., Pham, B. T. T., Gilbert, R. G., Serelis, A. K., Such, C. H., and B. S. Hawkett. 2005. Ab initio emulsion poly­mer­iz­ a­tion by RAFT-controlled self-assembly. Macromolecules 38:2191–2204. 11. Cunningham, M. F. 2008. Controlled/living radical poly­mer­i­za­tion in aqueous dispersed systems. Progress in Polymer Science 33:365–98. 12. Reimers, J. L., and F. J. Schork. 1996. Predominant droplet nucleation in emulsion poly­mer­i­za­tion. Journal of Applied Polymer Science 60:251–62. 13. Reimers, J., and F. J. Schork. 1996. Robust nucleation in poly­mer-stabilized miniemulsion poly­mer­iz­ a­tion. Journal of Applied Polymer Science 59:1833–41. 14. Reimers, J. L., and F. J. Schork. 1996. Miniemulsion copoly­mer­i­za­tion using water-insoluble comonomers as cosurfactants. Polymer Reaction Engineering 4:135–52. 15. Reimers, J. L., and F. J. Schork. 1997. Lauroyl peroxide as cosurfactant in miniemulsion poly­mer­i­za­tion. Industrial Engineering Research 36:1085–87. 16. Mouran, D., Reimers, J., and F. J. Schork. 1996. Miniemulsion poly­mer­iz­ a­tion of methyl methacrylate with dodecyl mercaptan as cosurfactant. Journal of Polymer Science, Part A: Polymer Chemistry 34:1073–81. 17. Pan, G., Sudol, E. D., Dimonie, V. L., and M. S. El-Aasser. 2002. Surfactant concentration effects on nitroxide-mediated living free radical miniemulsion poly­ mer­i­za­tion of styrene. Macromolecules 35:6915–19. 18. Pan, G., Sudol, E. D., Dimonie, V. L., and M. S. El-Aasser. 2001. Nitroxide-mediated living free radical miniemulsion poly­mer­i­za­tion of styrene. Macromolecules 34:481–88. 19. Matyajaszewski, K., Qiu, J., Tsarevsky, N. V., and B. Charleux. 2000. Atom transfer radical poly­mer­iz­ a­tion of n-butyl methacrylate in an aqueous dispersed system: A miniemulsion approach. Journal of Polymer Science, Part A: Polymer Chemistry 38:4724–34. 20. Moad, G., Chiefari, J., Chong, Y. K., Krstina, J., Mayadunne, R. T. A., Postma, A., Rizzardo, E., and S. H. Thang. 2002. Living free radical poly­mer­i­za­tion with reversible addition-fragmentation chain transfer (the life of RAFT). Polymer International 49:993–1001.

Polymer Latex Technology: An Overview

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21. Butté, A., Storti, G., and M. Morbidelli. 2001. Miniemulsion living free radical poly­mer­i­za­tion by RAFT. Macromolecules 34:5885–96. 22. Qi, G., Jones, C. W., and F. J. Schork. 2007. RAFT inverse miniemulsion poly­mer­ i­za­tion of acrylamide. Macromolecular Rapid Communications 28:1010–16. 23. Du, Y. Z., Ma, G. H., Ni, H. M., Nagai, M., and S. Omi. 2002. Morphological studies in thermally initiated emulsion (co)poly­mer­i­za­tion without conventional initiators. Journal of Applied Polymer Science 84:1737–48. 24. Cho, I., and K. W. Lee. 1985. Morphology of latex particles formed by poly(methyl methacrylate)-seeded emulsion poly­mer­i­za­tion of styrene. Journal of Applied Polymer Science 30:1903–26. 25. Nicolas, J., Charleux, B., Guerret, O., and S. Magnet. 2005. Nitroxide-mediated controlled free-radical emulsion poly­mer­i­za­tion using a difunctional water­soluble alkoxyamine initiator. Toward the control of particle size, particle size distribution, and the synthesis of triblock copolymers. Macromolecules 38:9963–73. 26. Okubo, M., Minami, H., and J. Zhou. 2004. Preparation of block copolymer by atom transfer radical seeded emulsion poly­mer­i­za­tion. Colloid and Polymer Science 282:747–52. 27. Mittal, V., Matsko, N. B., Butté, A., and M. Morbidelli. 2007. Functionalized polystyrene latex particles as substrates for ATRP: Surface and colloidal characterization. Polymer 48:2806–17. 28. Mittal, V., Matsko, N. B., Butté, A., and M. Morbidelli. 2007. Synthesis of temperature responsive poly­mer brushes from polystyrene latex particles functionalized with ATRP initiator. European Polymer Journal 43:4868–81. 29. Mittal, V., Matsko, N. B., Butté, A., and M. Morbidelli. 2008. Swelling deswelling behavior of PS-PNIPAAM copolymer particles and PNIPAAM brushes grafted from polystyrene particles & monoliths. Macromolecular Materials and Engineering 293:491–502. 30. Smulders, W., and M. J. Monteiro. 2004. Seeded emulsion poly­mer­i­za­tion of block copolymer core-shell nanoparticles with controlled particle size and molecular weight distribution using xanthate-based RAFT poly­mer­i­za­tion. Macromolecules 37:4474–83. 31. Monteiro, M. J., and J. de Barbeyrac. 2001. Free-radical poly­mer­i­za­tion of styrene in emulsion using a reversible addition-fragmentation chain transfer agent with a low transfer constant: Effect on rate, particle size, and molecular weight. Macromolecules 34:4416–23. 32. Farcet, C., and B. Charleux. 2002. Nitroxide-mediated miniemulsion poly­mer­i­ za­tion of n-butyl acrylate: Synthesis of controlled homopolymers and gradient copolymers with styrene. Macromolecular Symposia 182:249–60. 33. Tortosa, K., Smith, J.-A., and M. F. Cunningham. 2001. Synthesis of ­polystyrene-block-poly(butyl acrylate) copolymers using nitroxide-­mediated living radical poly­mer­i­za­tion in miniemulsion. Macromolecular Rapid Commun­ ications 22:957–61. 34. Keoshkerian, B., MacLeod, P. J., and M. K. Georges. 2001. Block copolymer synthesis by a miniemulsion stable free radical poly­mer­i­za­tion process. Macromolecules 34:3594–99. 35. Li, M., Jahed, N. M., Min, K., and K. Matyjaszewski. 2004. Preparation of linear and star-shaped block copolymers by ATRP using simultaneous reverse and normal initiation process in bulk and miniemulsion. Macromolecules 37:2434–41.

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36. Min, K., Li, M., and K. Matyjaszewski. 2005. Preparation of gradient copolymers via ATRP using a simultaneous reverse and normal initiation process. I. Spontaneous gradient. Journal of Polymer Science, Part A: Polymer Chemistry 43:3616–22. 37. Min, K., Gao, H., and K. Matyjaszewski. 2005. Preparation of homopolymers and block copolymers in miniemulsion by ATRP using activators generated by electron transfer (AGET). Journal of the American Chemical Society 127:3825–30. 38. Luo, Y., and X. Liu. 2004. Reversible addition-fragmentation transfer (RAFT) copoly­mer­i­za­tion of methyl methacrylate and styrene in miniemulsion. Journal of Polymer Science, Part A: Polymer Chemistry 42:6248–58.

2 Synthesis of Polymer Particles with Core-Shell Morphologies Claudia Sayer and Pedro Henrique Hermes de Araújo Contents 2.1 Introduction................................................................................................... 29 2.2 Equilibrium and Nonequilibrium Morphologies....................................30 2.2.1 Equilibrium Morphologies.............................................................. 31 2.2.2 Nonequilibrium Morphologies....................................................... 33 2.3 Synthesis of Core-Shell Particles................................................................ 35 2.3.1 Emulsion Polymerization................................................................ 35 2.3.1.1 Synthesis of Core-Shell Particles (CS)............................. 37 2.3.1.2 Synthesis of Inverted Core-Shell Particles (ICS)............ 41 2.3.2 Miniemulsion Polymerization........................................................43 2.3.3 Microemulsion Polymerization...................................................... 47 2.3.4 Dispersion Polymerization.............................................................. 47 2.3.5 Suspension Polymerization............................................................. 48 2.3.6 Other Techniques.............................................................................. 49 2.4 Characterization of Core-Shell Particles.................................................... 52 2.4.1 Transmission Electron Microscopy................................................ 52 2.4.2 Scanning Electron Microscopy.......................................................54 2.4.3 Atomic Force Microscopy................................................................54 2.4.4 Additional Techniques Used for Particle Characterization........54 References................................................................................................................ 55

2.1 Introduction Core-shell poly­mer particles have received a great deal of industrial and academic interest in the last decades. These multicomponent particles with controlled morphology create a versatile class of materials in which the final properties depend not only on the composition of each poly­mer phase but also on the morphology of these particles. This characteristic opens the

29

30

Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

­ ossibility for tailor-made properties for each application as, for instance, p soft core–hard shell results in particles suitable to act as impact modifiers, and hard core–soft shell latex particles result in paints with low film formation temperature. In addition, via core-shell poly­mer­i­za­tion, it is also possible to get incompatible polymers into one particle or to add functionality either into the core or into the shell (Koskinen and Wilén 2009). Structured particles can be obtained with different morphologies: welldefined core-shell structure, inverted core-shell, interface with a gradient of both core and shell, interface with microclusters, and multiple or irregularly shaped shells (Sundberg and Durant 2003). The final morphology depends on both thermodynamic and kinetic aspects, as quite frequently the equilibrium morphology may not be achieved due to kinetic control of the morphology development. The poly­mer­i ­za­t ion techniques play a major role in the particle size as well as in the kinetic control of the poly­mer­i ­za­t ion. Several heterogeneous poly­mer­i ­za­t ion techniques such as emulsion, miniemulsion, microemulsion, dispersion, and suspension ­poly­mer­i ­za­t ions could be employed to obtain poly­mer particles with core-shell structures. The first three techniques lead to the formation of submicrometric particles (10–800  nm), whereas the two last are used, respectively, to prepare small (1–30  µm) and large (50–1500  µm) micro­metric particles. The end use properties of the structured particles depend on the design and control of particle morphology; therefore, it is necessary to understand how this morphology can be controlled and which are the main features of each poly­mer­i ­za­t ion technique related to particle morphology control. The purpose of this chapter is to describe the factors that will lead to a certain particle morphology and to discuss the heterogeneous poly­mer­i­za­ tion techniques that could be employed to obtain those particles. Section 2.2 introduces the basics of equilibrium and nonequilibrium morphologies. Section 2.3 deals with the different heterogeneous poly­mer­i­za­tion techniques and the main features related to morphology control. Section 2.4 discusses briefly the characterization techniques, as any work in this area relies on the need to adequately characterize particle morphology.

2.2 Equilibrium and Nonequilibrium Morphologies The formation of core-shell particles is a challenging issue of poly­mer reaction engineering in dispersed media. In principle, the most stable particle morphology is determined by thermodynamics according to the minimum interfacial energy (González-Ortiz and Asua 1995), as given by Equation (2.1):

31

Synthesis of Polymer Particles with Core-Shell Morphologies



1 φ= 2

3

3

∑∑ a σ ij

ij



(2.1)

i=1 j=1 j≠i

where aij and σij are, respectively, the interfacial area and the interfacial tension between phases i and j. Nevertheless, frequently the equilibrium morphology is not achieved since particle morphology depends on the interplay between thermodynamics, which establishes the equilibrium morphology, and kinetics. If kinetic control prevails, nonequilibrium-type (metastable or kinetically stable) structures may be formed. In the following paragraphs, equilibrium morphologies and the main factors that establish these morphologies will be discussed, followed by nonequilibrium ones. 2.2.1 Equilibrium Morphologies Figure  2.1 shows four different equilibrium morphologies for a two­component system based on the poly­mer-poly­mer and poly­mer-aqueous phase interfacial tensions, which determine the interfacial energy and, consequently, also the equilibrium morphology for a given system. The equilibrium morphologies are: • Core-shell (CS), in which the second-stage poly­mer 2 (●) forms a continuous shell around the seed poly­mer 1 (○) dispersed in the aqueous phase 3. This equilibrium morphology might be achieved when either (a) poly­mer 1 is more hydrophobic than poly­mer 2 (σ13 > σ23) and poly­mer 2 has more affinity with poly­mer 1 than with the aqueous phase (σ12 < σ23) or (b) poly­mer 1 has more affinity with poly­mer 2 than with the aqueous phase (σ12 < σ13) and poly­mer 2 has less affinity with poly­mer 1 than with the aqueous phase (σ12 > σ23). • Inverted core-shell (ICS), in which the seed poly­mer 1 forms a continuous shell around the second-stage poly­mer 2. This equilibrium morphology might be obtained when poly­mer 2 is more hydrophobic than poly­mer 1 (σ23 > σ13) and poly­mer 2 has more affinity with poly­ mer 1 than with the aqueous phase (σ12 < σ23). • Hemisphere, snowman-like, Janus, half-moon, occluded, partially engulfed, depending on the different degrees of protrusion and on the different curvatures of the poly­mer/poly­mer interface and the coverage of one poly­mer upon the other (Sundberg and Durant 2003). This equilibrium morphology might be achieved under different conditions: (a) when poly­mer 2 has similar affinities with poly­mer 1 and with the aqueous phase (σ12 ≈ σ23); (b) when poly­mer 2 has more



◉

○●

32

Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

(σ23 – σ12) σ13

10

1

0.1 0.1

1

σ12 σ23

10

Figure 2.1 Equilibrium morphologies for a two-component system: ○ poly­mer 1 (seed), ● poly­mer 2 (produced by the poly­mer­i­za­t ion of the second-stage monomer). σ12: interfacial tension between polymers 1 and 2; σ13: interfacial tension between poly­mer 1 and aqueous phase; σ23: interfacial tension between poly­mer 2 and aqueous phase. (Reprinted from V. Herrera, R. Pirri, J. R. Leiza, and J. M. Asua, Macromolecules 39: 6969–74, 2006. With permission.)

○●

affinity with poly­mer 1 than with the aqueous phase (σ12 < σ23) and both polymers have similar affinities with the aqueous phase (ǀσ23 – σ12ǀ ≤ σ13); (c) when poly­mer 2 has less affinity with poly­mer 1 than with the aqueous phase (σ12 > σ23) and poly­mer 1 has similar affinities with poly­mer 2 and the aqueous phase (ǀσ23 – σ12ǀ ≤ σ13). • Separate particles of the different polymers. This equilibrium morphology might be obtained when both polymers have more affinity with the aqueous phase than with each other (σ13 < σ12) and (σ23 < σ12). As shown in Figure  2.1, equilibrium morphologies of two-component systems are established basically by three interfacial tension values. Notwithstanding, several factors influence these three interfacial tensions and may, therefore, be used for particle morphology control purposes. Besides poly­mer types, which determine the interfacial tension between the polymers and affect the interfacial tension between each poly­mer and the aqueous phase, poly­mer-poly­mer interfacial tension can be influenced substantially by compatibilizing agents, and the interfacial tensions between each poly­mer and the aqueous phase are also affected by the types and amounts of surfactant and initiator. In addition, it has been shown that the equilibrium morphology may also be affected by the level of cross-linking of poly­mer 1, which influences the free energy (Sundberg and Durant 2003), and by the molecular weights of the polymers, since the interfacial tension between the poly­mer phases, which is much lower than that between the poly­mer and the aqueous phase, depends on the molecular weight (Tanaka

Synthesis of Polymer Particles with Core-Shell Morphologies

33

et al. 2008). Finally, the ratio between polymers 1 and 2 may affect the curvature of the poly­mer-poly­mer interface in the hemisphere morphology (Sundberg and Durant 2003), and the CS and ICS morphologies may not be achieved if the amount of the shell forming poly­mer (poly­mer 2) in CS and poly­mer 1 in ICS is not enough to form a continuous shell with a minimum thickness. If copolymers are to be considered, the analysis becomes more complex since the surface and interfacial tensions depend on the copolymer compositions. 2.2.2 Nonequilibrium Morphologies As mentioned at the beginning of this section, quite frequently the equilibrium morphology is not achieved due to kinetic control of the morphology development. In this case, nonequilibrium-type structures may be formed. Three main processes have been used by González-Ortiz and Asua (1995, 1996a, 1996b) to describe the morphology development:

1. The formation of poly­mer chains occurs at a given position in the poly­mer particle.



2. Incompatible poly­mer chains cause phase separation leading to the formation of clusters.



3. Clusters migrate toward the equilibrium morphology in order to minimize the Gibbs free energy. During this migration the size of the clusters may increase by (i) poly­mer­i­za­tion of monomer inside the cluster, (ii) diffusion of poly­mer chains into the cluster, and (iii) coagulation with other clusters. The rates of process (ii) and (iii) depend strongly on the particle viscosity.

The Sundberg group has studied the effect of several factors on the morphology development during two-stage emulsion poly­mer­i­za­tions, especially those involving the less hydrophobic copolymer of methyl methacrylate and methyl acrylate as seed poly­mer and polystyrene as the more hydrophobic second-stage poly­mer. Durant et al. (1997) verified the influence of different amounts of cross-linking monomer (EGDMA) during the syntheses of the PMMA cores on the morphology of PMMA/PS particles. It was observed that 0.015  wt% EGDMA was enough to shift the particle morphology from ICS (second-stage PS in the core) toward CS. At 0.2 wt% EGDMA, the particles was essentially of the CS morphology. Cross-linking during the second stage, on the other hand, was observed by Stubbs and Sundberg (2006) to have very little, if any, effect on morphology, though it enhances the mechanical stability of the shell. The effect of the feed rate of the second-stage more hydrophobic monomer (styrene) when less hydrophobic high-Tg seed polymers (poly[methyl methacrylate]) are used was studied by Stubbs et al. (1999). Fast second-stage monomer addition resulted in CS

34

Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

particles, whereas slower addition increased the number of occlusions of the hydrophobic second-stage poly­mer. When less hydrophobic low-Tg seed poly­ mer (poly[methyl acrylate]) was used, ICS was obtained independently of the second-stage monomer feed rate. Ivarsson et al. (2000) and Karlsson et al. (2003) verified that it is possible to keep the more hydrophobic second-stage poly­mer (styrene) at the shell of the particles if the reaction temperature is less than 15°C above Tg of the seed copolymer (poly[methyl methacrylate]/ poly[methyl acrylate]). Stubbs and Sundberg (2004) observed that, though ionic initiators that are able to anchor the chains of the second-stage poly­mer to the particle surface make it more likely to obtain CS morphologies with poly(methyl methacrylate)/poly(methyl acrylate) core and polystyrene shell under some conditions, this effect is not dominant under most conditions. Based on these results, Stubbs and Sundberg (2008) proposed the decision flowchart shown in Figure 2.2 to be used for morphology prediction of latex particles obtained by emulsion poly­mer­i­za­tion. Stubbs and Sundberg (2008) considered three main questions for the prediction of the morphology of composite particles: the first one is whether radicals may penetrate during the second stage of the synthesis, the second is about phase separation, and the last is related to phase consolidation. The theory of radical penetration considers that in emulsion poly­mer­i­za­tion, radicals are typically created in the water phase, and thus enter latex particles at the outer particle surface.

1

Penetration possible?

Yes No

Yes Phase separation possible? Yes Phase consolidation possible? Yes Extent large or small?

No

2

σ13 > σ23 No

4 No

Core-shell

Gradient or mixed phase Small occlusions

Yes

Tg2 < Treaction No

Core-shell 3

5

Small

Large occlusions

Large

Equilibrium morphology

Lobed particle

6 7

Figure 2.2 Adaptation of the decision tree flowchart for predicting morphology development in multiphase particles proposed by Stubbs and Sundberg (2008). σ13: interfacial tension between poly­ mer 1 and aqueous phase; σ23: interfacial tension between poly­mer 2 and aqueous phase; Tg2: glass transition temperature of poly­mer 2. (Reprinted from J. M. Stubbs and D. C. Sundberg, Progress in Organic Coatings 61: 156–65, 2008. With permission.).

Synthesis of Polymer Particles with Core-Shell Morphologies

35

The extent of radical penetration will depend on the effective Tg of the seed poly­mer. The effective Tg considers that the particle will be partially swollen with second-stage monomer during the poly­mer­i­za­tion and this will lower its glass transition temperature below that of the pure poly­mer. When penetration is possible, a second-stage poly­mer chain will find itself inside the particle and fully entangled with the seed poly­mer chains. Phase separation then requires chain diffusion in order to get multiple chains together, and this process may be so slow that phase separation is not possible. The driving force for morphology rearrangement is the minimization of interfacial free energy, and the system will evolve toward the equilibrium morphology if given sufficient time. However, the process of phase consolidation requires an increased extent of poly­mer mobility compared to the previous two processes of oligomeric radical penetration and poly­mer phase separation.

2.3 Synthesis of Core-Shell Particles Particles with core-shell morphologies may be synthesized by a number of heterogeneous poly­mer­i­za­tion techniques such as emulsion, miniemulsion, microemulsion, dispersion, and suspension poly­mer­i­za­tions. The first three techniques lead to the formation of submicrometric particles (10–800  nm), whereas the two last are used, respectively, to prepare small (1–30 µm) and large (50–1500  µm) micrometric particles. Nevertheless, it must be kept in mind that in any of these techniques, the application of a two-stage strategy to build up a shell of the second-stage poly­mer onto the core of the first-stage poly­mer core will not necessarily lead to the formation of particles with coreshell morphology (Rajatapiti et al. 1997). In the next sections, the synthesis of particles with core-shell structure by these different techniques will be described. A detailed description of these poly­mer­i­za­tion techniques can be found in several excellent books involving emulsion poly­mer­i­za­tion (Piirma 1982; Gilbert 1995; Lovell and El-Aasser 1997; Van Herk 2005), as well as in recent book chapters about emulsion (de la Cal et al. 2005; Nomura et al. 2005), miniemulsion (Schork et al. 2005), microemulsion (Chow and Gan 2005), dispersion (Kawagushi and Ito 2005), suspension (Brooks 2005), and heterogeneous (Van Herk and Monteiro 2002) poly­mer­i­za­tion techniques. 2.3.1 Emulsion Polymerization Emulsion poly­mer­i­za­tion is a heterogeneous poly­mer­i­za­tion system composed of water, an initiator (usually water soluble), surfactant (usually above the critical micelle concentration [CMC]), and monomer with low water solubility, which under stirring forms droplets with diameters ranging from 1 to

36

Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

10  µm. The main locus of poly­mer­i­za­tion is not in these monomer droplets, but within the submicrometric monomer-swollen poly­mer particles (60–800 nm). In ab initio emulsion poly­mer­i­za­tions, these poly­mer particles are formed at the beginning of the poly­mer­i­za­tion by the entry of radicals into micelles, if the surfactant concentration is above the CMC (micellar nucleation mechanism) and/or by the precipitation of growing oligomers in the aqueous phase (homogeneous nucleation mechanism). Due to the relatively large size of the monomer droplets compared to the size of monomer-swollen micelles (10–20 nm), the surface area of the monomer droplets is orders of magnitude smaller than that of the micelles and, consequently, the radical entry into monomer droplets (droplet nucleation) is insignificant. Since monomer droplet nucleation is insignificant and monomer-swollen poly­mer particles, instead of monomer droplets, are the main poly­mer­i­za­tion locus, monomer droplets act as monomer reservoirs and the monomer must be transported from these droplets by diffusion through the aqueous phase to allow the growth of the poly­mer particles by poly­mer­i­za­tion. In seeded emulsion poly­mer­i­za­tions, poly­mer particles (seeds) are added at the beginning of the poly­mer­i­za­tion and, usually, these reactions are conducted in the absence of micelles to avoid secondary particle nucleation. Seeded emulsion poly­mer­i­za­tion is by far the most applied technique for the synthesis of structured poly­mer particles with core-shell morphology. And two operation modes, batch and semicontinuous, with or without preswelling of the seed particles, are commonly used in these seeded emulsion poly­mer­i­ za­tions. When direct CS particles with a first-stage poly­mer core and a secondstage poly­mer shell are to be obtained, usually the second-stage monomer is continuously fed at a prespecified rate in order to allow the second-stage poly­mer to build up upon the surface of the seed particles, forming a uniform and continuous shell. In this case, reaction conditions that avoid or minimize phase consolidation are often required, especially in those cases in which the CS morphology is not the equilibrium morphology. When, on the other hand, ICS particles with a second-stage poly­mer core and a first-stage poly­mer shell are to be obtained, usually seed particles are swelled by the second-stage monomer prior to either batch or flooded semicontinuous poly­mer­i­za­tion of the second monomer, since conditions that allow phase consolidation are required for phase inversion leading to the equilibrium ICS morphology. The choice of the best operation mode relies strongly on the poly­mer types and whether the core-shell morphology is to be achieved directly (CS) or through phase inversion (ICS). In the following, the syntheses of CS and ICS particles via emulsion poly­ mer­i­za­tion will be discussed. This also includes some works in which the first-stage poly­mer seeds were synthesized via miniemulsion poly­mer­i­ za­tion and the second-stage monomer poly­mer­i­za­tion was performed via emulsion poly­mer­i­za­tion.

Synthesis of Polymer Particles with Core-Shell Morphologies

37

2.3.1.1 Synthesis of Core-Shell Particles (CS) In this strategy the second-stage poly­mer should build up upon the surface of the seed particles, forming a uniform and continuous and, consequently, concentric shell. As a consequence, CS particles may be formed independently of this being the equilibrium morphology. If CS is not the equilibrium morphology, reaction conditions must be carefully adjusted to avoid and/or minimize phase consolidation. Several conditions may favor the formation of CS particles: • High superficial area of the first-stage poly­mer. This can be achieved by using small seed particles and/or high seed contents. • Reaction temperature below or close to the glass transition temperature of the poly­mer particles. If the Tg of the seed poly­mer is not too low, this might be achieved by starved second-stage monomer feed and/or high initiation rate to keep second-stage monomer concentration, and its plasticizing effect, low in the particles. • Cross-linked core poly­mer to reduce diffusion of the second-stage monomer and, especially, of the radicals into seed particles. • Enhanced hydrophobicity of seed poly­mer through its synthesis using an oil-soluble initiator and/or copoly­mer­i­za­tion with a hydrophobic monomer. • Aqueous phase initiator that is able to anchor the second-stage radicals at the particle surface. • If the incompatibility between the first- and second-stage polymers is too high to allow the formation of particles with a CS structure, the use of a compatibilizing agent is advised to reduce the poly­mer-­poly­ mer interfacial tension. This compatibilizing agent can be produced in situ by the incorporation of a proper macromonomer (Nelliappan et al. 1996), comonomer (Sherman and Ford 2005), or CRP agent (Herrera et al. 2006) during the synthesis of the seed poly­mer. Though this strategy might seem the most straightforward for the synthesis of CS particles with hydrophobic cores and hydrophilic shells, in some cases it may result in considerable secondary nucleation instead of the formation of CS particles, since several points listed previously, as for instance high aqueous phase initiator concentration, may lead to homogenous particle nucleation. A quite complete study was presented by Ferguson et al. (2002), who succeeded in synthesizing PS/PVAc core-shell latexes with small cores. In this case the small size of the PS seed particles (unswollen diameter of 88 nm) resulted in a high enough superficial area to capture PVAc radicals formed in the aqueous phase. When, on the other hand, PS seed particles with unswollen diameter of 400 nm were used, excessive new particle formation occurred and

38

Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

no PVAc shells could be detected. Numerous strategies for overcoming this were evaluated through simulations with a simplified nucleation model and/or implemented experimentally, as for instance using an organic-phase initiator in the seeded poly­mer­i­za­tion to avoid homogeneous nucleation or addition of surfactant during the seeded poly­mer­i­za­tion in order to maintain the surface charge density and keep the surfactant concentration below the CMC, but always either extensive secondary nucleation occurred or the system became colloidally unstable. Similar results were obtained by Sherman and Ford (2005). The authors used a cross-linked 80/20 PS/PMMA seed 70 nm in diameter to form cationic PS/PMMA CS particles with acentric cores with 530 nm in three steps of PMMA growth, using starved semicontinuous addition of MMA to avoid secondary nucleation and a single initial addition of aqueous phase initiator to provide fast radical generation. The increase of the diameter of the core latex, on the other hand, led to secondary particle nucleation. Due to the incompatibility of PS and PMMA, the equilibrium morphology of the PS/PMMA system is as a double-ball structure. Consequently, when PS homopolymer seeds are used without any procedure to reduce the interfacial tension between both polymers, the CS morphology usually is not attained. A good illustration of the effect of the operation mode on the morphology of PS/PMMA particles was shown in the work of Jönssin et al. (1991). On one extreme, in the seeded batch poly­mer­i­za­tion of MMA, the authors observed the formation of composite particles with large cluster sizes. Whereas when the seeded semicontinuous poly­mer­i­za­tion of MMA was conducted under starved conditions, composite particles with small cluster sizes were formed. Both reduction of particle viscosity and the rate of initiation lead to structures with increased cluster sizes. Postpoly­mer­i­za­tion treatment with solvents leads to the equilibrium morphology (double-ball). In a recent study, Jönssin et al. (2007) verified the morphology of PMMA (first-stage)/PS (second-stage) particles prepared by semicontinuous seeded emulsion poly­mer­i­za­tion of styrene in the presence of polar PMMA seed particles, using different conditions of nonpolar styrene feed rate, radical formation rate, seed particle concentration, and temperature of poly­mer­i­za­tion. The authors observed that, depending on the set of process conditions used, the morphology of the resulting two-phase particles varied from that of a PMMA/PS CS structure, over intermediate structures in which a shell of PS surrounded a PMMA core containing an increasing number of PS clusters, to a structure in which the entire PS phase was present as discrete PS phase clusters, more or less evenly distributed in a matrix of PMMA. Figure 2.3 (a–d) shows transmission electron microscopy (TEM) micrographs of the microtomed sections of samples of reactions A, B, and C conducted with the same formulation and under the same conditions except for the second-monomer (styrene) feed rate, which was increased from A to C and of reaction D, carried out with the same formulation and conditions of reaction C, but with a higher initiator (KPS) feed rate. The higher the feed rate of the second monomer, the higher is its plasticizing effect and the lower is the Tg of the poly­mer

Synthesis of Polymer Particles with Core-Shell Morphologies

(a)

(b)

(c)

(d)

39

Figure 2.3 (a–d) TEM micrographs of thin sections taken from particles obtained in experiments A–D. (e) Rate of poly­mer­i­za­t ion for experiments A–D. (f) The amount of styrene accumulated in the reactor as calculated from the poly­mer­i­za­t ion curves from experiments A–D, F, and G. (Reprinted from J.-E. L. Jönsson, O. L. Karlsson, H. Hassander, and B. Törnell, European Polymer Journal 43: 1322–32, 2007. With permission.)

40

Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

Rate of Polymerization (W)

1.2 D

1

C

0.8

B

0.6

A

0.4 0.2 0

0

100

200

300 400 Time (min.) (e)

500

600

Accumulated Styrene (g/g)

0.25 C

0.2 0.15

G

0.1 0.05 0

B

D

A F

0

100

200

300 400 Time (min.) (f )

500

600

Figure 2.3 (continued).

particles; consequently, the higher becomes the diffusivity of the entering oligo radicals, increasing the number and distributing more homogeneously the PS clusters in the PMMA matrix. Results of reaction D, conducted with the same styrene feed rate as reaction C, but with a higher initiator feed rate, indicate the formation of a direct CS structure; this is attributed to the high reaction rate (Figure 2.3e), leading to low monomer concentrations in the poly­mer particles (Figure  2.3f) and, consequently, increasing the Tg of the poly­mer particles to only a few degrees below the reaction temperature. Consequently, contrary to the expected equilibrium morphologies, twophase particles with a true core-shell structure were obtained in experiments where the estimated glass transition temperature of the PMMA phase was only a few degrees below the poly­mer­i­za­tion temperature, independently

Synthesis of Polymer Particles with Core-Shell Morphologies

41

of the feed rate of the second monomer, provided that the rate of initiation, using an aqueous phase initiator, was properly adjusted. The formation of particles with nonequilibrium morphologies was also observed by Zhao et al. (2004), who studied the morphological development of PVAc (first-stage)/PBuA (second-stage) in seeded semicontinuous starved emulsion poly­mer­i­za­t ion using an aqueous phase initiator in the synthesis of both seed and second-stage poly­mer. The authors observed that, despite the low Tgs of both seed and second-stage polymers, the PBuA was formed at the outside of the PVAc seed. After storage for 1.5 years at room temperature, latex morphology evolved to the equilibrium morphology, which for this system is ICS with PBuA core and a PVAc (more hydrophilic) shell. 2.3.1.2 Synthesis of Inverted Core-Shell Particles (ICS) As mentioned in the previous section (2.3.1.1), sometimes the synthesis of structured poly­mer particle presenting the core-shell morphology may be very difficult, either because the CS morphology is not favored thermodynamically or because secondary particle nucleation is difficult to avoid. Often in these cases, the synthesis of ICS particles formed by a core of the secondstage poly­mer and a shell of first-stage poly­mer is an alternative that should not be discarded. For the synthesis of inverted core-shell particles, conditions must be carefully chosen to favor phase inversion. Consequently, contrary to CS particles, ICS particles may be formed only if this is the equilibrium morphology. Several conditions may favor the formation of ICS particles: • High superficial area of the first-stage poly­mer to avoid secondary particle nucleation. This can be achieved by using small seed particles and/or high seed contents. • Reaction temperature much above (Ivarsson et al. 2000; Karlsson et al. 2003) glass transition temperature of the poly­mer particles. This might be achieved by either batch or flooded semicontinuous second-stage poly­mer­i­za­tion with preswelling and/or low initiation rate to keep second-stage monomer concentration, and its plasticizing effect, high in the particles. • Chain transfer agent (CTA) to reduce the molecular weight of the polymers. • Enhanced hydrophilicity of seed poly­mer through its synthesis using an aqueous phase initiator and/or copoly­mer­i­za­tion with a hydrophilic monomer. • Enhanced hydrophobicity of the second-stage poly­mer through its synthesis using an oil-soluble initiator that is not able to anchor the second-stage radicals at the particle surface.

42

Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

• If the incompatibility between the first- and second-stage polymers is too high to allow the formation of particles with an ICS structure, the use of a compatibilizing agent is advised to reduce the ­poly­mer-­poly­mer interfacial tension. This compatibilizing agent can be produced in situ by the incorporation of a proper macromonomer (Nelliappan et al. 1996), comonomer (Sherman and Ford 2005), or CRP agent (Herrera et al. 2006) during the synthesis of the seed poly­mer. Most of the factors just listed were mentioned by Lee and Ishikawa (1983), who found that when hydrophobic monomers are poly­mer­ized in the presence of highly hydrophilic poly­mer seed particles, the second-stage hydrophobic polymers form cores surrounded by the first-stage hydrophilic polymers, resulting in inverted core-shell latexes. They also observed that the formation of the core-shell morphology by this inversion process is favored by higher hydrophilicity, lower interfacial tension, lower molecular weight of hydrophilic first-stage poly­mer, and greater phase separation between both polymers, which is expected to increase with greater incompatibility between these polymers, lower glass transition temperatures of both polymers, lower molecular weights and cross-linking, higher poly­ mer­i­za­tion temperatures, and more flooded conditions. In the case of the soft poly­mer pair systems, the formation of inverted core-shell morphology was equally complete, regardless of the molecular weight of the hydrophilic poly­mer molecules, whereas in the case of the hard poly­mer pair systems, the efficiency of inversion was dependent on the molecular weights of both hydrophilic and hydrophobic polymers. In the work of Ferguson et al. (2002), the synthesis of PS(first stage)/ PVAc(second stage) core-shell particles with large cores was hampered by secondary nucleation. Nevertheless, in a different attempt, Ferguson et al. (2003) showed that it is possible to synthesize PS/PVAc core-shell particles with large PS cores through an inverse core-shell synthesis using PVAc seed particles in a batch styrene poly­mer­i­za­tion. For this system, the inverse coreshell morphology is favored thermodynamically, and undesired secondary particle nucleation is avoided by the low aqueous phase solubility of styrene. Nevertheless, the authors observed that conditions had to be chosen carefully in order to minimize the kinetic control on the morphology, allowing the achievement of the ICS morphology. To keep it short, the fast diffusion of the hydrophilic seed poly­mer had to be ensured, for instance by using a chain transfer agent (to reduce the molecular weight and, especially, the degree of branching), an initiator able to minimize grafting between both polymers, and a comonomer in the seed poly­mer to increase its hydrophilicity. An important aspect of ICS syntheses mentioned in this work is that even for those systems in which the ICS is thermodynamically favored and kinetically achievable, there is no driving force for this core to be concentric

Synthesis of Polymer Particles with Core-Shell Morphologies

43

100 nm

100 nm 100 nm (a) Latex 1 (with SG1)

(b) Latex 2 (without SG1)

(c) Latex 3 (with CTA)

Figure 2.4 TEM micrographs of PS/PMMA composite particles stained with PTA and RuO4. (Reprinted from V. Herrera, R. Pirri, J. R. Leiza, and J. M. Asua, Macromolecules 39: 6969–74, 2006. With permission.).

in an ICS latex (as long as the hydrophobic core is shielded from the particlewater interface region). The high incompatibility of the poly­mer phases may be overcome by the incorporation of a compatibilizing agent. Herrera et al. (2006) added during the miniemulsion poly­mer­i­za­tion for the formation of the PMMA seed a small amount of a CRP agent, so that at the end of the seed formation some of the poly­mer chains were capped with the CRP agent. Batch emulsion poly­mer­i­za­tion of the second-stage monomer (styrene, with previous swelling) in the presence of additional initiator led to the in situ formation of block copolymer chains. When PMMA seeds were synthesized in the presence of the CRP agent, ICS structures were formed (Figure  2.4a). On the other hand, in similar reactions with PMMA seeds synthesized without CRP agent, the hemisphere morphology was obtained, independently of the molecular weight of the seed PMMA poly­mer (PMMA seeds formed without, Figure  2.4b, or with chain transfer agent, Figure  2.4c). This result indicated that the in situ formation of block copolymer chains allowed the modification of particle morphology through the reduction of the interfacial tension between the two polymers, helping to increase their compatibility and, consequently, allowing the formation of the ICS morphology. 2.3.2 Miniemulsion Polymerization Miniemulsion poly­mer­i­za­tion differs from a conventional emulsion poly­ mer­i­za­tion in that the monomer droplets, formed with the aid of highshear devices (rotor-stator system, sonifier, high-pressure homogenizer), are in a submicrometric range (50–500 nm) forming a miniemulsion that is

44

Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

thermodynamically unstable, but kinetically metastable (stable for a period ranging from hours to months) due to the addition of a surfactant to minimize coalescence and a costabilizer to retard droplet diffusion degradation (Ostwald ripening). Free surfactant concentrations in the aqueous phase are usually kept below the CMC, and the relatively small size of the monomer droplets favors droplet nucleation. Thus, droplet nucleation and poly­mer­ i­za­tion within the submicrometric miniemulsion droplets are aimed in a miniemulsion poly­mer­i­za­tion. Either oil- or water-soluble initiators may be used. In miniemulsion poly­mer­i­za­tion, the first-stage poly­mer may be dissolved in the second-stage monomer, and this solution, with or without the addition of a costabilizer, is dispersed in the aqueous phase containing a surfactant using an adequate homogenization equipment; the formed miniemulsion of submicrometric organic phase droplets is subsequently poly­mer­ized, maximizing droplet nucleation. This approach has the advantage that the firststage poly­mer must not be in the form of nanoparticles, being well suited for the synthesis of hybrid poly­mer particles composed of a poly­mer produced by step-growth poly­mer­i­za­tion and a poly­mer produced by free radical poly­ mer­i­za­tion (Wang et al. 1996; Wu et al. 1999; Barrere and Landfester 2003; Li et al. 2005; Wang et al. 2005; Guyot et al. 2007; Jahanzad et al. 2007). The drawback of this approach is that the amount of first-stage poly­mer is limited by the viscosity increase of the organic phase, which depends strongly on the molecular weight of the first-stage poly­mer. However, this amount can reach up to 50 wt% related to the organic phase as shown by López et al. (2008), who succeeded in preparing miniemulsions with droplet sizes around 100 nm using first-stage polymers (alkyd resins and poly[ε-caprolactone]) dissolved in acrylic monomers. It has also been shown that hybrid poly­ mer particles may also be synthesized by simultaneous poly­mer­i­za­tion in miniemulsion, as in Barrere and Landfester (2003), who synthesized hybrid polystyrene/polyurethane and poly(butyl acrylate)/polyurethane particles via miniemulsion poly­mer­i­za­tion by combining polyaddition and radical poly­mer­i­za­tion. The hybrid particles obtained by miniemulsion poly­mer­i­za­tion will show only CS or ICS structures if these are the equilibrium morphologies and if they are kinetically achievable. This is the case of the work of Rodríguez et al. (2008), where it was shown that most particles obtained by silicon-acrylic miniemulsion poly­mer­i­za­tion presented nonreactive polydimethyl­siloxane divinyl terminated (PDMS)-rich core morphologies, as PDMS is highly hydrophobic. In the case of the ICS structures, the ratio (first-stage poly­ mer):(second-stage monomer) must be high enough to allow the formation of a continuous shell. An increasing number of publications involve the synthesis via miniemulsion poly­mer­i­za­tion of CS particles with a liquid core (nanocapsules). The procedure is quite the same as for the synthesis of hybrid particles using a

Synthesis of Polymer Particles with Core-Shell Morphologies

45

100 nm (a) Figure 2.5 (a) TEM micrograph of PS (styrene poly­mer­ized with 10 wt% acrylic acid) nanocapsules with hexadecane core in a 1:1 (PS:HD) ratio prepared by miniemulsion poly­mer­i­za­t ion. (Reprinted from K. Tiarks, K. Landfester, and M. Antonietti, Langmuir 17: 908–18, 2006. With permission.) (b) TEM and SEM (insert) micrographs of PMMA nanocapsules with Neobee M-5 core in a 1:1 (PMMA:Neobee M5) ratio obtained by miniemulsion poly­mer­i­za­t ion. Arrows with indexes TEC, PEC, and NEC indicate, respectively, totally engulfing capsules, partially engulfing capsules, and nonengulfing particles. (Reprinted from A. P. Romio, C. Sayer, P. H. H. Araújo, M. Al-Haydari, L. Wu, and S. R. P. da Rocha, Macromolecular Chemistry and Physics 210:747–51, 2009. With permission.)

preformed poly­mer. One difference in this latter case is that phase separation is facilitated by the lower viscosity of the liquid compared to that of a preformed poly­mer. When hydrophobic liquids are to be encapsulated by a poly­mer shell, direct miniemulsion poly­mer­i­za­tion may be applied (Tiarks et al. 2001; Crespy et al. 2006, 2007; Luo and Gu 2007; Romio, Bernardy et al. 2009; Romio, Sayer et al. 2009). In this case, the hydrophobe and monomer form a homogenous organic phase, which is miniemulsified in the aqueous phase, and phase separation in the organic phase occurs throughout the poly­mer­i­za­tion. Figure 2.5 (a and b) shows micrographs of polystyrene (Tiarks et al. 2001) and poly(methyl methacrylate) (Romio, Sayer et al. 2009) nanocapsules synthesized via miniemulsion poly­mer­i­za­tion. A special case of core-shell particles are the onion-like morphologies. This kind of structure can be obtained when block copolymers (of two immiscible homopolymers) are formed. Kagawa et al. (2005) synthesized

46

Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

2 µm

PEC

TEC NEC

1 µm (b) Figure 2.5 (continued).

(b)

(a)

200 nm

200 nm

Figure 2.6 TEM micrographs of ultrathin cross sections of PiBMA-b-PS particles, stained with RuO4 vapor for 30 min, prepared by seeded-ATRP with PiBMA-Br particles prepared by miniemulsion ATRP at Tween 80 concentrations of (a) 3 and (b) 6 wt% based on iBMA. (Reprinted from Y. Kagawa, H. Minami, M. Okubo, and J. Zhou, Polymer 46: 1045–49, 2005. With permission.)

s­ ubmicron-sized poly(i-butyl methacrylate)-block-polystyrene particles with an onion-like multilayered structure (Figure  2.6) using a two-step atom transfer radical poly­mer­i­za­tion (ATRP) in aqueous media: ATRP in miniemulsion to obtain the PiBMA seed particles followed by ATRP in seeded styrene emulsion poly­mer­i­za­tion.

Synthesis of Polymer Particles with Core-Shell Morphologies

47

2.3.3 Microemulsion Polymerization In the same way as emulsion poly­mer­i­za­tion, two-stage microemulsion poly­ mer­i­za­tion may also be used to synthesize CS particles. In this poly­mer­i­za­tion technique, extremely small monomer droplets (10–30 nm) forming a thermodynamically stable microemulsion are obtained by the combination of high surfactant (and cosurfactant) and relatively low monomer concentrations. The advantage of this two-stage microemulsion poly­mer­i­za­tion technique is related to the small sizes and, consequently, high superficial area of the particles that favors radical and monomer entry in detriment to undesired nucleation during the second stage of the poly­mer­i­za­tion. Nonetheless, CS particle synthesis by this technique shows the same drawbacks related to the low monomer content (0–10 wt%) and low monomer:surfactant ratio of other microemulsion poly­mer­i­za­tions. This technique has been used by Jang and Ha (2002) to prepare CS particles of 30 nm in size formed by PMMA core and PS shell with triblock copolymers of poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) [(EO)x(PO)y(EO)x] as surfactant. These CS particles were subsequently treated with a selected solvent to remove the PMMA in order to obtain nanosized hollow polystyrene microlatexes. 2.3.4 Dispersion Polymerization Seeded dispersion poly­mer­i­za­tion is another technique that may be applied for the synthesis of particles with core-shell structures with average particle diameters in the range of 1 to 30 μm. In dispersion poly­mer­i­za­tion, the monomer is completely miscible with the continuous phase that is also composed by one or more nonreactive components, usually an alcohol as methanol or ethanol with or without water and that contains a stabilizer, as for instance poly(vinyl pyrrolidone) and the initiator. As a consequence, dispersion poly­mer­i­za­tion starts as a homogeneous poly­mer­i­za­tion, but, since the poly­mer formed throughout the poly­mer­i­za­ tion is not soluble in the continuous phase, it precipitates, forming colloidal particles that are stabilized by the added stabilizer. Thus, poly­mer­i­za­tion takes place in both continuous and particle phases, in degrees that may be varied, depending on the partitioning of monomer and radicals between these phases. Okubo and Izumi (1999) synthesized PMMA/PS CS particles by seeded dispersion poly­mer­i­za­tion and showed that, when the reaction temperature is below the glass transition temperature of the seed particles, this technique has the advantage of producing core-shell poly­mer particles in which layers accumulate in their order of production (kinetic control of morphology), regardless of the hydrophobicity of polymers forming core and shell, even if the morphology is thermodynamically unstable. This is attributed to the enhanced solubility of the second-stage monomers in the continuous phase

48

Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

(due to the presence of an alcohol) combined with the high glass transition temperature of the seed poly­mer and fast adsorption of poly­mer radicals and inactive chains formed in the continuous phase onto the seed particles. When, however, the rate of adsorption of poly­mer radicals and inactive chains formed in the continuous phase onto the seed particles is slow, the second-stage poly­mer has the tendency to form clusters on the surface of the seed particle, and particles with different morphologies, egg-, snowman-, and confetti-like, may be formed (Fujibayashi et al. 2008). 2.3.5 Suspension Polymerization Suspension poly­mer­i­za­tion is a process in which the poly­mer­i­za­tion of relatively water-insoluble monomer droplets formed by vigorous stirring in the presence of a steric stabilizer leads to an aqueous dispersion of poly­mer particles in the size range of 50 to 1500 µm. To obtain CS particles by suspension poly­mer­i­za­tion, a two-step procedure should be employed, where the seed particles are obtained by suspension poly­mer­i­za­tion and the second-stage monomer is added afterward. The large particle size of the suspension poly­ mer­i­za­tion particles, and the consequently low superficial area, do not favor second-stage monomer absorption; as a consequence, undesired secondary particle nucleation is hard to avoid (Gonçalves et al. 2008a). In addition, if large amounts of second-stage monomer are used to swell seed particles, shear forces inside the reactor may lead to the undesired breakage of the swollen seed particles. And, even with small amounts, if this second-stage monomer concentrates at the outer layers of the seed particles due to slow monomer diffusion inside the particles, this would turn the particle surface very sticky and could lead to particle agglomeration. As a consequence, the synthesis of CS particles via suspension poly­mer­i­za­tion is a quite difficult and challenging task. Gonçalves et al. (2008b) synthesized large polystyrene (PS)/poly(methyl methacrylate) (PMMA) CS-structured particles by seeded (PS seeds) suspension poly­mer­i­za­tion of MMA in which the shell was composed by PMMA clusters densely dispersed in the PS matrix. The size and concentration of these clusters (shell) decreased from the outer shell to the core, and particle morphology was largely controlled by limitations to the diffusion of MMA through the poly­mer particle. As a consequence, thicker shells with a higher amount of incorporated PMMA were obtained by increasing the swelling time. Figure 2.7 shows a TEM micrograph and infrared (IR) data of the cross section of a particle. IR data confirm that the concentration of PMMA, denoted by the intensity of carbonyl absorption bands at 1740 cm–1, reached maximum values near the particle surface and decreased along the particle radius. An alternative for the synthesis of large particles with CS structures is the combination of suspension and emulsion poly­mer­i­za­tion to synthesize, respectively, the core and shell of the particles (Lenzi et al. 2003; Zhenqian

49

Synthesis of Polymer Particles with Core-Shell Morphologies

5 µm

5 µm

5 µm

(a) Figure 2.7 (a) TEM micrographs and the approximated representation of the cross section (stained with RuO4, PMMA appears as light gray and PS as dark gray; 6000x). (b) FTIR spectra of the cross section of a typical core-shell particle obtained with swelling time of 0 min and 0.23 mol% of BPO. (Reprinted from O. H. Gonçalves, J. M. Asua, P. H. H. Araújo, and R. A. F. Machado, Macromolecules 41: 6960–64, 2008. With permission.)

et al. 2009). In this case, the shell is composed by small aggregated emulsion poly­mer­i­za­tion particles, and the CS particles did not present a smooth spherical shape. 2.3.6 Other Techniques Several other techniques have also been described for the formation of CS particles. For instance, the preparation of preformed poly­mer blends in nanoor microparticles through the dissolution of both polymers in a common solvent followed by either the Shirasu porous glass membrane (SPG) emulsification technique (Ma et al. 1999, 2003), emulsification (Tanaka et al. 2008), miniemulsification using high-energy devices (Kietzke at al. 2007), or the nanoprecipitation technique always requires subsequent solvent evaporation

50

Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

0.12 0.10

0.06 0.04 0.02

w

1820 1800 1780 1760 1740 1720 1700 1680 1660 1640

intensity

0.08

–1

cm r(

be

um

en av

P1

P2

P3

P4

P5

P6

P7

0.00 P8

)

(b) Figure 2.7 (continued).

after the dispersion of the organic phase in the aqueous phase. The two former methods lead to the formation of hybrid microparticles, whereas the two latter methods may be used to form hybrid nanoparticles. In all four cases, particles with CS structures may be attained only if this is the equilibrium morphology. The SPG emulsification technique with dichloromethane (DCM) as solvent for the preformed polymers, lauryl alcohol (LOH) as costabilizer, and poly(vinyl alcohol) and sodium lauryl sulfate in the aqueous phase has been reported for the preparation of uniform composite polystyrene/poly(methyl methacrylate) microspheres with diameters around 10 μm (Ma et al. 1999). The morphology of the composite particles was varied by the amount of LOH and by the PMMA:PS ratio, as shown in Figure 2.8. Polymer microcapsules have also been produced by applying microfluidic devices using capillary instability-driven break-up of a liquid jet formed by two immiscible fluids (oil and monomer) followed by photopoly­mer­i­za­tion of the monomeric shells (Nie et al. 2005), resulting in precise control of core number, location, and diameter, as well as shell thickness. Finally, particles having hollow structures, either core-shell or multihollow, have also been synthesized by water-in-oil-in-water (W/O/W) emulsion poly­mer­i­za­tion (Kim et al. 1999) and by a modified emulsion poly­mer­i­za­tion with a watermiscible alcohol and a hydrocarbon nonsolvent for the poly­mer (McDonald et al. 2000).

Synthesis of Polymer Particles with Core-Shell Morphologies

51

(b) 402

(a) 398

10 µm

10 µm

(c) 396

10 µm

(e) 402

1 µm

(d) 398

(f ) 396

1 µm

1 µm

Figure 2.8 Optical micrographs of droplets (a–c) and TEM micrographs of embedded cross section with RuO4 vapor staining of particles (d–f) as a function of the PMMA:PS ratio when 11.9 ml of DCM and 0.1 ml of LOH were used for 0.24 g of poly­mer (PMMA and PS). PMMA/PS (w/w): (a, d) 5/5, (b, e) 4, 6, and (c, f) 1/9. (Reprinted from G. H. Ma, M. Nagai, and S. Omi, Journal of Colloid Interface Science 219: 110–28, 1999. With permission.)

52

Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

2.4 Characterization of Core-Shell Particles The characterization of core-shell particles includes determining the particle shape and the composition of the particle surface and the particle interior. Although microscopy data is required to make definite conclusions about particle morphology, according to Stubbs and Sundberg (2008), no single analytical technique is able to provide all the relevant details about the particle structure, but different techniques are required to adequately characterize the morphology of a given system, even for relatively simple systems. There are several relevant characterization techniques used for particle morphology determination including the direct microscopic techniques such as: TEM (transmission electron microscopy), AFM (atomic force microscopy), and SEM (scanning electron microscopy). Other indirect analyses could be performed by NMR (nuclear magnetic resonance), DSC (differential scanning calorimetry), and IR spectroscopy. And to characterize the latex particle surface, conductometric titration, among others, could also be used. The choice of the techniques used to characterize the core-shell latexes depends on whether the poly­mer particle is being characterized with respect to shape, structure, and/or surface. 2.4.1 Transmission Electron Microscopy TEM is the most widely used technique to characterize core-shell latexes (Gaillard et al. 2007) because a direct image of the structure can be obtained. However, the quality of the results obtained by TEM is a direct result of the sample preparation methods employed and the fact that this technique requires a high level of operator skill (Stubbs and Sundberg 2005b). TEM imaging presents several difficulties due to film formation during sample preparation of latex of low Tg, the weak contrast between the different phases and/or between the particles and the background, and their poor electron beam resistance, causing the deformation of the poly­mer particle during the analysis (Egerton et al. 2004). Most poly­mer analyses are carried out at accelerating voltages of 80 or 100 kV, although several polymers, like acrylic polymers, are more susceptible to radiation damage. Therefore, some limitations of TEM analysis are imposed by the poly­mer system. According to Gaillard et al. (2007), these difficulties could be overcome by using low temperature and/or low exposure to strong electron beam techniques and specimen preparation methods, like chemical staining, avoiding film formation, and stabilizing and enhancing the contrast between the different poly­ mer phases. Cold-stage holders could be used to investigate the particle morphology of low-Tg latex or microgels’ core-shell particles (Ballauff and Lu 2007) because

Synthesis of Polymer Particles with Core-Shell Morphologies

53

dispersions can be frozen, placed into TEM, and imaged. The low temperature also has the advantage of reducing radiation damage that occurs with all polymers (Dimonie et al. 1997). Chemical staining of the poly­mer particles generally has the advantage of hardening many types of poly­mer, which may facilitate specimen preparation and observation. To enhance the contrast between the particles and the background, “negative” staining with phosphotungstic acid (PTA) or uranyl acetate (UAc) is largely applied where the “negative” stain chemically interacts with the carbon film that covers the TEM grid. “Negative” staining is preferably used with latex particles not having reactive groups and that are not stable in the microscope or that are film forming (Karlsson and Schade 2005) like poly(vinyl acetate). “Positive” staining occurs when the chemical stain interacts directly with the poly­mer specimen by diffusion or reaction; the main use of selective “positive” staining with heavy elements (Ru, Os, tungsten, and uranium) is to increase high-angle Rutherford scattering, generating contrast between the stained and the unstained regions of the poly­ mer particle (Ferguson et al. 2002). The most common “positive” chemical staining agents are: osmium tetra oxide, OsO4, which is applied for unsaturated polymers that present residual allylic double bonds such as natural rubber-based latexes or polybutadiene; and ruthenium tetroxide, RuO4, which is more reactive than OsO4 and will react with double bonds in phenyl rings and with amine groups besides allylic double bonds (Trent 1984). RuO4 is particularly useful in morphological studies of multicomponent particles containing polystyrene in one of the phases (Stubbs et al. 1999). To avoid distortion of film-forming latex particles during drying, staining can be done in the liquid phase by adding the positive stain solution to a diluted latex dispersion (Karlsson et al. 1995). The combination of “positive” and “negative” staining methods is also useful to reveal internal structures and to fixate film-forming latexes like PS-PVAc core-shell latex where UAc is used for negative staining and RuO4 for staining the PS phase (Ferguson et al. 2002). Another way to increase the contrast between the poly­mer phases is to resolve one of the phases under exposure of a strong electron beam (200 kV) due to preferential degradation of one of the poly­mer phases. This is particularly true for PMMA/PS core-shell particles (Okubo and Izumi 1999) because PMMA homopolymers are significantly more beam sensitive than styrenic polymers; therefore, there will be a preferential beam-induced mass loss in the MMA-rich copolymer phase. Embedding and sectioning are sample preparation methods that enable one to cut the sample sufficiently thin for the microscope to increase its resolution (Karlsson and Schade 2005). In this technique, dried latex particles are embedded in epoxy resins and cured at room temperature. The cured epoxy/particle blend is then ultramicrotomed to obtain sections in the order of 50–100 nm.

54

Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

2.4.2 Scanning Electron Microscopy Compared to TEM, the resolution of SEM is lower but detailed images of particle surface can be obtained resulting in information regarding size, shape, and structure. High-resolution field emission SEM (FESEM) presents a much higher resolution than conventional SEM using a thermionic emitter (Karlsson and Schade 2005). Typically, the poly­mer dispersion is dried down onto a stub; and to increase the resolution of nonconductive poly­mer, specimen is sputter coated with a ~10- to 20-nm-thick layer of gold or palladium. To observe the different phases in a poly­mer blend, one of the poly­mer phases could be selectively chemically etched off to achieve topographical differences that could be imaged by SEM. However, this is normally not employed on particles obtained by emulsion poly­mer­i­za­tion due to the submicrometric dimensions of these particles. 2.4.3 Atomic Force Microscopy AFM can be used to determine the surface structure of poly­mer particles because it presents a much higher resolution than SEM, making it a very useful tool to study film formation of poly­mer dispersions. No vacuum is needed and no difficult preparation is involved. However, the direct use of AFM for studying single particles has not been widely employed, partly because not all dispersions are suitable for morphology studies by AFM as the poly­mer particle should present at least one accessible low-Tg phase in order to reveal internal morphologies (Karlsson and Schade 2005). 2.4.4 Additional Techniques Used for Particle Characterization Other techniques can be used to complement the information obtained from the direct microscopic techniques. Many of these techniques may be applied in films made from structured latex particles. NMR methods (1H spin-diffusion measurements) can be used in latex films to characterize the interface of two immiscible poly­mer phases and its thickness (Landfester et al. 1996). Careful interpretation of thermal analysis data from DSC can indicate the relative extent of phase separation within the structured latex particles by comparing the size of the ΔCp transitions in DSC for films of latex particles to the transitions for the same pure bulk poly­mer (Stubbs and Sundberg 2005a). Because IR spectroscopy is sensitive to poly­mer composition, it can be used to investigate the structure of core-shell latexes and to deduce the thickness of the interfacial layer from spectral characteristics (Lange et al. 1988). Besides that, when poly­mer particles are large enough, as particles produced by suspension poly­mer­i­za­tion, IR spectroscopy could be employed to quantify poly­mer composition along the particle radius (Gonçalves et al. 2008b).

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55

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Landfester, K., Boeffel, C., Lambla, M., and H. W. Spiess. 1996. Characterization of interfaces in core-shell polymers by advanced solid-state NMR methods. Macromolecules 29:5972–80. Lange, J., Hergeth, W.-D., and S. Wartewig. 1988. Infrared spectroscopy of polymeric core-shell latexes. Acta Polymerica 39:479–81. Lee, D. I., and T. Ishikawa. 1983. The formation of “inverted” core-shell latexes. Journal of Polymer Science, Polymer Chemistry Edition 21:147–54. Lenzi, M. K., Silva, F. M., Lima, E. L., and J. C. Pinto. 2003. Semibatch styrene suspension poly­mer­i­za­tion. Journal of Applied Polymer Science 89:3021–38. Li, M., Daniels, E. S., Dimonie, V., Sudol, E. D., and M. S. El-Aasser. 2005. Preparation of polyurethane/acrylic hybrid nanoparticles via a miniemulsion poly­mer­iz­ a­ tion process. Macromolecules 38:4183–92. López, A., Chemtob, A., Milton, J. L., Manea, M., Paulis, M., Barandiaran, M. J., Theisinger, S., Landfester, K., Hergeth, W. D., Udagama, R, Mckenna, T., Simal, F., and J. M. Asua. 2008. Miniemulsification of monomer-resin hybrid systems. Industrial Engineering and Chemistry Research 47:6289–97. Lovell, P. A., and M. S. El-Aasser. 1997. Emulsion poly­mer­iz­ a­tion and emulsion polymers. New York: John Wiley & Sons. Luo, Y., and H. Gu. 2007. Nanoencapsulation via interfacially confined reversible addition fragmentation transfer (RAFT) miniemulsion poly­mer­i­za­tion. Polymer 48:3262–72. Ma, G. H., Nagai, M., and S. Omi. 1999. Effect of lauryl alcohol on morphology of uniform polystyrene-poly(methyl methacrylate) composite microspheres prepared by porous glass membrane emulsification technique. Journal of Colloid and Interface Science 219:110–28. Ma, G. H., Su, Z.G., Omi, S., Sundberg, D., and J. Stubbs. 2003. Microencapsulation of oil with poly(styrene-N,N-dimethylaminoethyl methacrylate) by SPG emulsification technique: Effects of conversion and composition of oil phase. Journal of Colloid and Interface Science 266:282–94. McDonald, C. J., Bouck, K. J., and A. B. Chaput. 2000. Emulsion poly­mer­i­za­tion of voided particles by encapsulation of a nonsolvent. Macromolecules 33:1593–1605. Nelliappan, V., El-Aasser, M. S., Klein, A., Daniles, E. S., and J. E. Roberts. 1996. Compatibilization of PBA/PMMA core/shell latex interphase. II. Effect of PMMA macromonomer. Journal of Polymer Science, Part A: Polymer Chemistry 34:3183–90. Nie, Z., Xu, S., Seo, M., Lewis, P. C., and E. Kumacheva. 2005. Polymer particles with various shapes and morphologies produced in continuous microfluidic reactors. Journal of American Chemical Society 127:8058–63. Nomura, M., Tobita, H., and K. Suzuki. 2005. Emulsion poly­mer­i­za­tion: kinetic and mechanistic aspects. In Advances in poly­mer science, vol. 175, Polymer particles, ed. M. Okubo, 1–128. Berlin-Heidelberg: Springer-Verlag. Okubo, M., and J. Izumi. 1999. Synthesis of micron-sized monodispersed, core-shell composite poly­mer particles by seeded dispersion poly­mer­i­za­tion. Colloids and Surfaces A: Physiochemical Engineering Aspects 153:297–304. Piirma, I. 1982. Emulsion poly­mer­i­za­tion. New York: Academic Press. Rajatapiti, P., Dimonie, V. L., and M. S. El-Aasser. 1997. Latex particle morphology: The role of macromonomers as compatibilizing agents. In Polymeric dispersions: Principles and applications, ed. J. M. Asua, 189–202. Drodrecht: Kluwer Academic Publishers.

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3 Advanced Polymer Nanoparticles with Nonspherical Morphologies Yongxing Hu, Jianping Ge, James Goebl, and Yadong Yin Contents 3.1 Introduction................................................................................................... 62 3.2 Overview of Approaches to Nonspherical Polymer Nanoparticles Synthesis........................................................................................................63 3.3 Synthesis of Nonspherical Polymer Particles via Polymerization.........64 3.3.1 Phase Separation and Seeded Emulsion Polymerization...........64 3.3.1.1 Mechanism..........................................................................64 3.3.1.2 Thermodynamics of Swelling and Phase Separation............................................................................ 66 3.3.1.3 Kinetics of Phase Separation............................................ 68 3.3.1.4 Shape Control..................................................................... 69 3.3.1.5 Complex Structures through Multistep Polymerization................................................................... 70 3.3.1.6 Particles with Anisotropic Properties............................. 73 3.3.2 Solvent Evaporation and Seeded Dispersion Polymerization.................................................................................. 76 3.4 Physical Posttreatment Approaches........................................................... 78 3.4.1 Stretching........................................................................................... 79 3.4.1.1 Simple 1D Stretching......................................................... 79 3.4.1.2 Modified Stretching Scheme............................................ 81 3.4.1.3 2D Stretching......................................................................83 3.4.2 Compression...................................................................................... 86 3.4.3 Self-Assembly.................................................................................... 87 3.4.3.1 Self-Assembly in Soft Templates...................................... 87 3.4.3.2 Self-Assembly in Hard Template..................................... 91 3.5 Summary........................................................................................................ 92 References................................................................................................................ 93

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3.1 Introduction Polymer particles have been the subject of research in various fields for several centuries. The discovery of rubber latex, a class of naturally occurring colloidal dispersions of cis-polyisoprene particles, is usually regarded as the starting point of the development of modern poly­mer science (Whitby et al. 1933; Hohenstein et al. 1946). Driven by the need for rubber polymers, in the early twentieth century extensive research was carried out in order to find synthetic routes to polymers by mimicking Mother Nature’s process for producing natural rubber (Hofmann 1912; Gottlob 1910, 1912; Pond 1914). In 1912, Kurt Gottlob invented the first process that enabled the preparation of synthetic rubber latex by poly­mer­i­za­tion of isoprene in viscous aqueous solutions. The process involves the use of naturally occurring polymers such as gelatin, egg albumin, and starch to stabilize a dispersion of monomer droplets, which are then poly­mer­ized into solid particles. This process, now widely known as “emulsion poly­mer­i­za­tion,” has since become one of the dominant methods for synthesizing poly­mer particles from a wide variety of monomer materials. In most cases, the particles produced using emulsion poly­mer­i­za­tion or related processes have sizes within the range of 100 nm to 1 µm, although it is not uncommon to find recipes for making particles beyond this range. In this chapter, the term “nanoparticle” is used to broadly cover particles with sizes of a few nanometers to several micrometers. Polymer nanoparticles play an important role in worldwide commerce as well as scientific studies. Because of their versatile properties and applications, they are omnipresent parts of our daily life, with uses in paper making, paints and coatings, adhesives, textile processing, and also medical and pharmaceutical products (Xia et al. 2000). In fundamental research, poly­mer nanoparticles have been used as an interesting model system for studying the behavior of atoms because many of the forces that govern the structure and behavior of matter, such as excluded volume interactions or electrostatic forces, govern the structure and behavior of poly­mer particle suspensions. For example, the phase transitions in liquid are analogous to those in poly­ mer nanoparticle suspensions, which can be studied conveniently in real time using optical techniques. Due to the ease of making uniform samples with well-controlled sizes, recently poly­mer nanoparticles have become popular candidates for sacrificial templates in fabrication of functional nanostructures such as core-shell and hollow spheres. Many procedures have been developed to coat poly­mer particles with various materials such as metal, semiconductor, or inorganic-organic hybrid layers to imbue them with new properties while at the same time retaining the sample uniformity. The high monodispersity that is achievable with poly­mer nanoparticles has also gained them an important role in the exciting field of colloidal crystals. Similar to silica colloids, uniform poly­mer particles can self-assemble

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into highly ordered three-dimensional arrays over a very long range (Sutera et al. 1980) to form artificial crystals that appear analogous to their atomic or molecular counterparts. When the periodicity of the array is of the same order of magnitude as the wavelength of visible light, such colloidal crystals display brilliant iridescence, which can be attributed to the constructive interference of light waves as the result of interaction with the particle arrays. Macroporous materials have been produced by combining colloidal crystals with suitable structure-forming precursors, followed by selective removal of the poly­mer nanoparticle template from the solid composite by chemical or thermal methods. The resulting products are inverse replicas of the particle arrays, which can be viewed as three-dimensional structures of interconnected macropores with regular spacing and long-range order. Driven by the minimization of interfacial energy, the majority of poly­mer nanoparticles have been limited to spherical shapes. Spherical colloids have been the dominant subject of research in colloidal science for many decades because of the ease of production as monodispersed samples. However, it has been recently realized that spherical particles are not necessarily the best option for fundamental studies or practical applications that are associated with these materials. For example, they have limited use for modeling the interparticle interactions and hydrodynamic behaviors of various irregular colloidal particles that are commonly found in industrial products. When they are used as building blocks in fabricating three-dimensional colloidal crystals, they can provide only a very limited set of crystal structures. Crystals assembled from spherical colloids can have only incomplete photonic bandgaps, which do not allow full control of the propagation of light in all three dimensions (Lu et al. 2001). In these regards, nonspherical colloidal particles are believed to offer some immediate advantages over their spherical counterparts in applications that require lower symmetries and higher complexities. For example, core-shell particles produced using nonspherical poly­mer cores will inherit the anisotropic shape, which in many cases adds an additional parameter for tuning the physical properties of the material. In the case of colloidal photonic crystals, it has also been remarked theoretically that a face-centered cubic colloidal crystal composed of nonspherical particles could possess a complete bandgap if the relative orientation of the nonspherical particles met certain requirements (Lu et al. 2001, 2002).

3.2 Overview of Approaches to Nonspherical Polymer Nanoparticles Synthesis Since a sphere is the energetically most favorable shape for liquid droplets, nonspherical particles are rarely seen as products in the standard

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emulsion poly­mer­i ­za­t ion processes. Interestingly, however, emulsion poly­mer­i ­za­t ion still serves as the starting point for the synthesis of most nonspherical poly­mer particles. Generally, there are two important approaches for synthesizing nonspherical poly­mer nanoparticles: one refers to the direct synthesis, which involves swelling and phase separation processes in an emulsion poly­mer­i ­za­t ion system; the other refers to the indirect approach, which utilizes the physical posttreatment of preformed spherical poly­mer particles. Strictly speaking, the first approach is also indirect because the initial products in the emulsion poly­mer­i­za­tion are spherical particles, which transform to nonspherical shapes following the additional swelling and poly­mer­i­za­ tion steps. We classify it as a “direct synthesis” because in most cases these steps can be completed in one pot without the need for significant changes in the chemical environment. The transformation is due to differential interfacial tension between the preexisting cross-linked poly­mer particles and the absorbed monomer swelled in the polymeric matrix. By controlling the degree of cross-linking and the swelling processes, nonspherical particles with different asymmetries can be prepared. In the second approach, the spherical poly­mer precursors are first synthesized using standard emulsion processes and then transformed into different nonspherical shapes through posttreatment, which involves either physical deformation or controlled assembly processes. The posttreatment of preexisting structures includes a group of efficient methods that are able to yield particles with complex shapes/structures that are usually inaccessible by direct synthesis methods. In one of the typical indirect methods, pre­ prepared particles first can be heated above their glass transition temperature (Tg) and then deformed to form anisotropic particles with distinct shapes using physical techniques such as mechanical stretching. By controlling the direction and degree of deformation, a variety of shapes can be obtained. Another typical indirect method utilizes self-assembly approaches to organize poly­mer nanoparticles to form anisotropic structures and then applies a post physical or chemical method to fix the structures.

3.3 Synthesis of Nonspherical Polymer Particles via Polymerization 3.3.1 Phase Separation and Seeded Emulsion Polymerization 3.3.1.1 Mechanism Emulsion poly­mer­i­za­tion is a powerful method for the production of uniform spherical poly­mer particles. It is typically a radical poly­mer­i­za­tion

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65

process that occurs in an emulsion incorporating water, monomer, and surfactants. The most common type of emulsion poly­mer­i­za­tion is an oil-inwater emulsion, in which droplets of monomer (the oil) are emulsified with surfactants in a continuous phase of water. Since its discovery, this process has been widely employed for the preparation of monodispersed spherical nanoparticles from a wide range of poly­mer materials. However, its application in the synthesis of nonspherical particles is very difficult because the spherical shape is more favorable in terms of free energy. This limitation has been overcome by a seeded emulsion poly­mer­i­za­tion method, which was discovered by Ugelstad et al. (Skjeltorp et al. 1986) and further developed by Sheu, El-Aasser, and Vanderhoff (1990a, 1990b) and then Weitz, and Gilbert et al. (Kim et al. 2006, 2007; Mock et al. 2006). After ~30 years of development, it is now an effective method for synthesizing various poly­mer particles with anisotropic characteristics in both shape and physical properties. Essentially, this method utilizes the phase separation of swelling monomers from the cross-linked poly­mer seeds followed by poly­mer­i­za­tion at elevated temperature to produce nonspherical particles. A general mechanism for the phase separation and domain formation is discussed in this section, followed by a detailed discussion of its thermodynamics and kinetics, to present a clear first image of the major procedures (Sheu et al. 1990a, 1990b). As shown in Figure  3.1, the synthesis generally starts with cross-linked poly­mer particle seeds, also called latex interpenetrating poly­mer networks (IPNs), which can be prepared by conversional emulsion poly­mer­i­za­tion methods (Stage 1). Upon mixing with monomers, the poly­mer seeds are gradually swollen until an equilibrium state is reached at room temperature, at which the monomer-poly­mer mixing force is balanced with the elastic force of the poly­mer network and the particle-liquid interfacial tension 1

2 ∆

+

6

3

5

4

Figure 3.1 Schematic illustration of the monomer swelling and phase separation in a seeded emulsion poly­mer­i­za­t ion process. (Reprinted from H. R. Sheu, M. S. Elaasser, and J. W. Vanderhoff, Journal of Polymer Science, Part A: Polymer Chemistry 28: 629, 1990. With permission.)

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(Stage 2). With increasing temperature, the balance is broken due to the increased ­elastic-retractive force of the poly­mer chains, the decreased viscosity of the poly­mer phase, and thereby the enhanced mobility of monomers and short-chain linear polymers. As a result, the monomers and linear polymers are expulsed from the IPN upon heating and form a new phase domain adhered to the seeds (Stage 3). The new phase domain grows by absorption of monomer from the seed domain and is simultaneously poly­ mer­ized until the forces are balanced again for both domains (Stages 3–5). Finally, nonspherical poly­mer particles with two well-defined domains are formed at the end of the poly­mer­i­za­tion (Stage 6). 3.3.1.2 Thermodynamics of Swelling and Phase Separation It has been demonstrated that raised temperature will enhance the phase separation of monomers and linear polymers from an interpenetrating poly­ mer network, thus forming a liquid bulge adhered to the seed particle and further polymerizing into nonspherical particles. Sheu and El-Aasser et al. have developed a thermodynamic model to explain the swelling and phase separation through a comprehensive consideration of the monomer-poly­mer mixing force, the elastic retraction from the stretching of chains in crosslinked poly­mer networks, and the surface tension at the particle-solution interface (Sheu et al. 1990a). This model is built based on a physical fact that the chemical potential ΔGm,p of monomer in the particle phase is equal to that ΔGm,a in the aqueous phase when the swelling is at the equilibrium state. For monomers like styrene, whose solubility in water is extremely low, ΔGm,a is often negligible such that ΔGm,p approximately equals zero at the balanced state. The chemical potential of monomer in the particle phase can be considered as the sum of three ­contributions, including the monomer-poly­mer mixing force ΔGm, the elastic force of cross-linked poly­mer network ΔGel, and the surface tension at the particle-water interface ΔGt.

∆G m , p = ∆G m + ∆G el + ∆Gt = 0

(3.1)

Here, ΔGm = RT[ln(1 – νp) + νp + χmpνp2] according to the Flory-Huggins expression, ΔGel = RTNVm(νp1/3 – νp/2) according to the the Flory-Rehner equation, and ΔGt = 2Vmγ/r according to the Morton equation, R is the gas constant, T is the absolute temperature, νp is the volume fraction of poly­mer in the swollen particle, χmp is the monomer-poly­mer interaction parameter, N is the effective number of chains per unit volume, Vm is the molar volume of the monomer, γ is the particle-water interfacial tension, and r is the radius of the swollen particles. In a typical instance, where a cross-linked polystyrene (PS) seed 5.2 μm in diameter is swelled with styrene, the values of ΔGm/RT, ΔGel/RT, and

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67

0.01

∆Gm/RT, ∆Gel/RT, and ∆Gt/RT

0 ∆Gt RT

–0.01 ∆Gm RT

–0.03

∆Gel RT

–0.05 –0.07 –0.09 –0.11

0

0.10

0.20

VP

0.30

0.40

0.50

Figure 3.2 Relationship between the poly­mer volume fraction and the changes of each partial molar free energy (ΔGm/RT, ΔGel/RT, ΔGt/RT). (Adapted from H. R. Sheu, M. S. El-Aasser, and J. W. Vanderhoff, Journal of Polymer Science, Part A: Polymer Chemistry 28: 629, 1990. With permission.)

ΔGt/RT can be plotted as a function of poly­mer volume fraction νp, respectively (Figure 3.2). The mixing force ΔGm makes a negative contribution to the overall chemical potential, promoting the particle expansion and thereby further swelling of monomers. On the contrary, both the elastic force ΔGel and interfacial force ΔGt make positive contributions, which restrain the stretching of poly­mer chains and expansion of particles. For particles larger than 2 μm, the interfacial force is usually negligible compared to the elastic force, so that the swelling and phase separation are actually determined by the other two parameters. This thermodynamic model qualitatively explains the driving force of monomer swelling and phase separation. When the poly­mer seeds are mixed with a saturated solution of monomers, the latter is continuously absorbed into the former because the high initial poly­mer volume fraction νp in the poly­mer seeds results in negative chemical potential ΔGm,p that encourages the poly­mer seeds’ expansion. With further progress of swelling, the poly­ mer volume fraction νp decreases, and eventually the swelling stops when the chemical potential ΔGm,p reaches zero at room temperature. As the temperature is raised, the chemical potential ΔGm,p immediately increases and exceeds zero due to the increased retractive elastic force ΔGel, which contracts the swollen network and expels the monomer to form a new phase domain attached to the seed. The reduction of viscosity and enhancement of

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mobility upon heating in the poly­mer network also contribute to this phase separation process. The small new domain contains monomers at a higher concentration than that of the seed domain, and thereby possesses a higher poly­mer­i­za­tion rate and higher poly­mer volume fraction νp. The resulting low free energy of mixing and negative chemical potential ΔGm,p for the new domain facilitates the migration of monomer and further poly­mer­i­za­tion. Finally, the transportation of monomer ceases because of the decreased difference in monomer concentration in both domains, eventually resulting in poly­mer doublets. 3.3.1.3 Kinetics of Phase Separation Sheu and El-Aasser et al. have proven that the kinetics of phase separation are different for PS seeds with different degrees of cross-linking (Sheu et al. 1990a), as they noticed that lightly cross-linked seeds generally produced doublets, whereas highly cross-linked ones produced triplets and multi­ plets. In the case of lightly cross-linked PS seed (0.2% divinylbenzene [DVB]), the particle swollen with monomer retains its spherical shape throughout the swelling process, and its size stops increasing after 24 h (Figure  3.3). After the temperature is raised to 70°C for 2 min, a new domain appears due to the heat-induced retraction of poly­mer chains and expulsion of monomers. The new domain keeps growing while the seed shrinks, and they reach the same size after 177 min, forming a symmetric doublet. After 738 min, the new domain grows larger than the seed domain, which shrinks to a size slightly larger than its original dimensions. Finally, the poly­mer­i­ za­tion is completed after 1440 min with 100% conversion, producing asymmetric doublets (Figure 3.3h). By substituting monomer with toluene, Sheu and El-Aasser et al. confirmed that the phase separation is initiated by the a

b

c

d

e

f

g

h

20 µm

Figure 3.3 Optical microscopy images of 5.2-μm PS particles cross-linked with 0.20% DVB and swollen with styrene at 23.2°C for 1440 min (a), and the nonspherical particles after poly­mer­i­za­t ion at 70°C for (b) 2 min, (c) 77 min, (d) 97 min, (e) 177 min, (f) 390 min, (g) 738 min, and (h) 1440 min. (Reprinted from H. R. Sheu, M. S. El-Aasser, and J. W. Vanderhoff, Journal of Polymer Science, Part A: Polymer Chemistry 28: 629, 1990. With permission.)

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69

increase in temperature at the beginning of the poly­mer­i­za­tion, which is a quick process, and is further enhanced by the conversion from monomer to poly­mer in the new domain as the reaction proceeds. These two processes can be summarized as elastic-driven and poly­mer­i­za­tion-driven phase separation, respectively (Kim et al. 2006). Therefore, the entire phase separation can be considered as a burst in new domain generation, followed by further domain growth due to the monomer transportation and poly­mer­i­za­tion. In the case of highly cross-linked PS seeds, there are two remarkable characteristics that differ from the kinetic process with lightly cross-linked seeds. One is the early phase separation during the swelling process, which is believed to be caused by a progressive contraction of the poly­mer network as the chains are highly cross-linked. The second feature is the formation of multiple domains and multiplets. Once the temperature is raised, the new phase domain continues growing and some particles form additional domains. After poly­mer­i­za­tion, a mixture including some doublets, triplets, multiplets, and small free particles is produced. The formation of multiple domains is promoted when the degree of cross-linking in seeds is increased. This difference is attributed to the larger gel fraction and the formation of inhomogeneities in the highly cross-linked seed particles, which also localize the contraction because the diffusion of monomer is not fast enough to uniformize the monomer distribution in the poly­mer network before the creation of new domains. 3.3.1.4 Shape Control Various parameters including the degree of seed cross-linking, the monomer:poly­mer swelling ratio, temperature, seed size, and cross-linker level in swelling monomer contribute to the control over the shape of the nonspherical poly­mer particles (Sheu et al. 1990b). As summarized by Sheu and El-Aasser et al., the final products may vary from uniform spheres to ellipsoids, asymmetric and symmetric doublets, and multiplets through the manipulation of these parameters. Degree of seed cross-linking. As mentioned previously, the degree of seed cross-linking determines the elastic retraction and poly­mer chain conformation, which is critical for the proceeding of phase separation and homogeneity of swelling. Seeds with minimal cross-linking (0.06%) grow into larger spherical particles with no phase separation because the slightly increased elastic retraction upon heating is not strong enough to expel the monomer to form new phase domains. As the cross-linking increases (0.2–1.5%), the elastic retraction enhances upon heating and leads to phase separation, which eventually produces symmetric or asymmetric doublets. Besides these thermodynamic considerations, in a kinetic sense, a higher cross-link density indicates a larger fraction of the gel portion and a shorter poly­mer chain relaxation time, which also promote phase separation. As discussed earlier, when the seeds are highly cross-linked (2.0–6.0%), inhomogeneous swelling and localized contraction lead to the production of multiplets.

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Monomer:poly­mer swelling ratio. The degree of phase separation and the size of new phase domains increase with higher monomer:poly­mer swelling ratios, since the new domains grow by the absorption and poly­mer­i­za­tion of monomers transported from the seed domain until the chemical potentials of monomer in both domains become balanced. With a monomer:poly­ mer ratio of 1:1, no phase separation is observed and spherical particles are produced. A monomer:poly­mer ratio of 2:1 gives asymmetric doublets with a smaller new domain. Increasing the monomer:poly­mer ratio to 3:1 and 4:1 will produce symmetric doublets and asymmetric doublets with a larger new domain, respectively. Temperature. The reaction temperature is also a critical parameter for phase separation and poly­mer­i­za­tion. From a thermodynamic point of view, a higher poly­mer­i­za­tion temperature will cause a great increase in the retractive elastic force upon heating and a larger separated phase domain. In the kinetic sense, a higher temperature will increase the poly­mer chain relaxation time and lower the viscosity to accelerate the formation and growth of a new phase domain. It has indeed been observed that particles poly­mer­ized at 50°C grow to asymmetric doublets with smaller new domains, while those formed at 70°C contain an enlarged second domain. Size of seed particles. The size of the seed particles is important to the thermodynamics of phase separation because it directly affects the surface tension at the interface of the seed and the aqueous solution. According to the Morton equation ΔGt = 2Vmγ/r, a larger seed particle size leads to a smaller inter­ facial tension, which certainly enhances the phase separation. The 0.6-μm seed particles grow to spherical particles without phase separation, while 1.9-μm, 5.2-μm, and 8.1-μm seed particles change to uniform ellipsoids, symmetric doublets, and asymmetric doublets, respectively. Note that even for sub­micron scale seeds, it is still possible to create nonspherical particles when the degree of cross-linking of seed particles and the monomer:poly­ mer swelling ratio are sufficiently high. Cross-linker level of swelling monomer. Polymerization with no cross-linker (0% DVB) generates a latex semi-IPN, and with cross-linker produces a latex full-IPN as both the seed domain and new domain are cross-linked. The new domain shrinks as the cross-linker level increases in the monomer mixture, thus producing doublets with a smaller new domain. This occurs because the new domain with higher cross-linking has higher viscosity and stronger elastic retraction upon expansion, both of which limit the transportation of monomers from the seed domain. 3.3.1.5 Complex Structures through Multistep Polymerization In the previous section, the synthesis of basic nonspherical particles through swelling, phase separation, and poly­mer­i­za­t ion was discussed. However, it is of great interest to chemists and materials scientists to explore the possibility of fabricating more complex nonspherical poly­mer structures

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through this “seeded emulsion poly­mer­i­za­t ion” scheme. Recently, Weitz et al. advanced this technique by synthesizing a variety of uniform complex particles on a large scale through the tight control of the cross-linking density of the poly­mer network (Kim et al. 2007). Their synthesis starts with symmetric poly­mer doublets with controllable degrees of cross-linking in each domain, and utilizes the gradients in cross-linking density as the driving force to manipulate the direction of phase transfer, thus leading to the production of rod-, cone-, triangle-, and diamond-shaped particles after poly­mer­i­za­tion. The entire synthesis comprises three continuous seeded emulsion poly­mer­i­za­t ions, and the cross-linking degree of the seed and second domain of the doublets are adjusted by changing the concentration of cross-linker in the poly­mer­i­za­t ion of spherical seeds ([DVB]a) and doublets ([DVB]b), respectively. Since the IPN can be perfectly swelled in toluene, one can observe the swelling of dimers in toluene using optical microscopy and obtain the crosslinking density (ν) from the ratio of unswelled volume to the swelled volume (φ). According to the theory of Flory and Rehner, the cross-linking density can be calculated by the following equation, where NA is Avogadro’s number, V is the molar volume of the solvent, and χ is the poly­mer-solvent inter­action parameter. The dependence of cross-linking gradient (Δν) on the cross-linker ratio ([DVB]b:[DVB]a) can be plotted to investigate the influence of cross-­linking on the shape. It should be noted that in dimer particles, the cross-linking degree in the new domain (bulb b) can be estimated based on the concentration of cross-linker ([DVB]b) in the second reaction, where a small deduction must be considered as the poly­mer­i­za­tion also occurs in the original domain (bulb a). Accordingly, the cross-linking degree in the original domain (bulb a) is slightly larger than the one quantified with [DVB]a.

ν=

NA  ln(1 − φ) + φ + χφ 2  φ 1/3 − φ/2 V 

(3.2)

As shown in Figure 3.4, the gradient of cross-linking density (Δν) in dimers is critical to the shape of multiplets. IPN with high cross-linking density has been proven to generate stronger elastic retraction upon heating, thus facilitating the phase separation and new domain formation. When the degree of cross-linking of the second domain is as large as that of the original (ν b ≈ νa, Δν = 0.9 mol m–3), the elastic retractions in both domains are close enough that the new separated domain grows perpendicularly between the two bulbs, forming triangle-shaped particles. Decreasing the cross-linking density of the second domain in dimer seeds (ν b < νa, Δν = 15 mol m–3) will break the balance of elastic retraction upon heating, as the driving force of pushing the monomer mixture out of the original domain is stronger than that in the second domain. In other words, the gradient in cross-linking density drives the monomer mixture to flow down the gradient, leading to linear growth

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Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

(a)

(b)

(c)

(d)

45 ∆ν = νa – νb (mol  m–3)

40 35

5 µm

30 25 20 15 10 5 0 0.4

0.5

0.6

0.7

0.8

0.9

1.0

1.1

1.2

1.3

[DVB]b/[DVB]a (e) Figure 3.4 (a–d) SEM images of (a) triple-rod particles prepared at [DVB]b/[DVB]a = 0.7; (b) triangular particles at [DVB]b/[DVB]a = 1.1; (c) cone particles made similar to the triple-rod particles except with a higher volume of monomer mixtures in the final swelling stage; (d) diamond-shaped particles made similar to the triangular particles but with 20% more total cross-linker; and (e) cross-linking density gradient (Δν) tuned by changing the concentration of DVB in each swelling step ([DVB]b and [DVB]a). Insets show the optical microscope images of dimer particles before (upper) and after (lower) swelling at different [DVB]b:[DVB]a ratio, and the schematic images of the final particles grown from these dimers. (Adapted from J. W. Kim, R. J. Larsen, and D. A. Weitz, Advanced Materials 19: 2005, 2007. With permission.)

Advanced Polymer Nanoparticles with Nonspherical Morphologies

73

and rod-shaped particles. Further decreasing the cross-linking density of the second domain in dimer seeds (ν b < νa, Δν = 37 mol m–3) will seriously weaken the elastic retraction, such that no phase separation occurs and asymmetric dimers are produced. When Δν is tuned between these critical values, mixtures of two types of particles are generated after poly­mer­i­za­tion. This procedure represents a general method for the preparation of uniform and high-yield poly­mer triplets in a one-batch reaction, and also holds the potential for chemical fabrication of more complex nonspherical poly­mer particles. Modifications to the recipes for rod- and triangle-shaped particles will produce additional complex particles. For instance, the cone-shaped particles can be produced similarly to the rod particles, but with a higher volume of monomer mixtures in the final swelling stage; while the diamondshaped particles can be synthesized similarly to the triangular particles, but with higher cross-link densities in both domains of dimer seeds ([DVB]a = 1.2 vol%, [DVB]b = 1.32 vol%). 3.3.1.6 Particles with Anisotropic Properties The preceding sections have discussed seeded emulsion poly­mer­i­za­tion as an effective strategy to produce various nonspherical poly­mer particles. Here, we will introduce poly­mer colloids with not only nonspherical shapes but also anisotropic physical properties. By surface modification and other chemical treatments, or incorporation of inorganic functional materials, this method can be extended to the preparation of polymeric particles with anisotropic properties, such as amphiphilic particles and magnetically anisotropic particles. Particles with chemical rather than shape anisotropy play an important role in recognizing specific molecules, self-assembling, and emulsion stabilization. One particular kind of useful anisotropy of chemical ­property is “amphiphilicity,” which is generally induced by organic groups or polymeric blocks. Recently, Weitz et al. have reported a flexible approach, based on phase separation and seeded emulsion poly­mer­i­za­tion, for the synthesis of uniform and amphiphilic nonspherical particles (Kim et al. 2006). The experimental procedure includes the synthesis of cross-linked poly(styrene-co-glycidyl methacrylate) (PS-co-PGMA) spherical particles, PS-co-PGMA/PS symmetric poly­mer doublets, and surface treatment with poly(ethylene imine) (PEI). Glycidyl methacrylate is copoly­mer­ized to the original PS seed to provide epoxy rings on the surface, which offer reactive sites for hydrophilic chemicals that have active hydrogen. Through swelling by styrene monomer solution, phase separation upon heating, and thermal poly­mer­i­za­tion, the spherical seeds turn into PS-co-PGMA/PS doublets. It is important that the PGMA chains stay in the original domain during phase separation so that the distribution of surface epoxy rings is extremely asymmetric in the doublets. The half-sphere functionalized with the epoxy rings is then reacted with hydrophilic PEI, turning the hydrophobic doublets into

74

a

Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

b

c

Hydrophilic PEI PS PEI Hydrophobic PS 10 µm

10 µm

Figure 3.5 (a) SEM image of amphiphilic PS doublets obtained by the reaction of surface epoxy rings with PEI. (b) Fluorescence microscope image of fluorescein-labeled amphiphilic PS doublets. (c) Bright-field microscope image of the assembly of amphiphilic PS doublets at water/octanol interface. (Reprinted from J. W. Kim, R. J. Larsen, and D. A. Weitz, Journal of the American Chemical Society 128: 14374, 2006. With permission.)

amphiphilic structures. The PEI-coated part can then be labeled with fluorescein sodium salt and imaged using fluorescence microscopy to confirm the exact amphiphilic structure (Figure 3.5). Compared with the spherical amphiphilic Janus particle, these particles with both a nonspherical shape and amphiphilic properties may be more suitable to stabilize the interfaces and emulsion droplets. As shown in Figure 3.5, the water droplets inside 1-octanol can be stabilized by these colloid surfactants. The interface curvature and droplet size are expected to be conveniently tuned by controlling the geometry of the doublets. Besides selective surface modification to the premade nonspherical particles, incorporation of functional content into the poly­mer particle through core-shell fabrication is an alternative way to realize anisotropic properties. A series of spherical and nonspherical magnetite-PS composite colloids with anisotropic magnetic properties has been reported (Ge et al. 2007). In a typical process, 3-(methacryloyloxy)propyl trimethoxysilane (MPS)-modified Fe3O4@SiO2 particles are used as seeds to prepare concentric and eccentric Fe3O4@SiO2@PS core-shell particles through seeded emulsion poly­mer­i­za­ tion. The location of the Fe3O4@SiO2 core is determined by the degree of crosslinking in the poly­mer layer: the eccentric particles are prepared without the addition of DVB while concentric particles are obtained when the polymers are cross-linked. The formation of eccentric structure is due to the interfacial tension between the hydrophilic seed particle and the hydrophobic monomer (Park 2001; Minami et al. 2003; Mock et al. 2006). At the initial stage of poly­mer­i­za­tion, a thin layer of polystyrene shell is deposited in the form of small particles on the silica surface through copoly­mer­i­za­tion with the surface double bonds offered by MPS molecules. After absorbing hydrophobic monomers, the polystyrene chains in the shell tend to contract and reduce the surface area as a result of interfacial tension, leading to asymmetric distribution of poly­mer around the seeds (Figure 3.6a). Modification with MPS renders the silica surfaces considerable compatibility with the swollen poly­ mer shell so that the final products still maintain an overall spherical shape

Advanced Polymer Nanoparticles with Nonspherical Morphologies

a

b

c

d

e

f

g

75

h

400 nm

Figure 3.6 TEM images of (a) eccentric and (b) concentric spherical particles produced in one-step emulsion poly­mer­i­za­t ion, and evolution of doublets (c–f) prepared by swelling with particle b, phase separation, and poly­mer­i­za­t ion. Self-assembly of (g) concentric and (h) eccentric particles into chain structures in a magnetic field. (Reprinted from J. P. Ge, Y. X. Hu, T. R. Zhang, and Y. D. Yin, Journal of the American Chemical Society 129: 8974, 2007. With permission.)

with the majority part of the inorganic core engulfed in the poly­mer phase. The high viscosity of the monomer-swollen shell, achieved by introducing a cross-linker of DVB during poly­mer­i­za­tion, limits the transportation of monomers and leads to the formation of a concentric core-shell structure of Fe3O4@SiO2@PS (Figure 3.6b). The spherical symmetry of the external interface can be broken as a result of phase separation when monomer concentration is increased, forming ellipsoidal colloids with a magnetic core eccentrically located at one end. The considerable effects of swelling and phase separation are responsible for the ellipsoidal shape of the colloids. At the early stages of poly­mer­i­za­ tion, the particles have a spherical and concentric morphology similar to that in Figure 3.6b. As the thickness of shell poly­mer increases, more excessive styrene monomers are absorbed into the cross-linked poly­mer networks. In the final stage, the elastic stress driven by the entropy change of the swollen networks causes phase separation of the monomer from the network and eventually forms additional bulges attached to the original particles. As discussed in previous sections, phase separation is negligible when the starting monomer concentration is low so that the final products have a spherical shape. Further increasing the concentration of monomers induces phase separation and forms ellipsoidal particles. When the swelling and phase separation processes are performed in two separate steps, nonspherical colloids can be produced with a higher degree of control over the shape asymmetry. Starting with the cross-linked concentric core-shell particles, a series of nonspherical poly­mer particles with controllable size of the new domains can be prepared by taking advantage of the well-developed swelling and phase separation processes in seeded emulsion poly­mer­i­za­tion, where the relative size of the new domain to the original

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Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

inorganic sphere changes dramatically as the monomer:seed ratio increases (Figure 3.6c–f). The combination of anisotropic shapes and magnetic properties makes these composite colloids new types of building blocks for constructing secondary structures. The composite spheres with concentric and eccentric superparamagnetic cores display distinct assembly behaviors when they are subjected to an external magnetic field, as shown in Figure 3.6g and h. The concentric particles form simple linear chains, which are expected for building blocks with simple isotropic configurations, while more complicated zigzag chains have been observed when the eccentric particles are assembled under similar conditions. The zigzag configuration is a direct result of the eccentric structure: the strong magnetic dipole interactions that pull the magnetic cores in the neighboring colloids to the closest positions. 3.3.2 Solvent Evaporation and Seeded Dispersion Polymerization The combination of seeded dispersion poly­mer­i­za­tion (SDP) and solvent evaporation represents a unique kinetic-based technique for the preparation of nonspherical poly­mer particles, whose glass transition temperature (Tg) usually exceeds the poly­mer­i­za­tion temperature so that the viscosity within the particles is high enough to prevent equilibrium morphologies from being obtained. Recently, Okubo et al. have developed an SDP method for the preparation of nonspherical particles with the aid of organic solvents (Fujibayashi et al. 2007; Okubo et al. 2002). The solvent molecules are selectively absorbed into certain particle domains, whose volume decreases dramatically as the solvent evaporates after poly­mer­i­za­tion, leading to the formation of golfball-like, polyhedral, and disk-like particles. A typical system involves the SDP of 2-ethylhexyl methacrylate (EHMA) with PS seeds in the presence of various hydrocarbon solvents. The key to controlling the shape of the poly­mer particles lies in the absorption of hydrocarbon solvent into certain domains and their coalescence during the reaction. As the dispersion poly­mer­i­za­tion proceeds, both the PS and PEHMA domain absorb the hydrocarbon solvent, but the PEHMA/solvent domain grows much larger than the PS/solvent domain. The absorption of hydrocarbon solvent significantly increases the particle volume and decreases the viscosity of the poly­mer network, which accelerates the coalescence of the PEHMA/ solvent domain by collision and Ostwald ripening. Thermodynamically, the composite particle prefers to contain as few PEHMA/hydrocarbon domains as possible because the reduction of the interface between PEHMA/solvent and PS phase will decrease the interfacial free energy. However, the practical degree of domain coalescence is always affected by several kinetic considerations, such as the viscosity of the PS/solvent domain and the reaction time. Finally, the solvent evaporates and the PEHMA/solvent domain shrinks to produce nonspherical particles. The degree of coalescence of the PEHMA/ solvent domain determines whether the products are spheres, hemispheres,

77

Advanced Polymer Nanoparticles with Nonspherical Morphologies

(a)

(b)

2 µm (d)

(c)

2 µm (e)

2 µm

2 µm (f )

2 µm

2 µm

Figure 3.7 SEM images of PS particles after extraction of PEHMA and decane, prepared by seeded dispersion poly­mer­i­za­t ion at various conversions of (a) 5%, (b) 13%, (c) 34%, (d) 49%, (e) 57%, and (f) 69%. (Reprinted from T. Fujibayashi and M. Okubo, Langmuir 23: 7958, 2007. With permission.)

golf balls, polyhedra, or disks. Any experimental parameter with influence on the absorption of hydrocarbon and the coalescence of the PEHMA/solvent domain can be used to control the morphology of the nonspherical particles (Fujibayashi et al. 2007; Okubo et al. 2002). Reaction time. Particles with various percent conversions of EHMA collected at different reaction times show dramatically different morphologies (Figure  3.7). Initially, spherical particles with dents are observed after 5% conversion of EHMA. The number of dents on the surface increases as the poly­mer­i­za­tion proceeds, which leads to the formation of golf-ball-like particles at a conversion of 13%. This result can be explained by the increasing number of PEHMA/solvent domains as the EHMA is gradually poly­mer­ ized. The particles then keep on changing their shape to polyhedron at an EHMA conversion of 34 to 57%, as the PEHMA/solvent domains coalesce into several larger domains. Upon further coalescence, the PEHMA/solvent domains eventually combine into two large hemispherical domains at after 69% conversion, leaving a PS disc-like domain sandwiched in between to form a hamburger-like structure. Time-dependent hydrocarbon absorption and domain coalescence have great influence on the particle shapes produced by SDP. Type of hydrocarbon. PS/EHMA composite particles with different shapes can also be synthesized by introducing various hydrocarbon solvents. By

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Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

decreasing the length of the alkyl chain of the hydrocarbons, the particle shapes change from golf ball (hexadecane) to polyhedron (tetradecane, dodecane), and then to disks (decane, octane, hexane) at the same reaction conditions. Gas chromatography studies indicate that the amount of hydrocarbon absorbed by the PS particles increases in the order of hexadecane, tetradecane, dodecane, decane, octane, and hexane, suggesting that shortchain hydrocarbons have a higher affinity for the PS. DSC heating curves of swollen PS particles also show that the Tg shifts to a lower zone as the alkyl chain length decreases, which means the viscosity of the PS/solvent domain decreases accordingly. For PS particles swollen with short-chain hydrocarbons, both the increased amount of absorbed solvent and decreased viscosity promote the enlargement and coalescence of PEHMA/solvent domains, leading to the shape transformation from golf balls to disks. Methanol:water ratio. The aforementioned conclusions are consistent with the results when particles are prepared in methanol/water solutions with different ratios. A high methanol:water ratio (90:10 w/w) enhances the absorption of hydrocarbons so that a disk is the preferential shape. On the other hand, a low methanol:water ratio (70:30 w/w) leads to polyhedral particles. Amount of solvents. The influence of the amount of solvent has been investigated through a different reaction system, where particles are prepared by the SDP of poly(methyl methacrylate) (PMMA) seeds, styrene, and decalin (solvent droplet) in a mixture of methanol and water. In this case, all the particles are golf-ball-like and no transformation to disks is observed, probably due to thermodynamic reasons for the specific domains of PMMA/ decalin and PS/decalin. By increasing the decalin, the number of surface dents decreases, and the domains enlarge by the coalescence of neighboring domains. This result is consistent with the expectation that increasing the amount of solvent will enhance the solvent absorption and domain coalescence, making the dents on the golf balls fewer in number but larger in size.

3.4 Physical Posttreatment Approaches In addition to direct chemical synthesis, indirect approaches by posttreatment of preexisting structures have also been widely used to prepare particles with complex nonspherical shapes, including those that are usually inaccessible by direct methods. Spherical poly­mer particles are usually synthesized first using chemical methods such as emulsion poly­mer­i­za­tion, and then posttransformed into nonspherical structures by either physical or chemical means such as stretching and self-assembly (Champion et al. 2007; Courbaron et al. 2007; Hu et al. 2008; Jiang et al. 2001).

Advanced Polymer Nanoparticles with Nonspherical Morphologies

79

3.4.1 Stretching 3.4.1.1 Simple 1D Stretching The most straightforward indirect method involves one-dimensional (1D) physical deformation of poly­mer nanoparticles embedded in polymeric matrices at elevated temperatures. It was first developed by Felder while stretching a polyvinyl alcohol (PVA) film to produce monodisperse ellipsoidal dye-containing polyvinyl acetate microparticles embedded in the matrix (Felder 1966, 1968). Figure  3.8 shows the schematic procedure of this indirect method that employs uniaxial viscoelastic deformation to convert colloidal particles from spherical to ellipsoidal shapes (Keville et al. 1991). In this method, monodisperse, spherical particles of a poly­ mer—for example, PS, PMMA, and poly(vinyl toluene)—are first dispersed in a precursor solution of elastic matrix such as PVA or un-cross-linked poly(dimethylsiloxane) PDMS. An elastic film is formed after solvent evaporation or poly­mer­i­za­t ion of the matrix solution. By stretching the film at a temperature higher than the Tg of the poly­mer latexes, spherical particles can be transformed into uniform ellipsoids. The softened poly­mer spheres deform in the elongated matrix film and become ellipsoids whose aspect ratio can be controlled by changing the magnitude of uniaxial elongation and the ratio between the elastic moduli of the matrix and the poly­mer spheres (Ho et al. 1993). In the case of PS particles in PVA, the particle deformation is enabled by the strong adhesion arising from the hydrogen bond between the hydroxyl groups on the PVA and the surface groups on the PVA PS

M

at

rix

di

ss

ol

ut

io

n

St re tch

Figure 3.8 Schematic illustration of stretching polyvinyl alcohol films with embedded particles.

80

Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

latex particle surface (Champion et al. 2007; Ho et al. 1993). The ellipsoidal shape resulting from the viscoelastic deformation can be completely retained by cooling down the sample below the Tg of the poly­mer sphere, while the matrix remains constrained in the elongated state. These ellipsoidal particles can then be collected as a stable dispersion by dissolving the matrix with an appropriate solvent. To obtain well-defined microspheroids, the poly­mer particles should possess good chemical and physical stability to be able to withstand the subsequent heating/solvent treatment and be able to remain colloidally stable in the media used in the various synthesis steps. The matrix, which consists of cross-linked elastomer or thermoplastics with controlled elastic properties and high ultimate elongation, can determine the maximum aspect ratio of the obtained ellipsoids. The elastic modulus of the matrix can be adjusted by controlling the cross-linking density. With higher cross-linking density, the ultimate elongation is decreased and stress relaxation is less pronounced. A number of thermoplastics or elastomers have been found to be good elastic matrixes with typical examples including PVA and cross-linked PDMS. The difference between an elastomer and a thermoplastic is that an elastomer tends to relax back to the unstretched state, while a thermoplastic will remain in the stretched state forever once the sample has been cooled. In the ideal case, if the elastic properties of the particles and the matrix are identical and the materials are pure elastic, the aspect ratio could be predicted by using the equation suggested by Eshelby et al.: 3

1 = (1 + e) 2 , d



(3.3)

where l is the length of the major axis of the spheroid, d is the diameter of its cross section normal to the axis, and e is the axial strain e=(l-l0)/l0 (Eshelby et al. 1957). If the elastic properties of the particles are not identical to that of the matrix, the resulting aspect ratio will also depend on the ratio of elastic moduli, which will be predicted as



1 = d

  1 1+     = 0.4(1 − r ) 

e

1   1 + (1 + e) 2 − 1 1 − 0.4(1 − r )  

,

(3.4)

where r is the moduli ratio, r=G1/G, and G and G1 are the elastic moduli of the matrix and the particles. For matrix materials with nonlinear elastic or viscoelastic properties, or when contribution of interfacial energy is significant, the aspect ratio will deviate from the predictions. Moreover, it should be

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taken into account that the properties of the matrix embedded with poly­mer nanoparticles might be different from those of the pure material. The final shape of the poly­mer particles depends on a few key parameters, including the thickness of the film, the viscosity of a liquefied droplet, and the temperature. A practical problem of this simple stretching approach is that the uniaxial stretching is not always uniform throughout the whole film due to the formation and propagation of necks at the center of the poly­mer strip. To improve the uniformity of the recovered particles, strips of the film around the center with lengths corresponding to the expected draw ratio are cut out from the film and used for recovery of the particles. This indirect 1D deformation approach has been investigated by a number of research groups for generating small quantities of micrometer-sized ellipsoids of polymers for light scattering, rheological, or other fundamental studies. Ellipsoidal PS particles of a few micrometers with predesigned axial ratios were reported by Nagy and Keller through the affine deformation of uniform spherical PS beads in a deformable matrix (Ho et al. 1993). PMMA spheroids produced by deforming an elastic matrix of PDMS were later fully studied by Keville et al. (1991). Lu et al. (2002) also exploited the use of this method in generating long-range ordered three-dimensional (3D) colloidal crystals with poly­mer ellipsoids as building blocks. Xu et al. (2007) prepared hollow ellipsoids with desired aspect ratios by stretching a PVA film embedded with PS hollow spheres. The hollow ellipsoids can be used further as templates for the synthesis of composite ellipsoids. 3.4.1.2 Modified Stretching Scheme The 1D stretching scheme outlined previously allows only for the production of simple ellipsoidal particles. Modification of the stretching/heating sequence or using a liquefaction method makes it possible to produce particles with highly complex shapes. As demonstrated by Champion et al. (2007) in their recent reports, this modified stretching protocol can be used to generate particles of more than 20 distinct shapes including ellipsoids with flat ends, rods with circular cross section, rec­tangular disks, and sharp-ended worm-like particles. Figure 3.9 shows the general procedure, which can be categorized into two schemes. The first modification involves the liquefaction of particles by using toluene instead of heating, and then solidification by solvent evaporation after stretching. As indicated previously, the particle viscosity is a critical parameter that dictates whether a deformed particle will have pointed or flat ends and whether the original width is preserved. Since the liquefaction of the particles using toluene leads to a much lower viscosity than when they are heated under otherwise similar conditions, it is possible to produce nonspherical particles with different shapes. With 1D stretching under this condition,

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Scheme A

Liquefy

Stretch

Solidify

Stretch

Liquefy

Solidify

Scheme B

Figure 3.9 Methods used for making particles with different shapes can be categorized into two general schemes. (Reprinted from J. A. Champion, Y. K. Katare, and S. Mitragotri, Proceedings of the National Academy of Sciences of the United States of America 104: 11901, 2007. With permission.)

thin elliptical disks with curved ends can be obtained, while flat circular disks can be fabricated with two-dimensional (2D) stretching. The second modification involves changing the stretching/heating sequence. In this case, the elastic matrix embedded with particles is first deformed so that voids are created around the particles. Liquefaction of the particles by controlled heating above the Tg in the presence of voids allows the production of many additional complex shapes (Figure 3.10). During lique­ faction, softened PS will fill the voids by wetting the film (Figure 3.10e–f). At low liquefying temperature (~130°C), the high viscosity of PS inhibits complete filling of the voids and leads to barrel-like particles. At higher temperatures (~140°C), PS wets the PVA matrix better due to its decreased viscosity, and leads to the filling of one end of the void, eventually forming bullet-like structures. Moreover, by liquefying the PS particles with toluene, more different shapes will be formed as a result of the even lower viscosity: conducting 1D stretching in air can produce pill-like particles while moderate 2D stretching leads to pulley shapes. More extensive stretching forms biconvex lenses. The combination and/or repetition of multiple steps of stretching, heating, and toluene liquefaction can lead to even more unusual shapes including ribbon-like particles with curled ends, bicone, diamond disks, emarginated disks, flat pills, elongated hexagonal disks, ravioli, and tacos (Figure 3.10g–h). With further modification of the surface texture by relaxing the stretched

Advanced Polymer Nanoparticles with Nonspherical Morphologies

(a)

(b)

(c)

(d)

(e)

(f)

(g)

(h)

83

Figure 3.10 SEM images of shapes made by using (a–d) scheme A; (e–f) scheme B; (g–h) a combination of schemes A and B. (Adapted from J. A. Champion, Y. K. Katare, and S. Mitragotri, Proceedings of the National Academy of Sciences of the United States of America 104: 11901, 2007. With permission.)

film ahead of liquefaction, wrinkled prolate ellipsoids, wrinkled oblate ellipsoids, and porous elliptical disks can be formed. 3.4.1.3 2D Stretching While the majority of works involve simple uniaxial stretching, which yields prolate ellipsoids with defined aspect ratios, only a few reports have explored the possibility of the deformation of spheres using 2D stretching. As demonstrated by Champion et al. (2007), a 2D stretching method produces oblate shapes that are difficult to realize in the 1D stretching scheme. Since biaxial stretching with orthogonal forces may lead to nonuniform deformation of the film, particularly at high stretching ratios, few reports have detailed the possibility of the uniform deformation of spheres into well-controlled diskshaped structures. A simple blown film process has been developed that can uniformly deform poly­mer spheres across the blown film and allows the fabrication of disk-shaped ellipsoids with good control (Hu et al. 2008).

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Oil bath

PS/PVA film

PS oblate spherioids

PS spheres

Figure 3.11 Schematic outline of the blown film process. (Reprinted from Y. X. Hu, J. P. Ge, T. R. Zhang, and Y. D. Yin, Advanced Materials 20: 4599, 2008. With permission.)

Figure 3.11 schematically outlines the procedure. A thin composite PS/PVA film is first prepared and then mounted on top of the wide opening of a ceramic filtering funnel, and sealed with a steel clamp. The system is then immersed into a silicon oil bath preheated at 160°C. As this composite film softens and becomes deformable at this temperature, air is then injected into the funnel through the small opening using a syringe, allowing the film to blow into a dome-like shape. The funnel is removed from the oil bath and cooled in air with the pressure maintained so that the stretched PVA film does not show apparent shrinkage upon cooling. The liquefied PS particles experience a uniform 2D stretching force because of their small sizes compared to the PVA film, and eventually evolve into disk shapes during the bubble expansion. The transformation from spheres to disks can be controlled by the extent of bubble expansion, which can be represented simply by the ratio of the height of the bubble (H) to the original film size (D). Practically, the height of the bubble can be controlled by the amount of air injected into the funnel. Figure 3.12 shows that the major axis of the disks increases dramatically with the degree of expansion of the film (H/D). By assuming that both the particle and the matrix materials are purely elastic with identical elastic properties, a sphere will deform into a disk-shaped ellipsoid under biaxial tension by following the relation of

Rd R0 = 2

H D

.

Here Rd is the major axis of the disks, R0 the radius of the original spheres, H the height of the bubble, and D the original film diameter. In fact, the length of the major axis increases with the degree of bubble expansion at a

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(e) 2.2 2.0 1.8 1.6 1.4 1.2 1.0

b

Rd/Ro

a

0.0 c

d

0.2 0.4 H/D

Figure 3.12 (a) SEM image of the starting PS spheres. SEM images of PS disks with controllable diameters by injecting different amounts of air: (b) 716 nm; (c) 903 nm; (d) 1149 nm; (e) the stretching ratio Rd:R0 of PS disks as a function of the degree of bubble expansion (H/D). The insets in b–d show a gradual decrease in the minor axis during the stretching. Scale bars in insets are 500 nm and the others are 1 mm. (Reprinted from Y. X. Hu, J. P. Ge, T. R. Zhang, and Y. D. Yin, Advanced Materials 20: 4599, 2008. With permission.)

rate higher than the value predicted with this simple model, which could result from the viscoelastic nature of the materials, the difference in elastic moduli between the particles and the matrix, and the interfacial energy contribution. The blown film process can also be applied to transform nanoparticle­embedded poly­mer spheres into disk-shaped composite structures. Typ­i­ cally, the nanoparticles are dispersed in the poly­mer spheres without strong interactions between each other. As a result, they can move with the hydrodynamic flow during the transformation of the poly­mer particles. We have prepared magnetic microdisks using iron oxide–doped PS beads as the starting materials, and demonstrated the manipulation of their spatial orientation by using external magnetic fields. More complex structures can be achieved by stretching colloidal spheres containing multiple components with different elastic properties. For example, flying saucer–shaped particles can be produced when SiO2@PS core-shell composite particles are used

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(a)

(b)

(c)

(d)

Figure 3.13 TEM images of flying saucers (a) without magnetic core; (c) with magnetic core; SEM images of (b) flying saucers and (d) hollow disk-shaped PS. (Images (a) and (b) adapted from Y. X. Hu, J. P. Ge, T. R. Zhang, and Y. D. Yin, Advanced Materials 20: 4599, 2008. With permission.)

as the starting materials (Figure 3.13). When such core-shell composite colloids are ­subjected to blown film stretching, only the PS shell can be deformed into disks. The silica core remains spherical because of its rigid nature. As a result of the good adhesion between the PS and the silica surface, the original spherical core-shell particles are transformed into flying saucers with a thin poly­mer layer covering silica. If anisotropic composite particles are used as the starting materials, more geometrically complex structures can be fabricated through this blown film process. In addition, by incorporating active materials such as magnetic particles to the silica cores or using hollow poly­mer particles, it is possible to produce multifunctional colloids with complex shapes for various new applications (Figure 3.13c–d). 3.4.2 Compression In principle, a thin elastic film containing poly­mer particles can also be deformed by mechanical compression. However, such efforts have been rarely reported probably because of the requirement for a high uniformity in film thickness and pressing force in order to obtain uniform deformation. Nevertheless, literature still contains some elegant works that utilize mechanical compression for nonspherical particle fabrication. For example, Sun et al. (2005) recently reported the use of thermal pressing of colloidal crystals for preparing nonspherical particles with well-defined shapes such

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as polyhedrons. In this case, a crystalline array of monodispersed poly­ mer particles is sandwiched between two solid substrates and then compressed while heating the system at a temperature slightly lower than the Tg of the poly­mer. Heating at this temperature allows the softening of poly­ mer chains to facilitate particle deformation upon pressing, and at the same time prevents the colloidal crystals from fusing into continuous films. After the thermal pressing treatment, the spherical particles are transformed into polyhedrons in accordance to the structure of the colloidal crystal, and the long-range order of the 3D lattice is essentially preserved (Figure  3.14). In addition to the shape change of the poly­mer particles, the thermal pressing also leads to obvious changes in the optical properties of colloidal crystals. Another method that involves mechanical compression was reported by Courbaron et al. (2007), who produced disk-shaped poly­mer particles by compressing an elastic aqueous gel containing oil-in-water emulsion droplets. An emulsion containing various polymerizable oil droplets is first mixed with a hot solution of two polysaccharides. By lowering the temperature below the gelling point of the polysaccharide solution, the continuous phase of the emulsion becomes a gel and acquires the elastic properties. Upon compression, the emulsion droplets of polymerizable oil are deformed due to the local strain caused by the macroscopic stress applied to the gel. UV irradiation initiates the poly­mer­i­za­tion of the emulsion droplets and produces solid poly­mer particles. Heating the sample above 80°C melts the gel and releases the solid disk-shaped particles. Ellipsoids of a variety of poly­mer materials can be obtained by incorporating different polymerizable precursors inside the emulsion droplets. However, the particles are highly polydisperse due to the inhomogeneous nature of emulsion droplets. Another limit of this process is the difficulty in achieving higher aspect ratios as the gel ruptures easily when the elongation ratio is above 1.55. 3.4.3 Self-Assembly Besides posttreatment approaches that involve physical deformation, selfassembly represents another type of method that can produce poly­mer particles with complex structures. Generally speaking, these self-assembly methods always start with presynthesized uniform poly­mer particles and then use templates as physical confinement to assemble a limited number of particles into the desired geometric structures. Two types of templates have been used in the self-assembly processes: one variety is soft templates such as droplets in an emulsion system, and the other is hard templates such as patterned thin photo resist films. 3.4.3.1 Self-Assembly in Soft Templates In this method, a three-phase emulsion system is employed to form complex-shaped aggregates of colloidal particles (Velev et al. 2000). Suspended

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A)

(a)

(b)

(d)

Evaporation

(c)

B)

Thermalpressing

(a)

(b)

1 µm (c)

250 nm (d)

1 µm

250 nm

Figure 3.14 A: Schematic illustration of the procedure used to prepare NSCCs. B: (a) Morphology of the CCs fabricated by two substrate vertical deposition. (b–d) Typical SEM images of the NSCCs. (Images adapted from Z. Q. Sun, X. Chen, J. H. Zhang, Z. M. Chen, K. Zhang, X. Yan, Y. F. Wang, W. Z. Yu, and B. Yang, Langmuir 21: 8987, 2005. With permission.)

emulsion droplets are used as templates within which the colloidal particles such as polymers can be gradually concentrated by drying to form aggregates with unique packings, yielding different kinds of microstructured asymmetric assemblies (Yi et al. 2002, 2004; Cho et al. 2005a, 2005b). The shapes of the as-synthesized anisotropic clusters can be controlled by the

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size of suspended template droplets, the number of colloids per droplet, and the surface properties of the colloidal particles. Moreover, composite assemblies can be achieved by varying the components of the colloidal beads. This soft-template approach involving encapsulation and shrinkage is efficient at creating polymeric clusters containing a small number of spheres (n = ~12–15) and is a high-throughput method capable of producing a massive number of clusters, approximately 108–1010 in lab-scale experiments. The method was first reported by Manoharan et al. in 2003, and involves poly­ mer particles such as PS dispersed in an oil-in-water emulsion system with each oil droplet containing a small number (N) of spheres. By preferentially removing the liquid from a droplet containing particles absorbed onto its surface or confined in its core, compact clusters with different shapes can be obtained as a result of capillary forces and Van der Waals interactions during the drying process. Interestingly, the final particle packings are unique for all N < 11 and correspond to the clusters with minimized second moments of mass distribution, M = ∑i(ri–r0)2 (r0 is the center of mass of the cluster). Subsequently, clusters of different aggregation numbers are fractionated by density gradient centrifugation. However, this method lacks control of the emulsification conditions, leading to polydisperse emulsions and severely limited yields of different types of clusters. Since the size of the emulsion droplet is one of the crucial factors that determine the final shape of the poly­mer clusters, extensive research has been conducted to generate uniform emulsion droplets. A series of novel emulsification strategies have been exploited, including for example microfluidic devices, micropipette injection, and electrospray. All of these methods involve a droplet break-off technique to produce monodispersed droplets (Umbanhowar et al. 2000). The size of droplets detaching from a tip immersed in a coflowing stream has already been investigated (Yi et al. 2004). When the flow rate in the capillary is low, a balance between the interfacial tension and the drag force on the droplet at the end of the tip results in a droplet diameter dd given by

 γ  dd = dti 1 + ,  3µηc 

(3.5)

where dti is the inner diameter of the capillary tip, γ the interfacial tension between the water and oil, ηc the viscosity of the continuous phase, and µ the velocity of the continuous phase (the shear rate). The droplet sizes of oilin-water emulsions increases when the viscosity ratio between the continuous and dispersed phases is increased because their high internal viscosity resists fragmentation. Also, a low to moderate shear rate can generate the highest proportions of aggregates containing a small number of particles. In

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all, by controlling various parameters, droplets with different sizes can be obtained, thus generating different packing numbers in the emulsion template assisted assembly. The surface properties of these particles cannot be neglected when controlling the structures of the packings. The particles inside the droplets pack according to the capillary force acting upon them. The geometrical structure of clusters can be predicted as a function of constituent particle number through theoretical considerations of minimizing Lennard-Jones potential, second moment of the mass distribution, or Coulomb potential (Cho et al. 2005). By optimizing these functions respectively, three types of sphere packings or cluster structures have been proposed (Livshits et al. 1999; Maranas et al. 1992; Sloane et al. 1995; Wille 1986). The configurations of clusters predicted by the three models remain the same when the packing number is smaller than seven. When a large number of particles are assembled, the structure is sensitive to small differences in the interparticle forces, and therefore various configurations of clusters can be achieved when particles with different surface properties are used and consequently different particle interactions are involved. For example, it has been reported that 11 PS clusters assemble into a nonconvex structure in oil while the same number of PMMA spheres pack in a convex shape (Yi et al. 2004). The different packing behavior is attributed to the different swelling characteristics of these two types of particles. The van der Waals attraction, which varies between systems, also contributes to the structure determination in the assembly of large number particles by fixing them at different points in the consolidation process before all of the oil evaporates. Overall, the packing constraints imposed by the particle interaction and the inward pressure of the shrinking oil droplets determine the final configurations when a large number of particles are considered. Apparently, the number of spheres per droplet is another important parameter, which can be easily adjusted by controlling the volume fraction of poly­mer particles in the oil phase (Zerrouki et al. 2006). Largervolume fractions of the particles in the oil phase will result in anisotropic clusters with higher packing numbers while smaller-volume fractions generate clusters with lower packing numbers. Further control of the complex composite assemblies can be attained by controlling the original drop components, for example, by mixing two or more different types of particles (Cho et al. 2005a, 2005b; Reculusa et al. 2004; Rabideau et al. 2004). The segregation of two types of colloids with different sizes and physical properties during assembly yields complex anisotropic particles. For example, with a mixture of regular PS beads and paramagnetic particles, anisotropic particles can be produced by gravitational separation of these components or by the application of a constant magnetic field (Rabideau et al. 2004). Suspensions containing large latex particles (~270 nm) and small gold particles can form unconventional “glazed doughnut” shapes during the drying (Velev et al. 2000).

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3.4.3.2 Self-Assembly in Hard Template The soft-template method can create nonspherical complex assemblies in relatively large quantities. However, more effort is still needed to control the uniformity of the size and structural arrangement of the assemblies. By using hard templates that are lithographically patterned with designed shapes, homogeneous complex aggregates (such as polygonal and polyhedral clusters) assembled from monodispersed spherical colloids can be obtained with well-controlled sizes and near identical structures (Yin et al. 2001a, 2001b). Figure  3.15 outlines the schematic procedure of self-assembly with designed hard templates. The key strategy of this assembly approach is the dewetting of an aqueous dispersion of monodispersed spherical colloidal particles across a surface that contains template holes. As shown schematically in Figure 3.15a, the assembly is performed in a glass cell, which is composed of two glass substrates. The surface of the bottom substrate contains a 2D array of cylindrical holes lithographically patterned in a thin film of photo resist. When the particle dispersion is allowed to dewet slowly across the cell, the capillary force exerted on the rear edge of this liquid slug drags the spher­ical particles across the surface of the bottom substrate until they are physically trapped in the arrays of cylindrical holes. The structural arrangement of these beads can be controlled by the maximum number of poly­mer beads that can be possibly retained in each hole, which can be determined by the ratios between the dimensions (diameter and height) of the holes and the diameter of the poly­mer beads. A range of uniform, polygonal or poly­ hedral clusters can be formed in such 2D arrays of holes. When the solvent is

(a)

Gla

Water

Fe

Flow

(b)

c(c)

(d)

(e)

ss on

cti dire

Fc Fg Patterned photoresist

2 µm

Figure 3.15 (a) Schematic illustration of the procedure to assemble spherical colloids into well-controlled clusters under the physical confinement exerted by a 2D array of cylindrical holes patterned in a thin film of photo resist. The size, shape, and structure of these clusters can all be easily controlled by changing the ratios between the dimensions of the holes and the diameter of the poly­mer beads. (b–e) SEM images of dimers, trimers, squares, and pentamers formed in photo resist templates.

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completely evaporated, the poly­mer beads trapped in each hole always tend toward physical contact as a result of attractive capillary forces among them. Once the solvent is evaporated, clusters in each hole can be welded into a permanent form via thermal treatment at a temperature slightly higher than the glass transition temperature of the poly­mer. The extent of viscoelastic deformation of colloidal beads during thermal jointing depends on a number of parameters, in particular, the Tg of the beads. The anisotropic clusters such as dimers, trimers, or squares of PS beads can then be released by dissolving the photo resist film with ethanol under sonication. This self-assembly approach can be conveniently extended to the generation of asymmetric dimers from two types of monodispersed, spherical colloids that could be different in size, chemical composition, surface functionality, density or sign of surface charges, bulk properties, or a combination of characteristics (Yin et al., 2001a). Templates other than cylindrical holes have also been demonstrated to generate aggregates of spherical colloids with more complex geometric shapes and internal configurations (Yin et al. 2001a, 2001b; Xia et al., 2003).

3.5 Summary In this chapter, we have discussed the preparation of nonspherical poly­mer nanoparticles through either direct seeded poly­mer­i­za­tion or indirect posttreatment. Nonspherical particles with relatively simple structures can be prepared by controlling the swelling and phase separation processes in seeded poly­mer­i­za­tion procedures, while more complicated anisotropic polymeric particles can be obtained through indirect approaches such as the stretching of a matrix embedded with poly­mer particles. Self-assembly processes, as one type of unique posttreatment approach, do not rely on any physical or chemical deformation techniques; instead, they involve using templates to organize the precursor nanoparticles into secondary structures. The starting materials used in the indirect approaches are not necessarily limited to spherical particles. For example, nonspherical particles obtained by seeded emulsion poly­mer­i­za­tion might also be employed as precursors to fabricate even more complicated structures through self-assembly. Nonspherical poly­ mer nanoparticles can be used as interesting model systems for studying the behavior of molecules in solution, or modeling the behavior of irregular colloidal particles that can be found everywhere in our daily lives. They also have great potential in a wide range of technological applications including the fabrication of three-dimensional photonic colloidal crystals.

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Velev, O. D., Lenhoff, A. M., and E. W. Kaler. 2000. A class of microstructured particles through colloidal crystallization. Science 287:2240–43. Whitby, G. S., and M. Katz. 1933. Synthetic rubber. Industrial and Engineering Chemistry 25:1204–1210. Wille, L. T. 1986. Searching potential energy surfaces by simulated annealing. Nature 324:46–48. Xia, Y. N., Gates, B., Yin, Y. D., and Y. Lu. 2000. Monodispersed colloidal spheres. Old materials with new applications. Advanced Materials 12:693–713. Yin, Y. D., Lu, Y., Gates, B., and Y. N. Xia. 2003. Template-assisted self-assembly of spherical colloids into complex and controllable structures. Advanced Functional Materials 13:907–18. Xu, C., Wang, Q., Xu, H., Xie, S., and Z. Yang. 2007. General synthesis of hollow composite ellipsoids. Colloid and Polymer Science 285:1471–78. Yi, G. R., Manoharan, V. N., Klein, S., Brzezinska, K. R., Pine, D. J., Lange, F. F., and S. M. Yang. 2002. Monodisperse micrometer-scale spherical assemblies of poly­ mer particles. Advanced Materials 14:1137–40. Yi, G. R., Manoharan, V. N., Michel, E., Elsesser, M. T., Yang, S. M., and D. J. Pine. 2004. Colloidal clusters of silica or poly­mer microspheres. Advanced Materials 16:1204–8. Yin, Y. D., Lu, Y., Gates, B., and Y. N. Xia. 2001. Template-assisted self-assembly: A practical route to complex aggregates of monodispersed colloids with welldefined sizes, shapes, and structures. Journal of the American Chemical Society 123:8718–29. Yin, Y. D., Lu, Y., and Y. N. Xia. 2001a. A self-assembly approach to the formation of asymmetric dimers from monodispersed spherical colloids. Journal of the American Chemical Society 123: 771–72. ———. 2001b. Self-assembly of monodispersed spherical colloids into 1D chains with well-defined lengths and structures. Journal of Material Chemistry 11:987–89. Yin, Y. D., and Y. N. Xia. 2001. Self-assembly of monodispersed spherical colloids into complex aggregates with well-defined sizes, shapes, and structures. Advanced Materials 13:267–71. Zerrouki, D., B. Rotenberg, S. Abramson, J. Baudry, C. Goubault, F. Leal-Calderon, D. J. Pine, and J. Bibette. 2006. Preparation of doublet, triangular, and tetrahedral colloidal clusters by controlled emulsification. Langmuir 22:57–62.

4 Block, Graft, Star, and Gradient Copolymer Particles H. Matahwa, E. T. A. van den Dungen, J. B. McLeary, and B. Klumperman Contents 4.1 Introduction................................................................................................... 98 4.2 Polymerization Techniques for Complex Macromolecular Architectures................................................................................................. 99 4.2.1 Block Copolymer Topology........................................................... 100 4.2.2 Graft Copolymer Topology........................................................... 101 4.2.3 Star Copolymer Topology.............................................................. 103 4.2.4 Gradient Copolymer Topology..................................................... 103 4.3 Polymer Nanoparticles in Heterogeneous Polymerization.................. 104 4.3.1 Approaches for Successful Application of CRP in Heterogeneous Media.................................................................... 105 4.3.2 Challenges with the Application of CRP in Heterogeneous Media................................................................................................ 107 4.3.3 Characteristics of the Individual CRP Techniques in Miniemulsion Polymerization...................................................... 108 4.3.4 Nanoparticles with Complex Architecture Synthesized via CRP in (Mini)emulsion.................................................................. 110 4.4 Polymer Nanoparticles via Self-Assembly.............................................. 113 4.4.1 Synthesis of Amphiphilic Copolymers........................................ 113 4.4.2 Nanostructures via Self-Assembly of Copolymers.................... 114 4.4.3 Nanoparticles Synthesis by Cross-Linking of SelfAssembled Structures.................................................................... 115 4.4.4 Functionalization of Cross-Linked Micelles............................... 121 4.4.5 Potential Applications of Cross-Linked Nanoparticles............. 121 4.5 Conclusions.................................................................................................. 123 References.............................................................................................................. 124

97

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Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

4.1 Introduction This chapter describes routes that have been utilized in the synthesis of advanced poly­mer nanoparticles. The progress that has been made in the field of controlled radical poly­mer­i­za­tion (CRP) for the synthesis of nanoparticles consisting of advanced topology and morphology is highlighted. Advanced poly­mer topologies that will be discussed include block, graft, star, and gradient copolymers (Scheme 4.1). Heterogeneous poly­mer­i­za­tion techniques are most commonly used to synthesize poly­mer nanoparticles. Polymerization in heterogeneous media is relatively simple and high rates of poly­mer­i­za­tion are obtained, leading to high conversions and high molecular weight polymers in relatively short times. Latex polymers are predominantly synthesized via a free radical poly­mer­i­za­ tion mechanism. This leads to a wide variety of latex products with a large variation of physical and mechanical properties. Polymerizations in heterogeneous media, where the continuous medium is water, provide an environmentally friendly approach for the synthesis of materials, which is necessary due to the increasing restrictions for solvent-based systems. Because water is the medium in which the poly­mer­i­za­tion takes place, easy removal of exothermic reaction heat is facilitated and the final latex is a low-viscosity, easy-to-handle product.

AB diblock copolymer

A-B graft copolymer A-B star copolymer

A-BC heterograft copolymer

A-B gradient copolymer

A-BC miktoarm star copolymer

Scheme 4.1 Various topologies that can be obtained via the employment of various CRP techniques in homogeneous and heterogeneous media. The synthesis of nanoparticles consisting of these topologies is discussed in this chapter.

Block, Graft, Star, and Gradient Copolymer Particles

99

The successful application of CRP techniques in heterogeneous poly­mer­i­ za­tion would provide better control over the molecular weight and give narrow molecular weight distribution polymers. More importantly, due to the retention of the mediating agent as an end group at the poly­mer chain end, the synthesis of (co)polymers comprising advanced macromolecular architectures, such as shown in Scheme 4.1, is easily obtained. Synthesis of poly­mer nanoparticles via self-assembly and cross-linking of amphiphilic copolymers, and their modification for various applications are also discussed. Several approaches to achieving self-assembly of complex architectures can be used. Amphiphilic copolymers can readily self-assemble into nanostructures when a common solvent is replaced by a selective solvent. Additionally, response to stimuli (temperature, pH, or ionic strength) can be used to drive self-assembly of the copolymers. The stable nano­ particles are then obtained by cross-linking of the self-assembled nanostructures. Various chemistries for modification of the nanoparticles and possible applications are highlighted. Advantages, disadvantages, and the feasibility of the various approaches for industrial application are also discussed.

4.2 Polymerization Techniques for Complex Macromolecular Architectures The invention of so-called CRP techniques provided similar flexibility as observed in conventional free radical poly­mer­i­za­tion, but with additional advantages such as control over molecular weight and molecular weight distribution and the ability to easily synthesize structures of complex architecture [1–3]. This is attributed to the long lifetime of the poly­mer chains, which grow throughout the reaction. The poly­mer chains are initiated fast at the early stages of the poly­mer­i­za­tion, and all poly­mer chains grow simultaneously throughout the course of poly­mer­i­za­tion. Due to the involvement of the poly­mer chains in a reversible activation-deactivation mechanism, the majority of poly­mer chains are in a dormant state at any given instant. This means that the active propagating radical concentration is low and that between each activation-deactivation cycle, only a few monomer units are incorporated in the chain. The low active propagating radical concentration also leads to a significantly reduced rate of termination and consequently formation of dead chains. In conventional free radical poly­mer­i­za­tion, all poly­mer chains synthesized are involved in termination reactions leading to so-called “dead” poly­mer chains that are not capable of further growth. In CRP on the other hand, at the end of poly­mer­i­za­tion the poly­mer chains are end-capped with an activator that allows chain extension for the synthesis of structures with complex topology (Scheme 4.1).

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Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

NMP

O

kact

N

Pn•

kdeact

Pn

O• N

+

kp M

kact ATRP

Pn—X

Mnt —X/L

+

kdeact

Mn+1 t X2/L

+

P n• kp M

RAFT-mediated polymerization

P n• kp

+

Pm

S S Z

kdeact kact

M

Pn

S

• C

S

Z chain-transfer

Pm

kdeact kact

Pm• kp

+

Pn

S S Z

M

Scheme 4.2 Reversible termination mechanism for NMP and ATRP and degenerative transfer mechanism for RAFT-mediated poly­mer­i­za­t ion.

The three main CRP techniques that are employed in poly­mer science nowadays are nitroxide-mediated poly­mer­i­za­tion (NMP), atom transfer radical poly­mer­i­za­tion (ATRP) [4,5], and reversible addition-fragmentation chain transfer (RAFT)-mediated poly­mer­i­za­tion [6,7]. NMP and ATRP are examples of reversible termination, whereas RAFT-mediated poly­mer­i­za­ tion is an example of degenerative transfer (reversible chain-transfer), as illustrated in Scheme 4.2. Both NMP and ATRP are controlled by the persistent radical effect (PRE), which means that every radical-radical termination event leads to an irreversible accumulation of deactivator, shifting the equilibrium toward the dormant species and consequently decreasing the rate of termination. RAFT-mediated poly­mer­i­za­tion requires a conventional radical initiator to start poly­mer­i­za­tion, whereas both ATRP and NMP are self-initiating poly­mer­i­za­tion techniques that initiate poly­mer­i­za­tion via a halogen-containing ATRP initiator or an alkoxyamine, respectively. Scheme 4.3 shows examples of RAFT agents, ATRP ligands used in Cu(I)-mediated ATRP, and the nitroxides 2,2,6,6-tetramethylpiperidinyl-1oxy (TEMPO) and N-tert-butyl-N-(1-diethylphosphono-2,2-dimethylpropyl) nitroxide (SG1, also called DEPN). 4.2.1 Block Copolymer Topology CRP results in chains that are end-capped with a mediating agent, and chain extension is possible to form block copolymers by adding another monomer followed by initiation. The formation of homopolymer during chain extension experiments in RAFT-mediated poly­mer­i­za­tion is inevitable and reduces

101

Block, Graft, Star, and Gradient Copolymer Particles

RAFT agents

S

S

CH3

S C

S C

N

CH3 2-cyanoprop-2-yl dithiobenzoate

CH3 cumyl dithiobenzoate

H benzyl dithiobenzoate

O

S N

O

S

S C

OH

S C

O — poly(ethylene-co-butylene)

S PMMA

S

CH3 poly(ethylene-co-butylene) macroRAFT agent

PMMA macroRAFT agent H

CH3 O S C

S

S OH

CH3 S-butyl-S’-2-methylpropanoic acid trithiocarbonate

H

S S H3C H S-butyl-S’-benzyl trithiocarbonate

C18H37 N

N

N

H9C4

tris[(2-pyridyl)methyl]amine (TPMA) C4H9

H9C4

N

2-2'-bipyridine (bpy)

N

N

N

CH3

N,N,N’,N”,N”-pentamethyldiethylenetriamine (PMDETA) NMP mediators

C4H9 O• N

N

CH3

CH3

N bis(2-pyridylmethyl)octadecylamine (BPMODA)

CH3

S

H dibutyl-1,4-phenylenebis(methylene)bistrithiocarbonate

CH3 H3C

N

H

S

S

S

H3C

N

N

S

S H

ATRP ligands

N

H

S

S N

CH3 2-cyanopentanoic acid dithiobenzoate

H3C

S

CH3

N

4,4'-di(5-nonyl)-2,2'-bipyridine (dNbpy)

O

O• N

CH P OC2H5 OC2H5 SG1

TEMPO

Scheme 4.3 RAFT agents, ligands for complexation with Cu catalyst in ATRP, and NMP mediators employed in the various controlled radical poly­mer­i­za­t ion techniques.

the purity of the block copolymer. This leads to formation of block copoly­ mer in conjunction with the formation of homopolymer, which increases the molecular weight distribution of the final product. In addition, chains that do not contain the RAFT moiety as an end group after the synthesis of the first block cannot be chain extended during the synthesis of the second block and therefore will remain as an impurity in the final poly­mer product. In case the monomer conversion during the synthesis of the first block does not reach 100%, chain extension of the first block with a second monomer will lead to a second block consisting of a random copolymer instead of a homopolymer (provided excess monomer is not removed). 4.2.2 Graft Copolymer Topology Graft copolymers are a type of branched copolymer in which the side chains are structurally distinct from the main chain. The side chains can

102

Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

extend from poly­mer backbones [8–12] or ([in]organic nanoparticle) surfaces [13–21]. CRP controls the molecular weight and polydispersity index (PDI) of the backbone and the side chains, and either one may consist of a homo­polymer, block, alternating, or random copolymer topology. Three approaches for the synthesis of graft copolymers include “grafting from,” “grafting onto,” and “grafting through” [1,2,10]. “Grafting from” involves the creation of a predetermined number of initiating sites on the poly­mer backbone or surface, and the subsequent poly­mer­i­za­tion from these initiating sites. This technique inevitably leads to the formation of homopolymer impurity, which requires an extra purification step, unless the side chains are poly­mer­ized via ATRP or NMP, which are self-initiating CRP techniques that are exclusively initiated by halogen-containing ATRP initiators or alkoxyamine initiators, respectively. “Grafting onto” involves the covalent attachment of a preformed poly­mer chain onto a poly­mer backbone/ surface via radical reaction or reaction between complementary functional groups. A disadvantage is the low grafting efficiency due to steric hindrance. “Grafting through” involves the poly­mer­i­za­tion of the pendant vinyl groups of a macromonomer. Generally the degree of poly­mer­i­za­tion of the backbone is low due to the low concentration of vinyl groups and the high steric hindrance around the chain end propagating radical. A facile method to synthesize graft copolymers via CRP is to functionalize the repeating units of the poly­mer backbone with a RAFT agent or ATRP initiator (Scheme 4.4) [22]. After poly­mer­i­za­tion of the backbone, graft copolymers can be synthesized via CRP of the side chains. RAFT-mediated poly­mer­i­za­tion allows for two different approaches. The R-group approach Grafting from a surface using Z-group approach in RAFT-mediated polymerization

OH

O

+

Cl

surface

O

S S

pyridine S

O

R

O

S S

S

R

MA

O

S S

R

S

PMA

RAFT agent

Grafting from a polymer backbone via ATRP CH3

H2C

O O OH HEMA

n

ATRP

O

O

Br

pyridine Br

OH PHEMA

n

O

O

O O

n

Br

ATRP styrene O

O

O

Br

O

O

Br Br ATRP initiating site on side chain

PS Br

Scheme 4.4 Synthesis of graft copolymers with the “grafting from” approach via CRP.

Block, Graft, Star, and Gradient Copolymer Particles

103

involves anchoring of the leaving group to the poly­mer backbone from which the chains are grown. Two macroradicals allow for termination of the poly­ mer chains (and cross-linking between side chains) and loss of RAFT agent functionality. The Z-group approach involves anchoring of the stabilizing group to the poly­mer backbone. In this case, the degree of poly­mer­i­za­tion may be limited due to steric hindrance of the side chains in approaching the RAFT moiety close to the backbone. 4.2.3 Star Copolymer Topology Star poly­mer molecules can be defined as macromolecules containing a single branch point from which linear chains emanate. Polymerization techniques such as conventional free radical poly­mer­i­za­tion and anionic poly­mer­i­za­tion have been used to synthesize star polymers. Star polymers are best prepared by coupling of anionic living polymers with multifunctional electrophilic coupling agents. Multifunctional chloromethylated benzene derivatives or multifunctional chlorosilane compounds are often used as the electrophilic coupling reagents. CRP provided another approach for the synthesis of star polymers with control over molecular weight and PDI [23]. The basic requirement for star poly­mer synthesis is a multifunctional molecule (core) that covalently connects multiple poly­mer chains (arms) by either initiating poly­mer growth or linking preformed poly­mer chains through the multifunctional groups of the molecule [24]. The coupling of two (or more) chemically different polymers results in heteroarm star copolymers, which are often referred to as miktoarm star copolymers (Scheme 4.1). The synthesis of star copolymer particles is readily available by adopting multifunctional initiators for the various CRP techniques (Scheme 4.5). The R-group approach for RAFT-mediated poly­mer­i­za­tion results in the formation of homopolymer impurity and star-star coupling [25–27]. A whole range of products is obtained due to either premature termination of growing poly­mer chains or a mixture of branching point molecules from which a different number of poly­mer chains emanate. Star copolymers are also obtained via the synthesis of linear poly­mer chains and subsequent addition of (divinyl) cross-linker at high(er) conversion, as reported for ATRP [2]. 4.2.4 Gradient Copolymer Topology The synthesis of gradient copolymers can generally be carried out via two methods, that is, spontaneous (batch) and forced (M2 feed) gradient copoly­ mer­i­za­tion. The second method is advantageous for monomer pairs with unfavorable reactivity ratios. The formation of a gradient copolymer requires that the concentration ratio of the monomer pair changes during the course of the poly­mer­i­za­tion. A forced gradient copolymer could be obtained when a second monomer is continuously added to the poly­mer­i­za­tion mixture, which contains only the first monomer.

104

Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

S Z

S

Z

S

S

S S

Z

R

S Z

Br O Br

O O

S S S

multiple-arm ATRP initiator

Ph

Br

O N

O

O CH3 Br CH3

O CH3

CH3 O

1,1,1-tris(4-(2-bromoisobutyryloxy)-phenyl)ethane (TBiBPE)

O P O

O

O

O

CH3

CH3 O

O

O

Br

O

R

Ph O

O

Br

O

S

N O Br

O

R

multiple-arm RAFT agent (Z-group approach)

O O

O

S S R

S multiple-arm RAFT agent (R-group approach)

S

S

H3C

O

O

N

Ph

N O

O

O

O O N

O

O P

O

n

multiple-arm SG1 initiator

multiple-arm TEMPO initiator

Scheme 4.5 Multifunctional initiators for the synthesis of star copolymers via various CRP techniques.

4.3 Polymer Nanoparticles in Heterogeneous Polymerization Polymerizations in dispersed systems show a higher rate of poly­mer­i­za­tion and a lower viscosity at high conversion than poly­mer­i­za­tions carried out in solution or bulk. Due to the confinement of a radical within one particle (compartmentalization), radical-radical terminations are minimized and high conversions and high molecular weights are obtained in relatively short times. These are advantages that are of particular interest for industrial processes. Emulsion poly­mer­i­za­tion is one of the most important industrial processes via which stable poly­mer latexes are prepared. In most cases, the monomer swollen micelles are transformed into poly­mer particles via a free radical poly­mer­i­za­tion process. Emulsion poly­mer­i­za­tion requires transport of monomer from the droplets to the poly­mer particles. The fact that the primary nucleation mechanism in emulsion poly­mer­i­za­tion is either via micellar nucleation or via homogeneous nucleation (aggregation of insoluble chains in the continuous phase that are stabilized by surfactant molecules) complicates the synthesis of complex structures. These include core-shell particles that show homogeneity in composition throughout the particle size distribution and molecular weight distribution. The main mechanism of nucleation can be shifted to droplet nucleation if the size of the monomer droplets is small enough (large total surface area);

Block, Graft, Star, and Gradient Copolymer Particles

105

thus, monomer droplets could compete with the micelles for an incoming radical [28]. This technique is referred to as miniemulsion poly­mer­i­za­tion, and simplifies the process considerably as no monomer transport through the aqueous phase is required. For an ideal miniemulsion poly­mer­i­za­tion process, all kinetically stabilized monomer droplets are nucleated and are converted into poly­mer particles [29,30]. The disadvantages of miniemulsion are that the oil-in-water emulsion is subjected to sonication and that a (volatile) hydrophobe (e.g., hexadecane) is added to the formulation. This makes the realization of industrial implementation more cumbersome, although it has been shown that very hydrophobic (co)monomers (such as lauryl methacrylate) [31] or polymers (e.g., poly[methyl methacrylate], PMMA) [32] also can be used as effective hydrophobes. This eliminates the necessity of removing the hydrophobe after poly­mer­i­za­tion. Microemulsion is a heterogeneous poly­mer­i­za­tion technique that uses a very high surfactant load for the stabilization of monomer swollen micelles [33]. Typical weight ratios of surfactant to monomer range between 1 and 2.5. The surfactant concentration is well above the critical micelle concentration (CMC), and all monomer resides within these monomer swollen micelles. This eliminates the need for monomer transport through the aqueous phase, which makes latexes obtained from microemulsions (and miniemulsions) particularly suitable for use as seed. The seed latex can be swollen with monomer, and poly­mer­i­za­tion is then carried out via a batch emulsion poly­mer­i­za­tion process. Microemulsions are spontaneously formed and are therefore thermodynamically stable. Micelles that are not nucleated will disintegrate and the surfactant molecules will adsorb onto the surface of the growing latex particles to provide stabilization. Particle sizes obtained in microemulsion typically range between 10 and 50 nanometers. 4.3.1 Approaches for Successful Application of CRP in Heterogeneous Media The introduction of various CRP techniques (NMP, ATRP, and RAFTmediated poly­mer­i­za­tion, Scheme 4.2) opened up the way for the synthesis of poly­mer particles with complex architecture via a radical poly­mer­i­za­tion technique [1,2]. Application of these CRP techniques in heterogeneous media would combine the high rates of poly­mer­i­za­tion obtained in heterogeneous poly­mer­i­za­tion with the control over the poly­mer architecture offered with CRP [34–38]. Several approaches have been reported for successful application of CRP in heterogeneous media: • Microemulsion and miniemulsion poly­mer­i­za­tion • Preparation of a seed latex via micro- or miniemulsion poly­mer­i­ za­tion and swelling of the particles with monomer (polymerization takes place within these seed latex particles via a batch emulsion poly­mer­i­za­tion process)

106

Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

• In situ formation of poly­mer particles via nanoprecipitation • Self-assembly of block copolymers synthesized via CRP in bulk or solution Stable latexes can be synthesized via CRP in microemulsion [33] and miniemulsion [39–42] poly­mer­i­za­tion. Recently successful ab initio batch or semicontinuous (starved–feed) emulsion poly­mer­iz­ a­tion mediated via RAFT [43–48] and NMP [49–53] has been reported. In most cases, surfactant-free conditions were employed. Latex products were obtained without the formation of coagulum and particles that consist of poly­mer chains with complex topology of controlled molecular weight and low PDI. Additionally, these stable latex products could be used as a seed for (continued) poly­mer­ i­za­tion via a batch emulsion process. The advantage then is that the poly­ mer­i­za­tion starts in either Interval 2 or Interval 3, dependent on the presence of monomer droplets, and thus the process of particle nucleation is circumvented. This avoids the transport of the (hydrophobic) mediating agent to the locus of poly­mer­i­za­tion. The seed latexes are often synthesized under dilute conditions, and for this approach low molecular weight oligomers are targeted. Swelling of the poly­mer particles with monomer increases the solid content of the latex, and subsequent poly­mer­i­za­tion is carried out via a batch emulsion process. Nanoprecipitation involves the synthesis of an oligomer via CRP in solution or bulk. The resulting oligomer is dissolved in acetone, for example, and added dropwise to the aqueous surfactant solution. A stable latex is formed and the particles can be swollen with monomer, after which the poly­mer­i­ za­tion can proceed via a batch emulsion poly­mer­i­za­tion process. The formation of monomer droplets during swelling of the poly­mer particles should be avoided, as poly­mer­i­za­tion within the monomer droplets is one of the main causes for significant latex destabilization. An advantage is that the poly­mer particles are formed in situ and that no monomer transport through the aqueous phase is required. This significantly improves the stability of the latex and the control over the molecular weight and PDI, as the mediating agent is present at the locus of poly­mer­i­za­tion. Prescott et al. reported on the successful application of RAFT-mediated poly­mer­i­za­tion using a similar approach [54]. They prepared a polystyrene (PS) emulsion and transported the RAFT agent to the locus of poly­mer­i­za­tion via the acetone transport technique, after which they successfully conducted RAFT-mediated poly­mer­i­za­tion. The drawback of this technique in their case is that the seed was prepared via conventional radical poly­mer­i­za­tion, and hence the latex product also contained uncontrolled poly­mer that could not be chain extended. Similarly, synthesis of amphiphilic block copolymers via CRP in solution or bulk allows for self-assembly of these block copolymers in the aqueous phase [47]. The amphiphilic block copolymers simultaneously act as mediating agent and stabilizing agent, which eliminates the requirement for a

Block, Graft, Star, and Gradient Copolymer Particles

107

low molecular weight surfactant. The self-assembly process can be induced either via the use of a selective solvent (e.g., water) or upon a change in environment, such as pH, temperature, or concentration of electrolyte. Use of a surface active mediating agent also allows for self-assembly in the aqueous phase [43,44]. The resulting micelles can be swollen with monomer via a controlled feed, and the poly­mer­i­za­tion can take place via a semicontinuous emulsion process. The use of a water-soluble monomer, such as (meth) acrylic acid ([M]AA) or 4-vinyl pyridine (4VP), allows for direct synthesis in the aqueous phase, and the resulting oligomer can be used as stabilizer in seeded semicontinuous emulsion for the poly­mer­i­za­tion (chain extension) of a water insoluble monomer [45–51,53]. However, due to interference of the acid group with the catalyst complex, this approach is not suitable for use in ATRP. Protected group chemistry is often used in this case to protect the acid functionality. 4.3.2 Challenges with the Application of CRP in Heterogeneous Media A common problem that had to be dealt with was the exit of small, mediating agent-derived radicals from the monomer droplets into the aqueous phase. An inherent characteristic of CRP is simultaneous growth of the poly­ mer chains throughout the poly­mer­i­za­tion, and therefore slow formation of high molecular weight poly­mer. This could enhance exit of the radicals from the monomer droplets. Additionally, the resulting high concentration of oligomers at the early stage of the poly­mer­i­za­tion could lead to instability of the latex product because oligomers are known to be very effective swelling agents (superswelling) [55]. It should be noted that chain-transfer reactions in conventional free radical poly­mer­i­za­tion in (mini)emulsion also leads to the formation of small radicals, which can either terminate a long poly­mer chain (via short-long termination events) or exit the poly­mer particle. The absence of radicals in the poly­mer particle leads to rate retardation. In addition, partitioning of the mediating agent between the oil and aqueous phases determines the equilibrium concentrations in both phases and can be adequately controlled by using a sufficiently hydrophobic mediating agent. Initial attempts to perform CRP in a (mini)emulsion process were met with difficulties such as colloidal instability and poor control over the molecular weight and PDI [34,35]. The inability to carry out CRP directly in batch emulsion was attributed to negligible transport of the hydrophobic mediating agent from the large monomer droplets to the poly­mer­i­za­tion loci. The resulting latex was characterized by phase separation and coagulation of small droplets, which lead to instability of the final latex product. Therefore, CRP was applied to miniemulsion poly­mer­i­za­tion, which does not require transport of the (hydrophobic) mediating agent. When a rather hydrophilic mediating agent was used, the early stage of the poly­mer­i­za­tion was characterized by an inhibition period, due to the slow consumption of the

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Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

mediating agent and hence slow formation of surface active z-mers (oligo­ mers with chain length that gives sufficient hydrophobicity). 4.3.3 Characteristics of the Individual CRP Techniques in Miniemulsion Polymerization A large number of monomers have been used for RAFT-mediated poly­mer­ i­za­tion in miniemulsion, such as styrene (S), methyl methacrylate (MMA), (2-ethyl)hexyl methacrylate (EHMA), methacrylic acid (MAA), n-butyl acrylate (n-BA), etc. Chain extension of the resulting homopolymers to form block copolymers (via seeded emulsion poly­mer­i­za­tion) has been carried out [40,41,56]. Anionic and cationic low molecular weight surfactants and nonionic polymeric surfactants have been investigated for their influence on the stability of the latex particles. Provided that the concentration of surfactant (stabilization against coalescence/coagulation) and hydrophobe (stabilization against monomer diffusion [Ostwald ripening]) are sufficiently high, stable latex particles with a minimum of coagulation can be synthesized via RAFT-mediated poly­mer­i­za­tion in miniemulsion [57]. Care has to be taken that the pH of the system is properly buffered because RAFT agents are sensitive toward hydrolysis at elevated pH [58,59]. Commonly observed phenomena in RAFT-mediated poly­mer­i­za­tion are an inhibition period and a retardation of the rate of poly­mer­i­za­tion compared to conventional radical poly­mer­i­za­tion [60]. These are disadvantages that particularly limit industrial application. It has been suggested that rate retardation in RAFT-mediated (mini)emulsion poly­mer­i­za­tion could be caused by exit of the leaving group radical into the aqueous phase [61] or by using a block copolymer stabilizer that contains a poly(acrylic acid) (PAA) block [34]. PAA is susceptible to proton abstraction, which results in formation of midchain radicals (MCRs) that propagate slowly and terminate quickly. ATRP in miniemulsion is commonly carried out via “activators generated by electron transfer (AGET) ATRP” [62,63]. Cu(II) is added as the catalyst precursor, which is more stable to oxygen than Cu(I). This circumvents the use of Cu(I) species that is very sensitive to oxidation, which would occur during the formation of a miniemulsion via sonication. AGET ATRP uses a reducing agent such as ascorbic acid, instead of a conventional radical initiator, to create the activator [62,63]. A substoichiometric ratio of reducing agent is used to leave some excess of Cu(II) species to regulate ATRP. This approach also increases the tolerance of the system to air, as the reducing agent can be used to scavenge oxygen from the air. The presence of air would, however, require an increased amount of reducing agent. The optimal amount of the reducing agent depends on the partitioning of the Cu(II) species between the aqueous phase and the monomer droplets, ATRP equilibrium constant, target molecular weight, etc. Too small an amount of reducing agent would lead to very slow poly­mer­i­za­tion, whereas too high an amount of reducing agent would deteriorate the control over the poly­mer­i­za­tion. Partitioning of

Block, Graft, Star, and Gradient Copolymer Particles

109

the more hydrophilic Cu(II) species between the oil and aqueous phases disturbs the Cu(I)-to-Cu(II) ratio, which is undesirable as this ratio regulates the control over the poly­mer­i­za­tion. Another advantage of AGET ATRP is the ability to synthesize pure block copolymers without the formation of homopolymer, as no free radicals are present that initiate new chains during the formation of the second block. The earlier developments of reverse ATRP and simultaneous reverse and normal initiation (SR&NI) ATRP also allowed for application in miniemulsion. However, reverse ATRP employs an external initiator (such as AIBN) to reduce the Cu(II) to Cu(I) and therefore this technique does not allow for the formation of block copolymers. SR&NI ATRP employs a normal alkyl halide initiator in combination with a conventional radical initiator and thus allows for the synthesis of block copolymers and structures of more complex architecture. In addition, a significantly decreased concentration of catalyst is required. However, as a conventional radical initiator is used for the generation of radicals, the synthesis of a block copolymer also leads to the formation of homopolymer impurity from poly­mer­i­za­tion of the second monomer, which requires an additional purification step. Initial attempts to adopt “normal” ATRP in miniemulsion provided moderate success [64,65]. Only if a stable initial emulsion was obtained did the poly­mer­i­za­tion proceed in a controlled manner, that is, linear increase of molecular weight with conversion and low PDI throughout the reaction. An inherent disadvantage to ATRP is the use of a transition metal catalyst (mostly copper), which may be undesirable as it is retained as an impurity after the poly­mer­i­za­tion. The development of “activators re-generated by electron transfer (ARGET) ATRP” [68], which is similar in concept to AGET ATRP, allowed for the use of only parts per million (ppm) amounts of copper catalyst in the poly­mer­i­za­tion medium, while control over the poly­mer­i­za­ tion was retained [66–68]. This development is a big step forward to application in industrial processes. Interaction of anionic surfactants with the copper catalyst results in poor control over molecular weight and molecular weight distribution. Nonionic surfactants can be used in ATRP instead, but they are generally not as preferable as they give bigger particle sizes, result in less stable latexes, and become less effective at elevated temperatures [37]. The development of the “second-generation” nitroxides in NMP provided a solution to the high temperatures required for activation of the TEMPOderived alkoxyamine (Scheme 4.3) [69–71]. The equilibrium constant of these second-generation nitroxides is much higher at lower temperatures and therefore an acceptable rate of poly­mer­i­za­tion is obtained. In addition, the second-generation nitroxides allow for controlled poly­mer­i­za­tion of (meth)­ acrylates. An example is the commercially available nitroxide SG1 (DEPN, Scheme 4.3), which can be used at temperatures of 90–120°C. Due to the formation of a large amount of dead chains at high conversion during the synthesis of homopolymer via NMP in miniemulsion, it is important to keep the conversion low to render the majority of chains active for

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the synthesis of block copolymers. Alternatively, nitroxide end-capped oligo­ mers can be synthesized in bulk or solution and applied as both hydrophobe and mediating agent to miniemulsion poly­mer­i­za­tion [69]. 4.3.4 Nanoparticles with Complex Architecture Synthesized via CRP in (Mini)emulsion The successful application of CRP in heterogeneous media allows for the synthesis of nanoparticles with complex architectures such as block [40,41,44–51,53,54], graft [10,20], star, and gradient [72] copolymers in (mini)emulsion. The synthesis of these structures does not cause additional complexity to the system compared to the synthesis of homopolymers in (mini)emulsion. RAFT-mediated polymerization H Z S S H Z

S

H Miniemulsion polymerization of n-BA

H S

T = 75°C, AIBN, Brij 98, hexadecane

Z

H

Z

S

S

H PBA

H

S

S H

PBA

Z=CH3CH2CH2CH2S H

Z

Z

S

S

H PBA

H

PS

S PS

PBA

Sty, AIBN

S

T = 75°C

H

ATRP H2C

CuBr, PMDETA, EBiB

O O

T = 50°C, bulk

CH3

Br PMA

CuBr2, BPMODA, Sty, Brij 98, hexadecane, ascorbic acid

Br

T = 80°C, miniemulsion

PMA

PS

NMP H2C

O O

T = 115°C 2.5 mol% free SG1

C4H9 +

O N

O

N

O P

OCH3

Conversion to ~80%

O H3CO

PBA O

OC2H5

OC2H5 T = 115°C

O P

H2C

OC2H5

OC2H5 CH3-O(CO)-CH(CH3)-SG1

PBA

PS O

O OCH3

Scheme 4.6 Block copolymer synthesis via CRP in miniemulsion.

N

O P

OC2H5

OC2H5

111

Block, Graft, Star, and Gradient Copolymer Particles

(a)

(b)

250 nm

250 nm (c)

(d)

250 nm (e)

250 nm (f )

500 nm

500 nm

Figure 4.1 Height (a, c, and e) and phase (b, d, and f) images obtained with AFM from poly­mer brushes synthesized via AGET ATRP in miniemulsion, using various ratios of ascorbic acid to Cu(II): 0.20 (a and b) and 0.35 (c–f). Monomer conversion is ~21% for images a and b, ~25% for images c and d, and ~80% for images e and f. (Reprinted from K. Min, S. Yu, H.-I. Lee, L. Mueller, S. S. Sheiko, and K. Matyjaszewski, Macromolecules 40: 6557–63, 2007. With permission.)

Figures 4.1 and 4.2 show examples of atomic force microscopy (AFM) and transmission electron microscopy (TEM) images of polymers with complex architecture obtained in mini(emulsion). Min et al. synthesized poly­mer brushes by growing PBA chains from a poly­mer backbone via AGET ATRP directly in miniemulsion [10]. Figure 4.1 shows the corresponding height and phase images obtained with AFM from these poly­mer brushes for various ratios of ascorbic acid to Cu(II) used, at a given conversion for n-BA. Dire et al. reported on the surfactant-free ab initio batch emulsion poly­mer­ i­za­tion of MMA using a P(MMA-co-S)-SG1 macroalkoxyamine that simultaneously acted as initiator and stabilizing agent [49]. The TEM images they

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Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

500 nm Figure 4.2 TEM images obtained from surfactant-free ab initio batch emulsion poly­mer­i­za­t ion of MMA using a P(MMA-co-S)-SG1 macroalkoxyamine initiator. (Reprinted from C. Dire, S. Magnet, L. Couvreur, and B. Charleux, Macromolecules 42: 95–103, 2009. With permission.)

obtained from their stable latexes show a very narrow particle size distribution, as can be seen in Figure 4.2. Provided that stable latex particles are obtained, employment of the appropriate mediating agent during the poly­mer­i­za­tion (e.g., Scheme 4.7) will result in the formation of graft or star copolymers. The synthetic route is similar to that in homogeneous media, with the additional benefit in heterogeneous media of less termination/coupling reactions. Although coupling reactions can still occur within the latex particles, macroscopic gel formation will not occur as long as the (mini)emulsion system remains stable [10]. Cross-linking will not affect the fluidity of the system and therefore high conversions can be achieved. Although the synthetic route is not significantly more complex compared to the synthesis of block copolymers, few reports have appeared on the synthesis of graft and star copolymer nanoparticles directly in (mini)emulsion. H2C

O O

1. BPMODA, Cu(II)Br2, EBiB, hexadecane, T = 80°C Aqueous solution of Brij 98 2. AscA, t-BA (0.01 mL/min for 200 min) gradient n-BA - t-BA copolymer

H3C

Scheme 4.7 AGET ATRP of n-BA with a constant feed of tert-butyl acrylate (t-BA) in miniemulsion for the synthesis of gradient copolymers with controlled molecular weight and low polydispersity. (Reprinted from K. Min, J. K. Oh, and K. Matyjaszewski, Journal of Polymer Science, Part A: Polymer Chemistry 45: 1413–23, 2007. With permission.)

The synthesis of gradient copolymers has been reported for ATRP, where AGET ATRP was used for the synthesis of forced gradient copolymers [72]. The absence of a conventional radical initiator for the reduction of the precursor catalyst Cu(II) provides that the polymers exclusively be initiated via the

Block, Graft, Star, and Gradient Copolymer Particles

113

ATRP initiator, and therefore does not result in the formation of homopolymer. Factors that influence the gradient are, for example, the molar feed ratio of the monomers, the feeding rate, the hydrophobicity of the monomers, and the reactivity ratios of the monomers. SR&NI ATRP is not suitable for the forced gradient method because M2 is fed to the reaction mixture. Radicals derived from a conventional radical source could escape monomer droplets where the poly­mer­i­za­tion takes place, and initiate poly­mer­i­za­tion of M2 in the aqueous phase to form homopolymer of M2. This not only broadens the molecular weight distribution, but also leads to the formation of unstable latexes.

4.4 Polymer Nanoparticles via Self-Assembly 4.4.1 Synthesis of Amphiphilic Copolymers Most poly­mer­i­za­tion techniques can be used to synthesize amphiphilic copolymers. Several poly­mer­i­za­tion techniques can be used in tandem for the synthesis of amphiphilic copolymers with complex architectures. This requires that several functional groups or initiating/mediating agents are present either at the chain end (block copolymer synthesis) or along the poly­ mer backbone (for grafting reactions) or at the junction (for star copolymer synthesis). The amphiphilic nature is a result of having different poly­mer blocks in the same molecule that have different properties. Synthesis of complex macromolecular architectures by CRP has been highlighted already in the previous section. A combination of ATRP and “click chemistry” is widely used for the synthesis of amphiphilic copolymers. ATRP and click chemistry were used, for example, to synthesize a multiresponsive double hydrophilic ABC miktoarm star terpolymer [73] and two oppositely charged graft ionomers consisting of poly(methacrylic acid-co-­azidopropyl methacrylate)-g-poly(N-isopropyl acrylamide) (P[MAA-co-AzPMA]-g-P[NIPAM]) and methyl iodide quaternized poly(2-[dimethylamino]ethyl methacrylate-coazidopropyl methacrylate)-g-poly(N-isopropyl acrylamide) (P[DMAEMAco-AzPMA]-g-P[NIPAM]) [74]. ATRP was used to graft tert-butyl acrylate (t-BA) onto polystyrene-b-ethylene-co-butylene-b-polystrene (PSEBS) backbone [75]. The ATRP macroinitiator was initially prepared by hydrogenation and chloro­methylation of PSEBS. Free radical poly­mer­i­za­tion in conjunction with coupling chemistry can also be used to synthesize amphiphilic copolymers. A cross-linkable amphiphilic graft copolymer was synthesized via free radical poly­mer­i­za­tion of N-acryloxysuccinimide (NAS) as the backbone, and then HEMA, amino-functionalized polyethylene glycol (PEG), and amino-functionalized PNIPAM were attached to the backbone [76]. Other techniques such as ROP [77,78] and ROMP [79] can also be used to synthesize amphiphilic copolymers. Anionic poly­mer­i­za­tion was used to synthesize

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Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

tri­block terpolymers that self-assemble in organic media [80]. A combination of ATRP and anionic poly­mer­i­za­tion was used to synthesize star-like amphiphilic copolymers [81]. 4.4.2 Nanostructures via Self-Assembly of Copolymers Self-assembly of amphiphilic copolymers such as block [82,83], star [84–87], and graft copolymers [74,76,88–90] into nanostructures have been reported by various authors. Amphiphilic copolymers have a tendency of self­assembling into morphologies such as micelles, vesicles, lamellae, etc. when a selective solvent for one of the blocks is added. The driving force for self-assembly is the reduction in surface energy. The commonly used self-­assembly procedure is to synthesize the copolymer (or dissolving the copoly­mer) in its common solvent (solvent for all the blocks) followed by solvent exchange with a selective solvent via dialysis. The self-assembly of these copoly­mers is reversible upon addition of a common solvent for the copolymer and upon heating. It is important to note that the self-assembled copolymers are thermodynamically and kinetically more stable than self-assembly structures from low molecular weight molecules [91]. The process of self-assembly of amphiphilic copolymers is affected by a number of factors, which include their chemistry, topology, molecular weight, (co)solvent, etc. Self-assembly of copolymers is also induced by incorporating thermo- or pH-responsive poly­mer chains in the copolymer, and thus nanostructures are formed upon a variation in the pH or temperature [92–97]. A double hydrophilic ABC mikto­arm star terpolymer made up of PEG, PNIPAM, and poly(2-[diethylamino]ethyl methacrylate) (PDEAEMA) blocks was shown to self-assemble at 25°C and pH 10 and at 50°C and pH 4 but remained in solution at 25°C and pH 4 [73]. Narain and Armes used an aldehyde-­functionalized ATRP initiator to synthesize various sugar containing methacrylate block copolymers (glyco­polymers) that showed either pHor thermo-responsive behavior [98]. These copolymers formed well-defined micelles upon self-assembly, and the ­aldehyde-functional groups were found on the periphery of the micelles. Inverse polymeric micelles comprising a hydrophilic core and a hydrophobic shell can also be prepared. For example, micelles of an AB copolymer in a selective solvent for A can be reversed by adding a selective solvent for B while removing the selective solvent for A via dialysis. Cheng et al. prepared inverse polymeric micelles in chloroform using polystyrene-b-poly(4vinylpyridine) block copolymer by in situ quaternization of the pyridine moiety using HCl, and Figure 4.3 shows the latex particles obtained by varying the transfer time [99]. Self-assembly of macromolecules is useful for commercial applications such as coatings, detergents, cosmetics, electronics, thin films, drug delivery, and biocompatibility. The self-assembly structures are usually studied using (cryo) TEM, light scattering, and small-angle X-ray scattering. Freeze

Block, Graft, Star, and Gradient Copolymer Particles

(a)

(b)

(c)

(d)

(e)

(f)

115

Figure 4.3 TEM images of PS-b-P4VP inverse micelles at different transfer times (t): (a) 3 min, (b) 15 min, (c) 10 h, (d) 24 h, (e) 120 h, and (f) is the TEM image of PMACs (t = 120 h) noncovalently crosslinked by bivalent S2O82– ions. All the scale bars are 200 nm in length. (Reprinted from F. Cheng, X. Yang, H. Peng, D. Chen, and M. Jiang, Macromolecules 40: 8007–14, 2007. With permission.)

drying can be used to remove water without disrupting the micellar structure, allowing techniques such as AFM to be used. 4.4.3 Nanoparticles Synthesis by Cross-Linking of Self-Assembled Structures Synthesis of poly­mer nanoparticles is done via cross-linking of self-assembly structures of block, star, and graft copolymers. The synthesis of cross-linked nanoparticles requires cross-linkable groups to be part of the self-assembled structure. Scheme 4.8 illustrates different domains in the self-assembled structures that can be selectively cross-linked. Cross-linking of self-assembled structures will result in poly­mer nanoparticles that are resistant to changes in solvent, temperature, pH, or ionic strength. The advantage of cross-linking of self-assembly structures over synthesis in heterogeneous media for nanoparticle synthesis is that amphiphilic poly­mer nanoparticles of complex copolymer architectures can be easily

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Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

Copolymer Self assembly

Cross-linking

Shell cross-linking at the hydrophilic end

Cross-linked shell

Cross-linked core

Core cross-linking at the hydrophobic end

Scheme 4.8 Cross-linking of micelles at various possible strategic positions.

synthesized whereas their synthesis in emulsion may be more complex and induce latex stability problems. Depending on the position of the cross-linkable moieties in the copolymer, cross-linking can be carried out in the shell at the hydrophilic chain end, in the shell along the hydrophilic poly­mer backbone, at the hydrophilic­hydrophobic interface of the block copolymer, in the core along the hydrophobic poly­mer backbone, and in the core at the hydrophobic chain end [100]. The cross-linking density and the position of cross-links in the micellar structure hugely affect properties such as permeability, swellability, thermal stability, reactivity, etc. of the poly­mer nanoparticles. It is important to note that the self-assembled structures are preserved after adequate cross-linking at various strategic positions using various chemistries. Most research in this field focused on cross-linked, self-assembled structures of amphiphilic block copolymers. O’Reilly et al. wrote a brief review on block copolymers that self-assemble into poly­mer micelles in a selective solvent and that possess functional groups throughout the core and/or shell for cross-linking purposes [100]. Guo et al. synthesized cross-linked diblock copolymer micelles of polystyrene-b-poly(cinnamoylethyl methacrylate) (PS-b-PCEMA) via photo-cross-linking of the PCEMA block [101]. Figure 4.4 shows TEM images of core photo-cross-linked diblock copolymer micelles illustrating that increasing the molecular weight of both blocks of the diblock copolymer resulted in an increase in the particle size.

117

Block, Graft, Star, and Gradient Copolymer Particles

(a)

(b)

250 nm

100 nm

Figure 4.4 Transmission electron micrographs of core cross-linked diblock copolymer micelles; (a) PS276-bPCEMA90 and (b) PS302-b-PCEMA570. (Reprinted from A. Guo, G. Liu, and J. Tao, Macromolecules 29: 2487–93, 1996. With permission.)

A number of cross-linking chemistries can be employed for cross-linking of self-assembled structures. End-functionalized amphiphilic copolymers are required for shell and core cross-linking at hydrophilic or hydrophobic poly­mer chain end, respectively. Scheme 4.9a shows examples of functional groups that can be used for cross-linking of copolymers at the chain end. Self-assembly of end-functionalized copolymers presents the functional groups at either the exterior or interior of the self-assembled structures. The (a) Examples of functional groups for cross-linking or modification 1

alkynyl

N3 azide

5

(b) Examples of vinyl cross-linkers 9

O 2 H aldehyde 3

O acrylate 4

OH alcohol

N3 12 N3 1,4-diazidobutene

1,4-divinylbenzene 6 H2N amine 7 O

O

(c) Examples of chemical cross-linkers

O

13 O

NH

O O N,N’-methylenebisacrylamide

ketone 8

NH 10

OH

carboxylic acid

CH3 11

O

O O

O CH3

ethylene glycol dimethacrylate

glutaraldehyde

NH2 14 H2N ethylenediamine 15

O dipropagyl ether

(d) Examples of (co)monomers that impart functional groups for cross-linking or modification CH3 CH3 N O N H3C O O O O 19 O 16 O 17 O 18 2-vinylpyridine (2-VP) 21 N O O O OH N-acryloxysuccinimide (NAS) 20 OH N3 2-hydroxy ethyl methacrylate acrylic acid (AA) (HEMA) 3-azidopropyl methacrylate (AzPMA)

O

CH

O

CH3 O

7-(2-methacryloxyethoxy)4-methylcoumarin

Scheme 4.9 Examples of (a) end-functional groups, (b) vinyl cross-linkers, (c) chemical cross-linkers, and (d) vinyl (co)monomers that can be used for cross-linking and modifying cross-linked nanoparticles.

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Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

end-functional groups may also include RAFT moieties, ATRP initiators, and vinyl groups (i.e., macromonomer) that allow poly­mer chains to be crosslinked using a difunctional vinyl monomer (Scheme 4.9b). The copolymer chain end can also be functionalized with functional molecules and then cross-linked after self-assembly using multifunctional complementary molecules. Scheme 4.9c shows examples of chemical cross-linkers. Graft copolymers (a) P(AA-co-MEA)-g-PNIPAM and (b) P(AA-co-MEA)-g(PNIPAM and PEG) were synthesized by grafting amine-terminated polymers PNIPAM and PEG onto P(NAS-co-MEA) backbone [76]. The unreacted NAS units in the copolymer backbone were then hydrolyzed forming acrylic acid residues. Cross-linking of the MEA residues after thermally induced self-assembly of the graft copolymer was performed using ammonium persulfate, and Figure  4.5 shows the TEM images of the graft copolymers (a) P(AA-co-MEA)-g-PNIPAM and (b) P(AA-co-MEA)-g-(PNIPAM and PEG). Graft copolymer (a) resulted in bulk cross-linking while graft copolymer (b) resulted in exclusively shell cross-linking. Cross-linking of the shell or the core is done through cross-linkable groups in the shell or core of the self-assembled structures. Some functional monomers (Scheme 4.9d) can be used in copoly­mer­i­za­tion or in modification of the copolymer to provide cross-linkable groups. Bütün et al. reported on the synthesis of shell cross-linked block copolymer micelles with tunable hydrophilic/hydrophobic cores [102]. The core consisted of a thermo-responsive poly(N-[morpholino]ethyl methacrylate) (PMEMA) block that is hydrophilic at room temperature and hydrophobic above its lower critical solution temperature (LCST). Cross-linking of the PDMAEMA shell

(a)

(b)

100 nm

100 nm

Figure 4.5 TEM images of cross-linked micelles (a) P(AA-co-MEA)-g-PNIPAM and (b) P(AA-co-MEA)-g(PNIPAM and PEG). (Reprinted from W.-H. Chiang, Y.-H. Hsu, T.-W. Lou, C.-H. Chern and H.-C. Chiu, Macromolecules 42: 3611–19, 2009. With permission.)

119

Block, Graft, Star, and Gradient Copolymer Particles

above the LCST of PMEMA resulted in preserved micellar structure upon cooling to room temperature. Copolymers with carboxylic acid or amine functional groups in the hydrophilic part allow cross-linking to be done in the shell (or the core for inverse micelles). Scheme 4.9c shows examples of chemical cross-linkers. Difunctional amines such as 2,2’-(ethylenedioxy)bis(ethylamine) and aldehydes such as glutaraldehyde are used to cross-link the carboxylic acid and amino functional groups, respectively. Multifunctional (>2) molecules are statistically better cross-linkers. Monomers such as 2-vinyl pyridine (2VP) and NAS can be used in the copolymer and then cross-linked using difunctional halogenated molecules such as 1,4-dibromobutane and difunctional alcohols, respectively. Azide functionalized methacrylate can be used in copoly­mer­i­ za­tion to allow for cross-linking reactions with difunctional alkynyls such as dipropargyl ether. Monomers such as 2-hydroxyethyl methacrylate (HEMA) can be used to react with PNAS units in a copolymer to allow for free radical cross-linking. It is also possible to cross-link micelles at the hydrophilic-hydrophobic interface. Scheme 4.10 shows how ATRP and click chemistry can be used to specifically functionalize a copolymer at the hydrophilic-hydrophobic interface. Self-assembly of the amphiphilic copolymer will result in the monomer functionality at the hydrophilic-hydrophobic interface. Cross-linking of the micelles is then done using a difunctional or multifunctional free radical monomer. Alternatively the hydrophilic-hydrophobic interface can be modified with chemical groups, and the micelles are then stabilized by cross-linking using multifunctional cross-linkers. O

O

OH

Br O

O

O

(eg PEG-OH) OH O

Br O

CH

O O

N N

CH

CH

OH

N

N3

HC

DCC DMAP CH2Cl2 HO O

O

H3C

OH

Br

ATRP monomer (eg. MMA)

O O O

O

O CH3 O ‘click chemistry’

O O

O

O 1) self-assemble 2) cross-linking CH3 O O O CH3 EGDMA O

cross-linking at the hydrophilic-hydrophobic interface of micelles

Scheme 4.10 An example of cross-linking chemistry at the hydrophilic-hydrophobic interface.

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Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

Another method that can be used to cross-link micelles at the hydrophobic-hydrophilic interface is to use an ABC amphiphilic miktoarm star copolymer, for example. One of the blocks will be hydrophobic and the other two hydrophilic. One of the hydrophilic blocks should be pH- or thermoresponsive and bear cross-linkable groups. The micellization is carried out at normal conditions; then pH or temperature is changed and this results in the collapse of the pH- or thermo-responsive block. Cross-linking of this block is then carried out under these conditions to form micelles cross-linked at hydrophobic-­hydrophilic interface, and a change in the pH or temperature will have little or no effect on the cross-linked block. Alternatively, an ABC triblock copolymer can be synthesized with crosslinkable B-block, which can be varied in length and solubility in selective solvents for both A and C. The A and C blocks are designed to be hydrophilic and hydrophobic, respectively. Self-assembly of the triblock copolymer will position block B at the hydrophilic-hydrophobic interface and cross-linking of B can be carried out. Liu et al. synthesized a thermo-responsive triblock copoly­mer that formed micelles, and cross-linking of the micelles was performed on the central block to avoid intermicellar cross-linking [103]. Intermicellar cross-linking during shell cross-linking is also avoided or minimized using dilute conditions. Figure 4.6 shows a TEM image of a PEO-b-PDMAEMA-b-PMEMA (PMEMA = poly[N-morpholino]ethyl methacrylate) micelles cross-linked at the PDMAEMA block [104].

250 nm Figure 4.6 Transmission electron micrograph of a dilute suspension of cross-linked micelles prepared using the PEO-PDMAEMA-PMEMA triblock copolymer. (Reprinted from V. Bütün, X.-S. Wang, M. V. d. P. Banez, K. L. Robinson, N. C. Bilingham, and S. P. Armes, Macromolecules 33: 1–3, 2000. With permission.)

Block, Graft, Star, and Gradient Copolymer Particles

121

4.4.4 Functionalization of Cross-Linked Micelles Nanoparticles can be designed to have a particular functionality on the surface or in its interior to allow further modification. Amphiphilic copolymers have long poly­mer chain segments in both the hydrophilic and hydrophobic parts in which specific functional groups can be incorporated. After selfassembly and cross-linking, some of the functional groups may reside on the surface (for functional groups in the hydrophilic part) or interior (if functional groups are in the hydrophobic part) of the nanoparticles. The residual functionality is then used for modification of the poly­mer nanoparticles with (bio)macromolecules or fluorescent labels, for example. The use of functional initiators and CRP mediators (ATRP initiator, RAFT agent, alkoxyamine [NMP]) will result in cross-linked micelles with functional groups on the surface or in the micellar interior, which can be utilized for further CRP. Scheme 4.11 shows chemistries that have been used to modify the surface of cross-linked copolymer micelles. Alternatively, the copolymers can be functionalized first with organic, (bio)molecules, dyes, etc., followed by self-assembly and then cross-linking. A biotin-functionalized ATRP-initiator was used to synthesize a poly(acrylic acid)-b-poly(methyl acrylate) (PAA-b-PMA) block copolymer [105]. After selfassembly of the block copolymer and cross-linking of the shell, the biotin functionality was retained at the surface of the nanoparticles. 4.4.5 Potential Applications of Cross-Linked Nanoparticles Polymeric micelles have great potential application in the drug delivery field as nanocarriers. These self-assembled micelles have been widely studied in the field of drug delivery because hydrophobic drugs can be retained within the hydrophobic inner core of micelles. Chan et al. synthesized reversible core cross-linked micelles of an amphiphilic block copolymer for drug release studies [106]. The drug loading in the core cross-linked micelles was high (60 wt%) and the hydrolysis of the cross-links due to acidic pH resulted in faster drug release at low pH than at neutral pH. Liu et al. investigated the potential use of double hydrophilic block copolymers as carrier [83]. An aldehyde-modified ATRP initiator was used to prepare a triblock copolymer consisting of poly(oligo[ethylene glycol]methyl ether methacrylate((POEGMA), PDMAEMA, and PDEAEMA blocks (POEGMA-b-PDMAEMA-b-PDEAEMA) that self-assembled into micelles at alkaline pH and that molecularly dissolved at acidic pH. The middle block was cross-linked at alkaline pH to obtain shell cross-linked micelles that showed reversible pH-responsive ­swelling/deswelling behavior and formed bioconjugates by covalently attaching lysozyme to the aldehyde functionality of the triblock copoly­mer. Stenzel wrote a feature article showing how RAFT can be used to synthesize micelle-forming block copolymers for drug encapsulation and release [107].

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NH2

H2N

NH2

H2N

NH2

H2N

CH3-O

OH H N—R 2

O

O O

H

O

NH

NH

O NH2

Other coupling functional groups O H aldehyde

O

O H3C ketone

HO carboxylic acid

O

R—NH

NH—R O

O R

R = polymer chain, peptide, protein, dye etc. R= R=

N3 Further functionalization via ‘click chemistry’

O

HN

N

H

H

O

O H

NH2 NH

R

OH

O

HN

O

HO

NH

H N O 2

H2N O

NH2

NH2

HO

O

H2N—

H

N

O

O

Other coupling functional groups HO

BrMg

N

Br

Br

Br

Br

CRP grafting Br

Br

Br

Br

Br Br

Br

N3

Br 1) NaN3

2)

Br

Br

N N

N

N

Br

N N

N3

: polymer chain, protein, enzyme, dye, drug etc.

Scheme 4.11 Examples of surface modification reactions for cross-linked poly­mer nanoparticles.

Inorganic reactions can also be carried out in so-called poly­mer micelles with aqueous core (PMACs). Inorganic compounds such as silica, AgCl, and Fe(SCN)2+ were synthesized in the aqueous core of a polystyrene-b-poly(4vinylpyridine) (PS-b-P4VP) micellar structure [99]. Shell cross-linked micelles of poly([ethylene oxide]-b-glycerol monomethacrylate-b-[diethylamino]ethyl methacrylate) (PEO-b-PGlMA-b-PDEAEMA) were used as pH-responsive particulate emulsifers [108].

Block, Graft, Star, and Gradient Copolymer Particles

123

Reversible cross-linking has been employed in cross-linking of micelles. Controlled release of bioactive agents can be achieved by regulating the reversibility of the cross-linked micelles. Reversible cross-linking of micelles provides stability to the micelles due to cross-links and facilitates faster release of the contents (drugs, polymers, or inorganic products) due to cleavage of the cross-links. Several authors used disulfide links as degradable cross-links [80,109–111]. For example, Li et al. synthesized an ABC triblock copolymer that was thermo-responsive and underwent reversible cross-linking [111]. The triblock copolymer PEO-b-P(DMAEMA-stat-NAS)b-PNIPAM was cross-linked through the NAS units using cystamine. The cross-linked micelles were reductively cleaved using dithiothreitol or tris(2-carboxyethyl)phosphine and re-cross-linked by adding cystamine. Molecules that dimerize and decouple due to changes in external stimuli can also be used as reversible cross-links. Babin et al. synthesized a PDMAEMA-b-P(MMA-co-coumarin methacrylate [CMA]) (PDMAEMA54b-P[MMA55 -co-CMA19]) copolymer using ATRP and prepared reversible shell cross-linked poly­mer micelles that were stimuli responsive [110]. Thus, poly­mer chains in the copolymer were modified with coumarin molecules which cross-link at UV > 310 nm and de-cross-link at UV < 260 nm.

4.5 Conclusions Nanoparticles of block, graft, star, and gradient copolymers can be synthesized in dispersed systems and via cross-linking of self-assembled copolymers. The two routes to copolymer nanoparticles can be fine-tuned to produce particles of the required size and properties (both chemical and physical). The method for synthesis of copolymer nanoparticles depends entirely on the intended application. Polymerization in dispersed systems can be carried out in either oil-in-water or water-in-oil (inverse dispersion), and large-scale synthesis of copolymer nanoparticles is possible. CRP has been successfully applied to poly­mer­i­za­tion in dispersed systems to synthesize well-defined copolymer topologies. There is, however, limited literature on the synthesis of complex copolymer architectures such as star and graft copolymers in dispersed systems, although the synthetic tools are at hand. Copolymer nanoparticles synthesized via poly­mer­i­za­tion in dispersed systems are widely used in industry for various applications. The self-assembly route of making copolymer nanoparticles is relatively simple since the copolymer can be synthesized in any suitable media. Generally, all poly­mer­i­za­tion techniques can be employed for the synthesis of copolymers that have the ability to self-assemble. The copolymer can be purified

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before self-assembly and cross-linking. This route, however, applies only to copoly­mer architectures that are capable of self-assembly. Copolymer nanoparticle modification is easier on self-assembled nanoparticles, and both surface (shell) and core functionalization can be carried out selectively. Applications of cross-linked self-assembled copolymers are very broad and are not limited to the drug delivery and stimuli- (pH, temperature, ionic strength) responsive fields.

References



















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86. Peng, D., Zhang, X., and X. Huang. 2006. Novel starlike amphiphilic graft copolymers with hydrophilic poly(acrylic acid) backbone and hydrophobic poly(methyl methacrylate) side chains. Macromolecules 39:4945–47. 87. Zhang, W., Zhang, W., Zhou, N., Cheng, Z., Zhu, J., and X. Zhu. 2008. Synthesis and self-assembly behaviors of three-armed amphiphilic block copolymers via RAFT poly­mer­i­za­tion. Polymer 49:4569–75. 88. Qian, J., and F. Wu. 2009. Preparation of supramolecular graft copolymers and the subsequent formation of pH-sensitive vesicles. Chemistry of Materials 21:758–62. 89. Chiang, W.-H., Hsu, Y.-H., Chern, C.-H., and H.-C. Chiu. 2009. Thermally induced polymeric assemblies from the PAAc-based copolymer containing both PNIPAAm and mPEG grafts in water. Journal of Physical Chemistry B 113:4187–96. 90. Gu, L., Shen, Z., Zhang, S., Lu, G., Zhang, X., and X. Huang. 2007. Novel amphiphilic centipede-like copolymer bearing polyacrylate backbone and poly(ethylene glycol) and polystyrene side chains. Macromolecules 40:4486–93. 91. Astafieva, I., Zhong, X., and A. Eisenberg. 1993. Critical micellization phenomena in block polyelectrolyte solutions. Macromolecules 26:7339–52. 92. Förster, S., Abetz, V., and A. H. E. Müller. 2004. Polyelectrolyte block copolymer micelles. Advances in Polymer Science 166:173–210. 93. Sunintaboon, P., Ho, K. M., Li, P., Cheng, S. Z. D., and F. W. Harris. 2006. Formation of nanostructured materials via coalescence of amphiphilic hollow particles. Journal of the American Chemical Society 128:2168–69. 94. Stubenrauch, K., Moitzi, C., Fritz, G., Glatter, O., Trimmel, G., and F. Stelzer. 2006. Precise tuning of micelle, core, and shell size by the composition of amphiphilic block copolymers derived from ROMP investigated by DLS and SAXS. Macromolecules 39:5865–74. 95. Houillot, L. Bui, C., Save, M., Charleux, B., Farcet, C., Moire, C., Raust, J.-A., and I. Rodriguez. 2007. Synthesis of well-defined polyacrylate particle dispersions in organic medium using simultaneous RAFT poly­mer­iz­ a­tion and self-assembly of block copolymers. A strong influence of the selected thiocarbonylthio chain transfer agent. Macromolecules 40:6500–9. 96. Zhang, Y., Wang, Z., Zhao, J., and C. Wu. 2007. Facile preparation of pH-­ responsive gelatin-based core-shell polymeric nanoparticles at high concentrations via template polymerization, Polymer 48:5639–45. 97. Germack, D. S., Harrison, S., Brown, G. O. and K. L. Wooley. 2006. Influence of the structure of nanoscopic building blocks on the assembly of micropatterned surfaces. Journal of Polymer Science, Part A: Polymer Chemistry 44:5218–28. 98. Narain, R., and S. P. Armes. 2003. Synthesis and aqueous solution properties of novel sugar methacrylate-based homopolymers and block copolymers. Biomacromolecules 4:1746–58. 99. Cheng, F., Yang, X., Peng, H., Chen, D., and M. Jiang. 2007. Well-controlled formation of polymeric micelles with a nanosized aqueous core and their applications as nanoreactors. Macromolecules 40:8007–14. 100. O’Reilly, R. K., Hawker, C. J., and K. L. Wooley. 2006. Cross-linked block copolymer micelles: Functional nanostructures of great potential and versatility. Chemical Society Reviews 35:1068–83. 101. Guo, A., Liu, G., and J. Tao. 1996. Star polymers and nanospheres from crosslinkable diblock copolymers. Macromolecules 29:2487–93.

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5 Polymer Nanoparticles by Reversible Addition-Fragmentation Chain Transfer Microemulsion Polymerization J. O’Donnell and E. Kaler Contents 5.1 Introduction................................................................................................. 134 5.2 Uncontrolled Microemulsion Polymerization........................................ 135 5.2.1 Impact of Monomer Solubility...................................................... 136 5.2.2 Microemulsion Copoly­mer­i­za­tion............................................... 138 5.2.3 Multiple Addition and Semicontinuous Microemulsion Polymerization................................................................................ 139 5.3 Reversible Addition-Fragmentation Chain Transfer Polymerization............................................................................................ 140 5.4 Reversible Addition-Fragmentation Chain Transfer Microemulsion Polymerization................................................................ 143 5.4.1 Microemulsion Polymerization Kinetics..................................... 144 5.4.1.1 Uncontrolled Microemulsion Polymerization Kinetics.............................................................................. 145 5.4.1.2 RAFT Microemulsion Polymerization Kinetics.......... 147 5.4.1.3 Model Results................................................................... 150 5.4.1.4 Predicted RAFT Microemulsion Polymerization Kinetics with Negligible Biradical Termination.......... 150 5.4.1.5 Predicted RAFT Microemulsion Polymerization Kinetics with Biradical Termination............................. 152 5.4.2 Molecular Weight and Polydispersity......................................... 153 5.4.2.1 Effect of Chain Transfer Agent per Micelle Ratio....... 155 5.4.2.2 Effect of Monomer Solubility......................................... 155 5.4.2.3 Effect of Chain Transfer Agent Solubility.................... 158 5.4.3 Latex Particle Size........................................................................... 161 References.............................................................................................................. 163

133

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5.1 Introduction Microemulsion poly­mer­i­za­tion produces small latex nanoparticles (D < 50 nm) of high molecular weight (MN = 106 to 107 g/mol) poly­mer, and provides several advantages relative to other types of heterogeneous poly­mer­i­ za­tions, such as rapid reaction times and a product that is colloidally stable. Since the introduction of microemulsion poly­mer­i­za­tion by Stoffer and Bone [1] and Atik and Thomas [2] in the early 1980s, this technique has been widely studied because of the dramatic benefits the high surface area-to-volume ratio of the poly­mer particles provides for many applications including sensors [3], fluorescence markers [4], and conductive films [5]. Control of the microstructural properties (such as molecular weight, polydispersity, monomer sequences, chain ends, and degree of branching) in a microemulsion poly­mer­i­za­tion could lead to enhanced chemical and mechanical properties and an even broader range of applications. Of the many controlled free radical poly­mer­i­za­tion techniques that have been developed to control these microstructural properties, including nitroxide-mediated poly­mer­i­za­ tion (NMP) [6–9], atom transfer radical poly­mer­i­za­tion (ATRP) [10–13], and degenerative transfer (DT) [14,15], reversible addition-fragmentation chain transfer (RAFT) poly­mer­i­za­tion has emerged as the most promising due to its versatility and simplicity [16,17]. Also, in a RAFT poly­mer­i­za­tion the resulting poly­mer is free from the contamination of metal catalysts. Although the RAFT process has shown the ability to control a broad array of monomers over a wide range of poly­mer­i­za­tion conditions in numerous bulk and solution poly­mer­i­za­tions, very few RAFT poly­mer­i­za­tions have been successfully conducted in a heterogeneous poly­mer­i­za­tion environment [18–20]. Incorporating RAFT into heterogeneous poly­mer­i­za­tions (such as emulsion or miniemulsion) frequently leads to poor control of molecular weight, high polydispersity, and loss of colloidal stability [18,21]. Additionally, rate retardation is often more significant in heterogeneous poly­mer­i­za­tions than in homogeneous poly­mer­i­za­tions [21]. The increase in rate retardation in miniemulsions relative to bulk has been shown to result from compartmentalization effects [22] and increased radical exit from the polymerizing particles [23]. Microemulsion poly­mer­i­za­tions are advantageous relative to emulsion or miniemulsion poly­mer­i­za­tions due to the absence of large monomer droplets. Liu et al. were the first to demonstrate the feasibility of incorporating RAFT in oil-in-water microemulsion poly­mer­i­za­tions while maintaining both control of the poly­mer­i­za­tion and colloidal stability of the polymerizing latex [24]. Subsequently, several series of RAFT microemulsion poly­mer­i­za­tions of butyl acrylate and 2-ethylhexyl acrylate with the chain transfer agents methyl-2-(O-ethylxanthyl) propionate and methyl-2(O-dodecylxanthyl) propionate were performed to elucidate the effects of the chain transfer agent

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135

molecule per micelle ratio, and the monomer and chain transfer agent aqueous solubilities on the control of the poly­mer­i­za­tion, and the final poly­mer and latex characteristics [25,26]. To date, RAFT has not been incorporated into inverse water-in-oil microemulsion poly­mer­i­za­tions. This chapter will first review the key structure and transport properties that influence the final poly­mer and latex characteristics in an uncontrolled oil-in-water microemulsion poly­mer­i­za­tion. Then, the RAFT reaction mechanism will be reviewed, and the incorporation of RAFT into microemulsion poly­mer­i­za­tion will be described. Next, the development of a kinetic model to describe RAFT microemulsion poly­mer­i­za­tion will be summarized because it provides insight into the key parameters that affect the final poly­mer and latex properties. Finally, the characteristics of the polymers produced by RAFT microemulsion poly­mer­i­za­tion to date will be summarized with respect to the key parameters of chain transfer agent molecule per micelle ratio, and aqueous solubility of the monomer and the chain transfer agent.

5.2 Uncontrolled Microemulsion Polymerization Polymerization of one-phase, thermodynamically stable oil-in-water micro­ emulsions produces colloidally stable latex nanoparticles containing polymers of high molecular weight and low polydispersity [27–31]. Microemulsion poly­mer­i­za­tion begins when initiator-derived radicals (I•) react with the small amount of hydrophobic monomer (M) in the aqueous domain to form propagating polymers (P•) (Figure 5.1(1.)). The polymers propagate in the aqueous domain until a critical degree of poly­mer­i­za­tion is reached. At the critical degree of poly­mer­i­za­tion, the poly­mer is no longer soluble in the aqueous 1. Initiation

2. Propagation Pn–1

M

M

M M

P

M I

M

3. Final Latex Dispersion M

Polymer Particle

M Pn

Empty Micelles

Figure 5.1 Typical oil-in-water microemulsion poly­mer­i­za­t ion initiated with a water-soluble initiator. (1.) Initiator-derived radical (I•) reacts with monomer (M) in the aqueous domain to form a propagating poly­mer (P•), which partitions into a monomer-swollen micelle to form a particle. (2.) Propagation of a poly­mer in a particle with monomer diffusing from uninitiated micelles to the locus of poly­mer­i­za­t ion. (3.) Final latex dispersion of surfactant-stabilized poly­mer particles and empty micelles.

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domain, and the poly­mer partitions into a monomer-swollen micelle, thus forming a surfactant-stabilized poly­mer particle. In a typical microemulsion poly­mer­i­za­tion, the concentration of micelles is approximately 1000 times greater than the concentration of poly­mer particles, so the probability of a propagating poly­mer entering a particle as opposed to a micelle and causing a termination reaction is negligible. Propagation continues in the poly­ mer particles as monomer diffuses from surrounding uninitiated micelles to the locus of poly­mer­i­za­tion (Figure 5.1(2.)). The final poly­mer latex consists of surfactant-stabilized particles containing a single poly­mer and empty micelles (Figure 5.1(3.)). The transport and partitioning of monomer during a microemulsion poly­ mer­i­za­tion depends on the aqueous solubility of the monomer. As such, the aqueous solubility of the monomer has a significant effect on the final poly­ mer and latex characteristics, as well as the ability to perform semicontinuous or multiple addition microemulsion (co)poly­mer­i­za­tions. The following sections demonstrate the complications induced by monomer transport and partitioning. 5.2.1 Impact of Monomer Solubility The water solubility of the monomer dictates both the residence time of an oligomeric radical in a monomer-swollen micelle (τres) and the critical degree of poly­mer­i­za­tion (zcrit) that a propagating chain must reach before being segregated into a surfactant-stabilized particle. Decreasing the water solubility of the monomer decreases zcrit and increases τres, so an oligomeric radical explores fewer micelles and the probability of biradical termination is greatly reduced. The probability of an oligomeric radical entering a poly­ mer particle and terminating the propagating poly­mer can be quantified by the ratio of the characteristic propagation time (τprop) to τres. τprop is the average time required for a propagating poly­mer to add a single monomer unit, which depends on the propagation rate constant (kp) and the concentration of monomer in the micelle (Cmic),

τ prop ≈

1 k p Cmic

(5.1)

τres can be approximated as the characteristic time for diffusion of a monomeric radical from the surface of a sphere immersed in an infinite medium [32], which is

τ res ≈ q

2 R mic 3Daq mon

(5.2)

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137

where q is the partition coefficient of the monomer between the micelles and the aqueous domain, Rmic is the radius of the micelle, and D aq mon is the aqueous diffusion coefficient of the monomer. The τprop /τres ratio is the number of micelles that a radical explores before adding one monomer unit. This ratio must be multiplied by zcrit to estimate the total number of micelles that an oligomeric radical enters and exits before being segregated into a surfactantstabilized poly­mer particle. If zcrit τprop /τres is greater than the ratio of micelles to poly­mer particles, then biradical termination is statistically possible. Bleger et al. demonstrated the effect of the aqueous solubility of the monomer on particle nucleation [33]. These authors investigated microemulsion polymerizations of methyl methacrylate, which has high aqueous solubility, and found an initial period of slow poly­mer­i­za­tion during which the concentration of particles did not significantly increase. After this initial period of slow poly­mer­i­za­tion, the rate and the particle concentration increased rapidly, indicating fast particle nucleation. The transition from slow to fast poly­mer­i­ za­tion was hypothesized to signify a transition from homogeneous nucleation to nucleation by micelle entry. This hypothesis was supported by the observation that styrene, which has a much lower water solubility than methyl methacrylate, and therefore partitions into the micelles at a lower degree of poly­mer­i­za­tion, experienced a shorter period of slow poly­mer­i­za­tion. The aqueous solubility of the monomer also influences the phase behavior, and thus the microstructure, of a microemulsion [34]. The link between phase behavior and microstructure can be understood qualitatively in terms of the curvature elastic energy of the surfactant-rich film that separates the water and oil (or poly­mer) domains [35]. On one hand, the swelling of poly­ mer particles by monomer is promoted by the decrease in free energy of the bulk poly­mer as it is diluted, but on the other hand movement of the monomer to the poly­mer is opposed by the free energy penalty paid by changing the curvature elastic energy of the surfactant micelles that are swollen with monomer. Thus, there is a delicate balance between the curvature energy of the surfactant film and the solubility of the monomer in the poly­mer, and the result may lead to complex variations in particle diameter, molecular weight, and the ability to form copolymers as a function of monomer solubility. Capek et al. [30,36] have investigated series of alkyl acrylates and alkyl methacrylates to determine the effect of monomer solubility on the particle diameter, colloidal stability, and poly­mer­i­za­tion kinetics. Alkyl acrylates with more than four methyl groups are able to act as coemulsifiers, which increases the stability of the polymerizing particles and leads to the formation of smaller particles. Smaller alkyl acrylates are unable to serve as coemulsifiers, so agglomeration of the polymerizing particles occurs during these poly­mer­i­za­tions and dramatically increases the particle diameter. The particle diameter of the more hydrophobic methacrylates does not depend on the length of the alkyl chain.

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Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

5.2.2 Microemulsion Copoly­m er­i­z a­tion The synthesis of copolymers by microemulsion poly­mer­i­za­tion is complicated because of the partitioning of monomer between the micelles, the poly­ mer particles, and the aqueous domain. Gan et al. have shown that the reactivity ratios measured in microemulsion copoly­mer­i­za­tions of styrene and methyl methacrylate deviate significantly from those measured in bulk poly­mer­i­za­tions [37] and attribute this to uneven partitioning. Bahwal et al. have investigated the impact of monomer partitioning on microemulsion copoly­mer­i­za­tions by systematically varying the relative aqueous solubilities and polarities of the monomers [38]. As anticipated, the copoly­mer­i­za­tion of monomers with similar aqueous solubility and polarity, such as methyl methacrylate and ethyl acrylate, results in copolymers with a composition identical to that produced by bulk copoly­mer­i­za­tion. The combination of monomers with different aqueous solubilities and polarities produces unexpected results for microemulsion copoly­mer­i­za­tion [38]. When styrene (low aqueous solubility, nonpolar) is copoly­mer­ized with methyl acrylate (high aqueous solubility, polar), the ratio of styrene to methyl acrylate in the copolymer is expected to far exceed the monomer feed ratio because a significant amount of methyl acrylate will remain in the aqueous domain. However, when the monomer ratios were corrected for the aqueous solubility of the monomers, the authors found that the ratio of methyl acrylate in the copolymer was greater than anticipated from the monomer feed. The increased presence of methyl acrylate in the copolymer reflects the partitioning of the monomers within the poly­mer particles and the significance of the locus of poly­mer­i­za­tion. The more polar methyl acrylate preferentially partitions into the surfactant tails, while the nonpolar styrene partitions into the growing particle core. Therefore, because poly­mer­i­za­tion is occurring in the corona of the poly­mer particle, a greater degree of methyl acrylate than styrene is incorporated into the copolymers than would be predicted based on the aqueous solubilities. The effect of monomer partitioning within the poly­mer particles was confirmed by polymerizing two monomers with similar aqueous solubilities but different polarities (styrene and butyl acrylate). The copolymer showed a greater composition of the more polar butyl acrylate than predicted from the feed composition. Several groups have studied microemulsion copoly­mer­i­za­tions of a hydrophobic and a hydrophilic monomer [39–42]. Capek and Juranicova studied the microemulsion copoly­mer­i­za­tion of butyl acrylate and acrylonitrile in a three-component system, so as to simplify the kinetics [42]. Increasing the concentration of the more hydrophilic monomer decreases the rate of poly­ mer­i­za­tion and the calculated concentration of radicals per particle, as well as the number average molecular weight. Therefore, the authors conclude that the hydrophilic acrylonitrile monomer regulates the concentration of radicals in the particles, and the poly­mer­i­za­tion kinetics, by controlling the entry and exit events. Pokhriyal and Devi have also studied the microemulsion

Polymer Nanoparticles by RAFT Microemulsion Polymerization

139

copoly­mer­i­za­tion of butyl acrylate and acrylonitrile and concluded that the concentration of the hydrophilic monomer determines the concentration of radicals in the particles [40]. 5.2.3 Multiple Addition and Semicontinuous Microemulsion Polymerization A significant disadvantage to the commercial implementation of microemulsion poly­mer­i­za­tion is the high ratio of surfactant to monomer required to form the initial, thermodynamically stable microemulsions. Two solutions to this problem have been proposed: multiple-addition and semicontinuous microemulsion poly­mer­i­za­tion. However, both of these methods suffer from complications arising from the partitioning of monomer between the micelles and poly­mer particles, which is addressed in this section. A more complete review of these methods is provided by Xu and Gan [43]. Hermanson and Kaler have investigated the multiple addition microemulsion poly­mer­i­za­tion of n-hexyl methacrylate [44]. The rate of poly­mer­i­za­tion decreased with each subsequent addition of monomer. Therefore, either the number of propagating radicals must decrease or the concentration of monomer at the locus of poly­mer­i­za­tion must decrease. The multiple additions of monomer did not result in significant growth of the poly­mer particles, which indicates that new particles were initiated with each addition of monomer. In addition, examination of the poly­mer­i­za­tion kinetics confirmed that none of the radicals initiated prior to the addition of monomer contributed to the poly­mer­i­za­tion. Therefore, the additional monomer swelled the empty micelles and the corona of the poly­mer particles instead of the core of the poly­mer particles, and the concentration of radicals decreased with each addition as a result of the decrease in initiator decomposition rate with time. These results are consistent with the small-angle neutron-scattering studies of n-hexyl methacrylate microemulsion poly­mer­i­za­tions that demonstrated partitioning of the monomer between the micelles and the poly­mer particles throughout the poly­mer­i­za­tion [35]. Ramirez et al. showed that monomer accumulates in the polymer particle when butyl acrylate is added to a microemulsion poly­mer­i­za­tion after the initial microemulsion poly­mer­i­za­tion reaches 95% conversion [45]. The instantaneous conversion decreases to 60% upon the introduction of neat monomer and, after the monomer feed is complete, the instantaneous conversion returns to 90–95%. The particle size increases throughout the course of monomer feeding and during the post-addition period, while the number density of particles decreases slightly during the post-addition period. The increase in the number of particles during the feed results from the competition between micelles and poly­mer particles for the monomer. A fraction of the monomer partitions into the micelles to form new poly­mer particles, while the remaining monomer swells the original latex particles. Most of the

140

Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

increase in solids content results from the formation of new particles rather than the growth of the original particles. Xu et al. investigated semicontinuous microemulsion poly­mer­i­za­tion both by dropwise addition and by feeding monomer via a hollow tube [46]. In both poly­mer­i­za­tion methods, the feed of monomer must be slower than the rate of consumption of monomer. If the feed of monomer is greater than the rate of consumption of monomer, then the micelles swell with monomer and facilitate nucleation of new particles. In this case, the particle size remains approximately constant and the molecular weight of the polymers does not increase.

5.3 Reversible Addition-Fragmentation Chain Transfer Polymerization Reversible addition-fragmentation chain transfer (RAFT) is a robust method for controlling the free radical poly­mer­i­za­tion of a wide range of monomers in both homogeneous [16,47–51] and heterogeneous [24,52–55] poly­mer­i­za­tions. The original RAFT reaction mechanism proposed by Chiefari et al. [16] augments the standard free radical poly­mer­i­za­tion reactions of initiation, propagation, and termination with two transfer reactions: activation of the chain transfer agent and equilibrium between active and dormant poly­mer chains (Figure 5.2). The chain transfer agent is activated by reaction with a polymeric radical to form an intermediate RAFT radical that fragments to produce a dormant poly­mer chain and a radical R group. The radical R group then reacts with monomer to initiate a new propagating poly­mer chain. The dormant and propagating polymers react to form an intermediate macroRAFT radical that fragments to release either poly­mer for further propagation. The transfer of radical activity between propagating and dormant polymers is the key to controlling the poly­mer­i­za­tion because termination reactions are nearly eliminated and all of the polymers experience the same reaction conditions. One of the primary advantages of RAFT is the significant range of functionalities that can be incorporated into the poly­mer end groups through variations in the R and Z groups of the chain transfer agents. Figure  5.3 shows several examples of chain transfer agents, and the review by Moad et al. provides a more comprehensive list [17]. In an ideal RAFT poly­mer­i­za­tion the exchange of radical activity between propagating and dormant polymers is rapid relative to the rate of propagation, so the poly­mer­i­za­tion kinetics should be unaffected. However, ­inhi­bition and rate retardation are frequently observed in RAFT poly­mer­i­za­tions. Inhibition is commonly attributed to slow fragmentation of the RAFT radical and/or slow initiation by the R group radical [47]. The use of highly stable, electrophilic R groups eliminates inhibition and allows the chain transfer agent activation reaction to be simplified in kinetic investigations of the RAFT reaction

141

Polymer Nanoparticles by RAFT Microemulsion Polymerization

Activation of the transfer agent: P

•

S

+

S—R

P—S

Z RAFT agent

propagating polymer chain

S—R

•

S

P—S

Z RAFT radical

+

R M

•

Z dormant radical polymer chain R group

Simplified activation of the transfer agent: P

•

+

propagating polymer chain

S

S—R

ktr

Z RAFT agent

P—S

S

+

Z dormant polymer chain

R M

•

radical R group

Equilibrium between active and dormant chains: Pm

•

+

S

S—Pn

Z propagating dormant polymer chain polymer chain

ka kf

Pm—S

•

S—Pn

Z macroRAFT radical

kf ka

Pm—S

S

+

Pn

•

Z propagating dormant polymer chain polymer chain

Figure 5.2 Proposed reversible addition-fragmentation chain transfer mechanism. (Reprinted from J. Chiefari, Y. K. Chong, F. Ercole, J. Krstina, J. Jeffery, T. P. T. Le, R. T. A. Mayadunne, G. F. Meijs, C. L. Moad, G. Moad, E. Rizzardo, and S. H. Thang. Macromolecules 31: 5559–62, 1998. With permission.)

mechanism. The rapid activation of the chain transfer agent also provides improved control over the molecular weight of the resulting polymers [50]. Proponents of the original RAFT reaction mechanism proposed by Chiefari et al. attribute rate retardation to slow fragmentation of the macroRAFT radical, as opposed to termination. Experiments [48,50,51] and ab initio molecular orbital calculations [56,57] have shown that the structure of the Z group determines the stability of the macroRAFT radical, and therefore, the rate of fragmentation. Phenyl and O-alkyl Z groups cause the greatest degree of rate retardation in RAFT poly­mer­i­za­tions of styrene [48,50] and alkyl acrylates [50] because of the resonance structures available for radical stabilization. RAFT poly­mer­i­za­tions of vinyl acetate have shown that the stability of the macroRAFT radical caused by the lone electron pair on an oxygen atom can be reduced by replacing the alkyl chains with more efficient electronwithdrawing groups [51]. Moad et al. have compiled the available experimental data for RAFT poly­mer­i­za­tions and developed the guidelines shown in Figure 5.4 to assist with the selection of R and Z groups that will provide good control [17].

142

Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

S

S

S

N

C12H25S

OCH3

O

S

S

S

RS

S S

OR

S

O

S

OC2H5

S

O

S

S

S

S

N+ – Br

CO2H

F3C

O

S

S

O

CO2H

S S

S

CN

S

S

S

O

CO2H

S

S

S S

S

S

S S O

S

O

Si OCH2

S S

CO2H

HO2C

Figure 5.3 Examples of RAFT chain transfer agents. (Reprinted from G. Moad, E. Rizzardo, and S. H. Thang, Australian Journal of Chemistry 59: 669–92, 2006. With permission.)

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=

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5

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à 1

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Figure 5.4 Guidelines for selection of RAFT agents for various poly­mer­i­za­t ions. For Z, addition rates decrease and fragmentation rates increase from left to right. For R, fragmentation rates decrease from left to right. The dashed line indicates partial control (i.e., control of molecular weight but poor polydispersity or substantial retardation in the case of VAc or NVP). Monomer abbreviations: Methyl methacrylate (MMA), vinyl acetate (VA), styrene (S), methyl acrylate (MA), acrylamide (AM), acrylonitrile (AN), n-vinyl pyrrolidone (NVP). (Reprinted from G. Moad, E. Rizzardo, and S. H. Thang, Australian Journal of Chemistry 59: 669–92, 2006. With permission.)

143

Polymer Nanoparticles by RAFT Microemulsion Polymerization

5.4 Reversible Addition-Fragmentation Chain Transfer Microemulsion Polymerization The proposed mechanism of RAFT microemulsion poly­mer­i­za­tion is shown in Figure  5.5. Monomer (M) and chain transfer agent (XR) in excess of their respective solubility thresholds partition into micelles (Figure 5.5(1.)). Polymerization commences when a water-soluble initiator (I) decomposes and reacts with the monomer solubilized in the aqueous domain to form a propagating poly­mer (Figure  5.5(2.)). Upon reaching a critical degree of poly­mer­i­za­tion, the propagating radical is no longer soluble in the aqueous domain and enters a monomer-swollen micelle, thus initiating a poly­mer particle. Propagation continues in the poly­mer particle with monomer and chain transfer agent diffusing from surrounding uninitiated micelles to the locus of poly­mer­i­za­tion (Figure  5.5(3.)). The ratio of the number of chain 1. Monomer and RAFT Agent Swollen Micelles M XR

2. Initiation M XR

M XR M XR

XR Pn• M M XR

M

PnX•R XPn + R•

• Pn–1

M XR M XR

4. Reaction of Propagating Chain with RAFT Agent

3. Propagation

M

P•

M

I•

5. Radical Initiation and Propagation R• XP M M M XR

M Pn

•

M

M XR

6. Equilibrium Between Active and Dormant Chains • XPn + Pm M

P•

M M XR

PmX•Pn XPm + Pn•

Figure 5.5 Proposed reversible addition-fragmentation chain transfer microemulsion poly­mer­i­za­t ion mechanism. (1.) Initial microemulsion with monomer (M) and chain transfer agent (XR) partitioned into the micelles. (2.) Initiation and propagation in the aqueous domain followed by entry of the propagating poly­mer (P•) into an uninitiated micelle. (3.) Propagation in a surfactant stabilized poly­mer particle with monomer diffusing from surrounding micelles to the locus of poly­mer­i­za­t ion. (4.) Activation of the chain transfer agent to form a dormant poly­mer (XP) and a radical R group. (5.) Initiation of a new propagating poly­mer in the same poly­mer particle. (6.) Equilibrium between active and dormant polymers.

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transfer agents (XR) to the number of micelles is critical in setting the degree of poly­mer­i­za­tion that occurs in the monomer-rich particle before the propagating poly­mer (Pn•) reacts with a chain transfer agent (XR) to form a RAFT radical (PnX•R). Subsequently, the RAFT radical cleaves to give a dormant poly­mer chain (XPn) and a new radical (R•) (Figure 5.5[4.]). The new R• radical reacts with monomer to initiate a new poly­mer (P•) within the same particle (Figure 5.5(5.)). Once an active poly­mer (P•) and one or more dormant polymers (XPn) are present within one particle, an equilibrium is formed in which the polymers alternate between the dormant and active states. The final latex dispersion consists of empty micelles and surfactant-stabilized poly­mer particles in which the number of polymers per particle depends on the concentration of chain transfer agent (Figure 5.5[6.]). Table 5.1 summarizes the RAFT microemulsion poly­mer­i­za­tions that have been performed to date. The results of these poly­mer­i­za­tions have identified several key parameters for achieving controlled poly­mer­i­za­tion, including the chain transfer agent molecule per micelle ratio, and the aqueous solubility of the monomer and the chain transfer agent. Kinetic models of both uncontrolled and RAFT microemulsion poly­mer­i­za­tion have proven useful in understanding the impact of these key parameters. Therefore, the kinetic models will be introduced prior to discussing the effects of these parameters on the molecular weight, polydispersity, and particle size. 5.4.1 Microemulsion Polymerization Kinetics An understanding of RAFT microemulsion poly­mer­i­za­tion kinetics and the development of a model are critical for gaining information on the impact of several key parameters. Hermanson and Kaler have developed a kinetic model to describe the rate of RAFT microemulsion poly­mer­i­za­tions and to track the growth of the number average molecular weight as a function of conversion. However, this model requires the iterative solution of the rate equations for each species involved in the poly­mer­i­za­tion, which is computationally intensive and does not allow for an investigation of the effects of critical parameters. Alternatively, the Morgan model for uncontrolled microemulsion poly­ mer­i­za­tion kinetics provides a solid framework for the development of a kinetic model of RAFT microemulsion poly­mer­i­za­tion that requires at most the solution of four coupled differential equations [25, 59]. This model allows the effects of the chain transfer agent per micelle ratio, and the monomer and chain transfer agent aqueous solubilities to be investigated. The Morgan model is described next, and then the development of the RAFT microemulsion poly­mer­i­za­tion model and the results of this model, both with and without biradical termination effects, are summarized.

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145

Table 5.1 Summary of RAFT Microemulsion Polymerizations Performed to Date

Monomer (Solubility)

RAFT Agent (Solubility)

n-hexyl methacrylate [24] (0.4 mM)

2-cyanoprop-2-yl dithiobenzoate (0.12 mM)

n-butyl acrylate [58] (10.9 mM)

methyl-2-(Oethylxanthyl) propionate (1.0 mM)

methyl-2-(Ododecylxanthyl) propionate (<0.01 mM)

2-ethylhexyl acrylate [25] (0.5 mM)

methyl-2-(Oethylxanthyl) propionate (1.0 mM)

Chain Transfer Agents/ Micelle 0

MN,th [kDa]

MN [kDa]

MW/MN

Particle Diameter [nm]

—

>1*10

—

45.0

47

5.06

21.0

34 3.85 28 1.80 23 1.43 17 1.24 12 1.20 8.7 1.25 >1*104 — 29.1 1.16 18.0 1.38 10.1 1.43 5.3 1.38 3.6 1.37 2.8 1.25 multimodal multimodal multimodal multimodal multimodal >1*104 — 23.6 1.77 23.7 1.60 13.4 1.73 6.0 1.88 4.7 1.66 — —

18.5 20.5 20.7 22.6 29.4 30.0 39.8 17.8 18.8 19.5 21.1 24.6 30.5 18.1 20.2 18.6 18.0 19.2 45.0 6.7 7.6 9.2 7.0 11.0 12.5

0.35

75

0.50 0.75 1.12 1.50 2.25 3.00 0 0.3 0.6 1.2 2.4 3.7 4.9 0.3 0.6 1.2 2.4 4.9 0 0.3 0.6 1.2 2.4 3.7 4.9

53 35 24 18 12 8.8 — 39.8 20.4 10.7 5.5 3.5 2.6 — — — — — — 35.8 19.4 9.6 5.1 3.3 —

4

5.4.1.1 Uncontrolled Microemulsion Polymerization Kinetics The Morgan model for the rate of microemulsion poly­mer­i­za­tion provides a single rate equation that is able to predict the poly­mer­i­za­tion kinetics a priori [32,59]. Valuable information about the impact of monomer partitioning and biradical termination, which are directly related to monomer solubility and microemulsion composition, can be obtained from the comparison of microemulsion poly­mer­i­za­tion kinetics with the Morgan model predictions [32].

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The fundamental rate equation for the rate of fractional monomer conversion (df/dt) in a microemulsion poly­mer­i­za­tion is first order in both the concentration of monomer and propagating radicals,

part * df k p Cmon N = dt Mo

(5.3)

part where kp is the propagation constant, Cmon is the concentration of monomer at the locus of poly­mer­i­za­tion, N * is the concentration of propagating radicals, and Mo is the initial concentration of monomer in the microemulsion. Assuming negligible biradical termination, as a result of the low probability of a radical entering a particle as opposed to a micelle, N * increases linearly throughout the conversion as



N * = 2k d γ [I]t

(5.4)

where each initiator (at concentration [I]) is assumed to decompose into two radicals, kd is the dissociation rate constant, γ is the efficiency, and t is the reaction time. Equation (5.4) is often further simplified by noting that [I] is approximately constant for initiators with a long half-life relative to the total poly­mer­i­za­tion time, so this term can be replaced by the initial initiator ­concentration (Io). part ) The concentration of monomer at the locus of poly­mer­i­za­tion (Cmon depends on the partitioning of monomer between the micelles and the poly­mer particles. Assuming that monomer transport is more rapid than monomer consumption, equilibrium thermodynamics determine the partitioning of monomer [35]. Therefore, the relative solubility of the poly­mer in the monomer and the monomer in the surfactant tails determines the locus of poly­mer­i­za­tion. If the poly­mer is sufficiently soluble in the monomer, then the monomer swells the core of the poly­mer particles. Guo et al. have simulated the kinetics of styrene microemulsion poly­mer­i­za­tions and shown that in this case the monomer is depleted from the core of the micelles before the poly­mer­i­za­tion reaches 5% conversion [60]. If the monomer thermodynamically favors solubilizing the surfactant tails as opposed to the poly­mer, then the monomer remains partitioned between the micelles and the corona of the poly­mer particles throughout the poly­mer­i­za­tion. In this case, the poly­mer­i­ za­tion occurs in the corona of the poly­mer particles rather than the core. part Although Cmon  depends on the thermodynamics of monomer partitioning, the concentration profile is independent of the locus of poly­mer­i­za­tion. part In both cases, Cmon  decreases linearly as a function of conversion (f ):

(

)

part part Cmon = Cmon ,o 1 − f

(5.5)

Polymer Nanoparticles by RAFT Microemulsion Polymerization

147

part Substituting the expressions for N* and  Cmon   into Equation (5.3) and integrating results in the Morgan model for conversion as a function of time, viz.  k C part k γ I  f = 1 − exp − p mon ,o d o t 2  = 1 − exp −At 2 (5.6) Mo  

(

)

where all of the rate constants and concentrations are grouped into the single parameter A. A notable property of the Morgan model for the rate of microemulsion poly­mer­i­za­tion is that it predicts a rate maximum at a conversion equal to 1 – e–0.5 = 0.39, independent of the rate constants or initial composition of the microemulsion. Several monomers demonstrate rate maxima at conversions less than the 39% conversion predicted by the Morgan model, most notably styrene [32,61–66] and vinyl acetate [67–71]. deVries et al. have studied the deviations of the rate maximum from the Morgan model and predicted rate maximum in terms of nonlinear monomer partitioning, biradical termination, and diffusion limitations to propagation [32]. Both nonlinear monomer partitioning and biradical termination can be related to the monomer solubility; however, the deviations of low-water-solubility styrene and high-water-­solubility vinyl acetate from the Morgan model indicate that another parameter is also important. The rate of transfer of radical activity relative to the rate of propagation is also an important parameter for minimizing biradical termination reactions. When biradical termination is not negligible, the deVries et al. model describes N * as



 pterm  pterm    1 −  p p prop  dN * prop  part *  − 2 k mono = 2 γkd I o  Cmon (5.7) ,o 1 − f N tr   1 + pterm  1 + pterm  dt     p prop  p prop   

(

)

where

pterm N* = part p prop τ res k p Cmon ,o 1 − f N mic

(

)

(5.8)

ktrmono is the rate constant for radical transfer from the poly­mer to the monomer, τres is the residence time of the radical in a micelle, and Nmic is the concentration of micelles in the microemulsion [32]. 5.4.1.2 RAFT Microemulsion Polymerization Kinetics [72] In an uncontrolled microemulsion polymerization, biradical termination is unlikely, so all of the radicals that enter a micelle to form a polymer particle

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Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

propagate throughout the entire polymerization. A RAFT microemulsion poly­mer­i­za­tion is fundamentally different because at any given time a fraction of the radicals exist as stable macroRAFT radicals that do not propagate. Therefore, a term must be introduced to the fundamental microemulsion poly­mer­i­za­tion rate equation [Equation (5.3)] to describe the fraction of active radicals (xact) in a RAFT microemulsion poly­mer­i­za­tion. xact is expected to depend on the poly­mer­i­za­tion time (t) and the concentration of the chain transfer agent ([XR]). Introducing xact to the fundamental rate equation with linear monomer partitioning gives

(

)

part * df k p Cmon ,o 1 − f x act N = dt Mo

(5.9)

In the absence of biradical termination, N * increases linearly as a function of time according to Equation (5.4). However, if biradical termination is not negligible, then the deVries et al. model for biradical termination [Equation (5.7)] must be adjusted to consider transfer and termination reactions involving only active radical species. Also, in addition to termination reactions caused by the exit of monomer radicals, the radical R group may exit the particle and cause termination. xact depends on the concentrations of all four different radical species that are present in RAFT microemulsion poly­mer­i­za­tions, shown in Figure 5.5. Initiator (I•), R group (R•), and poly­mer (P•) radicals are active radical species that react with monomer to form poly­mer and thus contribute to the rate of conversion. The macroRAFT radical (PX•P) is inactive and does not contribute to the rate of conversion. Therefore, the fraction of active radicals in a RAFT microemulsion poly­mer­i­za­tion is

x act =

[I•] + [R•] + [P•] [I•] + [R•] + [P•] + [PX•P]

(5.10)

In principle, each time-dependent radical concentration in Equation (5.10) must be calculated by solving the coupled rate equations presented in the Hermanson model [73]. However, a simpler expression for xact can be obtained by modeling the kinetics in a single particle and calculating the fraction of time that the particle is in the active state as opposed to the dormant state. In this case,

x act =

t act t act + t dorm

(5.11)

where tact is the characteristic time that a particle is active and tdorm is the characteristic time that a particle remains dormant. The conversion from

149

Polymer Nanoparticles by RAFT Microemulsion Polymerization

Equation (5.10) to (5.11) inherently assumes that all of the particles in the polymerizing microemulsion are identical, but the particles in a RAFT microemulsion poly­mer­i­za­tion experience different poly­mer­i­za­tion kinetics because of the distribution of the chain transfer agent between the particles [25]. Therefore, Equation (5.11) must be averaged over the particles in the polymerizing microemulsion to give x act =



t act t act + t dorm



(5.12)

where ⟨tact ⟩ is the average time that a particle is in that active state and ⟨tdorm ⟩ is the average time that a particle remains in the dormant state. Modeling the kinetics in a single particle as opposed to in the entire microemulsion greatly simplifies the rate equations because each particle can contain only one radical, either P• in an active particle or PX•P in a dormant particle. The probability of a second radical entering a poly­mer particle as opposed to a micelle is typically negligible in a microemulsion poly­mer­i­ za­tion, as discussed previously, because the concentration of micelles is approximately 1000 times greater than the concentration of poly­mer particles. Additionally, the small particle size means that if a second radical enters a poly­mer particle, then rapid contact between the radicals occurs, and the radicals immediately terminate. The expressions for tact and tdorm in a single particle are determined from the rate equation for the concentration of propagating poly­mer molecules per particle [P•]part based on the mechanism shown in Figure 5.5. Integrating the rate equation for [P•]part for the conversion from a dormant particle ([P•]part = 0 and [PX•P]part = 1) to an active particle ([P•]part = 1 and [PX•P]part = 0), and from an active particle to a dormant particle, gives the expressions for tdorm and tact, respectively. In obtaining a closed expression for tact, it is necessary to assume that the concentration of dormant poly­mer molecules in the particle [XP]part and the volume of the poly­mer particle Vpart are constant over the time that a particle is active. These assumptions are supported by small-angle neutron-scattering experiments [26] and measured poly­mer­i­za­ tion kinetics [25]. The final closed expression for ⟨xact⟩ is then

()

x act t =

t act t act + t dorm

≈ 1+

ka

1

()

N A Vpart t k f

()

XP   part t



(5.13)

where ⟨[XP]part(t)⟩ and ⟨Vpart(t)⟩ can be approximated from the bulk RAFT microemulsion poly­mer­i­za­tion kinetics [72].

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Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

Table 5.2 Parameters for Modeling the Rate of Conversion of Butyl Acrylate in RAFT Microemulsion Polymerizations with the Chain Transfer Agent MOEP Rate Constants

Microemulsion Conditions

Monomer and Surfactant Properties

kd72 kpa

1.65 × 10–5 s–1 1.66 × 103 M–1s–1

Mo Io

0.389 M 0.003 M

MWmono ρmono

128.17 g/mol 890 g/L

ka73

4.00 × 105 M–1s–1

C(part) mon,o

2.9 M

τres

1.2 × 10–6 s

ktr73

4.00 × 105 M–1s–1 1.00

Nmic

3.2*10–3 M

ltail

1.67 nm

γ a

From fitting the uncontrolled butyl acrylate microemulsion poly­mer­i­za­ tion data to the Morgan model.

5.4.1.3 Model Results The dependence of the RAFT microemulsion poly­mer­i­za­tion rate on both the rate of macroRAFT radical fragmentation and the rate of diffusion of the chain transfer agent to the locus of poly­mer­i­za­tion can be investigated using the model described in the previous section. The reported values of kf in the literature range from 10 –2 s–1 when rate retardation is assumed to arise solely from slow fragmentation of the macroRAFT radical, [74] to 106 s–1 when rate retardation is assumed to arise solely from termination of the macroRAFT radical [75]. The characteristic diffusion time of a chain transfer agent from a micelle to a poly­mer particle ranges from approximately 10 –4 s to 10 s, while the characteristic activation time is approximately 10 –4 s. Therefore, the rate of chain transfer agent activation is likely diffusion limited rather than reaction limited. The rate constants, microemulsion characteristics, and monomer and surfactant properties used to calculate the rate of RAFT microemulsion poly­mer­i­za­ tion for butyl acrylate with the chain transfer agent methyl 2-(O-ethylxanthyl) propionate (MOEP) are summarized in Table  5.2. The kinetic trends predicted by the model using these reaction parameters are first examined in the absence of biradical termination. However, biradical termination is not negligible in butyl acrylate microemulsion poly­mer­i­za­tions, so the effects of biradical termination are subsequently considered [72]. 5.4.1.4 Predicted RAFT Microemulsion Polymerization Kinetics with Negligible Biradical Termination The rate of RAFT microemulsion poly­mer­i­za­tion depends on both the rate of macroRAFT radical fragmentation and the rate of diffusion of the chain transfer agent to the locus of poly­mer­i­za­tion. Decreasing the rate of macroRAFT radical fragmentation increases tdorm and, therefore, is expected

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Polymer Nanoparticles by RAFT Microemulsion Polymerization

to decrease the rate of poly­mer­i­za­tion, as shown by Equations (5.9) and (5.13). In fact, the model shows that decreasing kf from 106 s–1 to 10 –2 s–1 decreases the rate of poly­mer­i­za­tion by two orders of magnitude when the activation of the chain transfer agent is reaction limited. For diffusion-limited activation of the chain transfer agent, the poly­mer­i­za­tion rate decreases by only one order of magnitude when kf decreases from 106 s–1 to 10 –2 s–1. Diffusion-limited activation of the chain transfer agent results in a lower value of ⟨[XP]part⟩ relative to poly­mer­i­za­tions with reaction-limited chain transfer agent activation. Therefore, ⟨xact⟩ is greater for poly­mer­i­za­tions with diffusion-limited activation than reaction-limited activation [Equation (5.13)]. For RAFT microemulsion poly­mer­i­za­tions with rapid macroRAFT radical fragmentation and diffusion-limited activation, the rate of poly­mer­i­za­tion is identical to the rate of uncontrolled microemulsion poly­mer­i­za­tion, as anticipated. The rate of chain transfer agent diffusion to the locus of poly­mer­i­za­tion has a significant effect on the location of the rate maximum when fragmentation of the macroRAFT radical is slow. The Morgan model predicts that the maximum rate of an uncontrolled microemulsion poly­mer­i­za­tion occurs at 39% conversion irrespective of the rate constants and initial microemulsion composition [59]. The model for RAFT microemulsion poly­mer­i­za­tion presented in the previous section predicts that the maximum rate of RAFT microemulsion poly­mer­i­za­tion occurs at conversions greater than 39% when the activation of the chain transfer agent is reaction limited and fragmentation of the macroRAFT radical is slow (Figure  5.6a). This shift of the rate maximum corresponds to the trend observed by Liu et al. for RAFT micro­ emulsion poly­mer­i­za­tions of hexyl methacrylate with the chain transfer ×10–4 (a)

1

Increasing MOEP/Micelle

0.8

1

Rate (s–1)

Rate (s–1)

1.5

0.5

×10–3 Increasing MOEP/Micelle

(b)

0.6 0.4 0.2

0

0

0.2

0.4

0.6

Conversion

0.8

1

0

0

0.2

0.4 0.6 Conversion

0.8

1

Figure 5.6 Predicted rate of conversion as a function of conversion of butyl acrylate and increasing MOEP:micelle ratios for slow fragmentation (k f = 10 –2 s–1) and (a) reaction-limited activation, (b) diffusion-limited activation. In both panels MOEP:micelle = 0.1, 0.3, 0.6, 1.2, 2.4, 3.7, and 4.9. Note that the scale of the y-axis varies. (Redrawn from J. O’Donnell and E.W. Kaler, Journal of Polymer Science Part A: Polymer Chemistry, 48(3): 604-613, 2010.)

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Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

agent 2-cyanoprop-2-yl dithiobenzoate (CPDB) at CPDB:initiator ratios less than 3.0 [24]. Liu et al. suggest that the shift of the rate maximum to conversions greater than 39% is caused by the complete consumption of the chain transfer agent early in the poly­mer­i­za­tion so that particles initiated late-experience rapid uncontrolled poly­mer­i­za­tion. Solving the RAFT microemulsion poly­mer­i­za­tion model for the concentration of the chain transfer agent does in fact show that when the activation of the chain transfer agent is reaction–limited, the chain transfer agent is consumed before the poly­mer­i­ za­tion reaches 40% conversion. When activation of the chain transfer agent is diffusion-limited, the model predicts that the location of the rate maximum occurs at conversions less than 39% conversion (Figure 5.6b), in accordance with the measured kinetic trends for butyl acrylate and ethylhexyl acrylate RAFT microemulsion poly­mer­i­za­tions with MOEP and methyl 2-(O-dodecylxanthyl) propionate (MODP). However, the location of the rate maximum does not shift as a function of the MOEP:micelle ratio as observed experimentally for these RAFT microemulsion poly­mer­i­za­tions [58]. In addition, the maximum rate of conversion is experimentally observed to occur at conversions as low as 14% at an MOEP:micelle ratio of 4.9, and the lowest predicted conversion for the rate maximum using this model is 30%. Therefore, biradical termination must be considered as the source of the shift in the location of the rate maximum as a function of the MOEP:micelle ratio. 5.4.1.5 Predicted RAFT Microemulsion Polymerization Kinetics with Biradical Termination Both nonlinear monomer partitioning and biradical termination are known to shift the location of the rate maximum to conversions less than the 39% conversion predicted by the Morgan model [32]. However, small-angle ­neutron-scattering studies have shown that the concentration of butyl acrylate at the locus of poly­mer­i­za­tion decreases nearly linearly as a function of conversion during RAFT microemulsion poly­mer­i­za­tions with MOEP [26]. Therefore, nonlinear monomer partitioning does not cause the shift of the rate maximum and only biradical termination must be considered. The impact of biradical termination reactions on the rate of conversion is most evident when fragmentation of the macroRAFT radical is fast (kf = 106 s–1) (Figure 5.7). Fast fragmentation of the macroRAFT radical means that the concentration of active radicals remains high throughout the poly­mer­ i­za­tion, which facilitates biradical termination. When fragmentation of the macroRAFT radical is slow (kf = 10 –2 s–1) the concentration of active radicals is low, so a radical is likely to encounter a dormant particle as opposed to an active particle. Therefore, biradical termination is minimized and the kinetic trends are similar to the trends predicted without the inclusion of biradical termination reactions (Figure 5.6).

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Polymer Nanoparticles by RAFT Microemulsion Polymerization

0.02

(a)

0.018

0.03

Increasing MOEP/Micelle

0.025

0.016 0.012

Rate (s–1)

Rate (s–1)

0.014 0.01 0.008

Increasing MOEP/Micelle

0.02 0.015 0.01

0.006 0.004

0.005

0.002 0

(b)

0

0.2

0.4 0.6 Conversion

0.8

1

0

0

0.2

0.4 0.6 Conversion

0.8

1

Figure 5.7 Predicted rate of conversion with biradical termination reactions as a function of conversion of butyl acrylate and increasing MOEP:micelle ratios for fast fragmentation (k f = 106 s–1) and (a) reaction-limited activation, and (b) diffusion-limited activation. MOEP:micelle = 0.1, 0.3, 0.6, 1.2, 2.4, 3.7, and 4.9. Note that the scale of the y-axis varies. (Redrawn from J. O’Donnell and E. W. Kaler, Journal of Polymer Science, Part A: Polymer Chemistry, 48(3), 604–613, 2010.)

The experimental shift of the maximum rate of poly­mer­i­za­tion for butyl acrylate with MOEP is quantitatively captured by the model when biradical termination is included, kf = 1585 s–1, and the activation rate coefficient is approximately one-tenth of the activation rate constant; that is, the activation of the chain transfer agent is diffusion-limited. Comparison of model fits with and without biradical termination reactions shows that slow fragmentation of the macroRAFT radical is responsible for the decrease in the rate of poly­mer­i­za­tion. In addition to directly decreasing the rate of poly­mer­i­za­tion by decreasing the concentration of active radicals, slow fragmentation also increases the likelihood of termination reactions. 5.4.2 Molecular Weight and Polydispersity In a controlled poly­mer­i­za­tion when the concentration of the chain transfer agent is much greater than the initiator concentration, as is true for all of the chain transfer agent per micelle ratios that have been investigated, the number average molecular weight (MN) is expected to increase linearly as a function of conversion, that is,

MN =

MWmon Mo f XR o

(5.14)

where MWmonomer is the molecular weight of the monomer, and Mo and XRo are the initial concentrations of monomer and chain transfer agent in the microemulsion. Experimentally MN does grow linearly for the poly­mer­i­za­tions of hexyl methacrylate with CPDB and butyl acrylate with MOEP (Figure  5.8).

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Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

40000

MN (Da)

30000

20000

10000

0

0

20

40 60 80 Percent Conversion (f*100)

100

Figure 5.8 Number average molecular weight of poly(n-butyl acrylate) at MOEP:micelle ratios of (●) 0.3, (□) 0.6, (▲) 1.2, (◇) 2.4, (⬢) 4.9. The lines are least-squares linear fits to the data.

However, the linear fits to the growth of MN do not pass through the origin, which indicates there must be an initial period of rapid uncontrolled poly­ mer­i­za­tion or slow activation of the chain transfer agent. The poly­mer­i­za­tions of butyl acrylate with MODP exhibit multimodal molecular weight populations, so the growth of MN could not be traced as a function of conversion. An initial period of rapid uncontrolled growth is an unlikely source of the deviation of the MN from the origin because all of the polymers are significantly smaller than would be expected for an uncontrolled microemulsion poly­mer­i­za­tion. In an uncontrolled microemulsion poly­mer­i­za­tion, the very low concentration of polymers formed by decomposition of the initiator produces polymers with MN of ~106 Da. A more likely source of this deviation is slow activation of the MOEP due to the partitioning of MOEP between micelles and poly­mer particles. This partitioning means that at low conversions the concentration of polymers is significantly less than the initial concentration of chain transfer agent in the microemulsion. Therefore, the fraction of the chain transfer that has been activated as a function of converCTA sion (x act ) should be included in Equation (5.14), so

MN =

MWmon Mo f CTA x act XR o

(5.15)

Equation (5.15) can be used to approximate the fraction of the chain transfer agent that has been activated at a given conversion from the MN

Polymer Nanoparticles by RAFT Microemulsion Polymerization

155

calculated from the least-squares linear fits to the molecular weight data (Figure 5.8). For example, at 5% conversion of butyl acrylate the concentration of polymers calculated from the least-squares linear fits to MN for each of the MOEP:micelle ratios corresponds to only 7–10% of the initial MOEP concentration. As the poly­mer­i­za­tion proceeds, the MOEP diffuses from the uninitiated micelles into the poly­mer particles, eventually resulting in activation of the entire chain transfer agent, a constant concentration of polymers, and linear growth of MN as a function of conversion. 5.4.2.1 Effect of Chain Transfer Agent per Micelle Ratio The deviation of MN from the predicted values that occurs early on in the RAFT microemulsion poly­mer­i­za­tions of butyl acrylate decreases as the MOEP:micelle ratio increases, as anticipated. Increasing the chain transfer agent-to-micelle ratio reduces the probability of a propagating oligomer entering a micelle that does not contain a chain transfer agent, and therefore reduces the extent of uncontrolled poly­mer­i­za­tion that can occur in the poly­mer particles before MOEP diffuses to the locus of poly­mer­i­za­tion. However, increasing the MOEP:micelle ratio even as high as 4.9 does not completely eliminate uncontrolled poly­mer­i­za­tion because of the way that the MOEP is distributed among the micelles. The distribution of MOEP into the micelles may be approximated as a Poisson distribution about the mean MOEP:micelle ratio, and the Poisson distribution shows that 1% of the micelles do not contain any MOEP when the mean MOEP:micelle ratio is 5. The agreement between the measured and predicted final MN [Figure 5.9, Equation (5.14)] shows that the concentration of chains does in fact correspond to the initial concentration of MOEP in the microemulsion, which indicates that all of the MOEP is activated during the poly­mer­i­za­tion. Because the number of micelles is ~1000 times greater than the number of poly­mer particles, activation of all of the MOEP signifies that the MOEP is diffusing into the poly­mer particles. The polydispersity (MW/MN) of the polymers (Figure  5.9 inset) increases as the average MOEP:micelle ratio increases because the diffusion of MOEP into propagating particles results in a distribution of the MOEP:particle ratio. The MOEP:particle ratio distribution means that all of the propagating poly­mer chains are not experiencing the same poly­mer­i­za­tion kinetics. 5.4.2.2 Effect of Monomer Solubility The aqueous solubility of the monomer is known to affect uncontrolled microemulsion poly­mer­i­za­tion kinetics, as discussed in Section 5.2.1. In RAFT microemulsion poly­mer­i­za­tions, the aqueous solubility of the monomer may also affect the control of the poly­mer­i­za­tion. The probability of a chain transfer agent and a propagating poly­mer radical reacting in the aqueous domain is negligible. Therefore, zcrit is the minimum degree of uncontrolled

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Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

5

2.0 1.8 MW/MN

MN/104 (Da)

4 3

1.6 1.4 1.2

2

1.0

1 0

0

1

0

1

2 3 MOEP/Micelle

2 3 MOEP/Micelle

4

4

5

5

Figure 5.9 MN and MW/MN (inset) of poly(butyl acrylate) as a function of the MOEP:micelle ratio. (—) predicted MN from Equation (5.14).

poly­mer­i­za­tion that a propagating oligomer reaches in a RAFT microemulsion poly­mer­i­za­tion. The impact of monomer solubility has been examined by substituting butyl acrylate with 2-ethylhexyl acrylate (EHA). The τprop/τres ratios for butyl acrylate and 2-ethylhexyl acrylate are similar (Table 5.3), so the effect of the aqueous solubility of the monomer on biradical termination is negligible and any effects of the aqueous solubility of the monomer on the control of the poly­mer­i­za­tion are elucidated. The 2-ethylhexyl acrylate poly­ mer­i­za­tions are expected to experience less uncontrolled poly­mer­i­za­tion at low conversions than the butyl acrylate poly­mer­i­za­tions because the 2-ethylhexyl acrylate chains are segregated into surfactant stabilized poly­mer particles at a lower zcrit. However, the kinetics and poly­mer characteristics of the EHA poly­mer­i­za­tions indicate less control than the BA poly­mer­i­za­tions. The butyl acrylate RAFT microemulsion poly­mer­i­za­tions with MOEP demonstrate controlled, linear growth at all chain transfer agent:micelle ratios after the initial period of uncontrolled poly­mer­i­za­tion or slow chain transfer agent activation (Figure  5.8). In contrast, the 2-ethylhexyl acrylate RAFT microemulsion poly­mer­i­za­tions with MOEP do not demonstrate controlled growth at an MOEP:micelle ratio of 0.3 (Figure 5.10). Controlled, ­linear growth of the EHA poly­mer chains is observed at MOEP:micelle ratios of 0.6 and 1.2; and at MOEP:micelle ratios greater than 1.2, MN decreases slightly, which indicates an increase in the concentration of small, controlled poly­mer chains as the poly­mer­i­za­tion proceeds. At all chain transfer agent:micelle ratios investigated, the final MN of the butyl acrylate chains is consistent with the activation of all of the MOEP (Figure  5.9). However, the final MN of the 2-ethylhexyl acrylate chains is

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Polymer Nanoparticles by RAFT Microemulsion Polymerization

Table 5.3 Monomer and Chain Transfer Agent Aqueous Solubilities (Caq), Monomer Concentration in the Micelles (Cmic), Radical Residence Time in a MonomerSwollen Micelle (tres), and Characteristic Time for Propagation of a Monomer Radical (t prop) or Reaction of a Transfer Agent with a Propagating Polymer (tact) Caq (mM)

Cmic (mM)

τres (s)

τprop/act (s)

τprop /τres

Monomers BA EHA

10.9a 0.5a

4200c 4200c

1.2*10–6 d 2.5*10–5 d

2.5*10–4 4.0*10–3

2.1*102 1.6*102

Chain Transfer Agents MOEP MODP

1.0b <0.01b

10–6 – 10–5 e >10–4 – 10–3 e

~10–4 f ~10–4 f

a b c

d e f

Material safety data sheet values. Measured by ultraviolet absorption. Calculated from the concentration of monomer in a microemulsion at the phase boundary at 45°C. Calculated from Equation (5.2) with Rmic = 3.0 nm and Daqmon = 10–9 m2/s. Assumed based on values for monomers and relative solubilities. Concentration of a propagating poly­mer approximated as one propagating poly­mer in a spherical particle with a 3-nm radius.

40000

MN (Da)

30000

20000

10000

0

0

20 40 60 Percent Conversion (f*100)

80

100

Figure 5.10 Number average molecular weight of poly(ethylhexyl acrylate) at MOEP:micelle ratios of (○) 0.3, (■) 0.6, (△) 1.2, (◆) 2.4, and (▽) 3.7. The lines are least-squares linear fits to the data.

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5

2.0 1.8

MW/MN

MN/104 (Da)

4

3

1.6 1.4 1.2

2

1.0

0

0

1

2

3

4

5

MOEP/Micelle

1

0

1

2 3 MOEP/Micelle

4

5

Figure 5.11 MN and MW/MN (inset) polydispersity of poly(butyl acrylate) with MOEP (▲) and poly(ethylhexyl acrylate) with MOEP (□). The lines are predicted from Equation (5.14) with conversion equal to one.

greater than anticipated (Figure 5.11), which indicates that all of the MOEP is not activated. In addition, the polydispersity (MW/MN) of the 2-ethylhexyl acrylate chains is greater than the MW/MN of the butyl acrylate chains (Figure 5.11 inset). As discussed later with respect to the latex particle size, the fact that the butyl acrylate poly­mer­i­za­tions are better controlled than the 2-ethylhexyl acrylate poly­mer­i­za­tions is likely caused by coalescence of the poly(butyl acrylate) particles. 2-ethylhexyl acrylate poly­mer chains that partition into a surfactant stabilized poly­mer particle that does not ­contain a chain transfer agent must wait until a chain transfer agent diffuses into the particle, while the chain transfer agent is rapidly transported into the poly(butyl acrylate) particles by coalescence. 5.4.2.3 Effect of Chain Transfer Agent Solubility The aqueous solubility of the chain transfer agent is expected to impact the RAFT microemulsion poly­mer­i­za­tion kinetics and the characteristics of the poly­mer chains. The residence time of the chain transfer agent in the micelles (τres,CTA) is approximated in the same manner as τres [Equation (5.2)]. Decreasing the aqueous solubility of the chain transfer agent increases the residence time in the micelles and slows the transport of the chain transfer agent to the locus of poly­mer­i­za­tion. When the time necessary for a chain

Polymer Nanoparticles by RAFT Microemulsion Polymerization

159

transfer agent to diffuse to the locus of poly­mer­i­za­tion exceeds the time required for activation of the chain transfer agent by a propagating poly­mer (τact), the activation of the chain transfer agent is diffusion limited. The time necessary for a chain transfer agent to diffuse to the locus of poly­mer­i­za­tion is approximately τres,CTA multiplied by the micelle:poly­mer particle ratio, and τact is a function of the transfer rate constant (ktr) and the concentration of part radicals in the poly­mer particle (Crad ):

τ act ≈

1 part k tr Crad

(5.16)

Slow diffusion of the chain transfer agent to the locus of poly­mer­i­za­tion decreases the average and the standard deviation of the distribution of the chain transfer agent:particle ratio. Decreasing the standard deviation of the chain transfer agent:particle ratio is expected to decrease the polydispersity of the poly­mer chains because all of the poly­mer particles experience similar poly­mer­i­za­tion conditions. Decreasing the average chain transfer agent:particle ratio is expected to alleviate the rate retardation caused by slow fragmentation of the macroRAFT radical. The effect of the chain transfer agent aqueous solubility is investigated by replacing MOEP with MODP, which differs from MOEP only in the length of the alkyl chain in the Z group so that the functionality of the chain transfer agent is unaltered. Given that the ratio of micelles to poly­mer particles is 100–1000, the activation of both of the chain transfer agents is diffusion limited. Therefore, the average and the standard deviation of the chain transfer agent:particle ratio distribution are expected to be lower in the MODP poly­mer­i­za­tions than the MOEP poly­mer­i­za­tions. The RAFT microemulsion poly­mer­i ­za­t ions of BA with MODP, the low aqueous solubility chain transfer agent, demonstrate several distinct molecular weight populations (Figure 5.12). However, all of the polymers are smaller than those produced by uncontrolled poly­mer­i ­za­t ion (MN ~ 103 kDa), which indicates that the poly­mer­i ­za­t ion is controlled to some extent. At MODP:micelle ratios of 0.3 and 0.6, the gel permeation chromatography (GPC) traces show predominantly 40–60 kDa polymers with a low molecular weight tail. At an MODP:micelle ratio of 1.2, the concentration of low molecular weight polymers increases and two distinct peaks are observed in the GPC trace. The high molecular weight polymers are now 30–50 kDa and the low molecular weight polymers are less than 10 kDa. As the MODP:micelle ratio increases from 1.2 to 4.8, the ratio of the high molecular weight poly­mer to low molecular weight poly­mer decreases. Additionally, a large concentration of oligomers is apparent in the GPC traces. An examination of the experimentally observed molecular weight profiles as a function of the chain transfer agent per particle distribution using the kinetic model described in Section 5.4.1.2 has demonstrated that

160

Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

Refractive Index Response (a.u.)

4

Conversion = 90%

3

84% 73%

2

47% 37% 1

26% 9%

0

3% 0

5

10 Time (min) (a)

15

20

4 Refractive Index Response (a.u.)

Conversion = 92% 77%

3

67% 51%

2

36% 24%

1

18% 6%

0

2% 0

5

10 Time (min) (b)

15

20

Refractive Index Response (a.u.)

5 4

Conversion = 87%

3

69%

2

48%

1

24%

0

79% 59% 36%

11% 0

5

10 Time (min) (c)

15

20

Figure 5.12 Gel permeation chromatography traces of poly(butyl acrylate) with, from top to bottom, MODP/micelle = 0.3, 1.2, and 4.8.

Polymer Nanoparticles by RAFT Microemulsion Polymerization

161

the distinct molecular weight populations in the RAFT microemulsion poly­mer­i ­za­t ions with the low water solubility chain transfer agent are a direct result of the slow diffusion of the chain transfer agent to the locus of poly­mer­i ­za­t ion. 5.4.3 Latex Particle Size The poly(butyl acrylate) latex particles produced by RAFT microemulsion poly­mer­i­za­tion remain colloidally stable for at least three years. The latex particle size distribution depends on the distribution of MOEP in the poly­ mer particles (Figure 5.13). The uncontrolled microemulsion poly­mer­i­za­tion of butyl acrylate produces latex particles with a very narrow distribution of diameters between 35 and 45 nm. The addition of the chain transfer agent 0.5

0.5 MOEP/Micelle = 0

0.3 0.2

0

0

50 10 20 30 40 Particle Diameter (nm)

0.5 MOEP/Micelle = 1.2

0.3 0.2 0.1

MOEP/Micelle = 4.9

0.4 Volume Fraction

0.4 Volume Fraction

0.2

0.0

50 10 20 30 40 Particle Diameter (nm)

0.5

0.0

0.3

0.1

0.1 0.0

MOEP/Micelle = 0.3

0.4 Volume Fraction

Volume Fraction

0.4

0.3 0.2 0.1

0

10 20 30 40 50 Particle Diameter (nm)

0.0

0

10 20 30 40 50 Particle Diameter (nm)

Figure 5.13 Average of four CONTIN fits to quasi-elastic light scattering data for poly(butyl acrylate) latex particles initiated with 3.0 mM VA044. (From J. O’Donnell, 2007. Reversible addition-fragmenta­ tion chain transfer polymerizationin microemulsions. PhD diss., Chemical Engineering, University of Delaware.)

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Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

at an MOEP:micelle ratio of 0.3 drastically reduces the latex particle diameter, but the distribution is still narrow. As the MOEP/micelle ratio increases beyond 0.3, the particle size distribution broadens, and the average latex particle diameter increases. The initial decrease and subsequent increase in the average latex particle diameter as the MOEP:micelle ratio increases is directly related to the observed rate retardation. The increased poly­mer­i­za­tion time both increases the number of poly­mer particles formed by thermal decomposition of the initiator, resulting in smaller particles, and facilitates coalescence of the monomer-swollen poly­mer particles, thereby increasing the size of some of the particles. Both events contribute to the broader distribution. In contrast to the highly stable poly(butyl acrylate particles), the poly(ethylhexyl acrylate) particles are colloidally stable for only one month, and the poly(butyl acrylate) particles poly­mer­ized with MODP are stable for several months. The reason for the decrease in stability with the low­solubility monomer and chain transfer agent is unknown. The RAFT microemulsion poly­mer­i­za­tions of butyl acrylate with MODP and 2-ethylhexyl acrylate with MOEP also produce smaller latex particles than the corresponding uncontrolled microemulsion poly­mer­i­za­tions (Figure 5.14). The poly(butyl acrylate) particles poly­mer­ized with MOEP and MODP increase in diameter as the chain transfer agent:micelle ratio increases. As the chain transfer agent:micelle ratio increases the poly­mer­i­za­tion time 50

Particle Diameter (nm)

40 30 20 10 0

0

1

2 3 Chain Transfer Agent/Micelle

4

5

Figure 5.14 Average latex particle diameter from quadratic cumulants fits to four autocorrelation functions measured by quasi-elastic light scattering for poly(butyl acrylate) with MOEP (▲), poly(butyl acrylate) with MODP (●), and poly(ethylhexyl acrylate) with MOEP (□). Error bars are smaller than the size of the symbols. (From J. O’Donnell, 2007. Reversible addition-fragmentation chain transfer polymerizationin microemulsions. PhD diss., Chemical Engineering, University of Delaware.)

Polymer Nanoparticles by RAFT Microemulsion Polymerization

163

also increases, which provides an extended time where the ­poly­mer particles can coalesce with the high concentration of ­monomer-swollen micelles. The coalescence of the poly­mer particles and monomer-swollen micelles can impact the poly­mer­i­za­tion kinetics and poly­mer characteristics by increasing the chain transfer agent:particle ratio more rapidly than diffusion of the chain transfer agent alone. The poly(ethylhexyl acrylate) particles poly­mer­ ized with MOEP do not increase in size as the chain transfer agent:micelle ratio increases. The lower water solubility of 2-ethylhexyl acrylate relative to butyl acrylate likely limits coalescence because the 2-ethylhexyl acrylate is partitioned closer to the core of the poly­mer particles while the butyl acrylate may partition closer to the surface.

References













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47. Chong, Y. K., Krstina, J., Le, T. P. T., Moad, G., Postma, A., Rizzardo, E., and S. H. Thang. 2003. Thiocarbonylthio compounds S=C(Ph)S-R in free radical poly­mer­ i­za­tion with reversible addition-fragmentation chain transfer (RAFT poly­mer­i­ za­tion). Role of the free-radical leaving group (R). Macromolecules 36:2256–72. 48. Chiefari, J., Mayadunne, R. T. A., Moad, C. L., Moad, G., Rizzardo, E., Postma, A., Skidmore, M. A., and S. H. Thang. 2003. Thiocarbonylthio compounds (S=C(Z)S-R) in free radical poly­mer­i­za­tion with reversible addition-fragmentation chain transfer (RAFT poly­mer­i­za­tion). Effect of the activating group Z. Macromolecules 236:2273–83. 49. Davis, T. P., Barner-Kowollik, C., Nguyen, T. L. U., Stenzel, M. H., Quinn, J. F., and P. Vana. 2003. Influences of the structural design of RAFT agents on living radical poly­mer­i­za­tion kinetics. Advances in Controlled/Living Radical Polymerization 854:551–69. 50. Destarac, M., Taton, D., Zard, S. Z., Saleh, T., and Y. Six. 2003. On the importance of xanthate substituents in the MADIX process. Advances in Controlled/Living Radical Polymerization 854:536–50. 51. Stenzel, M. H., Cummins, L., Roberts, G. E., Davis, T. R., Vana, P., and C. BarnerKowollik. 2003. Xanthate mediated living poly­mer­i­za­tion of vinyl acetate: A systematic variation in MADIX/RAFT agent structure. Macromolecular Chemistry and Physics 204:1160–68. 52. Butte, A., Storti, G., and M. Morbidelli. 2001. Miniemulsion living free radical poly­mer­i­za­tion by RAFT. Macromolecules 34:5885–96. 53. Simms, R. W., Davis, T. P., and M. F. Cunningham. 2005. Xanthate-mediated living radical poly­mer­i­za­tion of vinyl acetate in miniemulsion. Macromolecular Rapid Communications 26:592–96. 54. Ferguson, C. J., Hughes, R. J., Pham, B. T. T., Hawkett, B. S., Gilbert, R. G., Serelis, A. K., and C. H. Such. 2002. Effective ab initio emulsion poly­mer­i­za­tion under RAFT control. Macromolecules 35:9243–45. 55. McLeary, J. B., Tonge, M. P., Roos, D. D., Sanderson, R. D., and B. Klumperman. 2004. Controlled, radical reversible addition-fragmentation chain-transfer poly­mer­i­za­tion in high-surfactant concentration ionic miniemulsions. Journal of Polymer Science, Part A: Polymer Chemistry 42:960–74. 56. Coote, M. L., and L. Radom. 2003. Ab initio evidence for slow fragmentation in RAFT poly­mer­i­za­tion. Journal of the American Chemical Society 125:1490–91. 57. Coote, M. L. 2004. Ab initio study of the addition-fragmentation equilibrium in RAFT poly­mer­i­za­tion: When is poly­mer­i­za­tion retarded? Macromolecules 37:5023–31. 58. O’Donnell, J. and E. W. Kaler. 2010. Reversible addition-fragmentation chain transfer in microemulsion polymerizations: Effect of chain transfer agent aqueous solubility, Macromolecules, 43 (4): 1730–1738. 59. Morgan, J. D., Lusvardi, K. M., and E. W. Kaler. 1997. Kinetics and mechanism of microemulsion poly­mer­i­za­tion of hexyl methacrylate. Macromolecules 30:1897–1905. 60. Guo, J. S., Sudol, E. D., Vanderhoff, J. W., and M. S. Elaasser. 1992. Particle nucleation and monomer partitioning in styrene O/W microemulsion poly­mer­iz­ a­ tion. Journal of Polymer Science, Part A: Polymer Chemistry 30:691–702. 61. Chern, C. S., and L. J. Wu. 2001. Microemulsion poly­mer­i­za­tion of styrene stabilized by sodium dodecyl sulfate and short-chain alcohols. Journal of Polymer Science, Part A: Polymer Chemistry 39:3199–3210.

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62. Chern, C. S., and C. W. Liu. 2000. Effect of short-chain alcohols on the oil-inwater microemulsion poly­mer­i­za­tion of styrene. Colloid and Polymer Science 278:329–36. 63. Puig, J. E., Perezluna, V. H., Perezgonzalez, M., Macias, E. R., Rodriguez, B. E., and E. W. Kaler. 1993. Comparison of oil-soluble and water-soluble initiation of styrene poly­mer­i­za­tion in a 3-component microemulsion. Colloid and Polymer Science 271:114–23. 64. Gan, L. M., Chew, C. H., and I. Lye. 1992. Styrene poly­mer­i­za­tion in oil-inwater microemulsions: Kinetics of poly­mer­i­za­tion. Makromolekulare ChemieMacromolecular Chemistry and Physics 193:1249–60. 65. Gan, L. M., Chew, C. H., Lye, I., and T. Imae. 1991. Microemulsion poly­mer­iz­ a­ tion of styrene. Polymer Bulletin 25:193–98. 66. Guo, J. S., Elaasser, M. S., and J. W. Vanderhoff. 1989. Microemulsion poly­mer­i­za­ tion of styrene. Journal of Polymer Science, Part A: Polymer Chemistry 27:691–710. 67. Trevino, M. E., Lopez, R. G., Peralta, R. D., Becerra, F., Mendizabal, E., and J. E. Puig. 1999. Polymerization of vinyl acetate in microemulsions stabilized with a mixture of dodecyltrimethylammonium bromide and didodecyldimethylammonium bromide. Polymer Bulletin 42:411–17. 68. Donescu, D., Fusulan, L., Petcu, C., Boborodea, A.-G., and D.-S. Vasilescu. 2000. Polymerization of vinyl acetate in microemulsions with methanol. Colloid and Polymer Science 278:927–35. 69. Gomez-Cisneros, M., Trevino, M. E., Peralta, R. D., Rabelero, M., Mendizabal, E., Puig, J. E., Cesteros, C., and R. G. Lopez. 2005. Surfactant concentration effects on the microemulsion poly­mer­i­za­tion of vinyl acetate. Polymer 46:2900–7. 70. Gomez-Cisneros, M., Lopez, R. G., Peralta, R. D., Cesteros, L. C., Katime, I., Mendizabal, E., and J. Puig. 2002. Polymerization of vinyl acetate in microemulsions stabilized with dodecyltrimethylammonium bromide and cetyltrimethyl­ ammonium bromide. Polymer 43:2993–99. 71. Sosa, N., Lopez, R. G., Peralta, R. D., Katime, I., Becerra, F., Mendizabal, E., and J. Puig. 1999. Electrostatic effects on the poly­mer­i­za­tion of vinyl acetate in three-component anionic microemulsions. Macromolecular Chemistry and Physics 200:2416–20. 72. O’Donnell, J., and E. W. Kaler. 2010. Kinetic model of reversible addition-fragmentation chain transfer poly­mer­i­za­tion in microemulsions. Journal of Polymer Science, Part A: Polymer Chemistry, 48(3):604–613. 73. Hermanson, K. D., Liu, S., and E. W. Kaler. 2006. Kinetic modeling of controlled living microemulsion poly­mer­i­za­tions that use reversible addition­fragmentation chain transfer. Journal of Polymer Science, Part A: Polymer Chemistry 44:6055–70. 74. Barner-Kowollik, C., Quinn, J. F., Morsley, D. R., and T. P. Davis. 2001. Model­ ing the reversible addition-fragmentation chain transfer process in cumyl ­dithiobenzoate-mediated styrene homopoly­mer­i­za­tions: Assessing rate coefficients for the addition-fragmentation equilibrium. Journal of Polymer Science, Part A: Polymer Chemistry 39:1353–65. 75. Wang, A. R., and S. P. Zhu. 2003. Modeling the reversible addition-fragmentation transfer poly­mer­i­za­tion process. Journal of Polymer Science, Part A: Polymer Chemistry 41:1553–66.

6 pH-Responsive Polymer Nanoparticles Jonathan V. M. Weaver Contents 6.1 Introduction................................................................................................. 169 6.2 pH-Responsive Polymer Micelle Particles............................................... 172 6.3 pH-Responsive Cross-Linked Micelle Particles..................................... 177 6.4 pH-Responsive Microgel Particles........................................................... 179 6.5 pH-Responsive Branched Copolymer Particles..................................... 182 6.6 Polymer Nanoparticles with pH-Responsive Surfaces.......................... 183 6.7 Applications of pH-Responsive Polymer Particles................................ 185 6.8 Outlook......................................................................................................... 189 References.............................................................................................................. 190

6.1 Introduction The field of pH-responsive poly­mer nanoparticles has stimulated growing academic and commercial interest in recent years due to significant developments in the synthetic methodologies used to make these materials and their broadening potential applicability in various applications. In this chapter, we highlight some of the most common pH-responsive polymeric particles currently accessible and highlight how advances in control over these systems has presented various new opportunities for this important class of material. The rapid development of pH-responsive poly­mer nanoparticles (PRPNs) over the past 10 years has been facilitated by the broad range of synthetic methodologies available to make these materials, such as emulsion and dispersion heterogeneous poly­mer­i­za­tions and controlled and conventional radical and ionic homogeneous poly­mer­i­za­tions. A variety of common PRPN structures are shown schematically in Figure 6.1. We restrict discussion to nanoparticles in water with submicron dimensions here although many of the principles discussed can be translated to responsive macroscopic materials at larger, micron-sized, length scales. In the course of this chapter, we will focus on the most common classes of PRPNs with fleeting mention of other less common, and in some instances less well-understood, responsive nanoparticle systems. This necessary restriction, however, emphasizes the 169

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+\GURSKLOLF K\GUDWHGIRUP

+\GURSKRELF GHK\GUDWHGIRUP pH change

pH-responsive block copolymer micelles: Section 6.2

pH change

pH-responsive cross-linked micelles: Section 6.3

pH change

pH-responsive micro(nano)gels: Section 6.4

pH change

pH-responsive branched copolymers: Section 6.5

Figure 6.1 Schematic of PRPN structures shown as idealized two-dimensional images. White components represent permanently hydrophilic domains and gray components represent pH-responsive domains.

magnitude of the rate of development of new synthetic capabilities to produce ever more elaborate organic nanoparticles. This is encouraging for the field and, of course, augurs well for stimulating further interest and broadening the potential applicability of PRPNs over the coming decade or so. Synthetic PRPNs are typically either weakly acidic or weakly basic polyelectrolytes. In aqueous solution and in their ionic form these polymers are hydrated and swollen, but dehydrate and become deswollen and compact in their neutral form. This swelling and deswelling process induces a size and volume change (Figure 6.1) and is usually reversible up to the point at

171

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which the buildup of background salt affects aqueous solubility. The reversible swelling process can be conveniently monitored using various common laboratory techniques such as nuclear magnetic resonance (NMR) to monitor the extent of hydration, light scattering to observe in situ size variations, and rheometry to measure changes in the flow of these materials. PRPNs are typically multicomponent in nature—that is, there are multiple domains within the structure. In the simplest sense PRPNs adopt “core-shell” morphologies where the core material is pH-responsive, and this domain is stabilized in aqueous solution by a permanently hydrophilic, nonresponsive, domain. The hydrophilic domain provides either steric or electrostatic stabilization when the responsive poly­mer is in its hydrophobic form similarly to the stabilization of colloidal particles. A range of highly complex morphologies are possible, some of which are shown in Figure 6.1. The precise morphologies are defined by the PRPN type and synthetic method and will be discussed throughout the chapter in the different sections. A key property of pH-responsive nanoparticles is that their response to solution pH occurs in a distinctly nonlinear fashion. Thus, PRPNs change between their swollen and deswollen states over a relatively small pH-range. This transitional window is defined by the apparent pKa (or pKb) of the acidic or basic residues of the polyelectrolyte and is governed by Equation (6.1), which is described for poly(methacrylic acid) (PMAA). Above the pKa, PMAA is in its deprotonated anionic form, and below the pKa it exists in its protonated neutral form. − +  CH 2C(CH 3 )COOH + H 2O   CH 2C(CH 3 )COO + H 3O



Ka =

[CH 2C(CH 3 )COO − ] + [H 3O+ ] [CH 2C(CH 3 )COOH]



(6.1)

The pKa of the monomer unit in the PRNP defines the transition between the swollen and deswollen states. The apparent pKa of PRPNs is also strongly influenced by poly­mer architecture. The Ka [Equation (6.1)] can be affected by the proximity of multiple acid groups in a poly­mer chain—this explains differences in pKa of monomers relative to the analogous polymers and is often referred to as the polyelectrolyte effect [1]. This effect is exacerbated in cross-linked or branched PRPN systems where high local concentrations of acid group are trapped by cross-linked or branched points. Thus, in these systems careful consideration of monomer choice and architecture can allow the swelling and deswelling transition to be adjusted over relatively large pH ranges. This presents interesting opportunities in terms of designing complex controlled delivery systems. The multiple cooperative interactions observed in responsive polymeric materials serve to amplify the effect of their response and induce dramatic and useful property changes.

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6.2 pH-Responsive Polymer Micelle Particles Conventional, “nonresponsive” poly­mer micelles are prepared from amphi­ philic copolymers, usually diblock copolymers, and are typically assembled using a cosolvent approach. This is a multistep process that involves dissolving the block copolymer in a thermodynamically good solvent for each component of the block. Providing the solvent is miscible with water (i.e., THF, low alcohols, etc.) slow addition of water causes the hydrophobic domains within the block copolymers to assemble via the hydrophobic effect. The structure of a model block copolymer micelle is shown in Figure  6.1 and involves a hydrophobic poly­mer core domain stabilized by a hydrophilic poly­mer corona or shell. The hydrodynamic diameter of the poly­mer micelle is defined by the relative block lengths, aggregation number, and the degree of solvation of the micelles. A variety of other self-assembled structures such as worm-like micelles [2], vesicles, and torroids can be assembled by simply altering the poly­mer architecture and solvent composition; however, here we will focus primarily on simple spherical micelles. In contrast to the permanently amphiphilic block copolymers, so-called responsive double hydrophilic block copolymers offer a direct assembly strategy. Double hydrophilic block copolymers typically comprise two hydrophilic poly­mer blocks where one of the blocks is permanently hydrophilic (i.e., poly[ethylene glycol], PEG) and the other is responsive or “smart.” When the hydrophilicity of the responsive block responds to changes in solution pH, these block copolymers are referred to as pH-responsive block copolymers. Using a pH-responsive diblock copolymer, comprising a weakly polybasic and permanently hydrophilic block as an example, the block copolymer can initially be dissolved in aqueous solution at acidic pH when the amine is in its protonated, cationic, and hydrophilic form. Slow addition of base to this solution deprotonates the amine group, and the block becomes increasingly hydrophobic. The hydrophobic blocks self-assemble into micellar structures, which are stabilized by the permanently hydrophilic block. Thus, the addition of base has a similar effect to water addition in cosolvent-­induced block copolymer assembly—that of slowly and selectively desolvating one block. The synthesis and pH-induced assembly of pH-responsive block copolymers is shown schematically in Figure 6.2. In 1996, Webber and co-workers reported the pH-induced micellization of a poly(2-vinylpyridine)-block-poly(ethyleneglycol) copolymer (P2VP-bPEG) synthesized by stepwise anionic poly­mer­i­za­tion [3]. This AB diblock copolymer was soluble in aqueous acidic solution as discrete unimers when the P2VP block was protonated and cationic, however it spontaneously selfassembled on raising the solution pH to neutral or basic conditions. The driving force for self-assembly was the deprotonation of the P2VP block, which became increasingly hydrophobic and phase separated from solution above pH 4.8. The covalently attached PEG block provided sufficient steric

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pH-Responsive Polymer Nanoparticles

(a) pH-responsive monomer

(b) pH-responsive homopolymer

(d) block copolymer micelle

(c) pH-responsive block copolymer

block copolymer micelle

(e) shell cross-linked micelle (amphiphilic)

shell cross-linked micelle (hydrophilic)

Figure 6.2 Schematic of the step-wise synthesis and self-assembly of core-shell poly­mer micelles. (a) Controlled poly­mer­i­za­t ion of pH-responsive monomer. (b) Controlled chain-extension poly­ mer­i­za­t ion of permanently hydrophilic poly­mer block. (c) Solution pH change to induce block copolymer self-assembly (and disassembly). (d) Selective cross-linking of the shell domain of the block copolymer micelle. (e) Solution pH change to induce shell cross-linked micelle swelling (and deswelling).

stabilization under these conditions to produce localized, as opposed to macroscopic, phase separation of the hydrophilic P2VP domains. The resulting assembled poly­mer structures comprised a dehydrated PVP “core” with a hydrophilic PEG “shell.” This process was reversible and the micelles could be disassembled back into individual unimers by addition of acid. Since this seminal work, an enormous number of advanced pH-responsive copolymers have been synthesized and shown to self-assemble into higher-order structures in aqueous solution. In the rest of this section, we emphasize some of the key developments in this area. Driven by the emergence of various controlled free radical poly­mer­i­za­tion techniques over the last two decades, the synthesis of pH-responsive block copolymers has become significantly more accessible. Techniques such as reversible addition fragmentation chain transfer (RAFT) poly­mer­i­za­tion [4,5], atom transfer radical poly­mer­i­za­tion (ATRP) [6,7], and nitroxide-­mediated poly­mer­i­za­tion (NMP) [8,9] permit the facile preparation of controlledstructure block copolymers with increasing architectural, compositional, and functional diversity. Matyjaszewski and co-workers demonstrated the first controlled ATRP of a pH-responsive monomer, 2-(dimethylamino)ethyl methacrylate (DMAEMA), in a variety of organic solvents [10]. Shortly after, Pelton and co-workers demonstrated that this monomer could be poly­mer­ ized using aqueous ATRP [11]—that is, ATRP conducted in a more convenient

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aqueous-based solution [12]. Following this the Armes group has demonstrated the synthesis of a range of weakly basic pH-responsive copoly­mers using protic ATRP—that is, solution ATRP performed in low alcohol and water solvents—and their pH-driven self-assembly in aqueous solution. In related work, Wooley and co-workers used NMP techniques to prepare a poly(acrylic acid)-block-poly(p-hydroxystyrene) (PAA-b-PpHS) diblock copolymer [13]. In contrast to the tertiary amine-based systems where the pKa of the conjugate acid forms of the amines occur over relatively narrow pH ranges, this acid-based copolymer functional polymer blocks with comprised vastly differing pKa values, which allowed the formation of PpHS-core micelles in aqueous solution from pH 4 to 10. At higher pH values (i.e., above pH 10) the entire poly­mer was water soluble, and at lower pH values (i.e., below pH 4) the copolymer was entirely hydrophobic and precipitated from solution. An intriguing extension of pH-responsive block copolymer assembly was reported by Armes and Bütün in 2000. It was shown that judicious choice of each block in a pH-responsive diblock copolymer could allow the synthesis of so-called “schizophrenic” diblock copolymers. These new materials required the synthesis of block copolymers with independent responsivity and were defined by their ability to form two distinct types of micelle, that is, micelles and reverse micelles, in aqueous solution by merely changing an external stimulus [14]. The first example of a purely pH-responsive schizophrenic copolymer concerned a zwitterionic block copolymer comprising a weak polyacid block and a weak polybases block [15] and is shown in Figure 6.3. The copolymer of 2-(diethylamino)ethyl methacrylate (DEAEMA)

(

CH CH2 )60

CH2

CH3 C C

68

O

O C OH

PVBA

PVBA-core micelles at pH 2

CH2

O

CH2 CH3CH2

N

CH2CH3

PDEA

base

base

acid

acid

PVBA-block-PDEA zwitterionic diblock copolymer insoluble at isoelectric point

PDEA-core micelles at pH 10

Figure 6.3 Schematic representation of the aqueous solution behavior of the first example of a pH-responsive “schizophrenic” diblock copolymer. (Reprinted from S. Liu and S. P. Armes, Angewandte Chemie, International Edition 41: 1413–16, 2002. With permission.)

pH-Responsive Polymer Nanoparticles

175

and 4-vinylbenzoic acid (VBA) was synthesized by a two-step ATRP process and formed PVBA-core micelles (Dh = 37 nm) with cationic PDEA shells at pH 2 and PDEAEMA-core micelles (Dh = 35 nm) with anionic PVBA shells in aqueous solution at pH 10. This PDEAEMA-b-PVBA copolymer underwent macroscopic phase separation from solution at around neutral pH due to the presence of an isoelectric point. While no realistic applications of these fascinating copolymers have currently been identified, they have undoubtedly served to stimulate substantial activity and interest in the field of responsive polymeric materials. A conceptually different approach to the formation of core-shell PRPNs is to use pH-driven reversible hydrophobic inter- or intrapolymer interactions to form the hydrophobic domains. Gohy et al. have shown that PEGblock-PMAA copolymers are molecularly soluble as discrete ­u nimers at neutral/basic solution pH; however, at low-pH hydrogen bonds form between the EG and MAA units [16]. Providing the block copolymers were asymmetric (in favor of the PEG block) an inter- and intrahydrogenbonded core was formed, which was stabilized by a shell of the excess PEG residues. Oppositely charged polyelectrolytes are known to form strong, multiple cooperative bonds and can facilitate the assembly of various highly complex polymeric structures [17,18]. In 1999, Harada and Kataoka demonstrated chain-length-dependent selectivity over polyelectrolyte interactions using oppositely charged pairs of poly(ethylene glycol)-block-poly(α,β-aspartic acid) and poly(ethylene glycol)-block-poly(L-lysine) [19]. The authors showed that mixtures of the oppositely charged polyions formed weak and illdefined assemblies when the charged blocks were asymmetric; however, when closely matched polyion block lengths were employed, highly monodisperse polyion complex-core micelles assembled, selectively. In an extension of this work, Weaver et al. have also shown that a binary mixture of PMAA with a PEG-b-PDEAEMA block copolymer can form three different types of micelle in aqueous solution by changing solution pH alone. The driving force for micellization is different in each case [20]. At basic pH, PDEAEMA-core micelles stabilized by the PEG block are formed and the anionic PMAA homopolymer is merely a noninteracting “­spectator” poly­mer in solution. On lowering the solution pH below neutral pH, the PDEAEMA residues start to protonate and form electrostatic bonds with the anionic PMAA poly­mer. Thus, electrostatically core-complexed micelles are formed that remain stabilized in solution by hydrophilic PEG shell. On further reducing the solution pH below around pH 4, the PMAA protonates and loses its anionic character. However, the neutral PMAA homopolymer hydrogen bonds with the PEG block thus forming a reverse micelle comprising a PEG/PMAA hydrogen-bonded core and a cationic PDEAEMA hydrophilic shell. An alternative strategy to reversible pH-induced poly­mer assembly is to incorporate a hydrophobic core-forming poly­mer block that can undergo

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acid-triggered degradation. This approach is particularly attractive if the hydrophobic component is a molecule which it would be desirable to deliver in a triggered manner, such as a drug. Park [21] and Kataoka [22] have independently attached doxorubicin, an anticancer drug, to micelle cores using labile hydrazone bonds, which break under acidic conditions. Heller and co-workers have used acid-labile poly(ortho esters) [23] while Fréchet and Gillies favor acetal groups [24]. In principle, covalent attachment of the drug within the PRPN is an attractive strategy since this ensures controllable encapsulation efficiencies while variation of the linking chemistry can provide optimized, or triggered, release rates that can be tuned to occur around physiological pH. In their initial studies, Fréchet and Gillies conjugated a hydrophobic model dye, Nile Red, via a sensitive cyclic acetal linker to a preformed poly(ethylene glycol)-block-poly(aspartic acid) double-hydrophilic block copolymer (Figure 6.4). The final dye-modified block copolymer was amphiphilic and thus assembled into core-shell micelles in aqueous solution. Hydrolysis of the acetal group located in the core of the micelle was shown to be pH-sensitive (faster at acidic pH), and since this bond-cleavage process produced more polar diol functionalities, the micelle simultaneously disassembled and released the encapsulated material. The use of pH-controlled hydrolytically labile bonds has more recently been extended by the same group to dendrimers [25]; the interested reader is pointed toward seminal articles for further information on dendrimers [26–28].

O

x

OH O O

H N O

MeO

OMe O

H N

y

O

x

EDC, NEt3, H2O, DMF OH O O

H N O

N H O

H N

y

O

O

Acid hydrolysis

O

x

OH O O

H N O

NH

‘Protected’ amphiphilic block copolymer

Hydrophilic block copolymer

OH NH2

O OMe

O

N H O

H N

OH OH OMe

OMe

y

NH

O

MeO

N H O

Hydrophilic block copolymer and release of 2,4,6-trimethoxybenzaldehyde

Figure 6.4 Schematic to show triggered release from poly­mer particles using acid-labile bonds.

O

pH-Responsive Polymer Nanoparticles

177

Block copolymer micelles with nonglassy, low-Tg cores are typically in dynamic equilibrium with free poly­mer, or unimers. Similarly to conventional low molar mass surfactants (i.e., sodium dodecylsulphate) the ­assembled micellar structures exist only above their critical micelle concentration, which can be determined by various techniques including fluorescence spectroscopy and surface tensiometry. While poly­mer nanoparticles are routinely touted as potential drug delivery vehicles, this inherent dynamic unimer-micelle transition unfortunately means that the particles are unstable to dilution and are thus unsuitable for these high-dilution applications.

6.3 pH-Responsive Cross-Linked Micelle Particles In 1996, Thurmond, Kowalewski, and Wooley reported the first example of covalently-stabilized block copolymer micelles or shell cross-linked micelles (SCMs) [29]. This strategy involved chemically cross-linking self-assembled block copolymer micelles thereby preventing their dilution-induced dissociation. In this first example, polystyrene-block-poly(4-vinyl pyridine) block copolymers quaternized with 4-(chloromethyl)styrene were used as building blocks to prepare conventional core-shell micelles using a THF/water cosolvent approach. Selective oligomerization of the pendant styrenic residues located in the shell domain at high dilution produced well-defined and chemically stabilized PS-core micelles that were single molecules and thus remained completely stable to dilution. The field of SCMs has now been developed into an extremely robust platform for the preparation of welldefined spherical poly­mer nanoparticles in the 10- to 100-nm diameter size range. Some key developments in the synthesis of SCMs have included the use of triblock copolymers (as opposed to diblocks) to allow cross-linking to be performed at high concentrations [30,31], the use of nontoxic physical cross-linking strategies [32] (as opposed to covalent), the formation of reversible cross-linking strategies to allow disassembly of the SCL micelles [33], and the ability to remove the core domain to produce hollow nanocages [34]. In 1999, the Armes group used pH-responsive block copolymers to prepare SCMs with tunable core hydrophilicities in aqueous solution and without recourse to cosolvents [35]. These micelles were assembled from a schizophrenic (see Section 6.2) poly[2-(dimethylamino)ethyl methacrylateblock-methacrylic acid] (PDMAEMA-b-PMAA) diblock copolymer. This copolymer was synthesized by group transfer poly­mer­i­za­tion and included a postpoly­mer­i­za­tion deprotection of poly(2-tetrahydropyranyl methacrylate) (THPMA) residues. This block copolymer could form either PMAAcore or PDMAEMA-core micelles depending on the precise sequence and

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Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

conditions of the assembly steps. Importantly, these responsive SCMs possessed cores that could be reversibly hydrated and dehydrated primarily in response to changes in the solution pH. These covalently stabilized block copolymer micelles expanded and contracted as the cores became hydrophilic and hydrophobic, respectively. Various analogous systems have since been developed [36] that have opened up potential applications as drug delivery vehicles that can target specific regions of the body and release their drug payload in response to subtle changes in the local pH [37] (see Section 6.7 for further applications). A generalized schematic of the cross-linking of block copolymer micelles is also shown in Figure 6.2. An array of shell cross-linking strategies now exist, such as carbodiimide-mediated strategies [38], oligomerization of pendant vinyl groups [29], quaternization of tertiary amines [39], Michael additions [40], inorganic condensation reactions [41], photo-cross-linking of cinnamoyl groups [42], and so-called “click” reactions such as Huisgen 1,3-dipolar cycloadditions between azides and terminal alkynes [43]. Unfortunately, the majority of cross-linking chemistries used to stabilize SCL micelles are invariably toxic and this limits their potential application, especially in vivo. A recent development has shown that polyion complexation can be used to electrostatically cross-link pH-responsive triblock copolymer micelles [32]. In this system, shown schematically in Figure  6.5, a cationic PEG113-block-[QDMAEMA33/ DMAEMA5]-block-DEAEMA50 triblock copolymer (where QDMAEMA O O

O

113

5

33

PEO stabilising corona

pH-tunable DEA core

54

O O O NaOH O O O PEO113-[QDMA33/DMA5]-DEA54 molecularly dissolved at pH 2 – – Cl– H N+ Cl H N+ Cl N+ Cationic QDMA inner-shell

+

+

+

+

DEA-core micelles at pH>7.5 27 nm diameter

+ +

+

+

O O

O

113

PEO113-NaSts34 addition at NaStS/QDMA >1.0 at 20°C Shell and core cross-linked micelles at pH <7.5 25–30 nm diameter

± ± ± ±

± ± ± ±

± ± ± ±

±

HCl

±

±

±

± ±

±

34

SO–3 Na+

Ionically cross-linked SCL micelles at pH >7.5 35–50 nm diameter

±

Figure 6.5 Schematic of the formation of shell cross-linked micelles using the ionic cross-linking strategy. (Reprinted from J. V. M. Weaver, Y. Tang, S. Liu, P. D. Iddon, R. Grigg, N. C. Billingham, S. P. Armes, R. Hunter, and S. P. Rannard, Angewandte Chemie, International Edition 43: 1389–92, 2004. With permission.)

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represents methyl-quaternized DMAEMA residues) are self-assembled into three-layer core-shell-corona micelles on increasing the solution pH from acidic to basic pH. This assembly process is entirely reversible in the absence of added polyelectrolyte; however, on addition of a PEG113-block-poly(sodium 4-styrenesulphonate)34 (PEO113-NaStS34) anionic diblock copolymer to the micelle at pH 10, polyion complexation in the central micelle domain occurred that effectively cross-linked the cationic micelles. Interestingly, the PDEAEMA cores remained responsive, and on reducing the solution pH of the electrostatically cross-linked micelles below the pKa of the conjugate acid form of the PDEAEMA residues, additional core cross-linking occurred as the PDEAEMA protonated, providing an excess of the PEO113NaStS34 was employed. These ionically stabilized SCMs were stable to relatively high electrolyte concentration, which, in conjunction with the benign cross-linking, implies that they could be suitable candidates for drug delivery applications.

6.4 pH-Responsive Microgel Particles Microgel particles [44] are cross-linked colloidal polymeric (nano)particles that swell in thermodynamically good solvents [45]. As such, microgels exist in solution in two states: as “hard,” desolvated and compact latexes, or as “soft,” solvated and swollen microgels as depicted in Figure  6.1. A proportionately large subset of these materials are pH-responsive microgels that exhibit a latex-to-microgel transition that is controlled by solution pH. The pH-induced transition between latex and microgel can be conveniently followed by standard techniques such as light scattering as a function of solution pH. A representative transition is shown in Figure  6.6c for a range of PEGMA-stabilized poly(2-vinylpyridine) microgels of different sizes [46]. Transitions such as these are often accompanied by a change in appearance from turbid, desolvated latexes to opaque, solvated microgels. The extent of swelling is defined by factors including the cross-linking density, nature of the cross-linking, presence of comonomers, and ionic strength. The overall degree of swelling is dictated by mobile counterions within the microgel that influence the internal osmotic pressure, and this is balanced by the internal electrostatic repulsion [47]. The kinetics of pH-responsive microgel swelling has been studied [46,48] following Tanaka’s work on macroscopic gels [49,50]. The precise nature of the swelling is an important component in defining the properties and potential application of these pH-responsive microgels but is relatively poorly understood. Most theories of microgel swelling assume a uniform cross-linking density; however, in reality this is unlikely to be the

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Figure 6.6 (a) Size distribution and (b) scanning electron microscopy images of a series of PEGMA-stabilized poly(2-vinylpyridine) particles in their latex form. (c) Mean hydrodynamic diameters as a function of solution pH to show the latex-to-microgel transition. (Reprinted from D. Dupin, S. Fujii, S. P. Armes, S. Reeve, and S. M. Baxter, Langmuir 22: 3381–87, 2006. With permission.)

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case for most systems. A more likely scenario is that cross-linking density decreases from the core of the microgel particles, and this hypothesis has been supported for poly(methyl methacrylate) microgel particles dispersed in benzene that demonstrated a distinctly inhomogeneous cross-linking density [51]. Flory’s theories concerning network swelling in organic solvents [52] are unfortunately inadequate for aqueous pH-responsive microgel systems with heterogeneous internal structures. However, Hoare and Mclean have recently developed a more suitable kinetic model to semiquantitatively predict the spatial distribution of functionality in microgel systems [53]. pH-responsive microgels are typically comprised of weakly ionic monomers where the swollen microgel phase is induced by electrostatic repulsion, and inherent hydrophilicity increases in the monomer units in their ionic state. The main classes include alkali-swellable microgels based on (meth)acrylic acid [54,55], acid-swellable microgels based on basic monomers such as vinyl pyridines [48], and tertiary amine methacrylates and N-isopropylacrylamide-based microgels with acidic or basic comonomers. They are commonly synthesized by precipitation [56] or inverse emulsion poly­mer­i­za­tion [57]. The microgel diameter is strongly influenced by the synthetic approach employed, and microgels have been reported with dimensions ranging from around 10 nm to several hundreds of microns. pH-responsive nanogels share many of the properties of microgels, however they have significantly smaller hydrodynamic diameters. They can be synthesized via emulsion poly­mer­i­za­tion, miniemulsion poly­mer­i­za­tion, or postmodification of self-assembled copolymers. Their smaller dimensions mean their surface-to-volume ratios are significantly higher than microgels, and these sizes are potentially more viable for biotechnology applications. Nagasaki’s group has prepared pH-responsive nanogels based on DEAEMA in the 50- to 350-nm size range [58]. These nanogels were synthesized via emulsion poly­mer­i­za­tion using a specially designed heterotelechelic PEGbased macromonomer as steric stabilizer. These nanogels exhibited a sharp volume transition around neutral pH, which was defined by the apparent pKa of the PDEAEMA residues. Such nanogels are postulated to have useful properties for bio-delivery such as the enhancement of the endosomal escape. In fact, it has been suggested that the buildup of osmotic pressure and endosomal protonation from polyelectrolyte nanogels may destabilize and disrupt endosomes [59,60]. Yusa’s group has developed a self-assembly based strategy to form welldefined pH-responsive nanogels based on DEAEMA [61]. A poly(ethylene glycol)-block-poly(DEAEMA-co-2-cinnamoyloxyethyl acrylate) statistical diblock copolymer synthesized by RAFT poly­mer­i­za­tion was self-assembled into PDEAEMA-core micelles using a solution pH-switch followed by core cross-linking of the cinnamoyl groups by photo-dimerization yielding a nanogel. These particles had smaller hydrodynamic diameters of around 25–30 nm at pH 10.

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6.5 pH-Responsive Branched Copolymer Particles The preparation of architecturally and compositionally controlled branched copolymers has been a perennial synthetic poly­mer challenge. They remain an active research area since branched polymers offer numerous different properties to linear polymers. For example, branched polymers have lower viscosities, higher solubilities, and higher concentrations of end groups compared to analogous linear polymers—each of which can be desirable for specific applications. The most common synthetic approach to branched copolymers has been step-growth poly­mer­i­za­tion [62]; however, there is a strong commercial drive to produce branching technologies that can be applied to vinyl monomers, and in pursuit of this goal Fréchet and co-workers developed self-condensing vinyl poly­mer­i­za­tion [63–65]. This strategy uses a multifunctional vinyl monomer that can undergo both conventional addition poly­mer­i­za­tion while also initiating new “branched” chains. While this technique is relevant to large classes of vinyl monomers, it remains restrictive by requiring specially designed branching monomers. In 2000, Sherrington’s group reported a generic, efficient, and scaleable route to the preparation of branched copolymers of essentially any vinyl monomer [66]. Their strategy, often referred to as the Strathclyde approach to branched polymers, uses a conventional divinyl cross-linking monomer to introduce branching points during a standard free radical poly­mer­i­za­tion. Providing sufficient chain transfer agent is employed, relative to the concentration of the multifunctional “branching monomer,” completely soluble branched poly­mer is produced in high yield and without recourse to tailor-made reactants. More recently it has been shown that controlled poly­mer­i­za­tion processes can be used to prevent gelation by targeting relatively low primary chain lengths [69]. While the mechanism of branching appears to alter slightly depending on the poly­mer­i­za­tion technique employed [67,68], in general, providing less than one branching monomer is employed, highly branched, soluble poly­ mer with controlled primary chain lengths is possible using this technique [69]. It should be emphasized that above this critical branching level, these structures transform from soluble branched polymers to “gel-like” materials, which will not be discussed in any detail here [70,71]. The Strathclyde approach to branched polymers has recently been exploited by groups at Liverpool as a platform to synthesize novel core-shell PRPNs, similar to micelles and shell cross-linked micelles; however, unlike these materials, they are prepared in one pot and do not require time-­consuming assembly and toxic cross-linking steps. One example of their synthesis involves the statistical conventional free radical branching poly­mer­i­za­ tion of the common pH-responsive tertiary amine methacrylate monomer, DEAEMA, with a permanently hydrophilic macromonomer, PEG22MA, in the presence of the branching monomer ethyleneglycol dimethacrylate, EGDMA, and a chain transfer agent that prevents gelation. A schematic of

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DDT O N DEA

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Figure 6.7 Schematic of the one-step synthesis of PRPNs via the Strathclyde approach. (Reprinted from J. V. M. Weaver, R. T. Williams, B. J. L. Royles, P. H. Findlay, A. I. Cooper, and S. P. Rannard, Soft Matter 4: 985–92, 2008. With permission.).

the synthesis is shown in Figure 6.7. There is a range of different poly­mer architectures with controllable compositions and chain ends that are defined by the choice of chain transfer agent. These branched copolymers can be dissolved molecularly in acidic aqueous solution to give cationic and highly hydrated structures; however, on addition of base, they contract to give core-shell structures similar to pH-responsive micelles or SCMs [95] (see Sections 6.2 and 6.3, respectively). Interestingly, although the free radical poly­mer­i­za­tion process is “uncontrolled” in terms of the molecular weight and polydispersity of primary chains, the resulting branched copolymer nanoparticles that exist in basic solution have relatively narrow particle size distributions as determined by dynamic light scattering and transmission electron microscopy (TEM). In principle, the core, shell, and chain end functionality can all be readily varied by judicious choice of monofunctional monomers, branching monomers, and chain transfer agent, and thus various applications are predicted from this new class of viable particles. These pH-responsive branched copolymer particles have some structural similarity to star polymers—that is, polymers synthesized by propagating several linear chains from a single, multifunctional core initiator [72,73]—however, discussion of this class of material is beyond the scope of this chapter.

6.6 Polymer Nanoparticles with pH-Responsive Surfaces The majority of PRPNs described so far comprise cores that respond to solution pH; however, surface or shell responsivity can also be highly desirable for certain systems. In these examples, however, the shell responsivity tends to produce a disperse-to-agglomerated nanoparticle transition as the shell functionality reversibly switches between being capable of stabilizing the core to having insufficient hydrophilicity to allow solubilization. A prevalent example includes surface-functionalized poly­mer latexes—that is, insoluble

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(or hydrophobic) poly­mer particles with surfaces that enable their efficient dispersion and stabilization in water. Conventional latexes are typically synthesized by techniques including emulsion or dispersion poly­mer­i­za­tion and use conventional surfactants to provide either electrostatic or steric stability. An alternative synthetic approach involves substituting the surfactant with a steric stabilizer such as a hydrophilic poly­mer. In this instance, the poly­mer is chemically or physically incorporated onto the latex surface during the poly­mer­i­za­tion via either the pendant reactive functionality or presence of hydrophobic domains, respectively. If the poly­mer stabilizer comprises weak polyacid or polybase, then the surfaces of the latex are effectively functionalized with a responsive poly­mer that can undergo a transition from charged and hydrophilic to neutral and hydrophobic. For example, well-defined polystyrene latexes can be prepared via alcoholic dispersion poly­mer­i­za­tion using a PDMAEMA-block-poly(alykyl methacrylate) copolymer as a physically adsorbed steric stabilizer [74]. Under optimized conditions, the latex size can be controlled by varying the concentration and molar mass of the hydrophilic stabilizer. Some applications of surface-responsive latexes are described in Section 6.7. Vincent and co-workers have exploited the pH-responsive surfaces of near-monodisperse poly­mer latexes to assemble these colloids into one­dimensional “microrods” using temporary electric dipoles induced by an applied ac electric field [75]. The particles are prevented from coming into direct contact by extensive electrostatic repulsion; however, the authors demonstrated that these transient structures could be “glued” together using a smaller, oppositely charged microgel particle thus maintaining the string structures after removing the external field. The observed periodicity in the particle separations of these assemblies in combination with the reversibility of the system suggests that these materials could be used as sensing devices where diffraction of white light by the ordered spacings could produce different colors in response to control of surface charges using solution pH. Wanless and co-workers investigated the interfacial adsorption behavior of pH-responsive diblock copolymers with responsive cores and shells on mica: a model flat, solid, and charged surface [76]. Weakly charged pH-responsive (PDMAEMA-stat-PQDMAEMA)-block-PDEAEMA diblock copolymers were shown not only to controllably self-assemble from solvated unimers to core-shell micelles in aqueous solution in response to increasing the solution pH from acidic to basic, but also to self-organize into ordered monolayertype films as judged by wet atomic force microscopy (AFM). Interestingly, micelle dissociation and desorption did not occur to any appreciable extent on reducing the solution pH, presumably due to the low levels of permanent cationic functionality present on the micelle surfaces. These results augur well for the organization of various polymeric species and encapsulants on surfaces in multiple dimensions.

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6.7 Applications of pH-Responsive Polymer Particles The self-assembly of pH-responsive block copolymers offers a number of opportunities because of their controllable and reversible nanoparticleunimer transition. Indeed this nonlinear transition from highly soluble and chain expanded to collapsed core is ideal for the controlled uptake and release of actives, and it is not surprising that perhaps the most widely mooted application of block copolymer micelles is as drug delivery vehicles [77]. For example, PRPNs capable of release of actives at acidic pH could have application in environments where local pH variances could be used as convenient triggers such as in tumor tissue or endosomic or lysosomic cellular compartments. Moreover their sizes, which are typically around 20–100 nm, are sufficiently small to avoid uptake by the reticuloendothelial system and also prevent rapid renal exclusion [78]. Of course, a prerequisite for these systems is the use of biocompatible and approved polymers and starting materials—concepts that are often ignored in favor of demonstrating viability. In terms of intrinsic physiological release of encapsulated drugs from PRPNs within the body, an important consideration is the presence and nature of inherent pH variation. The most widely suggested potential application of pH-responsive SCMs in the literature is as biological encapsulation and delivery vehicles for in vivo administration of drug payloads. Wooley and co-workers have investigated in detail the cross-linking of acidic shell functionality using diamines, thus producing SCMs with pH-responsive surfaces. The same group has used the responsive and functional surfaces of these SCMs as chemical handles onto which various biologically relevant motifs can be attached [79]. In an alternative approach, they prepared biotin-functionalized SCMs from biotin-labeled poly(acrylic acid)-block-poly(methyl acrylate) copolymers and also studied the competitive binding of these PRPNs with avidin [80]. Liu and co-­workers have prepared SCMs from α-aldehyde-functionalized poly(DMAEMAblock-DEAEMA) copolymers with both pH-responsive cores and shells [81]. The free surface aldehyde groups permitted their subsequent bioconjugation with lysozyme via the formation of Schiff bases. The McCormick group has shown that cystamine cross-linked poly(ethylene glycol)-block-poly(N,Ndimethylacrylamide/N-acryloxysuccinimide)-block-poly(N-isopropylacrylamide) triblock copolymers can retard the release of hydrophobic drugs from the core compared to un-cross-linked micelles [33]. While these SCL micelles are not truly pH-responsive, but rather thermally sensitive, it demonstrates the added benefit of cross-linking on release. Moreover, since these SCL micelles were cross-linked using cystamine, they could be readily un-cross-linked by cleavage of the disulfide bond using either tris(2-carboxyethyl)phosphine or dithiothreitol. This further supports their proposed applicability in terms

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of allowing their disassembly and thus efficient renal exclusion after use. Wooley and co-workers have prepared pH-responsive SCL micelles with hydrolytically labile cross-linkers that also bear UV-vis active components to detect SCL cleavage events during pH-induced destabilization [82]. The authors observed accelerated degradation of the cross-links at around lysosomal pH, which provides further corroboration that these diverse systems can, in principle, be optimized for specific bio-applications. An alternative potential application of PRPNs is as nanoreactors for chemical transformations and catalysis. O’Reilly points out in a recent review article on this subject [37] that micellar catalysis is already well explored, and provides examples of reaction rate enhancement and retardation; however, these systems typically use unstabilized, that is, un-cross-linked, conventional surfactant micelles and are thus inherently less robust and optimized than many PRPN systems highlighted in this chapter. To demonstrate this point, three-layer pH-responsive SCL micelles assembled and cross-linked from a poly(ethylene oxide)-block-poly(glycerol monomethacrylate)-blockpoly(2-diethylaminoethyl methacrylate) triblock copolymer have been used as nanoreactors for the preparation of gold nanoparticles [40]. Having prepared the SCM with hydrophobic PDEAEMA cores at basic solution pH, addition of an HAuCl4 solution protonated the tertiary amine groups thereby electrostatically binding the AuCl4-counterion selectively within the SCL core domain. Reduction of the gold salt by NaBH4 produced gold nanoparticles, presumably templated by the core, that exhibited excellent long-term colloid stability. Shell cross-linking is vital to this application as protonation of the PDEAEMA residues in the analogous un-cross-linked poly­mer micelle resulted in dissociation of the micelle back into individual unimeric chains. Several potential applications of responsive microgels have been postulated and are currently being investigated such as drug encapsulation and delivery, regenerative medicine, and templates for chemical syntheses [83,84]. Drug delivery is particularly well suited to microgel systems since they can be readily prepared to have sufficient “stealth” properties to successfully evade the immune system. Fréchet and co-workers have used labile acetalbased cross-linkers (see Section 6.2) as a pH-triggered release mechanism [85]. This approach has been further developed to produce biocompatible poly(2-hydroxyethyl methacrylate) (PHEMA) microgels that could release bovine serum albumin payloads over several hours. More importantly, the encapsulation and release process did not denature the protein. The mechanical strength of partially pH-responsive microgels has recently been exploited by Saunders and co-workers to aid degenerated intervertebral disks—a common global cause of back pain [86,87]. In this process, poly(methacrylic acid)-based microgel dispersions are delivered to affected areas by injection. A fluid-to-gel transition occurs in vivo as the pH increases above ~pH 6. The use of ionic pH-responsive microgels is crucial for this application since the charge concentration generated when the microgels swell results in significant swelling pressures.

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Surface-responsive poly­mer latexes have recently been exploited in the context of responsive or reversible interfacial stabilization of biphasic materials. Indeed, various PRPNs have been investigated because of their ability to controllably and reversibly adsorb at interfaces. Polystyrene latexes with pHresponsive PDMAEMA surfaces have been used as particulate emulsifiers for the preparation of oil-in-water emulsions when the PDMAEMA surface is in its neutral, and more hydrophobic, form [88]. Addition of acid to the emulsion causes the PDMAEMA residues to protonate and become cationic and hydrophilic, which induces desorption from the oil/water droplet interface. Consequently this pH switch behaves as a suitable trigger for rapid demulsification, or phase separation, which has various potential applications, not least in tertiary oil recovery where demulsification can be a key step in the recovery of the oil. More recently pH-responsive branched copolymers (see Section 6.5) based on PEGMA and DEAEMA have also been shown to efficiently stabilize relatively small emulsion droplets at basic solution pH and at relatively low poly­mer concentrations [89]. Importantly, judicious control of the degree of branching and the nature of the branching monomer in the PRPN allowed unprecedented control over the pH-responsive properties of the resulting emulsion droplets. Consequently responsive emulsions were prepared that could either remain completely stable (in which case the surface charge changes from neutral to cationic), partially demulsify, or completely demulsify by subtle variation of the branches’ length and chain end properties on reduction of the solution pH. This implies that these responsive emulsion systems could be used as controllable release devices for the delivery of substantial hydrophobic payloads. In addition to the ability to “make or break” emulsions, carefully designed functional branched copolymer particles have also been used to assemble and disassemble emulsion droplets in a process referred to as emulsion engineering [90,96]. Branched copolymers of PMAA and PEGMA with hydrophobic dodecane chain ends have been synthesized using the Strathclyde branching technique (see Section 6.5). The architecture and composition of these copolymers were specifically chosen so as to provide: (i) strong and multiple points of adhesion of the poly­mer onto the droplet surface via the dodecane chain ends, and (ii) simultaneous steric and electrostatic stabilization of the droplets at basic solution. On lowering the solution pH of the emulsion droplets below ~pH 4, the PMAA residues protonated and lost their ability to charge-stabilize the emulsion droplets. In addition, the PMAA residues in their neutral state formed hydrogen bonds with the ethylene glycol units of the PEGMA and thus secondary bonding cross-links were established between functionality on the emulsion droplet surfaces. The reversible transition between free-flowing emulsion dispersion at basic pH and the assembled emulsion droplets at acidic pH is shown in Figure  6.8a–b. The extensive hydrogen-bonded networks formed between surface-functionalized droplets at acidic pH can be used to kinetically trap the droplets in precise morphologies and with significant degrees of complexity, as shown

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Figure 6.8 (a–b) Schematic representation of the reversible assembly and disassembly of emulsion droplets—the emulsion engineering process [90]. (c–g) Images of various engineered emulsion structures. (h–i) Images of morphologically controlled engineered emulsions at increasing resolution. (j) Base-triggered disassembly of engineered emulsion fibers. (Reprinted from J. V. M. Weaver, S. P. Rannard, and A. I Cooper, Angewandte Chemie International Edition 48: 2131–34, 2009. With permission.)

in Figure 6.8c–i. However, since the emulsion droplet surface functionality is responsive to solution pH, the engineered emulsions can be readily disassembled into conventional, disperse, and free-flowing emulsions by raising the solution pH (Figure 6.8j). The ability to reversibly assemble emulsion droplets into controlled structure arrays without destabilizing the droplets has potential in advanced encapsulation and delivery applications where the controlled release and isolation of actives could be advantageous. In a process somewhat analogous to the stabilization of liquid-liquid interfaces in emulsions, under certain conditions solid colloidal particles can

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stabilize biphasic mixtures of air and water [91]. Binks and Murakami have shown that either air-in-water foams or water-in-air materials, dubbed “dry water,” can be stabilized by judicious control of the surface hydrophobicity of silica colloids [92]. The different phases can be accessed by varying the nature of the liquid/air phases and the contact angle of the particle at the interface. Foams and dry water have both existing and potential applications, and thus their extension to more complex, responsive systems stands to make substantial impact in areas such as home and personal care products, foods, separations, and the synthesis of advanced materials. The groups of Binks and Armes have shown that poly­mer latexes with poly(acrylic acid) surfaces can stabilize foams efficiently at low pH when the latex is in its less hydrophilic, neutral form [93]. Defoaming could be triggered by simply increasing the pH of the foam. This pH increase deprotonated the PAA residues and produced anionic, colloidally stable latexes that desorbed from the air-water interface. A similar concept is described in a recent manuscript by Dupin and Armes, who show that “liquid marbles”—millimeter-sized water droplets stabilized by hydrophobic particulates—can be formed using poly­mer latexes with pH-responsive PDEAEMA-surfaces at high pH when the PDEAEMA is in its neutral, hydrophobic form [94]. The liquid marbles remain intact on being placed on water at basic pH or solid surfaces for several hours at 20ºC. The authors postulate that instabilities over longer time frames are caused by water evaporation. In the case of the liquid marbles on water, reduction of the solution pH causes the structures to rapidly dissociate as the PDEAEMA residues are protonated and become cationic and hydrophilic. The authors demonstrate the encapsulation and triggered release of hydrophilic dyes within the liquid marbles, which suggests their potential application in microencapsulation and biotechnology processes.

6.8 Outlook In this chapter it has been possible to cover only a few of the most pertinent concepts in the rapidly progressing, expanding, and diversifying field of pH-responsive poly­mer nanoparticles. A number of excellent reviews have been cited throughout, which the interested reader is directed to for further information. The field of pH-responsive poly­mer particles is continuing to expand rapidly and broaden its applicability in ever more diverse areas of materials science and beyond. However, continued development is strongly reliant on two key factors: first, the development of new and more advanced synthetic routes to the preparation of responsive materials, and second, the identification and optimization of applications for these complex systems. These two factors should be inherently linked, especially where the synthesis stimulates further applications research. In this chapter, a number

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of direct and specific applications of PRPNs have been described, such as the use of pH-responsive particles for drug delivery applications and the use of pH-responsive microgels to address degenerated intervertebral disks (see Section 6.7); however, their broader scope should not be underestimated and may prove to be a fruitful application of these materials over the next few decades. PRPNs are incredibly versatile materials and their synthesis is fundamentally well understood and can be trivial. There are a number of examples of using PRPNs to effectively impart their responsivity onto other materials, such as in the case of emulsion engineering (see Section 6.7), and this is a clear opportunity to maximize the potential exploitation of these fascinating classes of materials.

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7 Smart Thermo-Responsive Nanoparticles Peng Tian and Qinglin Wu Contents 7.1 Introduction to Thermo-Responsive Polymer and Nanoparticles...... 197 7.1.1 Thermo-Responsive Polymer........................................................ 197 7.1.2 Phase Transition of Thermo-Responsive Polymer..................... 198 7.1.3 Thermo-Responsive PNIPAAm Nanoparticles.......................... 199 7.2 Thermo-Responsive Nanoparticle Synthesis and Characterization.......................................................................................... 200 7.3 Thermo-Responsive Nanoparticle Size Control..................................... 205 7.4 Thermo-Responsive Nanoparticle Applications.................................... 208 7.5 Conclusions and Future Development.................................................... 214 References.............................................................................................................. 215

7.1 Introduction to Thermo-Responsive Polymer and Nanoparticles 7.1.1 Thermo-Responsive Polymer Stimuli-responsive polymers, also called smart materials or intellectual materials, show an interesting property change behavior to external stimulus. These external stimuli, including pH [1,2], temperature [3–6], light [7,8], magnetic and electric field [9,10], and solvent/salt [11,12], result in a change of the polymers in conformation, solubility, and hydrophilic/hydrophobic balance. The property change of the poly­mer to external environmental condition change can be linear or nonlinear. The nonlinear change attracts more scientific interest since a small stimulus change may result in a large response. Based on their response to different stimuli, stimuli-responsive polymers can be classified into several categories: thermo-responsive poly­mer, pH-responsive poly­mer, magnetic-responsive poly­mer, and double-/multiresponsive poly­mer due to their response to a combination of two or more stimuli. Furthermore, based on different structures of stimuli-responsive polymers, there are linear polymers, cross-linked polymers (hydrogel), micelles, core-shell particles, and poly­mer-protein conjugates. Stimuli-responsive 197

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polymers have shown applications in many fields, such as drug encapsulation and delivery [13–17], diagnostics [18], sensing [19,20], fabrication of photonic crystals [21,22], nanoparticle templates [23,24], and separation and purification technologies [25,26]. Among the stimuli-responsive polymers, thermo-responsive polymers are one of the most widely studied polymers because of their temperature-sensitive properties [27,28]. 7.1.2 Phase Transition of Thermo-Responsive Polymer Thermo-responsive polymers undergo phase transition in a suitable solvent at certain temperature. The volume phase transition behavior of thermoresponsive poly­mer is an imbalance between repulsive and attractive forces acting in the poly­mer [29], such as hydrogen bonding, Van der Waals inter­ action, attractive ionic interaction, and hydrophobic interaction. This volume phase transition results in a sudden change of solubility of the poly­mer in the solvent. When the temperature is increased above the lower critical solution temperature (LCST) or decreased below the upper critical solution temperature (UCST), a phase separation or the coil-to-globule transition behavior is observed. When the poly­mer is immersed in a solvent like aqueous solution, negative entropy of mixing is formed. As temperature changes, the forces between the hydrophilic and hydrophobic parts of the poly­mer chain and water molecule, such as hydrogen bonding, come to a balance, and the poly­mer changes from transparent to opaque [30–32]. Compared to the poly­ mer-poly­mer and water-water interactions, the hydrogen bonding between the poly­mer and water becomes weak and unfavorable at LCST/UCST; thus, a transition occurs because the hydrated hydrophilic macromolecule dehydrates quickly [33]. Polymers that undergo LCST behavior include poly(N-isopropylacrylamide) (PNIPAAm or PNIPAM) [31,32,34], polymers of N-substituted acrylamides [35,36], poly(N,N-diethylacrylamide) (PDEAM) [37], poly(ethylene oxide)(PEO) [38], poly(methyl vinyl ether) (PMVE) [39,40], poly(N-vinylcaprolactam) (PNVCL) [41,42], and copolymers based on these polymers. Polymers that undergo UCST behavior include copolymers of acrylamide (PAAm) and acrylic acid (PAAc) interpenetrating poly­mer network (IPN) [43–46], etc. The LCST/UCST of polymers can be controlled by polymerizing copolymers of the aforementioned polymers with other hydrophilic or hydrophobic polymers. Furthermore, copolymers of the previously mentioned polymers and polymers having other stimuli-responsive behavior, such as pH or magnetic, have the capacity of double or multiresponse to environmental change [44]. For example, core/shell poly(N-isopropylacrylamide-co-glycidyl methacrylate) (PNIPAAm-GMA) particles can be synthesized with emulsion copoly­ mer­i­za­tion [45]. Thiol compounds are then used to modify the template particles for incorporating ionic groups such as amino, suffonate, or carboxyl groups and in situ synthesis of magnetic nanoparticles. Another example is

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Bhattacharya’s work on ferromagnetic nanoparticles, which show responsive ability to temperature, pH, and magnetic field [46]. Among thermo-responsive polymers, PNIPAAm- and PNIPAAm-based copolymers are well known and attract the most significant scientific research attention because they show a low critical phase separation from water at an LCST of approximately 30–34°C [35]. Unlike PDEAM, which has an LCST around 32–34°C as well [37], the LCST of PNIPAAm is irrelevant to the tacticity of the poly­mer and independent of molecule weight and concentration [47]. The close-to-human-body-temperature LCST and the biocompatibility property of PNIPAAm make it an ideal poly­mer for controlled drug delivery. We will mainly focus our discussion of thermo-responsive poly­mer on PNIPAAm and its copolymers. 7.1.3 Thermo-Responsive PNIPAAm Nanoparticles Although extensive work on thermo-responsive polymers based on PNIPAAm has been done in the past 20 years, and some promising results of the polymeric self-aggregates as drug carriers have been reported, study of thermo-responsive polymeric nanoparticles and nanogels is still a new field that attracts research and development interest just in recent years. The synthesis and characterization of the PNIPAAm-based copolymer nano­particles still need much research before they can be used for drug delivery, and how the nanoscale behavior of the particles affects the delivery efficiency needs to be thoroughly understood. Beside the thermo-responsive behavior as their macro counterpart, the micro- or nanoscopic dimension of thermo-responsive nanoparticles introduces more advantages [48–56]. For example, with their much smaller size, it is easier for thermo-responsive nanoparticles to access areas of the human body where macroscopic networks cannot reach. It is of significant importance for therapeutic drugs to be delivered to targeted cells. Besides, the larger surface area of nanoparticles has more benefit compared with macroscopic ones when conjugating with siRNAs and peptides, thus resulting in better in vivo treatment performance. Furthermore, thermo-responsive nanoparticles have the capacity of much rapid response to temperature change, which provides a broader choice for many applications. Some of the PNIPAAm-based thermo-responsive nanoparticles reported include poly(acrylonitrile-co-N-isopropylacrylamide) (p[AN-co-NIPAAM]), poly(N-isopropylacrylamide)-b-poly(ε-caprolactone), poly(NIPAAm-co-N-[2-hydroxypropyl] methacrylamide-dilactate) (poly[NIPAAm-co-HPMAm-dilactate]), poly(ethylene oxide)-b-poly(Nisopropylacrylamide) (PEO-b-PNIPAAm), and poly(N-isopropylacrylamide-co-N,N-dimethylacrylamide-co-10-undecenoic acid) (P[NIPAAm-co-DMAAm-co-UA]) [57–61]. For thermo-responsive poly­ mer nanoparticles and hydrogel, it is difficult to control the stability and size of the particles. In the following sections we summarize the research work

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on the PNIPAAm-based block copolymers as temperature-sensitive polymeric nanoparticles. It is noted that the “nanoparticles” here do not strictly limit to particles with diameter less than 100 nm.

7.2 Thermo-Responsive Nanoparticle Synthesis and Characterization By introducing hydrophilic or hydrophobic groups into PNIPAAm poly­mer, the LCST of the thermo-responsive nanoparticles can be controlled to some extent, as well as introducing other stimuli-responsive properties. Moreover, chemical or physical cross-linkers can help the poly­mer to form a network structure (i.e., the hydrogel), which increases the structure stability and hinders poly­mer chains from dissolving into aqueous solution, thus changing the LCST of the nanoparticles. For example, by adding a small amount of cross-linking agents with the poly­mer­i­za­tion, such as the methylene­ Bisacrylamide (BisAAm), cross-linked PNIPAAm hydrogels could be obtained. These hydrogels also show a volume phase transition at the LCST. Similar to the linear ones, when the temperature is increased above the LCST, the cross-linked PNIPAAm collapses substantially [62–64]. The different structures of the linear and cross-linked PNIPAAm give different levels of hydrogen bonds between the poly­mer chains and water, and thus lead to different phase transition behaviors, although the process is similar. At a temperature above the LCST, the hydrogel gives out water in the pore and becomes stiff and opaque. As the temperature is decreased below the LCST, the PNIPAAm hydrogel reswells in water, but at a slower rate than the initial deswelling process [62]. The hydrogel tends to shrink rapidly at first and then deswell slowly, as shown by Okano and co-workers [65,66]. Approaches for developing poly­mer nanoparticles include, but are not limited to, cross-linking of block copolymer micelles in solution, surface-­initiated poly­mer­i­za­tion of monomers, layer-by-layer adsorption of electrolyte polymers on templates, etc. [67–71]. The achievement of thermo-responsive nanoparticles and nanogels is often fulfilled by emulsion poly­mer­i­za­tion and precipitation poly­mer­i­za­tion methods [72,73], or by physical-chemical technology such as particle replication in nonwetting templates (PRINT) [74,75]. In both cases, the control of particle size, shape, particle size distribution (PSD), particle stability, the responsive time for temperature change, and poly­mer composition is vitally important, as it affects the LCST behavior of the nanoparticles, thus affecting their final applications. Fernandez et al. studied thermo-responsive nanostructured PNIPAAm hydrogel synthesized by a two-stage process [76]. First, slightly cross-linked PNIPAAm nanoparticles were fabricated via microemulsion poly­mer­i­za­tion.

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Second, the developed particles were cross-linked with N,N-methylene-bisacrylamide (BisAAm) in aqueous solution after drying, cleaning, and dispersing to form nanostructured hydrogel. It is shown that z-average diameter was 29.5 nm for the nanoparticles at first stage. Larger equilibrium water uptake, faster responsive behavior, and larger Young moduli were found for the nanogels compared with their macro counterparts, and a similar LCST of 34°C was shown. Sahiner and co-workers reported poly(acrylonitrile-co-N-isopropylacrylamide) (p[AN-co-NIPAAm]) hydrogel nanoparticles synthesized by microemulsion poly­mer­i­za­tion [77]. The nanoparticle has a core-shell structure with poly(N-isopropylacrylamide) as the shell and poly(acrylonitrile) (p(AN)) as the hydrophobic core. By adjusting the reaction conditions, highly mono­ dispersed nanoparticles with particle size of range 50–150 nm can be obtained. The synthesized nanoparticles were characterized with transmission electron microscopy (TEM), scanning electron microscopy (SEM), and dynamic light scattering (DLS) for morphology and particle size, and tested with release of a model drug, propranolol (PPL). The amidoximation of the hydrophobic core material helped increase the loading/release capacity by two times due to tunability in the hydrophobicity/hydrophilicity balance of the composite nanoparticle. Thermo-sensitive poly(N-isopropylacrylamide)-b-poly(ε-caprolactone) (PNIPAAm-CL) with different PCL block lengths was synthesized by hydroxyterminated PNIPAAm-initiated ring opening poly­mer­i­za­tion of ε-caprolactone by Choi et al. [78]. In their study, self-assembled polymeric nanoparticles were formed in aqueous solution with PNIPAAm as the shell. They showed that PCL block length had great effect on particle sizes as well as critical aggregation concentrations. Drug release tests with a model drug of clonazepam (CNZ) demonstrated that the thermo-sensitive hydrogel layer worked as an additional diffusion barrier and enhanced sustained drug release patterns. Another example is the core-shell nanoparticles of poly(ethylene oxide)-bpoly(Nisopropylacrylamide) (PEO-b-PNIPAAm) with N,N-bis(acryloylcysta­ mine) (BAC) slightly cross-linked, reported by Zeng and co-workers [79]. DLS and fluorescence measurements indicated the nanoparticle size was less than 150 nm with BAC content ranging from 0.75 wt% to 0.2 wt% of the mass of NIPAAm. Stability study showed that with 0.5 wt% BAC, the nanoparticles were stable up to two weeks at room temperature. Atom transfer radical poly­mer­i­za­tion (ATRP) was used to synthesize PEG-bPNIPAAm block copolymer nanoparticles with N,N’-ethylenebisacrylamide as cross-linker in different solvent [80]. It is shown that compositions of the mixed solvent have an effect on the final particle size. For example, hydrogel particles prepared in H2O and H2O/THF solvents had different particle sizes (i.e., 67.5 and 503.3 nm, respectively). Besides, photo-cross-link reactions can also be utilized for synthesizing nanogels, by which surfactant may or may not be used and nanogel with more

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homogeneous cross-linking density can be prepared [81,82]. Kuckling and co-workers developed poly(N-isopropylacrylamide-co-2-dimethylmaleinimido ethylacrylamide) (PNIPAAm-DMIAAm) nanogels by UV-irradiated solutions of thermo-sensitive polymers in water at 45°C and studied the factors that affect the particle size, such as the concentration of photopolymer solutions, the amount of DMIAAm in the photopolymer chains, and surfactant sodium dodecyl sulfate (SDS) concentrations [81]. Significant scientific effort has been made on the hybrid nanoparticles with PNIPAAm shell with a metal or inorganic/organic core [83–89]. The advantage of this method is that the particle size can be controlled by the mental or inorganic template, and specific optical, electronic, and magnetic properties can be introduced by the template materials. Furthermore, hollow nanoparticles can be obtained if needed. Chemical properties of the hybrid nanoparticles are determined by the poly­mer shell. To synthesize this kind of nanoparticle, physical or chemical surface modification of the metal or inorganic core particles is necessary for the polymers to be adsorbed or covalently grafted. Hollow nanoparticles can be achieved by etching of the metal or inorganic core from the poly­mer-coated nanoparticles. Hollow PNIPAAm nanoparticles with sub 50-nm dimension were synthesized by precipitation poly­mer­i­za­tion process onto Au nanoparticles, followed by etching of the Au core with KCN [83]. Similar work using isothiocyanate fluorescein (FITCentrapped SiO2) as the core template to synthesize novel thermo-sensitive PNIPAAm nanocapsules was reported by Gao et al. [88]. In their work, SiO2 core was etched by hydrofluoric acid, and the pretrapped FITC molecules left were used to study the permeability of the PNIPAAm nanogels. It was shown that the FITC could permeate the PNIPAAm shell around its LCST at 32.8°C. The preceding examples represent only a small number of PNIPAAmbased nanoparticles reported to show the synthesis and characterization of the thermo-responsive nanoparticles and nanogels. More discussion can be seen in published papers and review articles [90–94]. We use poly(N­isopropylacrylamided-co-methacrylic acid) (PNIPAAm-MAA) nanoparticles as an example for some detailed discussion on synthesis of nanoparticles and how the monomer ratio and the amount of cross-linker and surfactant affect the particle size and the phase transition behavior of the nanoparticles. The MAA group introduces additional ionized groups to the copolymer and results in pH responsive behavior, but this property is not the main focus in this chapter. The structure of PNIPAAm-MMA is shown in Figure 7.1. Temperature- and pH-responsive polymeric composite membranes prepared from nanoparticles of PNIPAAm-MAA, and their permeability to proteins and peptides in response to environmental stimuli were investigated by Zhang et al. [95]. They showed that permeability of the solutes across the membranes increased with increased temperature or particle concentration, and decreased with increased pH and molecular size of the solutes. However, there is a lack of detailed investigation on factors that affect the particle size and phase transition behavior. Huang et al. studied volume phase transition

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x

y

O HN

O

HO

Figure 7.1 Chemical structure of PNIPAAm-MMA.

of PNIPAAm-MAA copolymer nanoparticles in buffer solutions at various pH levels and in aqueous solutions of KCl or ionic surfactants using the DLS technique [96]. It was found that the swelling behavior of the nanoparticles had a close relationship with pKa of copolymer, and there was a sharp volume phase transition for these nanoparticles. PNIPAAm-MAA particles can be synthesized by precipitation poly­mer­i­ za­tion [97]. In preparing the particles, the target amount of NIPAAm, MAA, BisAAm, and SDS was added to deionized water, where NIPAAm and MAA served as the monomers, BisAAm as the cross-linking agent, and SDS as surfactant. To study how these components affect the particle size, different molar ratios of MAA to NIPAAm, and various levels of BisAAm and SDS were used (Table  7.1). The solution was stirred for 1 h followed by deoxygenating by bubbling with nitrogen for 40 min, and then heated to 70°C in a nitrogen environment. After that, 0.083 g of potassium persulfate (KPS) in a 10-ml water solution was added to the reactor to initiate poly­mer­i­za­tion. Reaction was kept at 70°C under nitrogen atmosphere for 4 h with constant stirring. The formed particle solution was then purified by membrane dialysis against distilled deionized (DDI) water using Spectra/Pros membrane (Fisher Scientific Inc., Pittsburgh, Pennsylvania) with a molecular weight cutoff of 12,000–14,000. LCSTs of the PNIPAAm-MAA particles can be measured by turbidity test or differential scanning calorimetry (DSC). The DSC allows the measurement of the heat of phase transition over a wide range of temperatures and pH-values. The onset of the thermogram corresponds to the temperature of collapse of the poly­mer and thus was treated as the LCST of PNIPAAm-MAA particles. Particle size and size distribution of the copolymers can be determined using DLS technology. Measurements were performed over a temperature range of 20–60°C for diluted PNIPAAm-MAA particles in 0.1M PBS solution. Z-average diameter was used as the hydrodynamic size because it is more reproducible than volume and number weighted mean diameters. Figure  7.2 shows the effect of monomer ratio, amount of surfactant, and cross-linker on phase transition temperature of pNIPAAm-MAA particles. Notice in the figure that phase transition temperatures (i.e., LCST) of PNIPAAm-MAA particles were all higher than that of PNIPAAm itself.

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Table 7.1 Summary of Experimental Design and Selected Results of Synthesized PNIPAM-co-MAA Particles (1.9 g N-isopropylacrylamide [NIPAAm] and 120 ml Water for Every Polymerization Process). Methacrylic Acid (MAA) (g)

N,N’methylenebisacrylamide (BisAAm) (g)

Sodium dodecyl sulfate (SDS) (g)

Potassium persulfate (KPS) (g)

Low Critical Solution Temperature (LCST) (°C)

Particle Diameter at 20°C (nm)

0 0.036 0.072 0.108 0.144 0.576 1.008

0.033 0.033 0.033 0.033 0.033 0.033 0.033

0.075 0.075 0.075 0.075 0.075 0.075 0.075

0.083 0.083 0.083 0.083 0.083 0.083 0.083

32.06 32.47 32.93 35.45 32.13 33.16 51.31

300.1(4.482) 311.3(2.454) 358.6(3.251) 425.4(5.347) 396.7(5.261) 444.5(5.828) 554.5(1.671)

0.036 0.036 0.036 0.036

0.033 0.033 0.033 0.033

0.100 0.150 0.225 0.300

0.083 0.083 0.083 0.083

35.23 40.02 40.02 45.20

274.4(1.054) 140.1(2.548)   50.5(0.228)   39.9(2.427)

0.036 0.036 0.036

0.017 0.500 0.067

0.075 0.075 0.075

0.083 0.083 0.083

32.76 34.35 37.42

341.3(1.577) 300.3(3.003) 292.0(4.055)

Source: Data from P. Tian, Q. Wu, and K. Lian, Journal of Applied Polymer Science 108: 2226–32, 2008. Note: Reaction time was four hours for every poly­mer­i­za­t ion process. The num-

bers in parentheses for diameter (D) at 20°C represent standard derivation of three measurements.

However, an obvious increase can be detected for MAA:NIPAAm ratios of only 0.075 and 0.7 (Figure 7.2). Apparently PNIPAAm-MAA particles inherited the thermo-responsive behavior of PNIPAAm. DSC results of particles under various pH levels suggested that LCSTs of the particles were also sensitive to pH changes. PMAA undergoes a marked pH-induced conformation transition. At low pH levels, PMAA chains are highly compacted to minimize the hydrophobic interaction, while at high pH levels, PMAA chains show expanded coil. The swelling/collapsing of PMAA gels are also highly pH dependent [98]. The polyelectrolyte behavior of the MAA unit introduced various coexistent intra- and intermolecular forces, thus complicating the phase transition process of the hydrogel particles. The MAA group introduced more hydrophilic group (COO-) to the copolymer, which decreased the hydrophobic interaction that determines the phase transition of the hydrogel. Besides, with highly ionized MAA groups, the electrostatic force also helped balance the hydrophobic interaction, thus leading to an increase of the LCST. This effect is especially obvious at MAA content level

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55

LCST (degree C)

50 45 40 35 MAA

30

SDS Cross-linker

25 20

0

0.08

0.16 0.24 0.32 0.4 0.48 0.56 0.64 MAA/NIPAM Ratio/SDS(g)/Cross-linker(g)

0.72

0.8

Figure 7.2 Effect of monomer ratio, surfactant content, and cross-linker content to phase transition temperature, LCST, of PNIPAAm-MAA copolymer particles. (Reprinted from P. Tian, Q. Wu, and K. Lian, Journal of Applied Polymer Science 108: 2226–32, 2008. With permission.)

of 0.7, where an LCST of about 51.31°C was observed. Acrylic acid groups of MAA in PNIPAAm-MAA copolymer made the particle gel undergo a discontinuous transition, a higher LCST, and a larger volume change, which is consistent with results reported by other researchers [99,100]. Figure 7.2 also shows the surfactant effect on phase transition temperature of the PNIPAAm-MAA particles with MAA/NIPAAm = 0.025. It is clear that as the surfactant content increased, there was an apparent increase of the LCST. This was due to the fact that amphiphilic structure of the surfactant SDS helped solubilize the poly­mer in aqueous solutions, thus isolating the hydrophobic poly­mer segments from the aqueous environment. The contents of the cross-linker also played an important role in the LCST of the copolymer particles, as depicted in Figure 7.2. Although not as obvious as the effect of surfactants, LCST of the copolymer particles increased with higher cross-linker contents. This is possibly because more cross-linker gave more compact size of the copolymer particles, thus increasing the electrostatic repulsion forces between the poly­mer chains and preventing the particles from shrinking.

7.3 Thermo-Responsive Nanoparticle Size Control For the nanoparticles, stability, mean particle size, and PSD are the main focus in design and synthesis of thermo-responsive polymers/copolymers.

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Besides, much research effort needs to be made on determining how particle size influences the phase transition behavior, thus the releasing mechanism of the nanoparticles or nanogels. The shape of the PSD, which includes the broadness of the PSD, the modality, and the specific particle size covered by the PSD, has a significant effect on the properties of nanoparticles and the performance of the products made with nano-sized precursors. The controlled adjustment of particle size is of great interest due to size-dependent physical and chemical properties of nanoparticles [101]. In the pharmaceutical industry, for example, PSD of the active pharmaceutical ingredients is one of the most important aspects of the dosage form that affect the effectiveness of drug release [102]. Besides, PSD may also affect the stability of the dosage and absorption rate of active intergradients. As a result, it is essential to control PSD in the development of pharmaceutical dosages [103]. Factors that influence the particle size of the thermo-responsive nanoparticles are complicated. It is strongly dependent on the ratio and block length of poly­mer/copolymer components, the amount of cross-linker and surfactant used, the reaction conditions, and the diameter of the template particles. When referring to “particle size” or “particle diameter,” the condition has to be defined since the particles are sensitive to temperature and environmental change. Neradovic and co-workers studied the dependence of nanoparticle size on the processing and formulation parameters of poly(N-isopropyl­ acrylamide-co-ethylene glycol) (PNIPAAm-PEG), where PEG is hydrophilic block and PNIPAAm or PNIPAAm-co-HPMAm-dilactate act as a thermoresponsive block with DLS [104]. They found that the formation of small and stable nanoparticles strongly depends on PEG molecule weight. Small particle size is more easily obtained with high molecular weight PNIPAAm and lower poly­mer concentration in water instead of PBS buffer as solvent. Moreover, the heating rate of the poly­mer solutions plays a dominant role for nanoparticle size control, and a fast heating rate is more favorable for smaller nanoparticle formation. Continuing with our discussion of PNIPAAm-MAA particles introduced earlier, hydrodynamic diameters of PNIPAAm-MAA particles with different MAA:NIPAAm ratios as a function of temperature are shown in Figure 7.3. It is clear that the Z-average diameter of particles was composition dependent. As the MAA ratio increased, the diameter of the copolymer particles increased because more MAA units resulted in longer chains. For each set of samples, the diameter of the particles tended to decrease as temperature increased because hydrogel shrunk as temperature increased, especially around its phase transition temperature. At a certain temperature level, PNIPAAm-MAA particles tended to aggregate. For example, for PNIPAAm particles without MAA, particles tended to aggregate at above 30°C (around its LCST). This made it difficult to measure the particle size, leading to incomplete data points over the temperature range of 20–60°C as shown in Figure 7.3. Increasing temperature weakened

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600

MAA/NIPAAm = 0 MAA/NIPAAm = 0.025 MAA/NIPAAm = 0.05 MAA/NIPAAm = 0.075 MAA/NIPAAm = 0.1 MAA/NIPAAm = 0.4 MAA/NIPAAm = 0.7

Diameter (nm)

500 400 300 200 100 0

15

25

35

LCST (°C)

45

55

65

Figure 7.3 The effect of temperature on the size of the PNIPAAm-MAA particles with different MAA:NIPAAm ratio. (Reprinted from P. Tian, Q. Wu, and K. Lian, Journal of Applied Polymer Science 108: 2226–32, 2008. With permission.)

the hydrogen bonding between copolymer and water, thus poly­mer chains tended to collapse with each other. As there were more MAAs, the particles were more stable in aqueous solution as temperature changed. This should ascribe to the fact that the MAA groups introduced electrolyte behavior, and the electrostatic repulsion force of the particles helped stabilize the copolymer particles in solution. The ratio of the particle diameter at a given temperature (D) to that at 20°C (D20), D/ D20, was used to indicate the changing tendency of particles. The ratio was reduced as the MAA ratio increased, showing that hydrophobic interaction was balanced by the effect of electrostatic repulsion from the charged MAA groups. With higher MAA ratios, the electrostatic force in particles became stronger. The temperature dependence of copolymer particles’ diameter with different surfactant contents is shown in Figure 7.4. Obviously, at the same temperature, the diameter of the copolymer particles decreased as the surfactant content increased. The amphiphilic structure of SDS surfactants helped solubilize poly­mer particles in aqueous solutions, thus making it possible for poly­mer chains to form smaller particles. The effect of surfactant on the diameter of the particles was significant. For example, as SDS changed from 0.10 g to 0.3 g, the particle size changed from 274.4 nm to 39.9 nm at 20°C. Since PNIPAAm-MAA copolymer was negatively charged because of ionization of COOH groups, and SDS was an anionic surfactant, the contents of the SDS helped disperse the copolymer particles in water. This could be beneficial for controlling the size of the particles for a specific purpose, such as drug delivery. The sharpness of the D:D20 ratio curve change was reduced as SDS increased. Higher surfactant contents gave stronger repulsion in particles and

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350

SDS = 0.075g

Diameter (nm)

300

SDS = 0.15g SDS = 0.1g

250

SDS = 0.225g

200

SDS = 0.3g

150 100 50 0

15

25

35

LCST (°C)

45

55

65

Figure 7.4 The effect of temperature on the diameter of the PNIPAAm-MAA particles with different surfactant contents. (Reprinted from P. Tian, Q. Wu, and K. Lian, Journal of Applied Polymer Science 108: 2226–32, 2008. With permission.)

smaller volume reduction as temperature increased. At temperatures higher than 30°C, the particles tended to aggregate, since higher temperature broke the balance of hydrogen bonds between poly­mer and water, and neighboring poly­mer chains had increased possibility to collapse with each other. Figure 7.5 shows the temperature dependence of the diameter of the copolymer particles with different cross-linking agent contents. It can be seen from the figure that although a decrease in diameter with increased cross-linker content was observed, the effect of cross-linker on the particle size was not as obvious as that of the monomer ratio and surfactant. At 20°C, the diameter of the particle decreased from 341.3 nm to 292.0 nm as the cross-linker content increased from 0.017 g to 0.068 g. The sharpness of the D/D20 curve transition was reduced upon the increase of the cross-linker. This was possibly because the increase of the cross-linking of the poly­mer helped increase the electrostatic repulsion within particles and thus reduced the volume change. This result suggested that by controlling the amount of surfactant and monomer ratio, PNIPAAm-MAA nanoparticles with desired size for specific applications could be developed.

7.4 Thermo-Responsive Nanoparticle Applications It was discussed earlier that thermo-responsive polymers show potential applications in many fields including targeted drug delivery, sensing,

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400 BIS = 0.017g BIS = 0.033g BIS = 0.05g BIS = 0.068g

350

Diameter (nm)

300 250 200 150 100 50 0

15

25

35

LCST (°C)

45

55

65

Figure 7.5 The effect of temperature on the diameter of the PNIPAAm-MAA particles with different cross-linker contents. (Reprinted from P. Tian, Q. Wu, and K. Lian, Journal of Applied Polymer Science 108: 2226–32, 2008. With permission.)

nanoparticle templates, and separation and purification technologies. Current research on thermo-responsive nanoparticles mainly focuses on utilizing them as drug carriers. For this purpose, the encapsulation of drugs onto the nanoparticles and the releasing behavior need to be investigated. Core/shell thermo-responsive nanoparticles with pH-sensitive ability of poly(N-isopropylacrylamide-co-N,N-dimethylacrylamide-co-10-­undecenoic acid) (PNIPAAm-co-DMAAm-co-UA) were self-assembled from the amphi­ philic tercopolymer, studied by Soppimath et al. [105]. Doxorubicin (DOX), an anticancer drug, was encapsulated into the nanoparticles and its release behavior was investigated. It is shown that multifunctional poly­mer core/shell nanoparticles provide a promising carrier for the releasing of DOX to cancer cells. Cuie and co-workers studied driving forces in the loading and release of protein onto PNIPAAm-based nanoparticles [106]. In their study, bovine serum albumin (BSA) and γ-globulins (γG) were loaded onto various cationically or anionically charged PNIPAAm-based nanoparticles and their release behavior was investigated. It was shown that the loading and release strongly depended on temperature, pH, and salinity. As temperature increased, the loaded amount of both proteins increased. Loaded proteins can be completely released after the temperature is above the LCST and the process is reversible. It is well-known that some ionized polymers can capture multivalent ions in cooperation with several ionized side chains (i.e., chelation) [107–109]. The chelation behavior of gel is very useful in detecting and/or capturing toxic multivalent ions in waste solutions and can be used to design ionized-gel

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sensor, which is sensitive to multivalent metal ions. Furthermore, the ion-capture property of the ionized gel is very useful in environmental purification technology. Several studies have been reported with stimuli-responsive poly­mer gels that adsorb metal ions by forming an ionic bond [110–115]. To design and develop a poly­mer gel that can selectively absorb and release metal ions, the poly­mer should consist of two monomer groups, each having a different role. One group forms a complex with the target (adsorption part) and the other allows the polymers to stretch and shrink reversibly in response to environmental change (the responsive part). Generally, for hydrogel to adsorb metal ions, the monomer with inherent properties that incorporates onto gelatin acts as a determinant of the water-absorption part, and metal ions are absorbed by effectively partitioning between hydrogels and solution phase. Apart from the nature of metal ions, the structural aspects of hydrogels also determine the quantum of metal ion uptake. The rates of adsorption and desorption were dominated by diffusion within the gel. For the synthesized PNIPAAm-MAA particles, beside their application as a drug delivery vehicle, one of the other applications is for heavy metal adsorption. It has been shown that bivalent ions, such as Cu, Cd, and Zn, can interact with methacrylic acid and form metal-polyacid complexes involving two carboxylate groups for each ion in a large domain of pH values [116,117]. Furthermore, stimuli-responsive poly­mer with nanostructure is expected to be more efficient in capturing or detecting metal ions because of their much greater contact areas. Another advantage with stimuli-responsive copolymers for target metal adsorption is that potentially it can be a temperature swing process. To our knowledge, there have been very few investigations on the ion-capturing feature of the stimuli-responsive poly­mer with nanostructure. Such investigations are very important because these systems are stabilized with a balance of the interactions in a nanoscopic scale as mentioned earlier. It is of great practical interest to show how the particle size affects the metal ion adsorption process. The mechanism of the Cu2+ adsorption with PNIPAAm-MAA is shown in Figure  7.6. Cu2+ can chelate with -COOH groups in PNIPAAm-MAA. Generally, a copper cation can chelate with two PNIPAAm-MAA molecules C O

O

Cu O

O

O

O

O C

C O

Cu O

O C

O

O

Cu

Cu O

C

C

C O

O

O C

Figure 7.6 Mechanism of the Cu2+ adsorption with PNIPAAm-MAA. (Reprinted from Q. Wu and P. Tian, Journal of Applied Polymer Science 109: 3740–46, 2008. With permission.)

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and two copper cations can further link four or more PNIPAAm-MAA molecules to form an interlocking structure. To test adsorption capacity of PNIPAAm-MAA particles to Cu2+ ion, a sample of 2 ml of poly­mer­ized PNIPAAm-MAA gel solution was put into 20 ml of 5mM CuSO4 aqueous solution in a test tube. The adsorption experiments were carried out at two temperatures, one at 5°C (below LCST) and one at 50°C (above LCST). Samples in test tubes were placed for two days for Cu2+ adsorption, which was sufficient time for reaching equilibrium. After adsorption, samples were centrifuged to separate the particle and the solution. The pH of the CuSO4 solution was adjusted with Clark-Lubs buffer sol­ ution. The initial and equilibrium concentration of Cu2+ ions in solution were measured by an inductively coupled plasma-atomic emission spectrometry (ICP-AES) system [118]. The equilibrium adsorption amount of Cu adsorbed by the particles, which was the net amount of Cu2+ interacted with copolymer, was determined from the mass balance of the initial and equilibrium Cu2+ ion contents in solutions, assuming that the concentrations of the nonreacted Cu2+ ion was retained in the equilibrium solution. The equilibrium adsorption amount, qe (mmol/g-drygel), was determined as follows:

qe =

Vl Co − Ce Wg

(

)

(7.1)

where Vl (ml) is the volume of the adsorption solution and Wg (g) is the weight of the corresponding dry gel adsorbent, and Co and Ce (mol/L) are the initial and equilibrium Cu2+ ion contents, respectively. The adsorption efficiency, η, which is based on the actual adsorption amount qe over the theoretical adsorption amount qt, was calculated as:

η=

qe × 100% qt

(7.2)

The theoretical adsorption amount, qt, was calculated based on 2 mol of Cu2+ chelating with 4 mol of -COOH group of PNIPAAm-MAA. MAA:NIPAAm ratio dependence for the amount of Cu2+ adsorbed from CuSO4 solution to the PNIPAAm-MAA copolymer particles at pH = 5 is shown in Figure 7.7. It is obvious that the adsorbed amount increased in a stepwise manner with the increase of MAA:NIPAAm ratio. Furthermore, the adsorbed amount at 5°C was slightly higher than that at 50°C. This could be due to the fact that at temperatures higher than its LCST, the copolymer shrunk, decreased the efficient contact area of the MAA unit with Cu2+ ions, and decreased part of the carboxyl groups of MAA in adsorption reaction. For pH change from 5 to 6, Cu2+ adsorption amount increased slightly at

Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

Cu Adsorption Amount (mmol/g-drygel)

212

0.7 0.6 0.5 0.4 0.3 0.2

5C 50C

0.1 0

0

0.1

0.2

0.3 0.4 0.5 MAA/NIPAAM Ratio

0.6

0.7

0.8

Figure 7.7 PNIPAAm-MAA particle Cu2+ adsorption with MAA:NIPAAm ratio at pH = 5. (Reprinted from Q. Wu and P. Tian, Journal of Applied Polymer Science 109: 3740–46, 2008. With permission.).

low MAA ratio. However, for higher MAA ratios (MAA/NIPAAm = 0.1 – 0.7), no apparent trend of Cu2+ adsorption amount with pH was detected. The equilibrium adsorption amount, qe, ranged from 0.1 to 0.7 mmol/g-dry gel, depending on different MAA contents. This is much higher than the adsorption efficiency reported in the literature. For example, the adsorption amount with PNIPAAm-VBEDA ranged from 0.001 to 0.012 mmol/g-dry gel [113], and that of PNIPAAm-MEP ranged from 0.015 to 0.035 mmol/g-drygel [119]. The magnificent increase of adsorption should ascribe to the nanoscale particle size. The PNIPAAm-MAA particle size ranged from 30 to 500 nm, which greatly increased the effective contact area of the MAA and Cu2+ ions. This is a beneficial and important factor of PNIPAAm-MAA particles for its potential application in purification processes. The particle size effect on the amount of Cu2+ adsorbed to the PNIPAAmMAA copolymer particles from CuSO4 solution at pH = 5 is shown in Figure  7.8. The adsorbed amount at temperature below LCST was higher than that above LCST, as discussed before. For particles with size in the range of 30–300 nm, the amount of Cu2+ adsorbed onto particles showed no significant change; the equilibrium adsorption amount was about 0.1 mmol/ g-drygel. For these samples, the MAA:NIPAAm ratio was the same (i.e., MAA/NIPAAm = 0.025). As the particle size increased from 300 to 500 nm, the total adsorbed amount increased. However, this does not necessarily suggest that increasing particle size increased the adsorption amount since the MAA contents in the copolymer particles also increased significantly. The adsorption of Cu ions onto PNIPAAm-MAA particles is a balance between the particle size and MAA contents.

213

Cu Adsorption Amount (mmol/g-drygel)

Smart Thermo-Responsive Nanoparticles

0.7 0.6 0.5 0.4 0.3 0.2

5C 50C

0.1 0 250

300

350 400 450 Particle Size at 25°C (nm)

500

550

Figure 7.8 PNIPAAm-MAA particle Cu2+ adsorption with particle size at pH = 5. (Reprinted from Q. Wu and P. Tian, Journal of Applied Polymer Science 109: 3740–46, 2008. With permission.)

As mentioned before, particles within 20- to 300-nm size range were synthesized with the same amount of MAA:NIPAAm ratio, but different cross-linker contents or surfactant contents, leading to different particle size. Particles with size range of 300–500 nm represented increasing MAA:NIPAAm ratio with the same cross-linker and SDS contents. As shown in Figure 7.9, with small particle size, the adsorption efficiency was pretty 1 Cu Adsorption Efficiency

0.9

5C 50C

0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0

250

300

350

400

450

500

550

Particle size at 25ºC (nm) Figure 7.9 Adsorption efficiency of Cu2+ with PNIPAAm-MAA with particle size at pH = 5. (Reprinted from Q. Wu and P. Tian., Journal of Applied Polymer Science 109: 3740–46, 2008. With permission.)

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high, most at 80–98% range. With increased particle size, although the absolute adsorption amount per g-dry gel increased, the adsorption efficiency decreased dramatically. This strongly suggested that particle size played an important role in the adsorption of metal ions with the copolymer particles. By controlling surfactant contents, PNIPAAm-MAA particles can be synthesized with higher MAA ratio but smaller particle size, and can be used to help the adsorption efficiency of metal ion adsorption with the copolymer.

7.5 Conclusions and Future Development Thermo-responsive copolymer is a very promising material for varieties of applications based on their response to temperature change. Extensive work on thermoresponsive polymers based on PNIPAAm has been done in the past 20 years. However, only recently has the investigation of the studies moved into micro- and/or nanoscale for this kind of polymer. A number of novel, thermo-sensitive nanoparticles and their synthesis route and property characterizations has been described in the literature. Each system has its own advantages and drawbacks. The choice of a particular nanoparticle and nanogel depends on its intrinsic properties and target application. The main focus of research in thermo-responsive nanoparticles lies in developing specific nanoparticles with designed properties for proper loading and release of specific drugs to targeted cells. The synthesis and characterization of the PNIPAAm-based copolymer nanoparticles still need much research effort before they can be widely used as drug delivery vehicles, and how the nanoscale behavior of the particles affects the delivery efficiency also requires much research attention. It is worth noting that current research still mainly focuses on design of the thermo-responsive nanoparticles. For these nanoparticles to be used in actual clinical applications, a cooperative effort needs to be carried out for studying the load and release efficiency of specific drugs, the toxicity of the poly­mer nanoparticles, the immunogenicity of the human body to the encapsulated particle-drug, and its release kinetics among chemist, pathologist, and therapist. Besides the intense interest in thermo-responsive nanoparticles’ biomedical application, other applications such as separation and purification are well worth scientific study as well since they may supply a swing process for adsorption and desorption.

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8 Surface Tailoring of Polymer Nanoparticles with Living Polymerization Methods Koji Ishizu and Dong Hoon Lee Contents 8.1 Introduction.................................................................................................223 8.2 Architecture of Polymer Particles Possessing Radical Initiating Sites on the Surface by Emulsion Copoly­mer­i­za­tion and Synthesis of Core-Brush Structures by Photoinduced ATRP Approach......................................................................................................225 8.3 Synthesis of Silica Particles Coated with High-Density Polymer Brushes......................................................................................................... 228 8.4 Synthesis of Polymer Brushes Encapsulated Silica Particles by DC-Mediated Living Radical Polymerization........................................ 230 8.5 Synthesis of Silica Hybrid Nanoparticles Modified with Photofunctional Polymers and Construction of Colloidal Crystals.... 235 8.6 Architecture of Polymer Particles Composed of Brush Structure at Surface and Application for Structural Color Materials................... 239 8.7 Surface Modification of Polymer Particles via RAFT Polymerization............................................................................................ 249 8.8 Surface Modification of Silica Nanoparticles via NitroxideMediated Radical Polymerization............................................................ 253 8.9 Conclusions.................................................................................................. 255 References.............................................................................................................. 255

8.1 Introduction Latex particles have exceptional uniform shape and wide diameter range, which is of interest because their combination with other inorganic (or metallic) colloid particles should extend their application in the field of academic research as well as industrial material development. This is especially true of the synthesis of composite particles comprised of organic and inorganic substances, in which the adoption of monodisperse poly­mer lattices as their one component largely expands the variety of composite particles because many 223

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techniques to prepare latex samples with different sizes and structures have been developed [1]. Control of poly­mer particle size and its uniformity has been a major area of interest especially for particles in the micron size range. Micron-size monodisperse latex particles have been prepared by seeded emulsion poly­mer­i­za­ tion, by either the successive seeding method [2] or the two-stage swelling method [3,4]. They have also been prepared by dispersion poly­mer­i­za­tion in organic media [5–8]. The dispersion poly­mer­i­za­tion method has recently received great attention because of the simplicity of the process and the wide variety of monomers that can be successfully poly­mer­ized. On the other hand, core-brush-type nanoparticles were prepared by cross-linking of core domains in block copolymers [9]. In general, block and graft copolymers with incompatible sequences exhibit characteristic morphological behavior and interesting properties, owing to micelle formation in a selective solvent and microdomain in the solid state. Many types of micelles formed by diblock copolymers in solution were reported. Spherical self-assembly formed in the solvent for one sequence and not for the other forms a so-called poly­mer micelle with core-corona morphology. As a result, the core-brush-type poly­ mer particles were prepared easily by cross-linking of the spherical parts (the spherical microdomains in the solid state and the core in solution). The microphase-separated structures in bulk film are more stable in thermal equilibrium than the micelle in solution. So the cross-linking of spherical microdomains in the film is a superior preparative method for core-brush type poly­mer particles than cross-linking of micellar cores. Recently, there has been rapid growth in the number of techniques employed in the area of controlled/living radical poly­mer­i­za­tion, such as atom transfer radical poly­mer­i­za­tion (ATRP) [10,11], nitroxide-mediated radical [12], and reversible addition-fragmentation chain transfer (RAFT) poly­mer­i­za­tion [13]. Until recently, ionic poly­mer­i­za­tions (anionic or cationic) were the only living techniques available that efficiently controlled the structure and architecture of vinyl polymers. Although these techniques ensure low-­polydispersity materials, controlled molecular weight, and defined chain ends, they are not useful for the poly­mer­i­za­tion and copoly­mer­i­za­tion of a wide range of functionalized vinyl monomers. On the other hand, the photochemical reactions and initiation poly­mer­i­za­tion of N,N-diethyldithiocarbamate (DC) derivatives have been extensively studied by Otsu [14]. Generally, this type is used as an inifeter. More recently, we demonstrated that density functional theory calculations provide a prediction of the trend in C-S bond dissociation energies and atom spin densities for radicals using model compounds as DC-mediated inifeters [15–17]. Such photopoly­mer­i­za­tions proceeded with a living fashion. We also presented a novel route to hyperbranched polystyrene from 4-vinylbenzyl N,N-diethyldithiocarbamate (VBDC) as an inimer by one-pot photopoly­mer­i­za­tion [18,19]. Photoinduced ATRP of multifunctional polymers having DC pendant groups with vinyl monomers (“grafting from” approach) formed nanocylinders consisting of graft-block

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225

copolymers [20]. More recently, Yamago et al. [21] reported several new ­organotellurium-based initiators for controlled/living radical poly­mer­i­za­ tion of vinyl monomers that allowed accurate molecular weight control with defined end groups. These living radical poly­mer­i­za­tions can be applied for the architecture of various types of nanostructured polymers. This chapter deals mainly with surface modifications of inorganic and organic particles with living radical poly­mer­i­za­tion methods.

8.2 Architecture of Polymer Particles Possessing Radical Initiating Sites on the Surface by Emulsion Copoly­mer­i ­za­t ion and Synthesis of Core-Brush Structures by Photoinduced ATRP Approach One [22–24] of the authors and Dai et al. [25] developed a convenient method for preparing cross-linked core-brush particles by free radical dispersion copoly­mer­i­za­tion with hydrophobic macromonomers in nonaqueous media. On the other hand, there are several reports concerning the synthesis of corebrush (or shell) particles [26–33]. In particular, Rühe et al. could demonstrate that photoinitiators chemically attached to the surface allow us to obtain planar brushes with defined structure [28]. As mentioned in the introduction, we presented a new method for hyperbranched poly­mer synthesis by DC-mediated living radical poly­mer­i­za­tion [18]. These hyperbranched polymers exhibited photofunctional DC groups on their surface. On the basis of these studies, cross-linked polystyrene (PS) particles possessing photofunctional DC groups on their surface were synthesized by free radical emulsion copoly­mer­i­za­tion of a mixture of styrene (St), divinylbenzene (DVB), and VBDC with redox system as an initiator under ultraviolet (UV) irradiation [34]. In short, the monomer droplets (VBDC, DVB, and St) were dispersed in the aqueous phase by means of surfactants (dodecylbenzenesulfonic acid sodium salt [SDBS] and 1-hexadecanol [HAD]), and a stable emulsion was produced. A water-soluble initiator potassium persulfate (K2S2O8), and one droplet of N,N-dimethylaniline (redox system) was used so that the initial locus of the poly­mer­i­za­tion was in the aqueous phase. This radical mechanism proceeded with a quasi-living radical nature because the initiating sites were very few. At the same time, the photolysis of inimer VBDC within monomer droplets led to the initiating benzyl radical with the inactive DC radical. This benzyl radical could add to the vinyl group of St, DVB, or VBDC. By repeating these elementary reactions, this poly­mer­i­za­tion system proceeded to form the hyperbranched structures. Then, this reaction system provided highly localized DC groups attached chemically to the surface. The copoly­mer­i­za­tion conditions and results for PS-MI1 to PS-MI4

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Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

Table 8.1 Emulsion Copoly­mer­i­za­tion Conditions and Results for PS-MI1 to PS-MI4a Surfactant (wt% for the Total Monomer) Experiment PS-MI1 PS-MI2 PS-MI3 PS-MI4

SDBS

HAD

Dn (nm)b

Dw/Dnb

 1  3  6 12

 2  6 12 24

523 420 230 214

1.05 1.10 1.10 1.08

Note: From K. Ishizu, N. Kobayakawa, S. Takano, Y. Tokuno, and M. Ozawa, Journal of Polymer Science, Part A: Polymer Chemistry 45: 1771–77, 2007. With permission. a The emulsion copoly­mer­i­za­tions were carried out at room temperature for 8 h of UV irradiation in feeds of [St] = 16 × 10–3 mol/L, [DVB] = 7.7 × 10–2 mol/L, [VBDC] = 6.3 × 10–2 mol/L, and [K2S2O8] = 3 wt% for the total monomer (one droplet of N,N-dimethylaniline). b Determined by a survey of 300 samples packed from SEM photographs.

are listed in Table  8.1. Typical scanning electron microscopy (SEM) photographs of the copoly­mer­i­za­tion products PS-MI1 and PS-MI4 are shown in Figure  8.1a and b, respectively. The products provided spherical particles (particle diameter Dn = 523 nm for PS-MI1 and Dn = 214 nm for PS-MI4) and relatively narrow size distributions (Dw/Dn = 1.05 for PS-MI1 and Dw/Dn = 1.08 for PS-MI4). Table 8.1 shows that the particle diameter decreased gradually with a decreasing feed ratio of the surfactants to the total monomer. This was a reasonable result for an emulsion poly­mer­i­za­tion system. The graft poly­mer­i­za­tion of monomer methyl methacrylate (MMA) initiated by the PS-MI macroinitiator under UV irradiation often led to macrogelation due to intermolecular radical couplings. The main reasons are (1) a highly localized radical concentration on the PS particle surface and (2) a high propagation rate of PMMA radicals. Then, we employed photo­ induced ATRP for such a grafting process because the propagation rate, especially of MMA with copper(I) chloride (CuCl)/2,2’-bipyridine (bpy), was very slow compared with that without CuCl/bpy. The core-brush particles were synthesized by the photoinduced ATRP of MMA monomer initiated by PS-MI2 as a macroinitiator in 8/2 (v/v) tetrahydrofuran (THF)/methanol (MeOH) for 8 h of UV irradiation under the following conditions: a monomer concentration of 66.7 wt% and a [DC]/[MMA]:[CuCl]/[bpy] ratio of 1:300:2:6, where [DC] indicates the DC concentration of the PS-MI2 macroinitiator. The reaction scheme for core-brush particle synthesis is shown in Scheme 8.1. In the size distributions for dynamic light scattering (DLS) data of PS-MI2 and CS-2 core-brush particles in THF, both profiles showed unimodal distributions, and after the grafting of the MMA monomer, the hydrodynamic

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Surface Tailoring of Polymer Nanoparticles

(a)

(b)

1.0 µm

2.5 µm

(c)

1.5 µm

Figure 8.1 SEM photographs of (a) PS-MI1 cross-linked PS particles, (b) PS-MI4 cross-linked PS particles, and (c) CS-2 core-brush particles. (Reprinted from K. Ishizu, N. Kobayakawa, S. Takano, Y. Tokuno, and M. Ozawa, Journal of Polymer Science, Part A: Polymer Chemistry 45: 1771–77, 2007. With permission.)

diameter (Dh) increased (to 477 nm) compared with that (Dh = 411 nm) of the PS-MI2 macroinitiator. On the other hand, a typical SEM photograph of the CS-2 core-brush particles is shown in Figure 8.1c. Spherical particles (Dn = 450 nm) are clearly visible for the sample. This result supports the solution data on DLS. The synthesis of the core-brush particles would result in the continuing growth of PMMA chains within PS beads. This is a possibility because THF and MMA monomer swell the beads extensively, and consequent PMMA chain on growth is highly probable and also may cause an increase in the particle size.

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Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

diethyldithiocarbamate group CH2

S

C S

N

Et

UV

Et

CH2•

•S

C

N

S

CuCl

Et Et

bpy

CH3 H C C H C OCH3 O

MMA

CH2

S

C S

N

Et Et

Scheme 8.1 Schematic illustration for the synthesis of core-shell particles by grafting from the approach of photo-initiated ATRP. (Reprinted from K. Ishizu, N. Kobayakawa, S. Takano, Y. Tokuno, and M. Ozawa. 2007. Journal of Polymer Science, Part A: Polymer Chemistry 45: 1771–77, 2007. With permission).

8.3 Synthesis of Silica Particles Coated with High-Density Polymer Brushes Silica (SiO2) nanoparticles received recent attention because of their su­perior properties over the microsize particles. The silica surface consists of two types of functional groups, siloxane (Si-O-Si) and silanol (Si-OH) [35,36], which provide functionalization with different functional groups. Thus, silica modification can occur via the reaction of particular molecules with either the siloxane or the silanol. Modification of the surface is mostly done by using an appropriate molecule designated as a precursor silane coupling agent. A covalent bond can be formed between the silica surface and the silane coupling agent to give a new modified silica surface with an anchored functionality. Strategies have been developed to tailor silica particle surfaces with polymers by surface-initiated living radical poly­mer­i­za­tion techniques, in particular, ATRP [37–50]. Patten et al. first succeeded in surface-initiated ATRP of styrene and MMA on silica particles with an average diameter of

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CH2=CH(CH2)4OH

+

BrOC(CH2)2Br

TEA

CH2=CH(CH2)4OOC(CH3)2Br

In THF

BPH

(CH3CH2O)3SiH Karstedt’s cat. in toluene

SiO2

(CH3CH2O)3Si(CH2)6OOC(CH3)2)Br BHE NH4OH cat. in EtOH

SiO2 O O Si(CH2)6OOC(CH3)2Br O

MMA CuCl/Nbipy 70°C

PMMA SiO2 PMMA

Scheme 8.2 Schematic representation for the synthesis of poly­mer-coated silica particle by surface-initiated ATRP. (Reprinted from K. Ohno, T. Morinaga, K. Koh, Y. Tsujii, and T. Fukuda, Macromolecules 38: 2137–42, 2005. With permission.)

75 and 300 nm [37,38]. Matyjaszewski et al. synthesized an initiator-functionalized silica particle with a diameter of about 20 nm via the sol-gel chemistry and grafted homo and block polymers on the silica surface by ATRP [40]. Carrot et al. used a commercially available silica particle with an even smaller average diameter of 12 nm and carried out ATRP of n-butyl acrylate from its surface [42]. Müller et al. synthesized a hybrid particle with a silica core and the shell of a hyperbranched poly­mer by surface-initiated ATRP initiating group-holding acrylic monomer [43]. In search for a better route to the modification of silica particle by surfaceinitiated ATRP, Fukuda et al. synthesized a new triethoxysilane derivative to introduce ATRP initiation sites onto silica surfaces without causing any aggregation of the particles [51]. Scheme 8.2 shows the schematic representation for the synthesis of poly­mer-coated silica particle by surface-initiated ATRP. The surface initiator, (2-bromo-2-methyl)pro-pionyloxyhexyltriethoxy­ silane (BHE), was synthesized via a two-step reaction. The first step was the reaction of 5-hexene-1-ol with 2-bromoisobutyryl bromide provided 1-(2-bromo-2-methyl)propionyloxy-5-hexene (BPH). The second step was the reaction of BPH with triethoxysilane provided the initiator BHE using Karstedt’s catalyst. Next, the reaction of silica particle suspension in ethanol (EtOH) with BHE using NH4OH catalyst provided the initiator-coated SiO2 particle. The surface-initiated ATRP of MMA mediated by CuCl/4,4’-dionyl2,2’-bipyridine (dNbipy) complex was carried out with the initiator-fixed SiO2 particle in the presence of a “sacrificial” (free) initiator. The poly­mer­i­ za­tion proceeded in a living manner in all examined cases, producing SiO2 particle coated with well-defined PMMA of a target molecular weight up to 480K with a graft density as high as 0.65 chains/nm2. These hybrid particles had an exceptionally good dispersibility in organic solvents.

230

Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

On the same analogy of the aforementioned works, gold nanoparticles coated with well-defined high-density poly­mer brushes were synthesized by the surface-initiated ATRP approach [52,53]. For example, the gold nanoparticle (AuNP) coated with an initiator group for living radical poly­mer­ i­za­tion was prepared by the simple one-pot reduction of tetrachloroaurate with sodium borohydrate in the presence of an initiator group-holding disulfide. The surface-initiated ATRP of MMA mediated by a copper complex was carried out with the initiator-coated AuNP [53]. Living poly­mer­i­za­tion proceeded exhibiting a first-order kinetics of monomer consumption and an evolution of molecular weight of the graft poly­mer proportional to monomer conversion, thus providing well-defined, low-polydispersity graft polymers with an approximate graft density of 0.3 chain/nm2.

8.4 Synthesis of Polymer Brushes Encapsulated Silica Particles by DC-Mediated Living Radical Polymerization As mentioned in Section 8.2, we established a new synthetic method for cross-linked PS particles possessing photofunctional DC groups on their surface by the free radical emulsion copoly­mer­i­za­tion. We expected that this method would be applied for the synthesis of PMMA brush encapsulated silica (SPM) particles [54]. The reaction scheme for the synthesis of the SPM particles is shown in Scheme 8.3. The synthesis of well-defined core-shell structures by the method devised here required the architecture of the crosslinked PS shell parts to possess as many photofunctional DC groups as possible on the surface. In this study, the monomer droplets (St, DVB, VBDC, and 2-hydroxyethyl methacrylate [HEMA])-encapsulated SiO2 particles (diameter Dn = 20 nm) were dispersed in the aqueous phases by means of a surfactant (SDBS), and a stable emulsion was produced. A small amount of HEMA that was miscible to the SiO2 surface was also used to achieve the initial formation of the random copolymer composed of rich poly(2-hydroxyethyl methacrylate) (PHEMA) sequences because of the rapid propagation rate constant. An organic-soluble initiator [2,2’-azobis(4-methoxy-2,4-dimethylvaleronitrile): V-70] was used so that effective initiation occurred in the monomer droplets. At the same time, the photolysis of the inimer VBDC within the monomer droplets led to the initiating benzyl radical with the inactive DC radical. This benzyl radical could add to the vinyl groups of St, DVB, HEMA, or VBDC. By repeating these elementary reactions, this poly­mer­i­za­tion system proceeded to form the hyperbranched structures. The copoly­mer­i­za­tion conditions and results for the SPS macroinitiator particles are listed in Table 8.2. The SPS1 and SPS2 particles were poly­mer­ized in the water phase only. A typical SEM photograph of the copoly­mer­i­za­tion product SPS2 is shown in Figure 8.2a.

SDBS

+

H2O/EtOH

+

+

Styreme

VBDS

CH2

C

O

V-70 hv

OCH2CH2OH

CH2DC Silica particle

C

DVB

HEMA

DC

SiO2

DC DC

DC

DC DC

SiO2-cross-linked PS particle (SPS) CH3

DC

DC MMA CuCl, bpy THF, hv

DC

DC

DC DC

SiO2

DC

DC DC

PMMA brushes encapsulated SiO2 particle (SPM)

(CH2 CH)a (CH2 CH)b (CH2 CH)c (CH2 C)d DC

Surface Tailoring of Polymer Nanoparticles

SiO2

DC

CH3

C O OCH2CH2OH CH2DC

(CH2

CH)a

DC

Scheme 8.3 Reaction scheme for the synthesis of SPM particles; VBDC is 4-vinylbenzyl N,N-diethyldithiocarbamate (Reprinted from K. Ishizu, D. H. Lee, Y. Tokuno, S. Uchida, and M. Ozawa, Journal of Applied Polymer Science 109: 3968–74, 2008. With permission.).

231

232

Emulsion Copoly­mer­i­za­tion Conditions and Results for SiO2-Cross-Linked PS Particles (SPS)a Feed of Monomer Code

SiO2b (mg)

St (mL)

VBDC (mg)

DVB (mL)

HEMA (mL)

SDBS (mg)

V-70 (mg)

Solvent (mL/mL)

Total Momonerc Conversion (%)

Dnd (nm)

Dw/Dnd

SPS1 SPS2 SPS3 SPS4

140 140 140 140

1.2 1.2 0.3 0.6

400 400 100 300

0.2 0.2 0.05 0.1

0.2 0.2 0.05 0.1

200 300 278 278

50 50 50 50

H2O (30) H2O (30) H2O (45)/EtOH (5) H2O (45)/EtOH (5)

56 55 45 52

55 50 35 40

1.20 1.16 1.04 1.05

Note: From K. Ishizu, D. H. Lee, Y. Tokuno, S. Uchida, and M. Ozawa, Journal of Applied Polymer Science 109: 3968–74, 2008. With permission. a Polymerized under UV irradiation at room temperature for 4 h in nitrogen atmosphere. b Particle diameter D = 20 nm. n c Determined by gravimetric method. d Determined by a survey of 300 samples picked from SEM photographs.

Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

Table 8.2

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Surface Tailoring of Polymer Nanoparticles

(a)

(b)

100 nm

100 nm (c)

100 nm Figure 8.2 SEM photographs of the (a) SPS2, (b) SPS3, and (c) SPM1 particles. (Reprinted from K. Ishizu, D. H. Lee, Y. Tokuno, S. Uchida, and M. Ozawa, Journal of Applied Polymer Science 109: 3968–74, 2008. With permission.)

The products provided large spherical particles (Dn = 50 nm) and a broad size distribution (weight-average particle diameter/number-average particle diameter [Dw/Dn = 1.16]). The result for SPS1 showed a similar trend. It was also found from both experiments that the particle diameter decreased gradually with increasing feed ratio of the surfactant SDBS to the total monomer. The thickness of cross-linked PS shell parts was too large because the particle diameter of the SiO2 core used in this study was 20 nm. Therefore, the SPS3 and SPS4 experiments were carried out with a small feed amount of total monomer in the water/EtOH phase. We expected that the addition of EtOH would promote uniform emulsion droplets in miscible water/monomer and the effect of the phase-transfer catalyst. A typical SEM photograph of SPS3 is shown in Figure 8.2b. From this texture, small spherical particles (Dn = 35 nm) were clearly visible and exhibited a narrow size distribution (Dw/Dn = 1.04). Figure 8.3 shows the size distribution for the DLS data of SPS3 in an emulsion aqueous solution. The profile showed unimodal distribution, and the hydrodynamic diameter (Dh) was 38 nm. This value was well in agreement with that observed from SEM. The result for the SPS4 particles showed almost the same trend. The content of DC groups for the SPS particles was determined with the radical transfer reaction. For example, SPS3 was reduced with a lower excess

Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

SPS3

Size Distribution (LS%)

234

SPM1

1

10

100 Dh (nm)

1000

104

Figure 8.3 Size distributions of the DLS data for the SPS3 particles in an emulsion aqueous and the SPM1 particles in THF. (Reprinted from K. Ishizu, D. H. Lee, Y. Tokuno, S. Uchida, and M. Ozawa, Journal of Applied Polymer Science 109: 3968–74, 2008. With permission.)

of tributyltin hydride (Bu3SnH) under 0.5–1.0 h of UV irradiation in THF. The consumed amount of Bu3SnH was constant for the previous irradiation times from gas chromatography with decahydronaphthalene as an internal standard sample. The DC groups were estimated to be 1785 number/particle. The formation mechanism of the SPS macroinitiator particles can be speculated as follows. PHEMA-co-PS (PVBDC or PDVB) copolymer was formed in the initial stage because the propagation rate constant of HEMA was very rapid. These copolymers covered the surface of the SiO2 particles because of good affinity between the PHEMA units and silanol (Si-OH) groups on the SiO2 particles. Subsequently, the network and hyperbranched structures at the shell part were generated during poly­mer­i­za­tion. The grafting from photoinduced ATRP conditions and results for the SPM particles are listed in Table 8.3. The monomer conversion for SPM1 was 24% after 8 h of UV irradiation. A typical SEM photograph of the SPM1 corebrush particles is shown in Figure 8.2c. Spherical particles (Dn = 65 nm) are clearly visible for the sample. This result supports the solution data from DLS. That is, the profile shows unimodal distribution, and Dh was 95 nm (see SPM1 in Figure 8.3). This means that the PMMA brush chains expanded in the THF solution because THF is a good solvent for PMMA. To determine the composition of core, cross-linked PS shell, and PMMA brushes, we

235

Surface Tailoring of Polymer Nanoparticles

Table 8.3 Grafting from Photoinduced ATRP Conditions and Results for PMMA Brushes Encapsulated SiO2 Particles (SPM)a Code

SPS3 (mg)

[DC]:[CuCl]:[bpy]:[MMA]

Time (h)

Conversionb (%)

Dnc (nm)

Dw /Dnc

Dhd (nm)

SPM1 SPM2

215   80

1:1.1:2.1:40 1:1:2:80

8 4

24 18

65 56

1.03 1.04

95 80

Note: From K. Ishizu, D. H. Lee, Y. Tokuno, S. Uchida, and M. Ozawa, Journal of Applied Polymer Science 109: 3968–74, 2008. With permission. a Polymerized in THF (60 vol% monomer concentration) under UV irradiation at room temperature in high vacuum. b Determined by gravimetric method. c Determined by a survey of 300 samples picked from SEM photographs. d Hydrodynamic diameter was determined by DLS in THF at 25°C.

also performed thermogravimetric analysis (TGA) measurements for SPS3 and SPM1. As a result, the volume ratio SiO2/PS shell:PMMA was estimated to be 1:2.43:11.04. The value of the radius of SPM1 (r3) was determined to be 24.9 nm. This value was in relative agreement with that observed from the SEM image (SPM1, Dn = 65 nm). The thickness of the PMMA brush phase was estimated to be 9.8 nm, in the solid state. Then, the molecular weight of the PMMA brush chain was estimated to be 1.85 × 104, with the assumption that all of the DC initiation sites on the macroinitiator led to the propagation of MMA.

8.5 Synthesis of Silica Hybrid Nanoparticles Modified with Photofunctional Polymers and Construction of Colloidal Crystals More recently, Park and co-workers [55] have prepared PMMA-SiO2 core-shell nanocomposite particles from the dispersion poly­mer­i­za­tion in supercritical carbon dioxide. In their approach, 3-(trimethoxysilyl)propyl methacrylatefunctionalized SiO2 were first dispersed in the reaction medium followed by the poly­mer­i­za­tion with MMA. The poly­mer-grafted SiO2 was also prepared as reported previously [56,57]. For example, the PMMA-grafted SiO2 particles were synthesized as follows [57]: (1) radical poly­mer­i­za­tion of MMA was carried out in the presence of (3-mercaptopropyl)-trimethoxysilane (MPMS) as chain transfer agent to obtain PMMA-Si(OMe)3; (2) the PMMA-grafted SiO2 was prepared by coupling of SiO2 particles with PMMA-Si(OMe)3. Moreover, colloidal crystals formed by PMMA-grafted SiO2 particles were immobilized by a procedure consisting of gelation by radical copoly­mer­i­za­tion. We also synthesized the silica hybrid nanoparticles (diameter Dn = 192 nm) modified with photofunctional poly­mer or monofunctional silane coupling

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Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

O SH O Si O (MPMS)

V-70 O

+ OMe

SCNEt2 S

MMA

in THF, 30°C, 24h, under dark room

VBDC

O O Si O

S

(

( (

O

OMe

(H SCNEt2 S

PFD

Scheme 8.4 Polymerization scheme for the synthesis of photofunctional polymers (PFD) as silane coupling agent. (Reprinted from K. Ishizu, Y. Tokuno, D. H. Lee, S. Uchida, and M. Ozawa, Journal of Applied Polymer Science 112: 2434–40, 2009. With permission.)

agents [58]. Scheme 8.4 shows the reaction scheme for the synthesis of photofunctional poly­mer as silane coupling agent (PFD). Such PFD was prepared by free radical copoly­mer­i­za­tion of VBDC and MMA in the presence of MPMS as chain transfer agent. Next, SiO2 nanoparticles were surface-­modified with PFD and 3-(trimethoxysilyl)propyl methacrylate (γ-MPS) by covalent bond formed between silanol groups and silane coupling agents (see Figure 8.4). The PFD and γ-MPS functionalizations changed the silica surface into hydrophobic nature and provided grafting initiation sites and methacrylate terminal groups, respectively (SiO2 hybrid nanoparticles ([H-SiO2]). A typical SEM photograph of H-SiO2 hybrid particles is shown in Figure 8.5b, where Figure 8.5a shows an SEM photograph of starting SiO2 particles (Dn = 192 nm, Dw/Dn = 1.01 ± 0.05). The product H-SiO2 provided somewhat large spherical particles (Dn = 198 nm) and kept narrow size distribution (Dw/Dn = 1.01 ± 0.06). Figure  8.6 shows size distribution (Dh, hydrodynamic diameter) on DLS data of H-SiO2 in THF and starting SiO2 particles in water. Both profiles show unimodal distribution. Because H-SiO2 particles were stabilized sterically with both PMMA grafted chains and γ-MPS fragments, these hybrid particles formed a single molecule in THF. Then, the hydrodynamic diameter of H-SiO2 showed a larger value (Dh = 243 nm) than that of starting SiO2 particles (Dh = 209 nm) in solution. DC

DC

SiO2

+

O O O

Si

O O

+

DC

DC O

Si O O

γ-MPS

DC

PFD

in Toluene, 30°C, 200h, under dark room

SiO2

DC O O

H-SiO2

Figure 8.4 Schematic illustration for the synthesis of SiO2 hybrid nanoparticles (H-SiO2). (Reprinted from K. Ishizu, Y. Tokuno, D. H. Lee, S. Uchida, and M. Ozawa, Journal of Applied Polymer Science 112: 2434–40, 2009. With permission.)

Surface Tailoring of Polymer Nanoparticles

237

(a)

400 nm

(b)

400 nm

Figure 8.5 SEM photographs of (a) SiO2 and (b) SiO2 hybrid nanoparticles (H-SiO2). (Reprinted from K. Ishizu, Y. Tokuno, D. H. Lee, S. Uchida, and M. Ozawa, Journal of Applied Polymer Science 112: 2434–40, 2009. With permission.)

To determine the composition of H-SiO2 particles, we performed TGA measurements for H-SiO2 particles. A 6.6 wt% mass increase was observed after silane coupling reaction. Assuming that this organic layer is composed of PFD, the number (NPFD) of grafted PFD on SiO2 surface is calculated to be 6.09 × 104 mol/one H-SiO2 particle, that is, (4/3)πr13 dSiO2 Nav(6.6/93.4Mn,PFD), where r1 (96 nm), dSiO2 (1.74 g/cm3), Nav (6.025 × 1023 mol–1), and Mn,PFD (4500) are radius of SiO2, density of SiO2, Avogadro’s number, and molecular weight of PFD silane coupling agent, respectively. Then, the number of DC groups on H-SiO2 particle surface was estimated to be 3.2 mol/nm2, that is, 6.4N/4πr22, where r2 (99 nm) is the radius of H-SiO2 hybrid particles. The content of DC groups for H-SiO2 hybrid particles was determined by using the radical transfer reaction. H-SiO2 (22.2 mg) was reduced with a less

238

Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

SiO2 in Water (Dn = 209 nm)

Intensity (LS%)

H-SiO2 in THF (Dn = 243 nm)

10

102

103

104

Hydrodynamic Diameter (nm)

Figure 8.6 Size distribution of DLS data for SiO2 in water and H-SiO2 in THF. (Reprinted from K. Ishizu, Y. Tokuno, D. H. Lee, S. Uchida, and M. Ozawa, Journal of Applied Polymer Science 112: 2434–40, 2009. With permission.)

excess of Bu3SnH under 30 min of UV irradiation in THF. The consumed amount of Bu3SnH (9.85 × 10 –7 mol) was constant for the aforementioned irradiation times from gas chromatography using decahydronaphthalene as the internal standard sample. The particle number of feed H-SiO2 is calculated to be 5.339 × 10 –12 using the following equation: (22.2 × 10 –3 × 0.934) ÷ [(4/3) πr13 dSiO2 Nav], where r1 = 96 nm, dSiO2 = 1.74 g/cm3, and Nav = 6.025 × 1023 mol–1. Then, the number of DC groups per particle can be estimated to be 1.845 × 105 mol. Finally, the number of DC groups on H-SiO2 particle surface was estimated to be 1.50 mol/nm2, that is, 1.845 × 105/4πr22, where r2 = 99 nm. This value is smaller than that (3.2 mol/nm2) calculated from TGA data because the organic shell consisted of PFD and γ−MPS silane coupling fragments. The number of grafted γ−MPS fragments (Nγ-MPS) can be estimated as follows. The molecular weight (MH-SiO2 ) of H-SiO2 hybrid particle is given by the relation: MH-SiO2 = MSiO2 + Mshell, where MSiO2 and Mshell are the molecular weights of SiO2 core and organic shell part, respectively. From TGA data, the ratio of MSiO2 to Mshell is given by MSiO2/Mshell = 93.4/6.6. Then, Mshell is estimated to be 2.744 × 108 using the relation: MSiO2 = (4/3)πr13 dSiO2 Nav. This organic shell is composed of a mixture of PFD and γ−MPS fragments. Then,

Surface Tailoring of Polymer Nanoparticles

239

the mass of PFD grafted chains can be estimated to be 1.296 × 106. So, the mass of grafted γ−MPS fragments is estimated to be 1.448 × 108. Therefore, the number of grafted γ−MPS fragments was calculated to be 5.83 × 105 mol/ one particle. We performed the construction of hybrid nanocomposites by using these modified SiO2 nanoparticles [58]. The MMA solution of H-SiO2 (H-SiO2; 84 wt%) was poured into a petri dish. This weight percent was determined from calculation to give a body-centered cubic (BCC) packing structure. The H-SiO2 was dispersed in MMA under ultrasonic irradiation before poly­mer­i­ za­tion. Radical photopoly­mer­i­za­tion was carried out in nitrogen atmosphere at 30°C under UV irradiation. This DC-mediated radical poly­mer­i­za­tion proceeded with living radical mechanism as proven previously by kinitic approaches [20,59]. All the poly­mer­i­za­tion products provided transparent films and exhibited opal-like color. Such prepared samples were then immersed in hydrofluoric acid (HF) solution to etch away SiO2 particles, yielding nanoporous PMMA films. Figure  8.7a shows an SEM photograph of a vertical section of composite film after etching SiO2 particles. The SEM image shows a matrix with quite uniform nanopore voids. On the other hand, Figure 8.7b shows an enlarged image of nanoporous films. The average pore size was about 190 nm, which agrees well with the size of colloidal SiO2 particles. The nearest-neighbor distance Ds of SiO2 particles was about 204 nm, which closes relatively to the calculated value (243 nm) within experimental errors considering the effects of the volume shrinkage of PMMA matrix and the cutting angle of a vertical section of composite film. This texture indicates that SiO2 particles are locked in a state of molecular dispersion in a PMMA matrix, but that the two-dimensional long-range order such as colloidal crystals is not perfectly maintained. The photofunctional SiO2 particles in this system undergo graft poly­mer­i­za­tion radially to form hybrid materials.

8.6 Architecture of Polymer Particles Composed of Brush Structure at Surface and Application for Structural Color Materials The unique ability of photonic crystals to manipulate the transmission of light may lead to potential applications ranging from simple optical switches to an optical computer. Opals are naturally occurring three-dimensional (3D) photonic crystals: their microstructure consists of SiO2 spheres of about 150–300 nm in diameter, which are tightly packed into repeating hexagonal or cubic arrangements [60]. Synthetic opals (colloidal crystals) use this same pattern, although they can be made from different materials. In the former section, we mentioned the construction method of colloidal crystals

240

Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

(a)

1 µm

(b)

500 nm

Figure 8.7 SEM photographs of (a) vertical section of composite film after etching SiO2 particles and (b) enlarged image. (Reprinted from K. Ishizu, Y. Tokuno, D. H. Lee, S. Uchida, and M. Ozawa, Journal of Applied Polymer Science 112: 2434–40, 2009. With permission.).

by DC-mediated radical poly­mer­i­za­tion of MMA initiated by DC groups on SiO2 hybrid nanoparticles modified with PFD [58]. In Section 8.4, we also mentioned the architecture of poly­mer brushes encapsulated SiO2 particles by DC-mediated living radical poly­mer­i­za­tion. This technique can be applied not only for SiO2 but also for the surface modification of various poly­mer particles. Scheme8.5 shows the schematic illustration for the synthesis of poly­mer particles composed of brush structure at surface [61]. First, the cross-linked poly(t-butyl methacrylate) (PBMA) core particles (CCP) were prepared by surfactant-free emulsion copoly­mer­i­za­tion of t-butyl methacrylate (BMA) and ethylene glycol dimethacrylate (EGDM). Table  8.4 lists the poly­mer­i­za­tion

C

CH3 H 2C

C

CH2

+

CH2

O

C H2C

90°C, H2O

MMA, VBDC

MMA, CuCl, bpy

45°C, H2O

in THF, UV, ct

O

O CH3

tBMA

K2S2O8

O

O C(CH3)

O

O

C CH2

C

EGDMA

Seed Particle (CCP) Emulsion Polymerization

Core-Shell Particle (CSP) Living Radical Photopolymerization

Brush-Core Particle (BCP) Photo-induced ATRP

Surface Tailoring of Polymer Nanoparticles

CH3 H2C

Scheme 8.5 Schematic illustration for the synthesis of poly­mer particles composed of brush structure at surface. (Reprinted from D. H. Lee, Y. Tokuno, S. Uchida, M. Ozawa, and K. Ishizu, Journal of Colloid and Interface Science, 340: 27–34, 2009. With permission.)

241

242

Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

Table 8.4 Surfactant-Free Emulsion Polymerization Conditions and Results for PBMA Cross-Linked Core Particles (CCPs)a Code

Temperature (°C)

Total Momonerb Conversion (%)

Dnc (nm)

Dhd (nm)

Dw /Dnc

CCP1 CCP2 CCP3 CCP4

93 90 83 82

83 80 88 87

194 229 251 282

197 233 252 288

1.0002 1.0002 1.0001 1.0003

Note: From D. H. Lee, Y. Tokuno, S. Uchida, M. Ozawa, and K. Ishizu, Journal of Colloid and Interface Science, 340: 27–34, 2009. With permission. a The emulsion copoly­mer­i­za­tions were carried out in feeds of BMA (5.8 mL, 3.62 × 102 mol/L), EGDM (1.7 mL, 0.014 × 10–4 mol/L), and K2S2O8 (0.206 g, 7.65 × 10–4 mol/L) under stirring speed condition for 800 rpm in nitrogen atmosphere for 2 h. b Determined by gravimetric method. c Determined by a survey of 300 samples picked from SEM photographs. d Hydrodynamic diameter was determined by DLS in H O at 25°C. 2

conditions and results for CCP series. The effect of poly­mer­i­za­tion temperature on particle morphology and particle size was studied under the constant condition of the feed monomer ratio of BMA to EGDM and total monomer concentration. Figure 8.8 shows the SEM photographs of CCP1–CCP4. In all the photographs, the spherical particles are clearly visible and each particle size distribution is extremely narrow (Dw/Dn = 1.001 – 1.003). The particle diameters of CCPs increase with decreasing the poly­mer­i­za­tion temperature. At high temperature, CCP particles formed in emulsion seem to be stabilized sterically in the scale of small particle size with not only initiator fragments (persulfate anion) but also solubility of PBMA units in water. Next, we synthesized photofunctional core-shell particles (CSPs) possessing DC groups on the surface by encapsulation of seed particles. The poly­mer­i ­za­t ion conditions and results are listed in Table 8.5. The core particles encapsulated in monomer droplets (MMA, EGDM, and VBDC) start the radical photopoly­mer­i ­za­t ion and form the thin layer of the shell part. The reaction was run at 45°C, which is much higher than room temperature. An organic-soluble initiator (V-70) was used so that effective initiation occurred in the monomer droplets. This reaction system formed a macroinitiator with highly localized DC groups attached chemically to the surfaces of the colloidal particles. The poly­mer­i ­za­t ion rate increased during the time in which the conversion reached 72% after 4 h. A typical SEM photograph of the copoly­mer­i ­za­t ion product CSP1 (CCP1 as seed particle) is displayed in Figure 8.9a. The texture shows that all particles have very smooth surfaces and remain unagglomerated (Dn = 204 nm; Dw /Dn = 1.002). The particle size distribution obtained from analysis of the DLS data is

243

Surface Tailoring of Polymer Nanoparticles

(a)

(b)

500 nm (c)

500 nm (d)

500 nm

500 nm

Figure 8.8 SEM photographs of cross-linked PBMA core particles (CCP): (a) CCP1, (b) CCP2, (c) CCP3, and (d) CCP4. (Reprinted from D. H. Lee, Y. Tokuno, S. Uchida, M. Ozawa, and K. Ishizu, Journal of Colloid and Interface Science, 340: 27–34, 2009. With permission.)

presented in Figure 8.9b. The texture shows spherical particles larger (D h = 209 nm) than the SEM image, and narrow size distribution. The content of DC groups for the CSP1 particles was also determined with the radical transfer reaction. As a result, the DC groups were estimated to be 7.59 × 105 number/particle. Brush-core particles (BCPs) were prepared by grafting from photoinduced ATRP. Table 8.6 lists the poly­mer­i­za­tion conditions and results for BCP1 initiated by CSP1 as macroinitiator. After 8 h of poly­mer­i­za­tion, the monomer conversion reached 15%. A typical SEM photograph of BCP1 is shown in Figure 8.10a. Spherical particles (Dn = 240 nm) are clearly visible for the sample and particle size distribution was very narrow (Dw /Dn = 1.007). The thickness of the grafted PMMA brushes was observed to be 18 nm. Figure 8.10b shows particle size distribution of BCP1 on DLS data. The distribution is unimodal, and hydrodynamic diameter Dh was 240 nm. This means that PMMA brush chains expanded in THF solution because THF is a good solvent for PMMA. The mass of the PMMA brush phase (MB) and molecular weight

244

Living Radical Photopoly­mer­i ­za­t ion Conditions and Results for Core-Shell Particles (CSP)a Feed of Monomer Code

CCP1 (mL)

CSP1

30

b

MMA (mL)

EGDM (mL)

VBDC (mg)

V-70 (mg)

Temperature (°C)

Total Momonerc Conversion (%)

Dnd (nm)

Dhe (nm)

0.2

0.05

0.05

0.05

45

72

204

209

Dw /Dnd 1.0002

Note: From D. H. Lee, Y. Tokuno, S. Uchida, M. Ozawa, and K. Ishizu, Journal of Colloid and Interface Science, 340: 27–34, 2009. With permission. a Polymerized under UV irradiation for 3 h. b D = 194 nm. n c Determined by gravimetric method. d Determined by a survey of 300 samples picked from SEM photographs. e Hydrodynamic diameter was determined by DLS in H O at 25°C. 2

Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

Table 8.5

245

Surface Tailoring of Polymer Nanoparticles

(a)

500 nm 35

(b)

Size Distribution (LS%)

30 25 CSP Dh = 204 nm

20 15 10 5 0

1

10

100

1000

104

Dh (nm) Figure 8.9 SEM photograph (a) and size distribution (b) on DLS data for core-shell particles (CSP1) encapsulated CCP seed. (Reprinted from D. H. Lee, Y. Tokuno, S. Uchida, M. Ozawa, and K. Ishizu, Journal of Colloid and Interface Science, 340: 27–34, 2009. With permission.)

246

Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

Table 8.6 Grafting from Photo-Induced ATRP Conditions and Results for PMMA Brush-Core Particles (BCP)a Code

[CSP1]:[CuBr]:[bpy]:[MMA]

Time (h)

Conversionb (%)

Dnc (nm)

Dhd (nm)

Dw /Dnc

BCP1

1:2:4:70

8

15

240

244

1.0007

Note: From D. H. Lee, Y. Tokuno, S. Uchida, M. Ozawa, and K. Ishizu, Journal of Colloid and Interface Science, 340: 27–34, 2009. With permission. a Polymerized in THF/EtOH(3:1v/v) under stirring speed condition for 800 rpm in UV irradiation. b Determined by gravimetric method. c Determined by a survey of 300 samples picked from SEM photographs. d Hydrodynamic diameter was determined by DLS in THF at 25°C.

of PMMA brush were calculated to be 1.999 × 109 and 1.625 × 103, respectively, with the assumption that all of the DC initiation sites on the microinitiator led to the propagation of MMA. The BCP particles exhibited one DC group at each PMMA brush end. We performed the construction of colloidal crystals and studied their optical properties. The brilliant monochromatic colors covering the visible parts were prepared by controlling the diameter of the monodisperse particles. Figure 8.11a displays color photographs of the prepared films CCP1~CCP4 deposited on the glass substrate. The CCP4, CCP3, CCP2, and CCP1 films show structural colors, that is, red, yellow, green, and blue, respectively. This means that each film forms a colloidal crystal (CC). Figure 8.11b shows the reflection spectra of CC-CCP1~CC-CCP4 under the condition of the incident angle θ = 90°. Table 8.7 lists the peak wavelength for colloidal crystals CC-CCP1~CC-CCP4. The Bragg equation is given by

(

λ max = 2Ds ( 2/3) neff 2 − cos 2 θ

)

1/2



(8.1)

which describes the bandgap position for light incident on the (111) face of a face-centered cubic (FCC) lattice, where λmax, Ds, θ, and neff are the peak wavelength, diameter of spheres, angle between the incident light and the normal to the diffraction planes, and the mean effective refractive index of this crystalline array, respectively. The neff can be defined by

neff = nP2ϕ P + nM2ϕ M

(8.2)

where nP, nM, ϕP, and ϕM are the refractive index of particles, refractive index of matrix, volume fraction of particles, and volume fraction of matrix, respectively. The CC-CCP film is an array composed of PBMA particles and air matrix. Then, neff is estimated to be 1.36 using nP (1.464)62, nM (1.0), ϕP (0.74), and ϕM (0.26). The calculated wavelength (λcald) from Equation (8.1) is 430 nm

247

Surface Tailoring of Polymer Nanoparticles

(a)

600 nm 35

(b)

Size Distribution (LS%)

30 25 BCP Dh = 240 nm

20 15 10 5 0

1

10

100 Dh (nm)

1000

104

Figure 8.10 SEM photograph (a) and size distribution (b) on DLS data for brush-core particle (BCP1). (Reprinted from D. H. Lee, Y. Tokuno, S. Uchida, M. Ozawa, and K. Ishizu, Journal of Colloid and Interface Science, 340: 27–34, 2009. With permission.)

90

(b)

75 Reflectance (%)

60 45

CC-CCP4

CC-CCP3

CC-CCP2

CC-CCP1

30 15 0

(c)

200

30° 50°

Reflection (%) 0

200

400 600 800 Wavelength (nm)

400 600 800 Wavelength (nm)

1000

1200

(d)

CC-CCP1

Reflectance (%)

20°

0

1000

1200

CC-CSP CC-BCP

0

200

400 600 800 Wavelength (nm)

1000

1200

Figure 8.11 Photographs and reflection spectra of colloidal crystals (CC): (a) color photographs of CC-CCP1 (blue), CC-CCP2 (green), CC-CCP3 (yellow), and CC-CCP4 (red), (b) reflection spectra of CC-CCP1~CC-CCP4 (θ = 90°), (c) angle dependence of the reflection for CC-CCP4, and (d) reflection spectra of CC-CCP1, CC-CSP1, and CC-BCP1.

Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

CC-CCP1 CC-CCP2 CC-CCP3 CC-CCP4

248

(a)

249

Surface Tailoring of Polymer Nanoparticles

Table 8.7 Optical Properties of Colloidal Crystals Code CC-CCP1 CC-CCP2 CC-CCP3 CC-CCP4

λmaxa (nm)

λcaldb (nm)

Dsc (nm)

Color

450 506 525 626

430 508 557 626

194 229 251 282

Blue Green Yellow Red

Note: From D. H. Lee, Y. Tokuno, S. Uchida, M. Ozawa, and K. Ishizu, Journal of Colloid and Interface Science, 340: 27–34, 2009. With permission. a λ max was determined from the wavelength of reflection. b λ cald was calculated by Bragg’s law. c D was determined by the SEM. s

using Ds = 194 nm. This value was well in agreement with the observed one (λmax = 450 nm). Figure  8.11c shows the reflection spectra of colloidal crystal CC-CCP4, varying the incident angle θ. The λmax at θ = 50°, 30°, and 20° were 581 (red), 558 (yellow), and 491 nm (green), respectively. The λmax led to blue-shift with decreasing the incident angle. On the other hand, Figure  8.11d shows the reflection spectra of colloidal crystals CC-CCP1, CC-CSP1, and CC-BCP1. The observed λmax at θ = 90° is 477 (sky blue) and 516 nm (green) for colloidal crystals CC-CSP1 and CC-BCP1, respectively. The wavelengths shift to the long wavelength side with the increment of particle diameters, and the reflection intensities for CC-CSP1 and CC-BCP1 somewhat decrease compared to that of CC-CCP1 due to weak FCC packing. Both colloidal particles had photofunctional DC groups on their surfaces. Therefore, polymeric superstructure films (mesoscopically ordered cubic lattices) will be able to construct by living radical graft copoly­mer­i­za­tion, initiated by using photofunctionalized poly­mer particles as macroinitiator. Future work will involve controlling the interplanar spacings of structures by changing monomer concentration and type of cubic lattices. These systems will have numerous applications in nanotechnology, such as optical and electronic devices.

8.7 Surface Modification of Polymer Particles via RAFT Polymerization RAFT is arguably the most applicable technique, since most of the monomers that can be poly­mer­ized by conventional radical poly­mer­i­za­tion can also be poly­mer­ized through RAFT, which is not possible with other living radical poly­mer­i­za­tion methods. The conditions for RAFT poly­mer­i­za­tion

250

Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

are similar to that of a conventional radical poly­mer­i­za­tion except for the addition of a RAFT agent [63–67]. The combination of surface-initiated poly­mer­i­za­tion and RAFT techniques has been widely explored as a route to design the surface properties and functionality of various substrates. Previous work has used the RAFT poly­mer­i­za­tion technique to graft polymers to silica particles either by using “grafting to” [68,69] or “grafting from” methods [70–73]. Li and Benicewicz [70] have reported the synthesis method for well-defined poly­ mer brushes grafted onto silica nanoparticles via surface RAFT poly­mer­ i­za­tion. Scheme 8.6 shows the synthetic procedures for attaching RAFT agent onto silica nanoparticles. Novel RAFT-silane agents were prepared that contained both an active RAFT moiety and a silane coupling agent. RAFT agents were anchored to silica nanoparticles by the functionalization of colloidal silica with the RAFT-silane agents. RAFT poly­mer­i­za­tions were then conducted from the particle surface to graft homopolymer and block copolymer brushes to the particle. The kinetics of styrene and n-butyl acrylate surface RAFT poly­mer­i­za­tions were investigated and compared with model poly­mer­i­za­tions mediated by free RAFT agent. The molecular weights of grafted polymers increased linearly with conversions, and first-order kinetics were observed in the conversion range studied, indicating that the surface graft poly­mer­i­za­tion proceeded in a controlled manner. More recently, Liu and Pan [73] have also reported the preparation method for surface modification of silica nanoparticles via “grafting onto” RAFT poly­mer­i­za­tion. Scheme 8.7 shows a synthetic scheme for RAFT agent onto silica nanoparticles. The RAFT agent, 2-butyric acid dithiobenzoate (BDB), was prepared by substitution of dithiobenzoate magnesium bromide with sodium 2-bromobutyrate under alkali conditions in aqueous solution. Epoxy groups were covalently attached to silica nanoparticles by condensation reaction of 3-glycidyloxypropyltrimethoxysilane (GPS) with the hydroxyl on the silica particle surface. RAFT agent–functionalized nanoparticles were produced by the ring-opening reaction of the epoxy group with carbonyl group of BDB. Then, PS chains with controlled molecular weights and narrow polydispersities (less than 1.1) were grown from the RAFT agent– anchored nanoparticle surface. On the other hand, PMMA-silica nanocomposites were produced by “grafting through” using RAFT poly­mer­i­za­tion [74]. Scheme 8.8 shows the synthesis procedures for methacrylate-functionalized silica nanoparticles. The surface of silica nanoparticle was modified covalently by attaching methacryl group to the surface using 3-methacryloxypropyldimethylchlorosilane. Polymerization of MMA using the 4-cyano-4-(dodecylsulfanylthiocarbonyl) sulfanyl pentanoic acid RAFT agent produced the PMMA-SiO2 nanocomposites. It is not different from the studies concerning the surface modification of poly­mer particles via RAFT poly­mer­i­za­tion, but there are several reports that the core-shell poly­mer particles were prepared by cross-linking of core

O H

Karstedt’s catalyst dimethylchlorosilane

1

O Br

O H

Si Cl

CH3OH/pyridine

O Br

O H

2

Si OCH3 3

S SMgBr stir at rt.

S

O S

O H 4

Si O

CH3 nanoparticles

S

O S

MIBK, 85°C

O

Si O

H 5 S

O S

Surface Tailoring of Polymer Nanoparticles

O Br

O H

6 Scheme 8.6 Synthesis procedures for attaching RAFT agent onto silica nanoparticles. (Reprinted from C. Li and B. C. Benicewicz, Macromolecules 38: 5929–36, 2005. With permission.)

251

252

Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

Br

1. H2O

Mg/EtO2 (C2H5)2O

Br

S

CS2

MgBr

C

(C2H5)2O

SMgBr

S

2. CH3CH2CHCOONa

CH3CH2CH S C

3. HCl

COOH

OH +

(CH3O)3Si(CH2)3OCH2CH CH2 O COOH

OSi(CH2)3OCH2CH

O

CH2

O OSi(CH2)3OCH2CH CH2OC OH

CH3CH2CH

S

S C

S CHSC C2H5

Scheme 8.7 Synthesis scheme for RAFT agent onto silica nanoparticles. (Reprinted from C.-H. Liu and C.-Y. Pan, Polymer 48: 3679–85, 2007. With permission.) O

O Cl

Si

O

+

SiO2

SiO2

~20 nm methacryloxypropyldimethylchlorosilane (MCPDCS)

O SiO2-MMA

RAFT Polymerization MMA + AIBN S CN S S CO2H

11

PMMA + SiO2 nanocomposite

SiO2

SiO2

Scheme 8.8 Synthesis procedures for methacrylate-functionalized silica nanoparticles. (Reprinted from P. S. Chinthamanipeta, S. Kobukata, H. Nakata, and D. A. Shipp, Polymer 49: 5636–42, 2008. With permission.)

Surface Tailoring of Polymer Nanoparticles

253

or corona parts in micelles formed by block copolymers via RAFT poly­mer­ i­za­tions [75–77].

8.8 Surface Modification of Silica Nanoparticles via Nitroxide-Mediated Radical Polymerization Actually, the controlled living poly­mer­i­za­tion technique nitroxide-­mediated radical poly­mer­i­za­tion (NMRP) in conjunction with surface-­initiated poly­ mer­i­za­tion is among the most useful routes to precisely design and functionalize the surfaces of various solid materials by well-defined polymers. However, because the preparation of functional alkoxyamine is a complicated, multistep process, there have been few explorations about synthesis of poly­mer/silica hybrid composites by NMRP in recent years [78–81]. 2,2,6,6-Tetramethylpiperidine-N-oxyl (TEMPO) bromide salt was used to functionalize a silica surface with nitroxyl moieties [81]. Scheme 8.9 shows schematic representation of the functionalization of silica mediated by oxoaminium bromide salt and the graft poly­mer­iz­ a­tion of poly[styrene-co(maleic anhydride)]. The functionalization reaction took place in 48 h under mild conditions. In a second step, grafts of styrene-maleic anhydride copolymer were grown from the functionalized silica surface by heating it in the presence of the monomers. FT-IR and TGA analysis showed that the silica surface first functionalized with nitroxide moieties, and then that grafts of styrene-maleic anhydride grew from the functionalized silica surface. The results suggest that the oxoaminium salts were good candidates for the functionalization and grafting of surfaces that contain hydroxyl groups and for the generation of hybrid materials with improved properties. More recently, Wang et al. [82] have also reported the synthesis of poly(styrene-co-maleic anhydride) (PSMA)/SiO2 hybrid composites via “grafting onto” strategy based on NMRP. Scheme 8.10 shows the grafting poly­mer­i­za­tion of styrene from vinyl trimethoxysilane (A-171) modified nanosilica surface. Two steps were used to graft styrene/maleic anhydride copolymer chains to the surface of nanosilica: first, anchoring A-171 onto the surface of nanosilica, and then, using TEMPO as a radical trap, trapping the radicals produced by reaction of benzoyl peroxide (BPO) with styrene, maleic anhydride, and the vinyl group in grafted A-171 molecules. Finally, well-controlled molecular weight and narrow molecular weight distribution of PSMA chains were grown from the surface of nanosilica. PSMA is a polymeric material available in the market that has some good properties such as solubility, filming, and miscibility when mixed with styrene polymers [83,84]. Meanwhile, the anhydride groups can easily react with low molecular

254

Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

(1)

OH HO

– Br + N O

OH

HO

OH HO

(2)

OH HO

OH

HO

Et3N, CH2Cl2 25°C, 48h

O HO

OH

+

Et3NHBr

OH

Unmodified Silica

O O 126°C

O HC

O

O HC

2h

HO

CH2

m

O

OH

(3) H2C

N

OH

OH

N O

O

OH

O

n

OH + HO

“Free” polymer

OH OH

Scheme 8.9 Schematic representation of the functionalization of silica mediated by oxiaminium bromine salt and the graft poly­mer­i­za­t ion of poly[styrene-co-(maleic anhydride)]. (Reprinted from B. C. José, L. C. Tania, S. G. Enrique, and J. R. Enrique, Macromolecular Rapid Communications 28: 1397–1403, 2007. With permission.)

OH Si

HO

OH

HO

OH OH

A-171 Ultrasound dispersed

HO HO

Si

O

O

HO HO

HO O O

O

Si

OH

HO Si

Si OH HO

Styrene/Maleic anhydride TEMPO/BPO/130°C

Scheme 8.10 The grafting poly­mer­i­za­t ion of styrene from the A-171 modified nanosilica surface. (Reprinted from Y. Wang, Y. Shen, X. Pei, S. Zhang, H. Liu, and J. Ren, Reactive and Functional Polymers 68: 1225–30, 2008. With permission.)

Surface Tailoring of Polymer Nanoparticles

255

weight compounds such as water, alcohols, and amines. So, PSMA can be readily subjected to modification and has been widely used in industry.

8.9 Conclusions We demonstrated various strategies for the surface modification of polymeric/inorganic particles via living radical mechanisms such as ATRP, NMRP, DC-mediated, and RAFT poly­mer­i ­za­t ions. Previous work has used these poly­mer­i ­za­t ion techniques to graft polymers to poly­mer or silica particles by using the “grafting to,” “grafting from,” or “grafting through” method. We also established a new synthetic method for crosslinked shell possessing poly­mer or silica particles encapsulated in photo­ functional DC groups by the free radical emulsion copoly­mer­i ­za­t ion using inimer VBDC as one component monomer. In this copoly­mer­i ­za­t ion, the inimer VBDC had the formation of hyperbranched structures at its surface by living radical photopoly­mer­i ­za­t ion. Subsequently, core-brush particles were synthesized by the photoinduced ATRP of vinyl monomers initiated by photofunctional cross-linked particles as a macroinitiator. Because of the promising combination of a nanostructured poly­mer with the properties of reactive particles, these nanoparticles can be applied in the fields of hybrid nanocomposites and optic materials (such as structural color materials).

References





1. Furusawa, K., Norde, W., and J. Lyklema. 1972. Method for preparing surfactantfree polystyrene lattices of high surface change. J Kolloid Z Z Polym 250:908–9. 2. Vanderhoff, J. W., El-Aasser, M. S., Micale, F. J., Sudol, E. D., Tseng, C. M., Kornfeld, D. M., and F. A. Vincente. 1984. Preparation of large particle-size monodisperse latexes in space-poly­mer­iz­ a­tion kinetics and process-­development. Journal of Dispersion Science and Technology 5:231–46. 3. Ugelstad, J., Mork, P. C., Kaggerud, K. G., Ellingsen, T., and A. Berge. 1980. Swelling of oligomer-poly­mer particles. New methods of preparation of emulsions and poly­mer dispersions. Advances in Colloid and Interface Science 13:101–4. 4. Ugelstad, J., Mfutakamba, H. R., and P. C. Mork. 1985. Preparation and application of monodisperse poly­mer particles. Journal of Polymer Science, Polymer Symposia 72:225–40.

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9 Effects of Nano-Sized Polymerization Locus on the Kinetics of Controlled/ Living Radical Polymerization Hidetaka Tobita Contents 9.1 Introduction................................................................................................. 264 9.2 Origin of Livingness in Controlled/Living Radical Polymerization (CLRP)............................................................................... 265 9.3 Polymerization Rate................................................................................... 267 9.3.1 Basic Concept................................................................................... 267 9.3.2 SFRP and ATRP (Radical Long Life-ization Process)................ 268 9.3.2.1 SFRP and ATRP in Bulk.................................................. 268 9.3.2.2 SFRP and ATRP in Dispersed Systems......................... 271 9.3.3 RAFT and DT.................................................................................. 282 9.3.3.1 RAFT and DT in Bulk...................................................... 282 9.3.3.2 RAFT and DT in Dispersed Systems............................ 285 9.4 Molecular Weight Distribution (MWD).................................................. 293 9.4.1 Fundamental Distribution in CLRP............................................. 293 9.4.1.1 Chain Length Distribution During a Single Active Period: Most Probable Distribution............................... 293 9.4.1.2 Fundamental Distribution: Broader than the Poisson Distribution........................................................ 295 9.4.2 SFRP and ATRP in Dispersed Systems....................................... 297 9.4.3 RAFT Polymerization in Dispersed Systems (Normal Lifetime Process)............................................................................. 298 9.4.3.1 Monomer-Concentration-Variation (MCV) Effect....... 299 9.4.3.2 Effect of Particle Size on the MWD............................... 299 9.5 Summary...................................................................................................... 302 Acknowledgment................................................................................................. 303 References.............................................................................................................. 303 Appendix: Formulation of Various Average Times........................................305

263

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9.1 Introduction This chapter is aimed at clarifying the effects of small reaction locus on the kinetics of controlled/living radical poly­mer­i­za­tion (CLRP). The poly­mer­i­za­ tion kinetics in a dispersed system is complex partly because of the transport phenomena of various species, which could be utilized to prepare functional nanoparticles. To clarify the very basic characteristics of poly­mer formation through controlled/living radical poly­mer­i­za­tion, the transport phenomena among particles are neglected in this chapter. Theoretical investigation is conducted on how the small reaction locus changes the kinetics of CLRP, assuming the poly­mer particles as ideally isolated micro­reactors. When the initiator in continuous phase is used, only the radical entry into the particles is accounted for and the exit of species from a particle is neglected. To further simplify the discussion, the particles are assumed to be monodisperse. The present poly­mer­i­za­tion systems correspond to the ideal miniemulsion poly­ mer­i­za­tion. The experimental and theoretical investigations conducted so far for various types of CLRPs in bulk (Goto and Fukuda 2004; Braunecker and Matyjaszewski 2007) and also in a dispersed medium (Butte, Storti, and Morbidelli 2001; Cunningham 2008; Zetterlund, Kagawa, and Okubo 2008) have already been summarized. In this chapter, I try to add a fresh dimension to the kinetics of CLRP. In the present chapter, the mathematical tool used for the analysis of poly­ mer­i­za­tion kinetics inside nano-sized particles is the Monte Carlo (MC) simulation method reported earlier (Tobita and Yanase 2007; Tobita 2009a, 2009b). The MC simulation method is a powerful tool to analyze the kinetics of emulsion poly­mer­i­za­tion (Tobita 1995), and it enables investigation of what is happening inside each particle. Very detailed information can be extracted from this numerical technique. The effects of statistical variation among particles on the kinetics of CLRP in nano-sized particles, introduced in this chapter by the name of the fluctuation effect (for stable free-radical mediated poly­mer­i­za­tion [SFRP] and atom transfer radical poly­mer­i­za­tion [ATRP]) and monomer-concentration-variation effect (for reversible additionfragmentation chain transfer [RAFT] poly­mer­i­za­tion, degenerative transfer [DT] poly­mer­i­za­tion, and conventional free radical poly­mer­i­za­tion), are fruitful discoveries made possible through this powerful technique. The effects of particle size on the poly­mer­i­za­tion rate and the formed molecular weight distribution (MWD) profiles are discussed for various types of CLRPs in a unified manner.

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265

9.2 Origin of Livingness in Controlled/Living Radical Polymerization (CLRP) In free radical poly­mer­i­za­tion, the bimolecular termination reactions are inevitable. Therefore, the living poly­mer­i­za­tion in a strict sense in which the chain termination reactions are totally absent is impossible. However, if a large percentage of poly­mer chains are dormant and can potentially grow further, such free radical poly­mer­i­za­tion systems can be regarded as pseudo-living poly­mer­i­za­tion. Because the lifetime of a generated radical is short, normally ~100 s, a basic strategy to keep the chain potentially active is to distribute very short active periods throughout the whole reaction time. Figure 9.1 shows a schematic representation of a pseudo-living poly­mer formation. The thickness of each vertical line shows the time length of an active period, which is typically 10 –4–10 –3 s. On the other hand, it takes hours for the whole poly­mer­i­za­tion time. From the point of view of the formation history of a chain, most of the time is spent as a dormant form. Two types of methods have been proposed to make the active periods distributed throughout the whole poly­mer­i­za­tion time. The first method is to protect a radical from termination reactions by reversible capping with a trapping agent. The trapping reaction provides a temporal protection of active radicals, and the pseudo-living condition is assured by reducing the frequency of bimolecular termination. SFRP and ATRP fall into this category (see Figure 9.2 for various reversible reaction schemes). The history of chain formation and that of a radical are the same and are both represented schematically by Figure  9.1. The time fraction of the active period in terms of growing chain, ϕA,Chain, and in terms of radical species, ϕA, is the same, and for both is given by tR•/(tR• + tPX), where tZ is the average lifetime spent in the chemical form, Z. Both ϕA,Chain and ϕA must be very much smaller than unity, essentially very close to zero. The fundamental procedure to explicitly represent various average lifetimes can be found in the Appendix to this chapter. In this poly­mer­i­za­tion process, the apparent lifetime of a radical is extended significantly, and such poly­mer­i­za­tion process is called the radical long lifeReaction time, tP Active period

Dormant period Figure 9.1 Schematic representation of the formation history of a poly­mer chain in CLRP.

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SFRP

Pi X

k1 k2

ATRP Pi X + Y RAFT Ri• + XPj DT

Ri• + XPj

Ri• + X k1 k2 k2 k1 kex kex

Ri• + XY PiXPj

k1 k2

Pi X + Rj•

Pi X + Rj•

Figure 9.2 Reversible reaction scheme in each type of CLRP. In the figure, Pi is the poly­mer with chain length i, and R•i is the active poly­mer radical with chain length i.

ization process in this chapter. Note, however, the actual total time length of all growth periods of a chain is still smaller than a few seconds and is very short. The lifetime is extended simply because of very long dormant periods in which an active radical is capped by a trapping agent. In addition, the radical long life-ization should not be confused with the persistent radical or stable radical. The persistent radical and/or stable radical in SFRP refer to the trapping agent, such as TEMPO and verdazyls, which cannot propagate. On the other hand, the long-life radical named here can propagate during the active period. The second method for distributing the chain growth period is to utilize the chain transfer reactions, such as in RAFT poly­mer­i­za­tion and DT poly­ mer­i­za­tion. In these cases, the pseudo-livingness does not necessarily come from a reduced frequency of bimolecular termination, but is provided by relaying an active radical to a large number of chains before finally being stopped by bimolecular termination. In this type of process, the initiation reaction is needed to start poly­mer­i­za­tion. The history of a radical lifetime is shown in Figure  9.3. All of the chains except for the finally terminated chains can grow further when the next chain transfer reaction occurs on the chain end. In this process, the termination reactions are anticipated and do not have to be prevented. The radical long life-ization is not necessarily required. The total number of relayed chains is important to keep the pseudo-livingness. The time fraction of the active period in terms of growing chain, ϕA,Chain, is given by tR•/(tR• + tXP) for RAFT and DT, and is much smaller than unity, as in the cases of SFRP and ATRP. This is why the theoretical MWD function is essentially the same for all CLRPs. On the other hand, when discussing the poly­mer­i­za­tion rate, what is important is the time fraction of the active radical period in terms of radical species, ϕA, which is given by tR•/(tR• + tPXP) for RAFT and is ϕA = 1 for DT. For RAFT, ϕA does not have to be much smaller than unity. Note that ϕA = 1 in the conventional, nonliving free radical poly­mer­i­za­tion.

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267

Termination

Initiating chain end Figure 9.3 Schematic representation of the chain formation in RAFT and DT.

9.3 Polymerization Rate 9.3.1 Basic Concept The rate of free radical poly­mer­i­za­tion is most popularly represented by:

Rp = k p [M][R• ]

(9.1)

where kp is the propagation rate constant, [M] is the monomer concentration, and [R•] is the active radical concentration. It might be less popular, but the following expression can also be used for free radical poly­mer­i­za­tion, as long as the initiation is slow and the lifetime of a radical is short:

R p = RI ν

(9.2)

where R I is the initiation rate, ν is the kinetic chain length, represented by ν = kp [M]/kt [R•], and kt is the termination rate constant. By using the relationship, R I = Rt = kt [R•] 2, it is straightforward to show that Equations (9.1) and (9.2) are equivalent. Note that the termination rate constant defined by Rt = kt [R•] 2 is used in this chapter, not Rt = 2kt [R•] 2. To facilitate the discussion on the CLRP, Equation (9.2) is generalized. Let RRG be the radical generation rate in the reaction locus (mol/[L•s]), and Lν be the average number of monomeric units added to the generated radical until the chain stops growing. Then, the poly­mer­i­za­tion rate, Rp, is represented by:

Rp = RRG Lν

(9.3)

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Table 9.1 Concentration of a Single Molecule Assuming the Density of a Particle Is 1 g/cm3 Diameter, Dp [nm]

Concentration of a Single Molecule in mol•L–1

200 100   50   30   10

3.98 × 10–7 3.18 × 10–6 2.54 × 10–5 1.18 × 10–4 3.18 × 10–3

In the conventional free radical poly­mer­i­za­tion in bulk, RRG = R I and Lν = ν. The theoretical usefulness of Equation (9.3) will be understood when the kinetics of SFRP and ATRP are considered in Section 9.3.2. In conventional, nonliving free radical poly­mer­i­za­tion, the poly­mer­i­ za­tion rate increases as the particle diameter, Dp, decreases, especially for Dp < 100 nm, due to so-called compartmentalization (Gilbert 1995). In terms of Equation (9.1), the rate increase can be explained by the increase in the radical concentration, [R•]. By separating radicals into different particles, the termination reaction between the radicals located in different particles is prohibited and the apparent (overall) termination rate constant decreases, leading to a higher radical concentration. A significant rate increase could be observed for the zero-one systems (Gilbert 1995) where the time fraction in which more than one radical exists in a particle can be neglected. When the exit of a radical from a particle can be neglected, the average number of radicals per particle is nR• = 0.5. In a nano-sized particle, the concentration of a single molecule becomes rather high, as shown in Table 9.1. Note that in usual free radical poly­mer­i­za­tion in bulk, [R•] is smaller than ~10 –6 mol•L–1, and a single radical concentration for Dp < 50 nm is extraordinarily high, leading to a very high poly­mer­i­za­tion rate. On the basis of Equation (9.2), Rp = R Iν, the poly­mer­i­za­tion rate increase in the conventional free radical poly­mer­i­za­tion in dispersed systems can be rationalized from the increase in the kinetic chain length ν. The bimolecular termination frequency in a particle is reduced because of the compartmentalization, which makes ν larger. In a typical zero-one system where radicals enter a particle one by one, the first radical entry generates a poly­mer radical that keeps on growing until the second radical entry. The ν-value can be made extraordinarily large in an emulsified system. 9.3.2 SFRP and ATRP (Radical Long Life-ization Process) 9.3.2.1 SFRP and ATRP in Bulk To simplify the discussion, first consider SFRP as an example of the radical long life-ization process, although the discussion also can be extended for

Effects of Nano-Sized Polymerization Locus on the Kinetics of CLRP

269

ATRP in a straightforward manner. The reversible reaction of SFRP is shown in Figure 9.2, and other elementary reactions are the same as conventional free radical poly­mer­i­za­tion. Figure 9.1 shows the history of chain growth, but it can also represent the history of a radical for SFRP and ATRP. To further simplify the discussion, let us neglect the initiation reaction. After a long dormant period, a radical is generated by the activation reaction whose rate constant is k1. The average time required to generate a radical from a PX is tPX = 1/k1, which is constant during poly­mer­i­za­tion in SFRP, assuming a constant reaction temperature. For a given poly­mer­i­za­tion time, tP, the average number of active periods is given by nA = tp/tPX , which is also a constant. The total number of monomeric units added during the poly­mer­i­za­tion time tp is equal to nA × Pn,SA, where Pn,SA is the average number of monomeric units added during a single active period. Therefore, the poly­mer­i­za­tion rate for a given initial dormant concentration [PX]0 is determined solely by Pn,SA, which is represented by: Rp ∝ Pn,SA = k p [M]tR• =



k p [ M] k 2 [ X]

(9.4)

Equation (9.4) shows that the poly­mer­i­za­tion rate is inversely proportional to the trapping agent concentration [X]. Let us generalize the discussion in the context given by Equation (9.3) proposed earlier. Imagine an active radical as a flashlight. When a radical is generated by the activation reaction, the light is on for about tR• = 10 –4 – 10 –3 s. After that there is a very long dark period for tens (or hundreds) of seconds (=tPX). During this long time interval, lots of flashlights are on in various locations. When the observed radical is active again and flashes, it would be very difficult for the observer to recognize that this is the very radical that the observer was watching. If the dark period (tPX = 1/k1) is much larger than the time required to add a monomeric unit (tM = 1/(kp[M])), the memory is practically lost and it would be reasonable to consider that the activation reaction is essentially the radical generation rate R RG in Equation (9.3). The activation reaction can be considered as the pseudo-initiation, and the deactivation reaction as the pseudo-­termination, as shown in Table 9.2. Table 9.2 Pseudo-Initiation and -Termination in the CLRP Based on the Radical Long Life-ization Process SFRP k

Pseudo-initiation

1 Pi X  → R•i + X

Pseudo-termination

2 R•i + X  → Pi X

k

ATRP k

1 Pi X + Y  → R•i + XY

k

2 R•i + XY  → Pi X + Y

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Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

The livingness in the long life-ization process results from the fact that the rate of pseudo-initiation and -termination are much more significant than the genuine initiation and termination, respectively. For SFRPs, the radical generation rate in the reaction locus, RRG, is given by:

RRG = RI + k1[PX] ≅ k1[PX]

(9.5)

and the average number of monomeric units added to the generated radical until the chain stops growing, Lν, is given by:

Lν =

k p [ M] kt [R • ] + k 2 [ X]

≅

k p [ M] = Pn,SA k 2 [ X]

(9.6)

Therefore, the poly­mer­i­za­tion rate, Rp, is given by:

Rp = RRG Lν = k1[PX]

k p [ M] = k1[PX]Pn,SA k 2 [ X]

(9.7a)

or

Rp = k p [M]K

[PX] [ X]

(9.7b)

where K ≡ k1/k2. Equation (9.7a) agrees with Equation (9.4) developed earlier. Normally, [X] << [PX], and therefore, [PX] ≌ [PX]0 for practically most of the poly­mer­i­za­tion time, and [PX] could be considered as a constant in many systems. An important characteristic of Equations (9.7a) and (9.7b) is that the rate of initiation and that of termination are not directly involved. On the other hand, for the TEMPO-mediated styrene poly­mer­i­za­tion, it is known that the poly­mer­i­za­tion rate is practically equal to the thermal poly­ mer­i­za­tion of styrene (Fukuda et al. 1996; Goto and Fukuda 1997). The radical concentration is determined by

[ R • ] = RI k t

in which the reversible reaction is not involved. This fact may appear not to conform to the aforementioned equations, but in fact, Equations (9.7a) and (9.7b) can explain this phenomenon as shown next. The balance equations for the active radical concentration [R•] and the trapping agent concentration [X] are given by:

d[R• ] = RI − kt [R• ]2 + k1[PX] − k 2 [R• ][ X] dt

(9.8)

Effects of Nano-Sized Polymerization Locus on the Kinetics of CLRP



d[ X] = k1[PX] − k 2 [R• ][ X] dt

271

(9.9)

When the initiation rate, R I , is large enough (R I for the TEMPO-mediated styrene poly­mer­i­za­tion is usually large enough because of a high poly­mer­ i­za­tion temperature), the stationary state hypothesis can be used for both Equations (9.8) and (9.9) (Tobita 2008b), except for the very beginning of the poly­mer­i­za­tion. Equating both equations to zero and summing up both equations leads to R I = kt [R•]2, that is,

[ R • ] = RI k t

(9.10)

From Equation (9.9), one obtains:

[R • ] = K

[PX] [ X]

(9.11)

By substituting Equation (9.11) for the relationship Rp = kp[M][R•], one obtains Equation (9.7b). Qualitatively, the increase of the poly­mer­i­za­tion rate by the addition of initiator in SFRP can be interpreted as follows. Addition of the initiator molecules makes the radical concentration [R•] higher, which reduces the trapping agent concentration [X] as shown in Equation (9.11). Because the poly­mer­i­za­tion rate is inversely proportional to [X], the poly­ mer­i­za­tion rate increases. As long as the number of chains started growing from the initiator is much smaller than those from [PX]0, that is, [I]0 << [PX]0, addition of slowly decomposing initiator is a wise method to increase the poly­mer­i­za­tion rate without significantly affecting the MWD and the livingness (Goto and Fukuda 1997; Tobita 2006b). When R I is not large enough, Equation (9.10) does not hold; however, Equation (9.11) is still valid as shown earlier (Tobita 2008b). Therefore, Equations (9.7a) and (9.7b) are always equivalent to Equation (9.1) in SFRP. In this section, SFRP was used to highlight the fundamental characteristics of the radical long life-ization process; however, a similar argument would hold also for ATRP. 9.3.2.2 SFRP and ATRP in Dispersed Systems 9.3.2.2.1 Single-Molecule-Concentration (SMC) Effect The radical long life-ization process aims to suppress the termination reaction as small as possible to attain high livingness. As a most idealized condition, let us first consider the case with neither initiation nor termination in

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Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

1.0

Bulk

Conversion

0.8

150 nm 100 nm

0.6

75 nm Dp = 50 nm

0.4 0.2 0.0

0

2000

4000

6000

8000

10000

Time (s) Figure 9.4 Monte Carlo simulation results for the conversion development for the SFRP with no initiation and no termination. (Reprinted from H. Tobita and F. Yanase, Macromolecular Theory and Simulation 16: 476–88, 2007. With permission.)

SFRP, that is, with only pseudo-initiation and pseudo-termination instead of genuine initiation and termination. Figure 9.4 shows an example of the MC simulation results (Tobita and Yanase 2007). As shown in Figure 9.4, the most fundamental characteristic of the radical long life-ization process in a nanosized reaction locus is the decrease of the poly­mer­i­za­tion rate as the reaction locus becomes smaller. The reversible reaction of SFRP in Figure  9.2 shows that an active radical and a trapping agent are always formed in pairs. When an active radical is formed in a particle, a trapping agent always coexists. Equation (9.7b) shows that the poly­mer­i­za­tion rate, Rp, is in inverse proportion to the trapping agent concentration, [X]. Therefore, if the trapping agent concentration in a particle [X] is larger than that in bulk [X]bulk , the poly­mer­i­za­tion rate in the particle must be smaller than in bulk. Note that a single molecule concentration in a nano-sized particle is large, as was shown in Table 9.1. The preceding discussion leads to the following simple theory. If a single molecule concentration of trapping agent exceeds [X]bulk , the poly­mer­ i­za­t ion rate in the particle must be smaller than in the corresponding bulk poly­mer­i ­za­t ion. The single molecule concentration in a particle is calculated from 1/(NA vp), where NA is Avogadro’s number and vp is the particle volume (=πDp3/6). Therefore, if the particle diameter is smaller than Dp,SMC given by the following equation, the poly­mer­i­za­tion rate must be smaller than that in bulk because of the single-molecule-concentration (SMC) effect.

  6 Dp ,SMC =    πN A [ X]bulk 

1/3



(9.12)

Radical Conc. (mol/L)

Effects of Nano-Sized Polymerization Locus on the Kinetics of CLRP

10–6

273

Bulk Slope = 3

10–7

Dp = 150 nm

10–8 2

3

4

5

6

7 8 9 100

2

Particle Diameter (nm) Figure 9.5 Calculated active radical concentration [R•]. The calculation conditions are the same as for Figure  9.4. (Reprinted from H. Tobita, Macromolecular Theory and Simulation 16: 810–23, 2007. With permission.)

Under the calculation condition shown in Figure 9.4, the trapping agent concentration in bulk poly­mer­i­za­tion is [X]bulk = 8.94 × 10 –7 mol/L, and Dp,SMC is calculated to be 153 nm. Figure  9.4 shows that the poly­mer­i­za­tion rate decreases significantly for Dp < Dp,SMC = 153 nm, which shows that the prediction based on the present SMC theory agrees well. The poly­mer­i­za­tion rate, Rp, is proportional to 1/[X] in the radical long life-ization process. For the particle size region where the kinetics are dominated by the SMC effect, the trapping agent concentration is given by [X]p = 1/(NA vp), and, therefore, it is expected that Rp is proportional to the particle volume vp, which means Rp ∝ D3p . Figure 9.5 shows the calculated results for the radical concentration, which clearly shows the relationship Rp ∝ D3p for the small-particle region, approximately for Dp < Dp,SMC, where the kinetics are dominated by the SMC effect. The relationship Rp ∝ Dp3 for Dp < Dp,SMC has been observed for the calculation results of both SFRP and ATRP conducted under realistic reaction conditions. Figure 9.6 shows the calculation results for the TEMPO-mediated styrene poly­ mer­i­za­tion reported in Zetterlund and Okubo (2007). They solved the modified Smith-Ewart equation numerically, and the MC method was not used. The SMC effect is examined in Figure 9.6. The trapping agent concentration in bulk poly­mer­i­za­tion [X]bulk can be determined by solving Equations (9.8) and (9.9). On the other hand, however, in the present case, the stationary state hypothesis is valid, and Equation (9.10) can be used to determine [X]bulk. The vertical lines are the Dp,SMC-values calculated from Equation (9.12). The poly­mer­i­za­tion rate, Rp, becomes smaller than bulk for Dp < Dp,SMC, and Rp ∝ D3p for Dp < Dp,SMC, as predicted by the SMC theory. Figure 9.7 shows some examples of the calculated results for ATRP reported in Zetterlund, Kagawa, and Okubo (2009). For ATRP, [X]bulk can be obtained by solving the following set of differential equations:

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Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

10

Rp/Rp,bulk

1

Dp,SMC

Dp,SMC

Dp,SMC

Slope = 3

0.1

[PX]0 mol/L 0.2 0.02 0.002

0.01

0.001 8 910

2

3

4 5 6 7 8 9100 Dp (nm)

2

Figure 9.6 Calculated poly­mer­i­za­t ion rate for the TEMPO-mediated styrene poly­mer­i­za­t ion at 10% conversion reported in Zetterlund and Okubo (2007). The horizontal dotted line shows the poly­mer­i­za­t ion rate in the corresponding bulk poly­mer­i­za­t ion. The Dp,SMC-values for [PX]0 = 0.2, 0.02, and 0.002 mol/L shown by the vertical lines are 22.7, 48.9, and 105.3 nm, respectively. (Reprinted from H. Tobita, Macromolecular Theory and Simulation 16: 810–23, 2007. With permission.)



d[R• ] = RI − kt [R• ]2 + k1[PX][Y] − k 2 [R• ][ XY] dt

(9.13)



d[ X] = k1[PX][Y] − k 2 [R• ][ XY] dt

(9.14)

For the present calculation condition in Zetterlund, Kagawa, and Okubo (2009) at 1% conversion, the stationary state hypothesis for Equation (9.14) is not valid, and one needs to solve the differential equation directly. As shown in Figure 9.7, the SMC theory represented by Equation (9.12) also agrees perfectly for ATRP; that is, Rp is smaller than bulk for Dp < Dp,SMC, and Rp ∝ D3p for Dp < Dp,SMC. Zetterlund, Kagawa, and Okubo (2009) argued that the SMC theory does not apply for ATRP because the particle size that shows the maximum poly­ mer­i­za­tion rate is larger than Dp,SMC. This is a pure misunderstanding of the SMC theory. The SMC theory gives the diameter below which the poly­mer­i­ za­tion rate is smaller than the corresponding bulk poly­mer­i­za­tion. The SMC theory does not give the particle size showing the maximum poly­mer­i­za­tion rate, Dp,Max. The Dp,Max -value is related to the fluctuation effect discussed in Section 9.3.2.2.3. In the present discussion, the exit of the trapping agent is neglected. The exit of the trapping agent may lead to forming particles having a radical but without a trapping agent. The uncontrolled, radical-only state leads to a conventional emulsion poly­mer­i­za­tion. The poly­mer­i­za­tion rate may increase significantly, while a noticeable amount of high molecular weight, dead poly­mer chains could be formed in such cases (Tobita and Yanase 2007).

Effects of Nano-Sized Polymerization Locus on the Kinetics of CLRP

10

Rp/Rp,bulk

1

Dp,SMC

Dp,SMC

275

Dp,SMC

Slope = 3 [PX]0 mol/L 0.0435 0.00435 0.00087

0.1

0.01

0.001

8 9 10

2

3

4 5 6 7 8 9 100 Dp (nm)

2

Figure 9.7 Calculated poly­mer­i­za­t ion rate for the ATRP at 1% conversion reported in Zetterlund, Kagawa, and Okubo (2009). The horizontal dotted line shows the poly­mer­i­za­t ion rate in the corresponding bulk poly­mer­i­za­t ion. The Dp,SMC-values for [PX]0 = 43.5, 4.35, and 0.87 mM shown by the vertical lines are 20.2, 44.0, and 89.0 nm, respectively.

9.3.2.2.2 Effect of Radical Segregation As shown in Figures 9.6 and 9.7, there may exist a particle size region where the poly­mer­i­za­tion rate is larger than that for the bulk poly­mer­i­za­tion. In this section, it will be shown that the segregation of radicals into different particles that reduce the bimolecular termination frequency in a particle, as in the case of conventional emulsion poly­mer­i­za­tion kinetics, cannot be the main reason for the rate increase in the pseudo-living radical poly­mer­i­za­tion based on the radical long life-ization process. As was shown in Figure 9.4, such a rate increase region is not observed in an idealized system with no initiation and no termination. Figure 9.8 shows the MC simulation results with termination but without initiation (Tobita and Yanase 2007). In this case, the poly­mer­i­za­tion rate increases by reducing the particle size until about Dp = 50 nm. The increase in poly­mer­i­za­tion rate by reducing the particle size is a usual phenomenon in conventional emulsion poly­mer­i­za­tion. In conventional, nonliving free radical poly­mer­i­za­tion, the radicals are separated into different particles, and the termination between radicals located in different particles is physically hindered. The decrease in the termination frequency inside each particle leads to a larger kinetic chain length, ν in Equation (9.2), leading to a higher poly­mer­i­za­tion rate. One may think that the same simple mechanism, called the segregation effect (Zetterlund and Okubo 2007; Zetterlund, Kagawa, and Okubo 2009), is operative also for the radical long life-ization processes. On the other hand, however, Equations (9.7a) and (9.7b) clearly show that the rate increase directly

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Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

0.20 75 nm Dp = 50 nm

Conversion

0.15

100 nm Bulk

0.10 30 nm 0.05

0.00

25 nm

0

2000

4000

6000

8000

10000

Time (s) Figure 9.8 MC simulation results for the conversion development for the SFRP with termination but without initiation. (Reprinted from H. Tobita and F. Yanase, Macromolecular Theory and Simulation 16: 476–88, 2007. With permission.)

due to the decrease in termination frequency in each particle is impossible, because neither termination rate nor ν are involved in Equations (9.7a) and (9.7b). The condition where the pseudo-termination is much more significant than the true termination is required for the pseudo-living radical poly­mer­ i­za­tion. True bimolecular termination cannot play an important role in both SFRP and ATRP, and therefore the segregation effect in a narrow sense can never play an important role in the radical long life-ization processes. On the other hand, the decrease in termination frequency in a particle may change the poly­mer­i­za­tion rate indirectly by way of the following three steps (Tobita 2007):



1. By isolating radicals into different particles, the frequency of termination reaction in a particle decreases. 2. Smaller frequency of bimolecular termination reduces the number of excess trapping agents. Note that two trapping agents are formed by a single bimolecular termination event. 3. Lower concentration of the trapping agent in a particle [X] leads to a larger poly­mer­i­za­tion rate as shown in Equations (9.7a) and (9.7b).

The rate increase based on the preceding three steps is called an extended segregation effect. The extended segregation effect is related to the persistent radical effect (Fischer 1999); that is, the progressive increase in trapping

Effects of Nano-Sized Polymerization Locus on the Kinetics of CLRP

277

agent concentration due to bimolecular termination leads to a shift in the equilibrium toward dormant species. By separating radicals into different particles, the increase of trapping agent concentration can be suppressed. The increase in the radical concentration through the extended segregation effect should not be confused with the direct segregation effect, where the radical concentration is increased directly by the decrease in the termination frequency as in the case of conventional free radical emulsion poly­ mer­i­za­tion. Note that the fact that the radical concentration is the highest or that the bimolecular termination frequency is the lowest at a certain particle size showing a maximum poly­mer­i­za­tion rate does not prove that the segregation effect in a narrow sense is operative. A direct segregation effect can never be important, as clearly represented by Equations (9.7a) and (9.7b), where the bimolecular termination reaction rate is not involved. Let us examine the extended segregation effect represented by the aforementioned three steps. Figure 9.9 shows the time development of [X] for Dp = 50 nm, which shows a fast poly­mer­i­za­tion rate in Figure 9.8. The dotted line in Figure 9.9 is obtained from the MC simulation. Figure 9.9 shows that the trapping agent concentration [X] is smaller than in bulk, which appears to show that the extended segregation effect plays a role. On the other hand, however, what is important in the relationship Rp ∝ 1/[X] shown in Equation (9.7b) is the trapping agent concentration at a time when an active radical grows, as shown in the SFRP mechanism represented in Figure 9.2. In most of the data points plotted in Figure 9.9, not a single radical exists in the particle. (Note that the average number of active radicals in a particle is extremely small in SFRP miniemulsion poly­mer­i­za­tion.) Therefore, one more trapping agent must be introduced in the particles when an active radical is formed. Figure  9.10 shows the trapping agent concentration when an active radical exists [X]Act. The effect of a single molecule cannot be neglected in such small particles as Dp = 50 nm (see Table 9.1). The trapping agent concentration 1.2×10–4

[x] mol/L

1.0 0.8 0.6

Bulk Dp = 50 nm

0.4 0.2 0.0

0

2000

4000 6000 Time (s)

8000

10000

Figure 9.9 Simulation results for the time development of the trapping agent concentration whose conversion development is shown in Figure 9.8. (Reprinted from H. Tobita, Macromolecular Theory and Simulation 16: 810–23, 2007. With permission.)

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Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

1.2×10–4

× × × × × × × × × × × × × × × × × × Bulk × × Dp = 50 nm × With an active radical

[x]Act mol/L

1.0 0.8 0.6 0.4 0.2 0.0

× 0

2000

6000 4000 Time (s)

8000

10000

Figure 9.10 Trapping agent concentration with the coexistence of an active radical, [X]Act, for the cases whose conversion development is shown in Figure 9.8. For a bulk poly­mer­i­za­t ion, the active radicals always exist in the reaction system, and [X]Act = [X]. (Reprinted from H. Tobita, Macromolecular Theory and Simulation 16: 810–23, 2007. With permission.)

during the active period is essentially the same as in bulk poly­mer­i­za­tion, and the extended segregation effect is not the reason for the faster poly­mer­ i­za­tion rate of Dp = 50 nm in Figure 9.8. Depending on the poly­mer­i­za­tion condition, there are cases where the extended segregation effect plays a role in a limited time range (Tobita 2007); however, the main reason for the faster poly­mer­i­za­tion rate is the fluctuation effect elucidated in the next section. 9.3.2.2.3 Number Fluctuation of Trapping Agents Figure 9.11 shows some examples of the conversion-time curve in each particle. With Dp = 50 nm, the conversion development is significantly different from particle to particle, compared with Dp = 100 nm. At each bending point of the curve for Dp = 50 nm, bimolecular termination occurs, and two more free trapping agents are formed. As the concentration of trapping agent X increases, the poly­mer­i­za­tion rate is decreased significantly. For large particles, such statistical difference among particles is rather small. Figure  9.11 clearly shows that the effect of the difference in the number of trapping agents in different particles must be accounted for properly for smaller particles. As shown in Equation (9.7a), the poly­mer­i­za­tion rate is proportional to the average number of monomeric units added during a single active period; that is, Rp ∝ Pn,SA = kp[M]/k2[X]Act if the concentration is the same for all particles. On the other hand, when the number of trapping agents is different significantly among particles, Pn,SA must be calculated from:

1 Pn,SA = Nt

Nt

∑k n i=1

k p nM ,i 2 X , Act , i



(9.15)

Effects of Nano-Sized Polymerization Locus on the Kinetics of CLRP

Conversion

0.20

Dp = 50 nm

0.15 0.10

Particle 1 2 3

0.15 0.00

0

2000

4000 6000 Time (s)

0.10

10000

Particle 1 2 3

0.15 0.00

8000

Dp = 100 nm

0.15 Conversion

279

0

2000

4000 6000 Time (s)

8000

10000

Figure 9.11 Conversion-time curves in each poly­mer particle for the systems whose overall conversion development is shown in Figure  9.8. The poly­mer­i ­za­t ion behavior is significantly different from particle to particle at D p = 50 nm. (Reprinted from H. Tobita and F. Yanase, Macromolecular Theory and Simulation 16: 476–88, 2007. With permission.)

where nM,i and nX,Act,i are the number of monomer molecules and trapping agents in the i-th particle, respectively. In nX,Act,i , the subscript Act is used to designate that this is the number when at least one active radical exists in the particle. Nt is the total number of particles. Remember that we are considering cases where the particle volume is the same for all particles, and therefore the number of molecules and the concentration is interchangeable. Note that because the average concentration [X]Act is essentially the same for Dp = 50 nm and bulk poly­mer­i­za­tion, as was shown in Figure 9.10, the use of kp[M]/k2[X]Act instead of Equation (9.15) cannot explain the rate increase; that is, the kp[M]/k2[X]Act for Dp = 50 nm is the same as the bulk poly­mer­i­za­tion. Figure  9.12 shows the calculated results of Equation (9.15), which clearly shows that the Pn,SA-value is significantly larger than that in bulk, resulting in a larger poly­mer­i­za­tion rate as shown in Figure 9.8. The rate increase cannot be rationalized by the average concentrations, and one needs to account for the statistical variation in the number of trapping

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Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

8

Bulk Dp = 50 nm

– Pn,SA

6 4 2 0

0

2000

4000

6000

8000

10000

Time (s) Figure 9.12 Average number of monomeric units added during a single active period Pn,SA to which the poly­mer­i­za­t ion rate is proportional. The same MC data shown in Figures 9.9 and 9.10 are used for Dp = 50 nm. (Reprinted from H. Tobita, Macromolecular Theory and Simulation 16: 810–23, 2007. With permission.)

agents in a particle. In Equation (9.15), because nM,i >> 1, the difference in the number of monomer molecules among particles nM,i can be neglected, at least for low conversion regions. What is important here is the variation of nX,Act. The rate increase because of the number fluctuation of trapping agents in a particle was named the fluctuation effect (Tobita 2007). The rate increase due to the fluctuation effect can be assessed by considering the following ratio:

Ω=



1 Nt

Nt

∑1 n

X , Act , i

i=1

1 nX , Act



(9.16)

Mathematically, the ratio Ω is always larger than unity, or equal to unity for a uniform distribution. Let us consider a simple example. Suppose we have two systems, both with nX,Act = 3. All particles contain three trapping agents in system 1, while 50% of particles contain one trapping agent and 50% contain five trapping agents in system 2. In this case, the Ω-value is given by:

Ω=

0.5 × 1 1 + 0.5 × 1 5 0.6 = = 1.8 13 13

(9.17)

Equation (9.17) illustrates that system 2 shows an 80% faster poly­mer­ i­za­t ion rate than system 1. This simple example shows that the fluctuation in nX,Act can accelerate the poly­mer­i ­za­t ion rate. Note, however, that “acceleration” in the present context is that Rp is larger than the system having the same number of nX,Act, not compared with the corresponding bulk poly­mer­i ­za­t ion.

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Effects of Nano-Sized Polymerization Locus on the Kinetics of CLRP

2.2

= 0.047

Ω

2.0 1.8

1 0.5 0.1

= 0.211

1.6 1.4 Ω = 1.1

1.2 1.0

0

5

10 – nX,Act

15

20

Figure 9.13 Estimated rate increase due to the fluctuation in the number of trapping agents among particles, as a function of the average number of trapping agents during the active period nX,Act. In the figure, ξ = k2/kt.

To quantify the acceleration due to the fluctuation effect, one needs to determine the distribution function of the trapping agents among particles. Of course, the MC simulation can provide the distribution function. However, the MC method may not be a convenient tool for everybody. To roughly assess the degree of acceleration, a simple model for the number distribution was proposed (Tobita 2007). Note that the model is not exact but based on rather simplified assumptions. However, it could be used to roughly estimate the condition where the fluctuation effect becomes important. In addition, the exit of the trapping agent from the particle did not change the distribution profile significantly in a preliminary investigation (Tobita 2007). Figure 9.13 shows the relationship between Ω and the average number of free trapping agents during the active period nX,Act . The fluctuation effect can be neglected for large values of nX,Act , and it becomes significant as the particle size is reduced. In the figure, ξ = k2/kt , and ξ is usually smaller than unity. As ξ becomes smaller, there is a tendency to cause bimolecular termination more frequently, which makes the distribution of nX,Act broader, leading to a more significant acceleration. For 0.5 < ξ < 1, the fluctuation effect becomes significant when nX,Act is smaller than about 10. In the case of Figure 9.10, nX,Act/ (vpNA) ≌ [X]bulk. Let the threshold nX,Act-value below which the acceleration is significant be nf . The particle diameter below which the fluctuation effect becomes important, Dp,Fluct , can be estimated from the following equation:

  6n f  Dp , Fluct =   πN A [ X]bulk 

1 3 13

= n f Dp ,SMC

(9.18)

For Dp,SMC < Dp < Dp,Fluct , an acceleration window (Tobita 2007), a particle diameter range for which the poly­mer­i­za­tion rate is larger than that for bulk poly­mer­i­za­tion, may exist.

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Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

Dp,SMC

Dp,Fluct

2 1 Rp/Rp,bulk

6 4

Slope = 3

2

Fluctuation effect

Single molecule conc. effect

0.1 6 4

Acceleration window

8

9

10

3

2

4

5

6

7

Dp (nm) Figure 9.14 Estimated values of Dp,SMC and Dp,Fluct for the SFRP system shown in Figure 9.6 with [PX]0 = 0.2. (Modified from H. Tobita, Macromolecular Theory and Simulation 16: 810–23, 2007.)

Under the calculation condition shown in Figure  9.6, ξ = 0.211. From Figure 9.13, nf is about 13 for ξ = 0.211. Figure 9.14 shows the calculated acceleration window for [PX]0 = 0.2 shown in Figure 9.6. The acceleration window reasonably applies for the present reaction condition. Note that Ω shows the relative rate increase compared with the cases without the statistical variation, and not necessarily compared with the bulk poly­mer­i­za­tion. As discussed earlier (Tobita 2007), there are cases in which the [X]Act-value in a particle is larger than [X]bulk . In such cases, the poly­mer­ i­za­tion rate certainly becomes larger compared with the system without the statistical variation; however, Rp could be smaller than the corresponding bulk poly­mer­i­za­tion. Figure  9.15 shows the comparison for the cases with ATRP, shown in Figure  9.7. In this case, ξ = 0.047, and nf is about 20. The acceleration window agrees reasonably well for all [PX]0 conditions. Figure 9.13 shows that the maximum rate increase is predicted to occur at nX,Act = 5.3 for ξ = 0.047. (However, in ATRP shown in Figure 9.2, X corresponds to XY.) Zetterlund, Kagawa, and Okubo (2009) reported that the number of trapping agents at the maximum poly­mer­i­za­tion rate is about five, which also agrees satisfactorily with the present fluctuation theory. 9.3.3 RAFT and DT 9.3.3.1 RAFT and DT in Bulk The chain formation process in RAFT and DT was schematically shown in Figure 9.3. In this mechanism, the radical long life-ization is not required. The generated radicals are terminated after causing a large number of chain

Effects of Nano-Sized Polymerization Locus on the Kinetics of CLRP

283

10

Rp/Rp,bulk

1

0.1

Acceleration window

0.001

[PX]0 mol/L

Slope = 3

0.01

89

10

2

3

0.0435 0.00435 0.00087

4

5 6 7 89 100 Dp(nm)

2

Figure 9.15 Estimated acceleration window for the ATRP system shown in Figure 9.7.

transfer reactions. The time fraction of the active radical period is ϕA = 1 for DT, and does not have to be very small for RAFT. Note that the condition ϕA << 1 is requisite for SFRP and ATRP. Let us consider the expression for the poly­mer­i­za­tion rate based on Equation (9.3). In the case of DT, RRG = R I and the average number of monomeric units added to the generated radical, Lν = ν, as in the cases of the conventional, nonliving free radical poly­mer­i­za­tion, that is, Rp = R Iν. The reversible reaction in RAFT is represented by Equation (9.19).

k2

k1

k1

k2

  → Pi XPj ←   → Pi X + R•j          K ≡ R•i + XPj ←  

k1 [mol•L−1 ] k2

(9.19)

In RAFT poly­mer­i­za­tion, it is known that the rate retardation occurs by increasing the RAFT concentration. Monteriro and Brouwer (2001) proposed a cross-termination between propagating and adduct radical, that is, the reaction between R• and PXP.

k

ct R•i + Pj XPk  →

Pi |

Pj XPk



(9.20)

The intermediate termination (IT) reaction forms the three-arm star chain if termination is by combination. The IT model usually leads to a large value of k1.

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Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

Table 9.3 Rate Constants Used for the RAFT Polymerization Based on the Intermediate Termination (IT) Model and the Slow Fragmentation (SF) Model IT model SF model

k1 [s–1]

k2 [L•mol–1•s–1]

kp [L•mol–1•s–1]

kt [L•mol–1•s–1]

kct [L•mol–1•s–1]

1 × 104 0.5

1 × 106 1 × 106

500 500

1 × 107 1 × 107

1 × 107 0

On the other hand, Barner-Kowollik et al. (2001) attributed the retardation to the slow fragmentation of adduct radicals (slow-fragmentation [SF] model), and a small k1-value that could be about 104 times smaller than the IT model might be obtained even for the same set of experimental data for a bulk poly­mer­i­za­tion. There is an ongoing discussion of this problem (Barner-Kowollik et al. 2003; Wang et al. 2003; Kwak, Goto, and Fukuda 2004; Barner-Kowollik et al. 2006). A combined type of model that assumes that the cross-­termination occurs only with very short propagating radicals was also proposed recently (Konkolewicz 2008). Table  9.3 shows the kinetic parameters used in the present investigation (Tobita and Yanase 2007; Tobita 2008b, 2009a, 2009b). The initial concentrations used for the simulation are [M]0 = 8 mol•L–1, and [XP]0 = 0.04 mol•L–1. Although the magnitude of k1 is 2 × 104 times larger for the IT model, the conversion development in bulk poly­mer­i­za­tion does not differ significantly, as shown in Figure 11 in Tobita and Yanase (2007). According to the IT model listed in Table 9.3, the average lifetime of the intermediate, PXP, is tPXP = 1/k1 = 1 × 10 –4 s, which is the same order of magnitude as the average time required for an active radical to add one monomer molecule, tM = 1/kp[M], which is 2.5 × 10 –4 s at t = 0; that is, [M]0 = 8 mol/L. As was illustrated in Section 9.3.2.1 for SFRP and ATRP, imagine an active radical as a flashlight. When a new radical is generated by the initiation reaction in the dark, the flashlight moves by the addition of the next monomer through propagation. When the radical forms the intermediate, PXP, the light goes out, but the time length of the dark period is the same order of magnitude required to add one monomer molecule through propagation. The observer can follow the whole process of monomer addition until the radical is terminated. The Lν-value, that is, the average number of monomeric units added to the generated radical before it stops growing, is practically equal to the kinetic chain length, that is:

Lν = ν   (for the IT model in RAFT)

(9.21)

which is the same as for DT poly­mer­i­za­tion and for conventional, nonliving free radical poly­mer­i­za­tion. The lifetime of a radical until termination is in a similar magnitude as the conventional free radical poly­mer­i­za­tion in the IT model. Let us call the IT

Effects of Nano-Sized Polymerization Locus on the Kinetics of CLRP

285

model in RAFT and the DT poly­mer­i­za­tion the normal lifetime process in this chapter. On the other hand, let us consider the SF model. In this case, the dark period is tPXP = 2 s, which is much larger than tM = 1/kp[M]; that is, tPXP >> tM. Similarly to the SFRP and ATRP process discussed in Section 9.3.2.1, the memory is practically lost, and pseudo-initiation and pseudo-termination dominate the kinetics. This is the case of another radical long life-ization process. Therefore, the Lν-value is represented by: Lν = Pn,SA =



k p [ M] (for the SF model in RAFT) k 2 [ XP]

(9.22)

The SF model in RAFT belongs to the radical long life-ization process. Equations (9.21) and (9.22) are the key equations to clarify the differences in the kinetics of two types of models in dispersed media. 9.3.3.2 RAFT and DT in Dispersed Systems For DT and the IT model for RAFT, the kinetic chain length ν becomes larger as the particle size decreases, and therefore the poly­mer­i­za­tion rate Rp is expected to become larger as the particle size is made smaller. Figure  9.16 shows that the poly­mer­i­za­tion rate increases significantly by reducing the particle size (Tobita and Yanase 2007; Tobita 2008b, 2009a). In Figure 9.16, the monomer:initiator ratio is kept constant in order to focus attention on the effect of particle size. The radical generation rate is chosen 1.0

Dp = 50 nm

Conversion; x

0.8

75 nm 100 nm

0.6 0.4

150 nm

0.2 0.0

300 nm Bulk 0

2000

4000

6000

8000

10000

Time (s) Figure 9.16 Conversion development calculated for the IT model in RAFT poly­mer­i­za­t ion. The kinetic parameters used are shown in Table 9.3. (Reprinted from H. Tobita and F. Yanase, Macromolecular Theory and Simulation 16: 476–88, 2007. With permission.)

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Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

2.0×10–2

Bulk 50 nm 75 nm 100 nm 150 nm

Conversion; x

1.5

1.0

0.5

0.0

0

2000

4000

6000

8000

10000

Time (s) Figure 9.17 MC simulation results showing the effect of particle size on the conversion development for the SF model in RAFT poly­mer­i­za­t ion. The kinetic parameters used are shown in Table 9.3. (Reprinted from H. Tobita and F. Yanase, Macromolecular Theory and Simulation 16: 476–88, 2007. With permission.)

to make the average time interval between radical entry te = 50 s for Dp = 100 nm. On the other hand, the SF model in RAFT belongs to the radical long lifeization process, similarly to SFRP and ATRP. In RAFT, the RAFT concentration [XP] is large compared with the trapping agent concentration in SFRP and ATRP, and the number of the RAFT molecules in a particle is rather large. Therefore, the SMC effect, as well as the fluctuation effect, is insignificant. The Lν-value inside a nano-sized reaction locus represented by Equation (9.19) is essentially the same as for the bulk poly­mer­i­za­tion, and the poly­mer­i­za­tion rate is expected to be the same as for the bulk poly­mer­i­za­tion. The MC simulation results for the SF model are shown in Figure  9.17 (Tobita and Yanase 2007). The conversion development is essentially the same as bulk poly­mer­i­za­tion irrespective of the particle size, within the statistical errors. The present simulation results show that the miniemulsion poly­mer­i­za­tion experiment is a convenient method to discriminate the IT and SF models. If the poly­mer­i­za­tion rate increases significantly by reducing the particle size, the k1-value must be large enough, and the IT model might be an appropriate model to choose. 9.3.2.2.1 Monomer-Concentration-Variation (MCV) Effect in Normal Lifetime Process As clarified in the previous section, an increase of the poly­mer­i­za­tion rate by reducing the particle size is an important feature of the normal lifetime

Effects of Nano-Sized Polymerization Locus on the Kinetics of CLRP

287

Table 9.4 Average Time Interval between Radical Entry to a Particle Dp [nm] te [s]

   30 1852

  50 400

100   50

150 14.8

300 1.85

process. On the other hand, it will be clarified in this section that the poly­ mer­i­za­tion rate may be reduced for very small particles because of the statistical variation of the monomer concentration among particles (Tobita 2009a). This type of rate reduction applies to the IT model in RAFT, DT, and the conventional free radical poly­mer­i­za­tion in miniemulsion. In the present MC simulation condition, the monomer:initiator ratio is kept constant, and the average time interval between radical entry te used for the simulation is shown in Table 9.4. When the particle size is small, the radical entry interval is large, and the transient behavior of the radical concentration development in the earlier stage of poly­mer­i­za­tion cannot be neglected. For a RAFT polymerization, a growing radical experiences two different states, R• and PXP. The sum of the numbers of R• and PXP is represented by n (= nR• + nPXP). Assuming a zeroone system, the time development of the average number of n per particle, n, is given by (Tobita 2009a): nR• = e −t



te

( )

sinh t te ⇒ n = e −t

te

( )

sinh t te

(9.23)

Figure 9.18 shows a comparison with the MC simulation results for Dp = 50 nm, which shows an excellent agreement. Note that the n-development is not affected by the initial RAFT concentration because both R• and PXP can 0.5 0.4 0.3 – n

– – n– = e –t/te sinh(t/te)

0.2

MC Simulation (5000 particles) [XP]0 = 0

0.1 0.0

[XP]0 = 4×10–2 0

500

1000 Time (s)

1500

2000

Figure 9.18 Time development of n for Dp = 50 nm. The theoretical calculation is based on Equation (9.23).

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Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

be terminated by an entered radical. The case without RAFT agent, [XP]0 = 0, corresponds to the DT poly­mer­i­za­tion and also to the conventional free radical poly­mer­i­za­tion. The conversion development of poly­mer­i­za­tion in the emulsified system is normally given by: R p = k p [ M]



nR• φ A nφ A ⇒ R p = k p [ M] Vp N A Vp N A

(9.24)

In Equation (9.24), the time fraction of the active radical period ϕA is needed because the monomer addition occurs during that fraction of time. For DT and the conventional free radical poly­mer­i­za­tion, ϕA = 1. By substituting Equation (9.23) into Equation (9.24), the conversion development would be obtained. Figure  9.19 compares Equation (9.24) and the MC simulation results for Dp = 50 nm. The poly­mer­i­za­tion rate is clearly slower than that calculated from Equation (9.24). For the particles with Dp > 100 nm, such rate reduction was not observed. Figure 9.20 shows the time development of conversion, x in each poly­mer particle for Dp = 50 and 100 nm, for [XP]0 = 0, that is, the conventional miniemulsion poly­mer­i­za­tion without using RAFT agent or DT poly­mer­i­za­tion. The smooth curves are the average of all particles simulated, which corresponds to the conversion-time curve that can be obtained in an experiment. [XP]0 = 0

1.0

[XP]0 = 4×10–2

Conversion

0.8 0.6 0.4 MC simulation

0.2 0.0

Rp = kp[M]nR•φA/(VpNA) 0

500

1000

1500 Time (s)

2000

2500

3000

Figure 9.19 Conversion development for Dp = 50 nm. The poly­mer­i­za­t ion rate is slower than the calculation based on Equation (9.24), assuming the same monomer concentration for all particles.

Effects of Nano-Sized Polymerization Locus on the Kinetics of CLRP

289

1.0

Conversion

0.8

Dp = 50 nm

0.6

Average

[XP]0 = 0

0.4 0.2 0.0

0

500

1000 Time (s)

1500

2000

1.0

Conversion

0.8

Dp = 100 nm

0.6

Average

[XP]0 = 0

0.4 0.2 0.0

0

1000

2000 3000 Time (s)

4000

5000

Figure 9.20 Conversion development in each poly­mer particle obtained in the MC simulation for Dp = 50 and 100 nm, with [XP]0 = 0.

When the particle size is small, the statistical variation in the conversion development among particles is significant. Equation (9.24) tacitly assumes that the monomer concentration is the same for all particles. Such an assumption might be reasonable for large Dps, but not so for smaller particles, as shown in Figure 9.20. Note that the monomer transfer among particles may not be neglected in real systems, depending on the types of monomer used. When the monomer is transferred from one particle to another, the monomer concentration would be equalized, and therefore the present simulation results show the extreme cases where the monomer transfer is totally absent. As shown in Figure  9.20, some particles are almost dried out while the other particles have not started poly­mer­i­za­tion. In the radicals that exist in the particles with high conversion levels, the poly­mer­i­za­tion rate is much slower than that expected from the average monomer concentration, which may slow down the overall poly­mer­i­za­tion rate.

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Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

For the zero-one system without monomer and radical exit, the analytical solution for the conversion development that accounts for the monomerconcentration-variation (MCV) effect is given by Tobita (2009a): ∞

x(t) = 1 −



∑ y (t)

(9.25)

i

i=0



λ y 2 i (t) =    η

2i

(−1)

i

i!

{ (

)

(

e − λt U −i, 1 − 2i, −ηt − ie − ηtU 1 − i, 1 − 2i, ηt

)}

(9.26)

(for i = 0, 1, 2, …) λ y 2 i+1 (t) =    η

2 i+1

(−1) ⋅ (ηt) i

i!

i+(1/2 )

π

e

−λ+( η/2 ) t

{(−1)

i+(1/2 )

(

)

(

K i+(1/2) −ηt/2 − K i+(1/2) ηt/2

(for i = 0, 1, 2, …)

)}

(9.27)

where U(a,b,z) is the confluent hypergeometric function of the second kind, Kν(z) is the modified Bessel function of the second kind, λ ≡ 1/te, and η ≡ k p ϕA/(v p NA). Figure  9.21 compares the conversion development x from Equations (9.25)–(9.27) and the MC simulation results. The theoretical calculation results [XP]0 = 0

1.0

Conversion

0.8

[XP]0 = 4×10–2

0.6 0.4

MC simulation MCV model

0.2 0.0

0

500

1000

1500

2000

2500

3000

Time (s) Figure 9.21 Conversion development for Dp = 50 nm. The dotted curves are calculated from Equations (9.25)–(9.27). The statistical variation of monomer concentration needs to be accounted for in order to rationalize the MC simulation results.

Effects of Nano-Sized Polymerization Locus on the Kinetics of CLRP

1.0

Dp = 50 nm

75 nm

Conversion

0.8

30 nm 100 nm

0.6 0.4

150 nm

0.2 0.0

291

300 nm Bulk 0

2000

4000

6000

8000

10000

Time (s) Figure 9.22 Effect of particle size on the poly­mer­i­za­t ion rate for the RAFT poly­mer­i­za­t ion with [XP]0 = 4 × 10 –2 mol/L. (Reprinted from H. Tobita, Macromolecular Theory and Simulation 18: 108–19, 2009. With permission.)

agree perfectly with the MC simulation. The MCV effect also may need to be considered for the conventional miniemulsion poly­mer­i­za­tion with smaller particle sizes. The rate reduction due to the MCV effect is expected to be significant for the smaller particles. Figure 9.22 shows the conversion development for the RAFT poly­mer­i­za­tion with the IT model, which is the same as Figure  9.16 except that the MC simulation results for Dp = 30 nm are added. Because the rate reduction by the MCV effect is very significant for Dp = 30 nm, the poly­mer­i­za­tion rate is smaller than that for Dp = 50 nm in the present calculation condition. The MCV effect may play a role also in microemulsion poly­mer­i­za­tion, whose particle size is even smaller. 9.3.2.2.2 Retardation of RAFT in the Intermediate Termination Model In this section, the RAFT poly­mer­i­za­tion whose t PXP is small (t PXP << 1s and t PXP ≈ t R•) is considered. In this case, the poly­mer­i­za­tion rate is given by Rp = R Iν, which is the same as DT poly­mer­i­za­tion and conventional free radical poly­mer­i­za­tion. It will be shown that IT is required to account for the retardation by increasing the RAFT concentration in bulk, but not so for the poly­mer­i­za­tion conducted inside nano-sized particles. First, to clarify the retardation in bulk poly­mer­i­za­tion in terms of the IT model, Figure  9.23 shows the calculated conversion development for bulk poly­mer­i­za­tion. In the absence of the IT (kct = 0), the poly­mer­i­za­tion rate is unchanged even when the RAFT concentration is increased. This is because the kinetic chain length ν is not changed by the chain transfer reaction.

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Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

1.0

Conversion

0.8 0.6

kct = 0 [XP]0 = 0

Bulk Polym.

4×10–3 4×10–2

kct = 1×107

0.4

[XP]0 = 4×10–3

0.2 0.0 0.0

[XP]0 = 4×10–2 0.2

0.4

0.6

0.8

1.0×105

Time (s) Figure 9.23 Calculated conversion development for bulk poly­mer­i­za­t ion. (Reprinted from H. Tobita, Macromolecular Theory and Simulation 18: 108–19, 2009. With permission.)

On the other hand, with kct ≠ 0, the poly­mer­i­za­tion rate is reduced by the decrease in ν given by:

(

)

ν = k p [M] kt [R• ] + 2 kct [PXP]

(9.28)

By increasing the initial RAFT concentration [XP]0, the intermediate adductradical concentration [PXP] increases, making the kinetic chain length ν smaller. In the normal lifetime process, Rp = R Iν, and the poly­mer­i­za­tion rate is decreased by increasing the RAFT concentration. Figure  9.24 shows the MC simulation results for miniemulsion poly­ mer­i ­za­t ion with D p = 50 nm. Compared with bulk poly­mer­i ­za­t ion shown in Figure 9.23, two important characteristics must be pointed out. First, the rate retardation by increasing the RAFT concentration is observed without contribution of IT (kct = 0). Second, IT does not change the poly­mer­i­ za­t ion rate. From the MC simulation data, it was confirmed that the miniemulsion poly­mer­i­za­tion with Dp = 50 nm conforms to the zero-one kinetics; that is, the time fraction in which more than one radical exists in a particle can be neglected. In the zero-one system, the first radical entered to the particle generates a new growing chain, while the second radical terminates the chain. Therefore, the kinetic chain length for the zero-one system is given by:

ν = k p [M]te φ A

(9.29)

In Equation (9.29), kp[M] is the number of monomeric units added to a single rad­ical per second. The radical takes two forms, R• and PXP, and therefore, the actual chain growth time is teϕA. An important characteristic is that Rp ∝ ν ∝ ϕA.

Effects of Nano-Sized Polymerization Locus on the Kinetics of CLRP

293

1.0

Conversion

0.8

Dp = 50 nm kct = 0 [XP]0 = 0

0.6 0.4

4×10–3

0.0

0

1000

[XP]0 = 4×10–3

[XP]0 = 4×10–2

4×10–2

0.2

kct = 1×107

3000

2000

4000

5000

Time (s) Figure 9.24 MC simulation results for the conversion development with and without intermediate termination for Dp = 50 nm. (Reprinted from H. Tobita, Macromolecular Theory and Simulation 18: 108–19, 2009. With permission.)

The time fraction of the active period ϕA is given by:

φA =

tR• K = tR• + tPXP K + [ XP]

(9.30)

Equation (9.30) clearly shows that ϕA becomes smaller as the RAFT concentration [XP] increases. The retardation by increasing the RAFT agent may occur without the assistance of IT in miniemulsion poly­mer­i­za­tion. Another important characteristic of Equation (9.29) is that the mode of termination is not involved. The magnitude of kct does not change the poly­ mer­i­za­tion rate, although it may change the molecular weight distribution of the dead polymers. Because the poly­mer­i­za­tion rate does not change with the kct-value in the zero-one system, the miniemulsion poly­mer­i­za­tion is a poor experimental technique to determine this value. The transitional kinetic behavior by increasing the particle size, from the zero-one system to the pseudo-bulk kinetics, can be found in Tobita (2009a).

9.4 Molecular Weight Distribution (MWD) 9.4.1 Fundamental Distribution in CLRP 9.4.1.1 Chain Length Distribution During a Single Active Period: Most Probable Distribution The history of poly­mer chain formation in CLRP was schematically shown in Figure 9.1. The poly­mer chain is formed through the intermittent monomer

294

Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

addition. The probability of connecting the next unit during the active radical period, p, is given by:

p=

k p [ M] k p [ M] + k 2 [ X ]

(for SFRP)

(9.31)



p=

k p [ M] k p [M] + k 2 [ XY]

(for ATRP)

(9.32)



p=

k p [ M] k p [M] + k 2 [ XP]

(for RAFT)

(9.33)



p=

k p [ M] (for DT) k p [M] + kex [ XP]

(9.34)

Because the active radical period tR• is very small, the p-value can be considered as a constant during a single active period. Therefore, the chain length distribution during a single active period follows the most probable distribution, whose number fraction distribution is given by:

(

)

N SA (r ) = p r 1 − p

(9.35)

Note that the distribution starts from r = 0 because with probability 1 – p, the activated chain end is stopped before adding a single monomeric unit. This is why the distribution function is slightly different from the most probable distribution introduced in a textbook, N(r) = p r–1 (1 – p). In addition, for conventional, nonliving free radical poly­mer­i­za­tion, the probability of connecting a next unit, p, is large and close to unity, but for the CLRP, p is rather small. The number- and weight-average chain lengths formed during a single active period are given by Tobita (2006a):

Pn,SA =

p 1− p

(9.36)



Pw ,SA =

1+ p 1− p

(9.37)



Pw ,SA 1 + p = Pw ,SA p

(9.38)

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Effects of Nano-Sized Polymerization Locus on the Kinetics of CLRP

Note that the polydispersity index of chains formed during a single active period, Pw,SA/Pn,SA, could be much larger than two for small p-values. In RAFT poly­mer­i­za­tion, the active period on the same chain could be repeated via the two-armed intermediate PXP with probability 1/2. This possible repetition was accounted for by introducing the overall active/­dormant periods (Tobita 2008a). The overall connection probability P was introduced as follows: P=



2p   (for RAFT) 1+ p

(9.39)

For RAFT poly­mer­i­za­tion, by using the P-value instead of p, the mathematical formulation becomes the same as the other CLRPs (Tobita 2008a). 9.4.1.2 Fundamental Distribution: Broader than the Poisson Distribution To highlight the most fundamental aspects of the CLRPs, let us consider the MWD formed under the following simplifying conditions:

1. The probability of connecting the next unit during the active radical period, p, is constant throughout the poly­mer­i­za­tion.



2. The average time length of the dormant period shown in Figure 9.1 is constant, and the active periods are distributed randomly.



3. The bimolecular termination, as well as the chain transfer to small molecules, does not have a significant effect on the formed MWD.

The average time of a single dormant period for a chain, tDC , is summarized for each type of CLRP in Table A9.1 in the Appendix at the end of this overall chapter. In the case of RAFT, the overall dormant period, tDC , is given by Tobita (2008a):

(

)

overall tDC = 2 tXP + tPXP



(9.40)

overall For RAFT, tDC is used instead of tDC . For example, the average number of overall overall active periods is nAoverall = tP / tDC , where tP is the poly­mer­i­za­tion time. On the basis of the preceding three assumptions, the weight fraction distribution is given by Tobita (2006a):



(

)

2

(

(

) )

W (r ) = 1 − p p r−1re − nA F 1 + r , 2 ; 1 − p nA

(9.41)

where nA is the average number of active periods, nA = tP / tDC , and F(a,b;x) is the confluent hypergeometric function (Kummer’s function of the first kind), represented by:

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Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

F ( a , b ; x) = 1 +

( (

) )

ax a a + 1 x 2 + ⋅ +⋅⋅⋅ b b b + 1 2!

(9.42)

overall For RAFT, P and tDC are used instead of p and tDC , respectively. The number- and weight-average chain lengths are given by Tobita (2006a):



Pn = nA Pn,SA

(9.43)



Pw = Pw ,SA + nA Pn,SA

(9.44)



Pw 1 Pw ,SA 1+ p = 1+ ⋅ = 1+ Pn nA Pn,SA nA p

(9.45)

The ideal conventional living poly­mer­i­za­tion leads to the Poisson distribution for which Pw − Pn = 1. Equations (9.43) and (9.44) give that Pw − Pn = Pw ,SA > 1, which means that CLRP always leads to a broader distribution than the Pois­ son distribution. Equation (9.45) shows how to produce narrow MWD through CLRP. The most dominant factor is nA . By increasing the number of active periods, the MWD becomes narrower, and approaches unity irrespective of the p-value. On the other hand, for a given nA -value, the MWD is narrower for a larger p-value. It is sometimes stated that a higher number of monomer units added per activation-deactivation cycle leads to a broader distribution, but such a statement is wrong, as clearly shown in Equation (9.45). A higher number of monomer units added per activation-deactivation cycle is preferable to obtain a narrower MWD for a fixed value of nA as long as the bimolecular termination reaction and other chain transfer reactions are suppressed effectively. For a RAFT poly­mer­i­za­tion, the possible repetition of the active periods makes the P-value larger than p, while the nAoverall -value is about one-half of the cases without repetition nA , such as DT poly­mer­i­za­tion. Figure  9.25 shows a comparison with the cases without the repetition (Tobita 2008a). The repetition of the active periods forms clusters of active periods, and such clustering makes the MWD slightly broader than the cases without the repetition. The fraction of dead poly­mer chain must be made small in CLRP. Other than the bimolecular termination, chain transfer reactions lead to the formation of dead poly­mer chains. Within various types of chain transfer reactions, the monomer transfer reactions can never be totally suppressed. The maximum number-average chain length attainable in free radical poly­mer­i­ za­tion is limited by the monomer transfer reaction, and Pn, Max = 1/Cm , where

Effects of Nano-Sized Polymerization Locus on the Kinetics of CLRP

3 30

W(log10r)

2.5 – nAOA = 10

2

40

297

50 RAFT Process

20

No repetition of active radical periods

1.5 1 0.5 0.25

0.5

0.75

1

1.25

1.5

log10 r Figure 9.25 Example of the calculated weight fraction distribution development of RAFT polymers (solid curves). Comparison is made with the cases without the repetition of the active radical periods. (Reprinted from H. Tobita, Macromolecular Theory and Simulation 18: 120–26, 2009. With permission.)

Cm is the monomer transfer constant. A simple calculation method to account for the effect of monomer transfer reaction on the MWD profile was proposed in Tobita (2006a). To obtain a narrow distribution with high livingness, it is better to design Pn smaller than about 5% of Pn, Max (Tobita 2006a). The fundamental MWD function represented by Equation (9.41) is useful to consider with regard to the basic characteristics of the MWD formed in CLRP. On the other hand, the three assumptions discussed earlier need to be modified to calculate the MWD formed in more realistic conditions. The full MWD profiles were obtained by numerically solving an infinite set of differential equations using a commercial package (Predici®), and also by applying an MC simulation method. For the CLRP in dispersed systems, the MC method is the most powerful tool for the simulation. 9.4.2 SFRP and ATRP in Dispersed Systems Figure 9.26 shows the calculated MWD profiles for the SFRP whose conversion development was shown in Figure 9.8. Because the poly­mer­i­za­tion rate is the largest at Dp = 50 nm within the particle sizes shown in Figure 9.8, the MW is the largest at Dp = 50 nm. Figure 9.27 shows Dp polydispersity index (Pw /Pn ) of the MWD shown in Figure 9.26. The polydispersity index is the largest at which the poly­mer­i­za­ tion rate is the largest, that is, at Dp = 50 nm. The broadening of the MWD can be rationalized on the basis of the fluctuation theory. The main reason for the rate increase is the number fluctuation of trapping agents, and therefore, the conversion development is different among particles, as was shown in

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Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

2.5

W(log10r)

2.0 1.5 1.0

t = 10,000 [s]

Dp[nm] 50 75 100 150

0.5 0.0 0.5

1.0

1.5

2.0

2.5

log10r (a) 2.5

W(log10r)

2.0 1.5 1.0

t = 5,000 [s]

Dp[nm] 50 75 100 150

0.5 0.0 0.5

1.0

1.5

2.0

2.5

log r 10

(b)

Figure 9.26 Calculated weight fraction distribution of the SFRP polymers formed in miniemulsion poly­mer­i­za­t ion at t = 5000 s (a) and 10,000 s (b), whose conversion development is shown in Figure 9.8. (Reprinted from H. Tobita and F. Yanase, Macromolecular Theory and Simulation 16: 476–88, 2007. With permission.)

Figure 9.11. The MWD profiles formed in each particle are different significantly when the fluctuation effect is important. Therefore, the polydispersity index is the largest at Dp = 50 nm where the fluctuation effect accelerates the poly­mer­i­za­tion rate most significantly. The acceleration window could be used to increase the productivity; however, the MWD becomes broader because of the fluctuation effect at that particle size region. 9.4.3 RAFT Polymerization in Dispersed Systems (Normal Lifetime Process) In this section, the MWD formed in the IT model whose kinetic parameters are shown in Table 9.3 is considered.

Effects of Nano-Sized Polymerization Locus on the Kinetics of CLRP

299

1.5 Bulk

PDI

1.4

t = 5,000 [s]

1.3 1.2 t = 10,000 [s]

1.1 1.0

50 nm 40

60

80

100

120

140

160

Dp (nm) Figure 9.27 The polydispersity index (=Pw/Pn) of the MWDs shown in Figure  9.26. (Reprinted from H. Tobita and F. Yanase, Macromolecular Theory and Simulation 16: 476–88, 2007. With permission.)

9.4.3.1 Monomer-Concentration-Variation (MCV) Effect In Section 9.3.3.2.1, it was shown that the MCV effect may slow down the poly­mer­i­za­tion rate for small particle sizes because the time interval between radical entry tends to become larger for small Dps. When the MCV effect is significant, the MWD formed in different particles may differ significantly, leading to a broad distribution. One of the methods to prevent the broadening is to increase the radical entry frequency, which reduces the necessary transient time to reach the steady state radical concentration in the particle. (See Figure  1 of Tobita 2009b.) The problem with this hasty method is that the effect of dead poly­ mer chains becomes significant especially at higher conversions. Another simpler way to obtain a narrow MWD is a wait-and-see method. The MWD becomes narrower as the number of active periods increases, as shown in Figure 9.28. 9.4.3.2 Effect of Particle Size on the MWD Figure 9.29 shows the effect of particle size on the MWD at the final conversion level (x > 0.99). A significant amount (weight) of dead poly­mer chains is formed in larger particles. These dead poly­mer chains are large in weight, but small in the number, and therefore these peaks cannot be found if the distribution is plotted on the number basis (Tobita 2009b). Mainly because of a significant dead poly­mer chain formation in the larger particles, the MWD is narrower for smaller particles. The chain lengths of dead polymers are about twice and three times as large as the main peak polymers at the final conversion level. Because the main peak keeps on moving to larger chain lengths as the poly­mer­i­za­tion

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Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

12

W(log10r)

10

Dp = 50 nm t[s] 1000 5000

8 6 4

er

w e ro m ar ti N ith w

Broadened by the MCV Effect PDI = 1.39

2 0

PDI = 1.02

Conv. 55.2% 99.1%

1.6

1.8

2.0

2.2

2.4

log10r Figure 9.28 Calculated MWD development for the RAFT miniemulsion poly­mer­i­za­t ion with the IT model for Dp = 50 nm. The MWD broadening due to the MCV effect weakens as the time goes by. 12

W(log10r)

10

Dp[nm] 50

8

100

6

150

Dead polymers

300

4 2 0

2.2

2.4

log10r

2.6 2-armed

2.8 3-armed

Figure 9.29 Simulated MWD for the RAFT miniemulsion poly­mer­i­za­t ion with the IT model at the final conversion levels, x > 0.99. (Reprinted from H. Tobita, Macromolecular Theory and Simulation 18: 120–26, 2009. With permission.)

proceeds, this fact shows that the dead poly­mer chains are formed mainly at the final stage of poly­mer­i­za­tion. In fact, the dead poly­mer peaks were not observed at lower conversion levels. The reason for forming dead poly­mer chains in a final stage of poly­mer­i­za­tion can be rationalized as follows. Figure 9.30 shows the conversion developments for various Dps. Because the poly­mer­i­za­tion rate is slower for larger particle cases, it takes a very long time to reach high conversion levels for larger Dps. In addition, the poly­mer­ i­za­tion rate becomes very slow at higher conversion levels. Figure 9.31 shows how the number of dead poly­mer chains increases with time. The initiation and termination rates are balanced for both bulk and

Effects of Nano-Sized Polymerization Locus on the Kinetics of CLRP

1.0

50

0.8 Conversion

301

100 Very long time is needed.

150

0.6

Dp = 300 nm

0.4 0.2 0.0 0.0

0.5

1.0

1.5

2.0

2.5

3.0×105

Time (s) Figure 9.30 Conversion development for the RAFT miniemulsion poly­mer­i­za­t ion with Dp = 50, 100, 150 and 300 nm. (Reprinted from H. Tobita, Macromolecular Theory and Simulation 18: 120–26, 2009. With permission.)

Dead Polym. Conc. [mol/L]

1.0×10–3

0.8

0.6

0.4

Bulk Polym. Dp = 30 nm

0.2

50 nm 100 nm 150 nm 300 nm

0.0 0.0

0.5

1.0

1.5

2.0

2.5

3.0×104

Time (s) Figure 9.31 Time development of the dead poly­mer chain concentration for the RAFT poly­mer­i­za­t ion with various particle sizes. (Reprinted from H. Tobita, Macromolecular Theory and Simulation 18: 120–26, 2009. With permission.)

miniemulsion poly­mer­i­za­tion. In the present series of calculations, a constant initiation rate RI is used, and the number of dead poly­mer chains increases linearly with time. In terms of the required reaction time, the longest time is required at the final stage of poly­mer­i­za­tion as shown in Figure 9.30. This is why a significant number of dead poly­mer chains are formed at that stage.

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Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

A larger number of dead poly­mer chains are formed for larger Dps, simply because it takes a longer time to reach a high conversion level.

9.5 Summary The effect of nano-sized poly­mer­i­za­tion locus on the poly­mer­i­za­tion rate of CLRP can be rationalized conveniently by using the formula, Rp = R RGLν, where R RG is the radical generation rate in the reaction locus, and Lν is the average number of monomeric units added to the generated radical until the chain practically stops growing. SFRP and ATRP belong to the radical long life-ization process, identified in this chapter, R RG is equal to the radical generation rate from the dormant species, and Lν is given by the average number of monomeric units added during a single active period, Pn,SA ; that is, Rp = k1[PX]Pn,SA ∝ 1/[ X] for SFRP. An important conclusion is that (1) the poly­mer­i­za­tion rate is in inverse proportion to the trapping agent concentration [X], and (2) the bimolecular termination rate does not directly change the poly­mer­i­za­tion rate. The bimolecular termination affects the poly­mer­i­za­tion rate only through the production of free trapping agents through bimolecular termination. The poly­mer­i­za­tion rate cannot be increased significantly through the compartmentalization of radicals, as in the case of the conventional, nonliving radical poly­mer­i­za­tion. Two important factors control the poly­mer­i­za­tion rate of SFRP and ATRP inside nano-sized poly­mer­i­za­tion locus, namely, (1) the single-molecule­concentration (SMC) effect, and (2) the statistical fluctuation in the number of trapping agents in a particle. With the SMC effect, the poly­mer­i­za­tion rate 3 RP decreases significantly by making the particle size smaller; that is, Rp ∝ Dp . Below the diameter Dp,SMC, the poly­mer­i­za­tion rate must be smaller than that in bulk poly­mer­i­za­tion, and the Dp,SMC-value can be determined by equating the single molecule concentration in a particle and the trapping agent concentration in bulk poly­mer­i­za­tion, [X]bulk. On the other hand, when the average number of trapping agents in a particle is smaller than about 10–20, the statistical variation among the particles becomes significant, which makes the poly­mer­i­za­tion rate faster, compared with the cases without fluctuation. Because of the effects of SMC and fluctuation, Rp may show an acceleration window, Dp,SMC < Dp < Dp,Fluct where Rp is slightly larger than that in bulk poly­ mer­i­za­tion. The acceleration occurs because of the fluctuation, and therefore the MWD obtained becomes slightly broader in this region. For the cases of DT and RAFT conforming to the IT model, the lifetime of a radical is in the same order of magnitude as conventional free radical poly­ mer­i­za­tion, and the termination reaction does not have to be avoided. For the normal lifetime process, Lν = ν, where ν is the kinetic chain length. Because ν can be made larger by separating the radicals into different particles through

Effects of Nano-Sized Polymerization Locus on the Kinetics of CLRP

303

compartmentalization, the poly­mer­i­za­tion rate can be increased significantly by reducing the particle size, as in the case of the conventional free radical poly­mer­i­za­tion. On the other hand, the RAFT poly­mer­i­za­tion system conforming to the SF model belongs to the radical long life-ization process, and the poly­mer­i­za­tion rate is essentially the same as that in bulk. The normal radical lifetime process, including conventional free radical poly­mer­i­za­tion, may show the reduction in the poly­mer­i­za­tion rate for small particles due to the MCV effect. For RAFT, the rate retardation by increasing the RAFT concentration occurs with or without IT in a zero-one system. For RAFT following the normal radical lifetime process, smaller particles are advantageous in implementing a faster poly­mer­i­za­tion rate, narrower MWD, and a smaller number of dead poly­mer chains. The present theoretical model might be too simple to apply to real systems. However, it is hoped that the present theoretical investigation will provide greater insight into the kinetics of CLRP.

Acknowledgment This work was supported by a Grant-in-Aid for Scientific Research, the Ministry of Education, Culture, Sports, Science and Technology, Japan (Grant-in-Aid 21560790).

References Barner-Kowollik, C., et al. 2001. Kinetic investigations of reversible addition fragmentation chain transfer poly­mer­i­za­tions: Cumyl phenyldithioacetate mediated homo­ poly­mer­i­za­tions of styrene and methyl methacrylate. Macromolecules 34:7849–57. ———. 2003. The reversible addition-fragmentation chain transfer process and the strength and limitations of modeling: Comment on “The Magnitude of the Fragmentation Rate Coefficient.” Journal of Polymer Science, Part A: Polymer Chemistry 41:2828–32. ———. 2006. Mechanism and kinetics of dithiobenzoate-mediated RAFT poly­mer­iz­ a­ tion. 1. The current situation. Journal of Polymer Science, Part A: Polymer Chemistry 44:5809–31. Braunecker, W. A., and K. Matyjaszewski. 2007. Controlled/living radical poly­mer­ i­za­tion: Features, developments, and perspectives. Progress in Polymer Science 32:93–146. Butte, A., Storti, G., and M. Morbidelli. 2001. Miniemulsion living free radical poly­ mer­i­za­tion by RAFT. Macromolecules 34:5885–96. Cunningham, M. F. 2008. Controlled/living radical poly­mer­i­za­tion in aqueous dispersed systems. Progress in Polymer Science 33:365–98.

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Fischer, H. 1999. The persistent radical effect in controlled radical poly­mer­i­za­tion. Journal of Polymer Science, Part A: Polymer Chemistry 37:1885–1901. Fukuda, T. et al. 1996. Mechanisms and kinetics of nitroxide-controlled free radical poly­mer­i­za­tion. Macromolecules 29:6393–98. Gilbert, R. G. 1995. Emulsion poly­mer­iz­ a­tion. London: Academic Press. Goto, A., and T. Fukuda. 1997. Effects of radical initiator on poly­mer­i­za­tion rate and polydispersity in nitroxide-controlled free radical poly­mer­i­za­tion. Macro­ molecules 30:4272–77. ———. 2004. Kinetics of living radical poly­mer­i­za­tion. Progress in Polymer Science 29:329–85. Konkolewicz, D. et al. 2008. RAFT poly­mer­i­za­tion kinetics: Combination of apparently conflicting models. Macromolecules 41:6400–12. Kwak, Y., Goto, A., and T. Fukuda. 2004. Rate retardation in reversible addition­fragmentation chain transfer (RAFT) poly­mer­i­za­tion: Further evidence for cross-termination producing 3-arm star chain. Macromolecules 37:1219–25. Monteiro, M. J., and H. de Brouwer. 2001. Intermediate radical termination as the mechanism for retardation in reversible addition-fragmentation chain transfer poly­mer­i­za­tion. Macromolecules 34:349–52. Tobita, H. 1995. Monte Carlo simulation of emulsion poly­mer­i­za­tion—linear, branched, and crosslinked polymers. Acta Polymerica 46:185–203. ———. 2006a. Molecular weight distribution of living radical polymers. 1. Fundamental distribution. Macromolecular Theory and Simulation 15:12–22. ———. 2006b. Molecular weight distribution of living radical polymers. 2. Monte Carlo simulation. Macromolecular Theory and Simulation 15:23–31. ———. 2007. Kinetics of stable free radical mediated poly­mer­i­za­tion inside sub­ micron particles. Macromolecular Theory and Simulation 16:810–23. ———. 2008a. Fundamental molecular weight distribution of RAFT polymers. Macromolecular Reaction Engineering 2:371–81. ———. 2008b. Kinetics of controlled/living radical poly­mer­i­za­tion in emulsified systems. Macromolecular Symposia 261:36–45. ———. 2009a. RAFT miniemulsion poly­mer­i­za­tion kinetics. 1. Polymerization rate. Macromolecular Theory and Simulation 18:108–19. ———. 2009b. RAFT miniemulsion poly­mer­i­za­tion kinetics. 2. Molecular weight distribution. Macromolecular Theory and Simulation 18:120–26. Tobita, H., and F. Yanase. 2007. Monte Carlo simulation of controlled/living radical poly­mer­i­za­tion in emulsified systems. Macromolecular Theory and Simulation 16:476–88. Wang, A. R. et al. 2003. A difference of six orders of magnitude: A reply to “The Magnitude of the Fragmentation Rate Coefficient.” Journal of Polymer Science, Part A: Polymer Chemistry 41:2833–39. Zetterlund, P. B., Kagawa, Y., and M. Okubo. 2008. Controlled/living radical poly­ mer­i­za­tion in dispersed systems. Chemical Reviews 108:3747–94. ———. 2009. Compartmentalization in atom transfer radical poly­mer­i­za­tion in dispersed systems: Effects of target molecular weight and halide end group. Macromolecules 42:2488–96. Zetterlund, P. B., and M. Okubo. 2007. Compartmentalization in TEMPO-mediated radical poly­mer­i­za­tion in dispersed systems: Effects of macroinitiator concentration. Macromolecular Theory and Simulation 16:221–26.

Effects of Nano-Sized Polymerization Locus on the Kinetics of CLRP

305

Appendix Formulation of Various Average Times First, consider the average time required for an active radical to add one monomer molecule, tM . The average number of times for the monomer addition to the active radicals in a unit volume per second is the poly­mer­i­za­ tion rate, Rp mol•L–1•s–1. Therefore, the average number of times that a single active radical adds monomer molecules in a second is Rp/[R•] = kp[M] s–1. The average time required to add one monomer molecule is the inverse of this value, and is given by: tM =



1 k p [ M]

(9.A1)

Next, consider the average lifetime of an active radical, tR• , in the reversible reaction in SFRP. The average number of times the active radical is deactivated by the coupling reaction with X in a unit volume per second is k2[X][R•] mol•L–1•s–1. Therefore, the average number of times that a single radical forms PX from R• in a second is k2[X] s–1. The average lifetime of an active radical, tR• is given by: tR• =



1 k 2 [ X]

(9.A2)

Similarly, various lifetimes can be obtained. In the cases of SFRP and ATRP, the dormant period of a radical tDR and the dormant period of a chain tDC are the same. On the other hand, tDR and tDC are different for RAFT and DT. The results are summarized in Table A9.1. Table A9.1 Various Average Lifetimes tDR

tR• (<
tDC

SFRP

tPX =

1 >> tM k1

1 ≈ tM k 2 [ X]

tPX =

1 >> tM k1

ATRP

tPX =

1 >> tM k1 [Y]

1 ≈ tM k 2 [ XY]

tPX =

1 >> tM k1 [Y]

RAFT

tPXP =

1 ≈ tM k 2 [ XP]

tXP + tPXP =

tDC

0

1 ≈ tM kex [ XP]

tXP =

1 ≈ tM or >> tM k1

1 1 + >> tM k 2 [R• ] k1

1 >> tM kex [R• ]

10 Functional Polymer Particles by Emulsifier-Free Polymerization V. Mittal Contents 10.1 Introduction................................................................................................. 307 10.2 Particle Nucleation......................................................................................308 10.3 Functional Particles by Surfactant-Free Polymerization.......................309 Acknowledgments............................................................................................... 324 References.............................................................................................................. 325

10.1 Introduction The presence of emulsifier during emulsion poly­mer­i­za­tion helps the particles to retain colloidal stability. It forms the micelles in the beginning of the poly­mer­i­za­tion, which subsequently become the loci of poly­mer­i­za­tion due to the entry of the radicals in them [1,2]. The amount of the surfactant can also be varied to achieve different rates of poly­mer­i­za­tion or different sizes of the particles, so the presence of surfactant is important in more than one way to tune the properties of the poly­mer particles. Therefore, the majority of the emulsion poly­mer­i­za­tion reactions are carried out in the presence of the surfactants. However, there are also some cases where the poly­mer­i­za­tion is achieved in the absence of any surfactant. Such a poly­mer­i­za­tion process is then termed surfactant-free poly­mer­i­za­tion [1,3]. This kind of poly­mer­ i­za­tion is carried out when the poly­mer particles are required for specific applications (like calibration of particle characterization methods or use of the particles as standards) that cannot tolerate the presence of even minor amounts of impurities on the surface of the particles or in the aqueous phase due to the desorption of the surfactant. Surfactant-free poly­mer­i­za­tion is also required when the surface charges are needed to be accurately known. Apart from that, this mode of poly­mer­i­za­tion is required when the particles are subjected to subsequent surface functionalization processes that are not compatible with the presence of the emulsifier molecules on the surface. One example is the poisoning of the copper catalyst by reaction with emulsifier 307

308

Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

when carrying out particle surface functionalization by atom transfer radical poly­mer­i­za­tion (ATRP) [4,5].

10.2 Particle Nucleation The mechanism of the particle nucleation in this mode of poly­mer­i­za­tion is completely different as compared to emulsified poly­mer­i­za­tion methods. In the case of poly­mer­i­za­tion in the presence of surfactant, the micelles nucleate the poly­mer particles as these provide ideal conditions for the radical to enter and subsequently initiate the poly­mer­i­za­tion. When no surfactant is present in the system, the generated radicals in the aqueous phase in the absence of micelles start reacting with the monomer dissolved in the aqueous phase. The chains so formed are colloidally unstable and keep on collapsing with each other to attain stability [1,3,6]. This mass of collapsed chains gets swollen with the monomer and continues to poly­mer­ize monomer in these particles. The negative charges from the potassium persulphate initiator moieties present at the end of the poly­mer chains make these ends hydrophilic, and as a result these groups are present on the surface of the particles. The presence of the charges on the surfaces helps to give colloidal stability to these particles. Figure 10.1 shows the representation of such particles stabilized by the negative charges from the initiator. Because the surfactant is absent, the number of particles reaching the stable state is generally two orders of magnitude less than the number of particles generated in conventional emulsion poly­mer­i­za­tion. The smaller particles keep on collapsing with each other owing to the colloidal instability, thereby generating particles much bigger in size as compared to the size in the emulsified poly­mer­i­za­tions. Also, because the number of particles is less, the time required to achieve the full conversion or higher extents of conversion is high. Figure 10.2a also shows the effect of different amounts of surfactant on the conversion of the monomer as a function of time [3]. As mentioned earlier, the conversion is much faster when the amount of surfactant is increased due to the nucleation of more particles. The effect of changing the amount of surfactant on the mean particle size is also depicted in Figure 10.2b [3]. The particle size reached near 900 nm in the absence of surfactant as compared to roughly 100 nm in the presence of 3% surfactant (based on the amount of monomer) when all other reaction components were kept the same. Figure 10.3 also demonstrates the scanning electron microscopy (SEM) micrographs of the particles generated without and with surfactant. The differences in particle sizes owing to the surfactant are clearly visible [6,7]. The reaction outcome, that is, colloidal stability and surface morphology of the particles in the case of surfactant-free poly­mer­i­za­tion, is very sensitive to the changes in the reaction parameters or components; therefore, it is

309

Functional Polymer Particles by Emulsifier-Free Polymerization

–

SO4

–

SO4

–

SO4

–

SO4

–

SO4

SO4– SO4– –

SO4

SO4–

SO4–

SO4–

SO4–

SO4–

SO4–

SO4–

SO4– SO4–

SO4–

Figure 10.1 Representation of poly­mer particles stabilized by the sulphate ions from the initiator.

important to study these changes and their respective effects on the particles in order to tune the particles according to the requirement. It is particularly important to understand the behavior of the system for the successful functionalization of the particle surfaces by surfactant-free poly­mer­i­za­tion to generate functional latexes.

10.3 Functional Particles by Surfactant-Free Polymerization ATRP is a versatile method to achieve controlled morphologies in the poly­ mer particles. It is also used to control the molecular weight as well as molecular weight distribution of the poly­mer chains in the particles [8–17]. ATRP can also be used to functionalize the poly­mer particles by grafting the polymers of interest from the surface of the particles. One example is the grafting of poly(N-isopropylacrylamide) from the surface of the particles to achieve thermally responsive behavior in the particles. Similarly, other polymers can be grafted on the surface to tune the properties of the polymers. To achieve such poly­mer grafting, it is important to functionalize the surface of the particles with an ATRP initiator first, which can subsequently be used to

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Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

(a) 100 3% Surfactant 1% Surfactant

Conversion (%)

80 60

No surfactant 40 20 0 0

100

200

300 400 Time (min)

500

600

(b) 900

Particle Size (nm)

750 No surfactant

600 450

1% Surfactant

300 150

3% Surfactant 0

100

200

300 400 Time (min)

500

600

Figure 10.2 Monomer conversion and mean particle size as a function of amount of surfactant used in the poly­mer­i­za­t ion. (Reprinted from V. Mittal, Advances in Polymer Latex Technology. New York: Nova Science Publishers, 2009. With permission.)

graft the chains of various polymers of interest. Because the ATRP catalyst gets poisoned by the ionic emulsifier used in the emulsion poly­mer­i­za­tion, the poly­mer­i­za­tion is required to be carried out in the absence of surfactant. There is also a possibility of using the nonionic surfactants when using ATRP method, but even with such surfactants, it is not an optimal process and colloidal stability can be a problem.

Functional Polymer Particles by Emulsifier-Free Polymerization

300 nm

311

100 nm (a)

(b)

Figure 10.3 SEM images of the particles generated (a) without surfactant and (b) with surfactant.

The most promising way for the controlled functionalization of the particles’ surface with ATRP initiator to achieve functional latexes is to poly­ mer­ize a functional monomer (i.e., ATRP initiator carrying a terminal acrylic or methacrylic reactive group) onto the seed poly­mer particles in the form of a thin shell. One example of such a functional monomer is 2-(2-bromo­ propionyloxy) ethyl acrylate (BPOEA) reported in the literature [6,18]. The process can be achieved in two ways: In the first, a two-step method that is based on batch poly­mer­i­za­tion, the seed is poly­mer­ized to 100% conversion of the monomer followed by poly­mer­i­za­tion of the functional monomer on the surface of the seed particles either alone or together with styrene. However, the process can also be achieved in a single step by using the semibatch conditions, where the seed is not allowed to fully poly­mer­ize and the shell forming functional monomer is added when the seed is poly­mer­ized to 60–70%. Because the surfactant-free poly­mer­i­za­tion is sensitive to the changes in reaction conditions, the different methodologies lead to different surface morphologies depending on the kinetic and thermodynamic factors [19–22]. The factors whose effect on the particles’ functionalization need to be studied are homopoly­mer­i­za­tion or copoly­mer­i­za­tion of the functional monomer, preswelling of the seed particles before functionalization, mode of addition of the shell-forming monomers, cross-linker, etc. One must be careful that the aforementioned parameters are optimized so as to achieve a uniform layer of the ATRP initiator on the surface of the particles, indicating uniform functionalization. It is also required that the amount of initiator on the surface of the particles be controlled, which can subsequently help to control the amount of poly­mer grafting.

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300 nm

250 nm

(a)

(b)

300 nm

(c) Figure 10.4 (a) Fully poly­mer­ized polystyrene particles when modified with (b) styrene and (c) functionalizing monomer on the surface.

Figure 10.4 demonstrates the first trials to generate functional particles [6]. Fully poly­mer­ized polystyrene seed particles (Figure  10.4a) were used for these trials, and the batch poly­mer­i­za­tion route was taken for the particle functionalization. As a reference, the polystyrene seed particles were also functionalized on the surface with a thin layer of polystyrene (Figure 10.4b). First, functionalization reactions were carried out by polymerizing a thin layer of BPOEA on the surface of the particles as shown in Figure  10.4c after the surface functionalization reactions. This way, the behavior of the homopolymers toward the shell formation on the surface formation could be understood. Also, the surface morphologies obtained in both cases are quite different from each other. The particles after functionalization with styrene were smooth, and the increase in the size of the particles after the functionalization reactions also indicated corresponding diffusion of the monomer

Functional Polymer Particles by Emulsifier-Free Polymerization

313

and subsequent poly­mer­i­za­tion on the surface of the particles. However, the morphology in the case of BPOEA functionalization of the particles is more like orange peel or patchy. It was opined that the observed behavior is a result of the mismatch between the compatibility of the fully poly­mer­ized seed particles and BPOEA. It also indicated that the BPOEA chains may not be colloidally stable on their own, thus leading to the kinetic adsorption of these chains on the surface of the particles during stirring. Therefore, the diffusion of BPOEA on the surface of the particles may not be thermodynamic but more a kinetic effect. This process proceeds as a precipitation poly­mer­ i­za­tion where the precipitation of the BPOEA poly­mer nuclei takes place on the surface of the seed particles. BPOEA chains then continue to poly­mer­ize on the surface and lead to the patchy morphology after the completion of the poly­mer­i­za­tion. Some coagulum was also observed in the aqueous phase, indicating that a part of functional monomer may also be present away from the particles, which was confirmed by the nuclear magnetic resonance investigation of the dried particles. The amount of functionalizing monomer groups present in the particles was observed to be less than originally added during poly­mer­i­za­tion. However, the uniform coverage of the particles with even a thin layer of the ATRP initiator can be enough to achieve the surface functionalization as it is only the surface initiation sites that are usable in the subsequent poly­mer­i­za­tion reactions. As another functionalization trial, styrene and BPOEA were both used to generate the functioning shell on the surface of the particles. It is also important to vary the amount of styrene as it helps to control the amount of ATRP initiator on the surface and hence subsequently the density of the grafted brushes. Figure 10.5 shows the results of the functionalization trials when both styrene and BPOEA are added during the functionalization step. Two modes of addition of shell-forming monomer can be tried: In the first mode, styrene can be added first to swell the preheated seed particles to some extent followed by the addition of functional monomer. In the second mode, both the monomers can be added together. It is obvious from Figure 10.5 that the morphologies of the resulting particles in both cases are quite different from each other, indicating the impact of monomer addition protocols on the final outcome. In both cases, secondary nucleation of the particles was observed. The morphology of the particles in the first case (as shown in Figures 10.5a and b) is more like a strawberry type, whereas the particles in the second case are smoother at the surface. To further understand the poly­mer­i­za­tion behavior of BPOEA in the presence of styrene, poly­mer­i­za­tion of particles with 1:1 styrene:BPOEA and 3:1 styrene:BPOEA molar ratios were also separately carried out. The system with equimolar ratio of the monomers was slow to poly­mer­ize and generated only very small particles (Figure 10.6a) and coagulum, whereas the system with higher amounts of styrene led to the fast generation of larger and stable particles (Figure 10.6b), indicating that monomer composition has significant effects on poly­mer­i­za­tion rate as well as formation of particles. It can

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Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

250 nm

300 nm (a)

(b)

250 nm

500 nm (c)

(d)

Figure 10.5 (a) SEM and (b) TEM (transmission electron microscopy) images of the functionalized particles where styrene was added before the functionalizing monomer in the shell-forming batch; (c) SEM and (d) TEM images of the functionalized particles where styrene and the functionalizing monomer in the shell-forming batch were added together.

also be concluded from Figure 10.6 that the presence of styrene promotes the formation of stable particles by homogenous nucleation. Thus, the results in Figure 10.5 can be explained in light of these findings. The differences in the morphology of the particles probably originate from the initial stages of the functionalization reaction. When styrene is added first to the system, it can be expected to swell the polystyrene seed; thus, the overall styrene:BPOEA mole ratio is lower than the originally added amount. This explains the colloidal instability of the copolymer particles formed by the reaction of styrene with BPOEA, leading to their sticking or coagulation with the seed latex and thus generating the strawberry morphology. On the other hand, when both the monomers are added together, the formed copolymer chains owing to the higher amount of styrene present in the system can quickly form stable

Functional Polymer Particles by Emulsifier-Free Polymerization

250 nm (a)

315

300 nm (b)

Figure 10.6 SEM images of the particles demonstrating the copoly­mer­i­za­t ion of styrene and BPOEA in the absence of any seed particles using styrene to BPOEA mole ratios of (a) 1:1 and (b) 3:1.

secondary particles. On the other hand, the higher amount of styrene present also allows more compatibility of these copolymer chains with the seed particles. This results in one part of the monomer mixture forming the secondary particles and the other part forming a uniform layer on the surface of the seed particles. This is also confirmed by the increase in the size of the seed particles after the functionalization reaction. Generation of secondary nucleation is not optimal as it leads to nonuniform distribution of the ATRP initiator in the particles, which then subsequently affects the quality of the poly­mer grafts from the surface of the particles. It should also be noted that the time provided to the shell-forming monomers to equilibrate with the seed particles may also have an effect on the final particle morphology. In the aforementioned trials, the time provided for these monomers to swell the seed was 30 minutes, which may not be sufficient owing to the very hydrophobic nature of BPOEA, thus requiring a greater amount of time for swelling the seed particles. To analyze such effects, the seed particles were added with either styrene or the functional monomer BPOEA, or a mixture of styrene and BPOEA, and were allowed to stir at room temperature overnight in order to better swell the seed particles with the monomers. Figure 10.7 shows the results of such trials. The resulting particle morphologies were similar to the earlier case, indicating that the amount of time provided to the system did not impact the resulting morphology in this case. Functionalization reactions in the semibatch mode of monomer addition can also be carried out. In this process, which consists of a single step, the seed particles are not allowed to poly­mer­ize fully, and the shell-forming monomers are added to the system at certain conversion of the seed monomers (e.g., 70%). Two different possible types of the addition of shell-forming

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Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

300 nm

300 nm

(a)

(b)

300 nm

500 nm (c)

(d)

Figure 10.7 (a) SEM image of the particles obtained after overnight swelling of the seed particles with styrene and subsequent poly­mer­i­za­t ion, (b) SEM image of the particles obtained after overnight swelling of the seed particles with BPOEA followed by poly­mer­i­za­t ion, (c) TEM image of the particles obtained after overnight swelling of the seed particles with BPOEA and styrene in the mole ratio of 1:3 followed by poly­mer­i­za­t ion, and (d) SEM image of the particles shown in (c).

monomers can be analyzed: shot addition or delayed addition. In the shot addition mode, the whole amount of BPOEA with or without styrene was added to the seed as a shot, whereas in the delayed-addition mode, the monomers forming the shell are added by a syringe in a delayed fashion. Shot addition adds the monomer at a rate that is higher than the poly­mer­i­za­tion rate, whereas delayed addition adds the monomers at a rate that may be comparable to or smaller than the poly­mer­i­za­tion rate. However, in the case of emulsifier-free poly­mer­i­za­tion, even delayed addition may have some buildup of the monomer in the system owing to the very slow poly­mer­i­za­ tion in the absence of emulsifier. Figures 10.8 and 10.9 represent these results of shot and delayed addition of the monomers to the partially poly­mer­ized

317

Functional Polymer Particles by Emulsifier-Free Polymerization

200 nm

500 nm (a)

(b)

500 nm

300 nm (c)

(d)

Figure 10.8 (a) and (d) TEM images of the partially poly­mer­ized seed particles; (b,c) TEM and SEM images of functionalized particles obtained by the shot addition of BPOEA to the seed particles and subsequent poly­mer­i­za­tion; and (e,f) TEM and SEM images of functionalized particles obtained by the shot addition of a mixture of styrene and functionalizing monomer followed by poly­mer­i­za­tion.

seed particles. The shot addition of the shell-forming monomers to the seed poly­mer­ized to 70% led to the generation of smooth and fairly monodisperse particles, and there was no secondary nucleation of the shell-forming monomers. A smooth surface also indicates a uniform distribution of the ATRP initiator on the surface of the particles. The increase in the size of the particles as compared to the partially poly­mer­ized seed particles also indicates the incorporation of the shell-forming monomers on the surface of the particles. The behavior is completely different from the case when fully poly­mer­ized seed was used, indicating that the compatibility of the seed particles toward the copolymer chains can also affect the final morphology of the particles. The fully poly­mer­ized seed may be considered to be more compact than the

318

Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

500 nm

300 nm (e)

(f )

Figure 10.8 (continued).

partially poly­mer­ized seed swollen or enriched with the remaining monomer. The delayed addition of the shell-forming monomers, on the other hand, led to the generation of varying amounts of secondary particles depending on whether the functional monomer was added alone or was added in the presence of styrene. This behavior is significantly different from the shot addition, confirming the earlier notion that the monomer addition methodology has a significant effect, especially on the poly­mer­i­za­tion reactions carried out in the absence of surfactant. The behavior of pure BPOEA is also different from the case when the fully poly­mer­ized seed was used. The generated particle morphologies in the case of shot addition of the monomers to the seed have the following factors affecting them. First, the presence of unreacted styrene owing to the incomplete poly­mer­i­za­tion of seed particles causes the effective ratio of styrene as compared to BPOEA to increase. Also, because the particles are already swollen with styrene, monomer from the second batch can partition at the interphase much faster. As mentioned previously, the partially poly­mer­ized seed particles can also be considered to be “softer” as compared to the fully poly­mer­ized seed particles, thus improving their compatibility with the poly­mer chains formed by the second batch of monomers. In the case of shot addition of BPOEA to the system, because the formed poly­mer chains from BPOEA are colloidally unstable, they keep on collapsing with the seed particles. Because the seed particles, owing to their softer surface, favor the coalescence or adsorption of the nuclei produced by homogenous nucleation, the seed surface is more compatible with the collapsing BPOEA chains, and thus smoother particle surfaces are formed in the end. Similarly, when BPOEA is added together with styrene, similar monomer partitioning at the interphase happens, which

319

Functional Polymer Particles by Emulsifier-Free Polymerization

500 nm

300 nm (a)

(b)

1000 nm

250 nm (c)

(d)

Figure 10.9 (a) SEM and (b) TEM images of the functionalized particles obtained by the delayed addition of BPOEA to the partially poly­mer­ized seed particles and subsequent poly­mer­i­za­t ion; and (c) SEM and (d) TEM images of the functionalized particles obtained by the delayed addition of a mixture of styrene and functionalizing monomer followed by poly­mer­i­za­t ion.

occurs at a much faster rate than the monomer poly­mer­i­za­tion. Thus, most of the styrene added in the secondary batch of monomers is used to swell the seed particles, causing BPOEA to initiate poly­mer­i­za­tion alone; and owing to the similar reasons mentioned earlier, these chains intermix with the seed particles, generating the smooth particles. In the case of delayed addition of monomers to the seed particles, the morphology is affected by the effective mole ratio of the monomers at a particular time during the course of

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Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

poly­mer­i­za­tion. Slow addition of monomers to the poly­mer­i­za­tion medium leads to the ratio of styrene to BPOEA being higher than in the case of shot addition, as all of the added styrene is not quickly taken by the seed particles to swell them. Therefore, this increased amount of styrene in the system leads to the quick generation of the stable secondary particles. Thus, the difference in the case of both shot and delayed addition is the competition between the rate of coalescence of the copolymer chains or nuclei to the seed and the rate of growth of the secondary particles to stability. In order to again underline the sensitivity to the reaction conditions in the absence of the surfactant, particles synthesized in the emulsified conditions were compared with the particles generated by emulsifier-free poly­mer­i­za­ tion. The homopolymer particles have already been compared in Figure 10.3, but the comparison of the functionalized particles generated with or without the surfactant is also required to gain further insights into the particles’ morphology changes. Figures  10.10a and b show the particles generated without the addition of surfactant for comparison with the particles synthesized in the presence of surfactant shown in Figures 10.10c and d. The particles in the nonemulsified conditions are the same as shown in Figure 10.5 and were synthesized by the addition of a batch of styrene and BPOEA to the fully poly­mer­ized seed particles. The differences between the particle morphologies in the two systems are quite visible. The seed particles in the emulsified poly­mer­i­za­tion were smooth (Figure 10.10c), similar to the seed particles in emulsifier-free poly­mer­i­za­tion conditions. However, the functional particles modified by a copolymer layer of styrene and BPOEA in the emulsified poly­ mer­i­za­tion conditions are also smooth in nature in contrast to the strawberry morphology in the case of emulsifier-free poly­mer­i­za­tion. Also, owing to the presence of the surfactant, the generated particles are much smaller in size. The particles in Figure 10.10d were functionalized by the addition of the shell-forming monomers to the fully poly­mer­ized seed particles. Other trials to achieve the functionalization of the particles by other modes like semibatch poly­mer­i­za­tion, shot addition, delayed addition, addition of BPOEA either alone or with styrene, etc., in the presence of emulsified conditions also led to particles similar to those in Figure 10.10d. These particles are demonstrated in Figure 10.11 [7], clearly indicating that the presence of the emulsifier eliminates most of the difficulties associated with the emulsifier-free poly­mer­i­za­tion reactions. Though the functional poly­mer particles with the thin shell of poly­mer containing ATRP initiator could easily be formed in the emulsified poly­mer­i­za­tion conditions, it should be noted that the presence of surfactant adsorbed on the particles would interfere with the functioning of the ATRP imitator when used later onto graft-controlled poly­mer brushes from the surface. One possibility is to desorb the poly­mer particles by successive washing, but this may generate colloidal instability in the particles. Thus, it is justified to approach such functionalization by following the surfactant-free poly­mer­i­za­tion conditions.

Functional Polymer Particles by Emulsifier-Free Polymerization

250 nm

300 nm (a)

200 nm

321

(b)

100 nm (c)

(d)

Figure 10.10 Comparison of particles generated without and with surfactant: (a,b) particles generated without surfactant and functionalized with a copolymer of styrene and functionalizing monomer, (c) pure seed polystyrene particles generated by the use of surfactant, and (d) particles of (c) functionalized with a copolymer of styrene and functionalizing monomer.

Additional functionalization reactions can be carried out in the presence of cross-linker, as a certain extent of cross-linking is required in many applications of the poly­mer particles. The cross-linker was added to both the seed and the shell. Similar permutations of poly­mer­i­za­tion reactions with shot or delayed addition of the secondary batch of monomers, batch or semibatch functionalization, poly­mer­i­za­tion of only BPOEA or in copoly­mer­i­za­tion with styrene, etc., in the shell were carried out. These particles are shown in Figure 10.12. There were significant differences in the morphology of the poly­mer particles in the presence of cross-linker as compared to un-crosslinked particles. The cross-linked particles were smaller in size than their un-cross-linked counterparts. Also, the surface of the cross-linked particles

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Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

200 nm

(a)

250 nm

(b)

100 nm

100 nm (c)

(d)

Figure 10.11 SEM images of the functionalized particles using emulsified poly­mer­i­za­t ion conditions. Functionalization methodologies, that is, shot addition, starved addition, batch or semibatch generation of particles, etc., were varied.

was rougher in nature. No secondary nucleation of the particles was observed in any of the functionalization reactions in the presence of cross-linker. The surface morphologies were also different if only BPOEA was used to form the shell or if the copolymer of styrene and BPOEA were used to functionalize the particles. BPOEA functionalization without the addition of styrene was observed to generate somewhat smoother particles. This is quite surprising as only a small amount of cross-linker led to significant changes in the morphology of the resulting particles. The molar ratio of styrene to divinylbenzene cross-linker in the seed latex was approximately 50, whereas a ratio of 40 was used for the shell-forming monomers. Most importantly, the secondary nucleation was completely eliminated. Divinylbenzene is generally

Functional Polymer Particles by Emulsifier-Free Polymerization

323

250 nm

300 nm (a)

(b)

250 nm

250 nm

(c)

(d)

Figure 10.12 SEM images of the functionalized latex particles obtained by the use of cross-linker in core and shell: (a) when BPOEA and divinylbenzene were added as a shot to 70% poly­mer­ized seed latex followed by poly­mer­i­za­t ion, (b) when styrene, BPOEA, and divinylbenzene were added as a shot to 70% poly­mer­ized seed latex succeeded by poly­mer­i­za­t ion, (c,d) when delayed addition of the monomers of cases (a) and (b), respectively, was carried out, and (e) when styrene, BPOEA, and divinylbenzene were added in a delayed mode to fully poly­mer­ized seed latex and subsequent poly­mer­i­za­t ion.

observed to enhance the colloidal instability of the forming particles as well as to reduce the swelling of the seed with the functionalizing monomers. This generates a large number of nuclei, which keep on coalescing with the seed particles owing to their colloidal instability. Because the presence of styrene leads to the fast generation of the particles, their coalescence on the surface of the particles is more clearly visible than the case of BPOEA functionalization only, owing to the colloidal instability of the formed BPOEA chains.

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300 nm (e) Figure 10.12 (continued).

The amount of the functionalizing monomer BPOEA used during the shell-forming reaction also affects the resulting morphology of the particles. These trials are shown in Figure 10.13. In the first case (Figure 10.13a), 15 g of fully poly­mer­ized seed with a solid content of 4.4% was added with 0.21 g of the functionalizing monomer. In the second and third case, the amount of the functionalizing monomer was increased by two and three times, respectively. Increasing the amount of the functionalizing monomer led to the generation of different morphologies. The morphology in the first case was more like an “orange peel” type, whereas it changes to “moon crater” type morphology in the second case; in the third case, these craters were absent probably owing to a large amount of shell-forming monomer. However, the surface of the particles was still rough as a result of the collapse of the BPOEA chains on the surface purely kinetically and not thermodynamically because of the incompatibility between the BPOEA and seed particles.

Acknowledgments The author would like to express heartfelt gratitude to Professor M. Morbidelli at Institute of Chemical and Bioengineering at Swiss Federal Institute of Technology, Zurich. The technology described in this chapter has also been reported in Polymer, 2007, Volume 48, pp. 2806–2817.

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250 nm

300 nm (a)

(b)

300 nm (c) Figure 10.13 Change in the surface morphology of the surface of the particles when the amount of functionalizing monomer is increased in the shell-forming monomer batch.

References

1. Odian, G. 2004. Principles of poly­mer­iz­ a­tion. Hoboken, NJ: John Wiley & Sons. 2. Gowariker, V. R., Viswanathan, N. V., and J. Sreedhar. 1986. Polymer science. New Delhi, India: John Wiley & Sons. 3. Mittal, V. 2009. Advances in poly­mer latex technology. New York: Nova Science Publishers. 4. Matyjaszewski, K., and T. P. Davis. 2002. Handbook of radical poly­mer­i­za­tion. Hoboken, NJ: John Wiley & Sons.

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5. Cunningham, M. F. 2008. Controlled/living radical poly­mer­i­za­tion in aqueous dispersed systems. Progress in Polymer Science 33:365–98. 6. Mittal, V., Matsko, N. B., Butté, A., and M. Morbidelli. 2007. Functionalized polystyrene latex particles as substrates for ATRP: Surface and colloidal characterization. Polymer 48:2806–17. 7. Mittal, V., Matsko, N. B., Butté, A., and M. Morbidelli. 2008. PNIPAAM grafted polymeric monoliths synthesized by the reactive gelation process and their swelling/deswelling characteristics. Macromolecular Reaction Engineering 2:215–21. 8. Wu, T., Efimenko, K., and J. Genzer. 2001. Preparing high-density poly­mer brushes by mechanically assisted poly­mer assembly. Macromolecules 34:684–86. 9. Zhao, B., and W. J. Brittain. 2000. Synthesis, characterization, and properties of tethered polystyrene-b-polyacrylate brushes on flat silicate substrates. Macromolecules 33:8813–20. 10. Kim, J., Bruening, M. L., and G. L. Baker. 2000. Surface-initiated atom transfer radical poly­mer­i­za­tion on gold at ambient temperature. Journal of American Chemical Society 122:7616–17. 11. Sun, T., Wang, G., Feng, L., Liu, B., Ma, Y., Jiang, L., and D. Zhu. 2004. Reversible switching between superhydrophilicity and superhydrophobicity. Angewandte Chemie International Edition 43:357–60. 12. Coca, S., Jasieczek, C., Beers, K. L., and K. Matyajaszewski. 1998. Polymerization of acrylates by atom transfer radical poly­mer­i­za­tion. Homopoly­mer­iz­ a­tion of 2-hydroxyethyl acrylate. Journal of Polymer Science, Part A: Polymer Chemistry 36:1417–24. 13. Gaynor, S. G., Qiu, J., and K. Matyajaszewski. 1998. Controlled/“living” radical poly­mer­i­za­tion applied to water-borne systems. Macromolecules 31:5951–54. 14. Qiu, J., Gaynor, S. G., and K. Matyajaszewski. 1999. Emulsion poly­mer­iz­ a­ tion of n-butyl methacrylate by reverse atom transfer radical poly­mer­i­za­tion. Macromolecules 32:2872–75. 15. Kizhakkedathu, J. N., Norris-Jones, R., and D. E. Brooks. 2004. Synthesis of well-defined environmentally responsive poly­mer brushes by aqueous ATRP. Macromolecules 37:734–43. 16. Jayachandran, K. N., Takacs-Cox, A., and D. E. Brooks. 2002. Synthesis and characterization of poly­mer brushes of poly(N,N-dimethylacrylamide) from polystyrene latex by aqueous atom transfer radical poly­mer­i­za­tion. Macromolecules 35:4247–57. 17. Kizhakkedathu, J. N., and D. E. Brooks. 2003. Synthesis of poly(N,N-dimethylacrylamide) brushes from charged polymeric surfaces by aqueous ATRP: Effect of surface initiator concentration. Macromolecules 36:591–98. 18. Matyajaszewski, K., Gaynor, S. G., Kulfan, A., and M. Podwika. 1997. Preparation of hyperbranched polyacrylates by atom transfer radical poly­mer­iz­ a­tion. 1. Acrylic AB* monomers in “living” radical poly­mer­i­za­tions. Macromolecules 30:5192–94. 19. Sundberg, D. C., Casassa, A. P., Pantazopoulous, J., Muscato, M. R., Kronberg, B., and J. Berg. 1990. Morphology development of polymeric microparticles in aqueous dispersions. I. Thermodynamic considerations. Journal of Applied Polymer Science 41:1425–42.

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20. Juang, M. S., and I. M. Krieger. 1976. Emulsifier-free emulsion poly­mer­i­za­tion with ionic comonomer. Journal of Polymer Science, Polymer Chemistry Edition 14:2089–2107. 21. Zukoski, C. F., and D. A. Saville. 1985. The formation of small scale granularities in latex particles. Journal of Colloid and Interface Science 104:583–86. 22. van Herk, A. M., and R. G. Gilbert. 2005. Chemistry and technology of emulsion poly­mer­i­za­tion. Oxford: Blackwell Publishing.

11 Polymer Nanoparticles with Surface Active Initiators and Polymer Initiators Klaus Tauer Contents 11.1 General Introduction.................................................................................. 329 11.2 Historical Introduction.............................................................................. 330 11.3 Specific Introduction.................................................................................. 333 11.4 Role of Initiators in Aqueous Emulsion Polymerization.......................334 11.5 Initiation and Interfaces............................................................................. 338 11.6 Surface Active Initiators—Inisurfs........................................................... 341 11.7 Polymers as Initiators for Emulsion Polymerization............................. 347 11.8 Summary...................................................................................................... 353 References.............................................................................................................. 353

11.1 General Introduction Heterophase poly­mer­i­za­tion can be defined as poly­mer­i­za­tion reaction involving two or more different phases leading eventually to so-called poly­ mer dispersions or latexes. Examples of such poly­mer­i­za­tion are dispersion poly­mer­i­za­tion, suspension poly­mer­i­za­tion, emulsion poly­mer­i­za­tion, miniemulsion poly­mer­i­za­tions, and microemulsion poly­mer­i­za­tion. All these systems are characterized by a continuous phase containing segregated or dispersed phases. Two phases in direct contact with different compositions are characterized geometrically by an interface and energetically by an interfacial tension. In comparison to the bulk phases of the two major components (continuous phase and monomer/poly­mer), the dispersed state possesses an excess free energy that roughly corresponds to the product of interfacial area and interfacial tension. Due to this excess free energy, latex particles made of lyophobic polymers possess an inherent tendency to decrease the inter­facial area and, hence, are prone to coagulation. In order to stabilize the colloidal state at a given interfacial area, certain measures are required to reduce the interfacial tension. The most effective way to do this is the deco­ration of the interface with lyophilic groups mediating between both phases. 329

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Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

Here, only water is considered as continuous phase, which means that the dispersed particles are hydrophobic and stabilized by hydrophilic groups attached to their surface via either adsorption or covalent binding. Although aqueous heterophase poly­mer­i­za­tion is fundamentally not restricted to a particular chain growth mechanism, this contribution is exclusively focused on classical free radical poly­mer­i­za­tion, which is under practical aspects nowadays still the most important method of synthetic latex production. Under these constraints, stabilization via adsorption requires emulsifiers with Krafft temperatures below the poly­mer­i­za­tion temperature [1], high HLB (­hydrophylic-lipophilic balance) values, and phase inversion temperatures above the poly­mer­i­za­tion temperature [2]. Covalent attachment of hydrophilic groups is possible via any kinetic event of radical poly­mer­i­za­ tion—that is, initiation, chain propagation, chain transfer, and chain termination. However, the title of this chapter requires focus on the initiation step of free radical poly­mer­i­za­tion. It deals with various possibilities to initiate the chain growth in aqueous heterophase poly­mer­i­za­tion that have been developed over the decades that this poly­mer­i­za­tion technique has been in practical use.

11.2 Historical Introduction Emulsion poly­mer­i­za­tion or more general heterophase poly­mer­i­za­tion was invented in the early twentieth century at Bayer in Germany [3]. The merit belongs to Kurt Gottlob, who poly­mer­ized isoprene in an aqueous system and made for the first time ever artificial caoutchouc. This was at a time before the application of radical initiators was common and also before the invention of synthetic emulsifiers or stabilizers. Consequently, the procedure was quite simple but long lasting [4]. A mixture of 500 g of water containing 7 g of natural stabilizer (egg albumin, starch, or gelatin) and 300 cm3 of isoprene was placed in a pressure vessel and kept under stirring or shaking at 60°C for several weeks. The polyisoprene separated spontaneously over time from the latex-like liquid that was obtained at the end of the reaction, due to clotting of the stabilizers under ambient conditions. The addition of alkali or organic bases led to an improvement of the latex stability, and coagulation could be deliberately induced by decreasing the pH. In these experiments the poly­mer­i­za­tion was started obviously either thermally or due to the action of oxygen more or less randomly depending on the particular amount of oxygen in the reaction vessel. It has been known for more than a century that oxygen plays a double role in radical poly­mer­ i­za­tion as it can either initiate and accelerate or decelerate and inhibit the poly­mer­i­za­tion [5,6].

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In the same years, the first patents were filed on the usefulness of ozonides or organic peroxides to improve the properties of rubber-like polymers (butadiene and its homologues) [7] and to start the poly­mer­i­za­tion of vinyl­ esters with inorganic or organic peroxides (peroxoborates, peroxycarbonates, benzoyl peroxide) [8]. However, these reactions were not carried out under aqueous heterophase conditions. In 1913, Ludwig Lautenschläger completed his doctoral thesis on the autoxidation and poly­mer­i­za­tion of unsaturated hydrocarbons under supervision of Hermann Staudiger [9]. This topic for his doctoral studies was chosen following a suggestion of C. Engler, who did a great deal of work on autoxidation in the second half of the nineteenth century [10]. With progressing studies and applications of radical initiators, poly­mer­i­ za­tion efficiency was considerably enhanced and a much better control of the process was achieved. In the early 1930s, various types of compounds were known that were useful in influencing the course of poly­mer­i­za­tions (poly­ mer­i­za­tion accelerators) such as halides, stannic fluoride or boron tri­fluoride, caustic alkyls, alkali peroxides [11,12], and sodium persulfate [13]. Note that at this time there was not yet a clear distinction between catalysts and initiators or radical and ionic poly­mer­i­za­tion (cf. the discussion in [14]). From today’s perspective, this is quite astonishing as it was already known at this time that free radicals (alkyl radicals generated during thermal decomposition of mercury dialkyls start poly­mer­i­za­tion in an ethylene gas phase) [15] and alkali metals (sodium for starting isoprene poly­mer­i­za­tion to get sodium rubber) [7] or alkali metal alkyls (such as butyllithium for butadiene poly­mer­i­za­tion) [16] can also be used to start poly­mer­i­za­tion reactions. It was, however, generally accepted that these substances accelerate the radical production rate (rate of initiation) and decrease the average chain length of the poly­mer molecules under homogeneous conditions. It was also known that under heterogeneous reaction conditions (emulsion poly­mer­i­za­tion) acceleration of the monomer conversion is possible without simultaneously decreasing the degree of poly­mer­i­za­tion. It is interesting to note that the initiation mechanism with persulfate, which nowadays can be considered as a kind of standard initiator for aqueous poly­mer­i­za­tions, was not yet understood during the early 1940s [17]. The initiation was thought to take place via complex formation between Caro’s acid (formed via the reaction S2O82– + H2O → SO42– + H2SO5) and the monomer followed by splitting off of the labile peroxide oxygen, which then starts chain growth. Organic peroxides became popular initiators for poly­mer­i­za­tions in organic solvent, including bulk poly­mer­i­za­tions. During the 1930s the stateof-the-art initiator for aqueous emulsion poly­mer­i­za­tion was hydrogen peroxide, because the poly­mer­i­za­tion was started in the aqueous phase [18–20]. Later it was shown that aqueous emulsion poly­mer­i­za­tion could also be carried out with oil-soluble initiators such as benzoyl peroxide and azo-bis-

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1-phenylethane [21,22] or 2,2-azobisisobutyronitrile (AIBN) and p-tert-butylisoproylbenzenehydroperoxide [23–25]. The latter authors assumed, based on their systematic studies on the influence of potassium peroxodisulfate as water soluble and the mentioned oil-soluble initiators, that radical generation and poly­mer­i­za­tion takes place in the adsorbed surfactant layer around the latex particles. First reports on the application of azo-compounds as catalyst or initiator appeared in the late 1930s. The action of triphenylmethylazobenzene as accelerator of styrene poly­mer­i­za­tion (bulk and solution poly­mer­i­za­tion) applied in a molar ratio between 0.345 × 10 –5 and 6.67 × 10 –4 relative to the monomer at a temperature of 50–60°C was described in 1939 [26]. Possibly the first example of the application of an azo-compound in radical heterophase poly­ mer­i­za­tion was reported in 1942 when it was found that p-­bromobenzene diazonium hydroxide can start styrene poly­mer­i­za­tion [27]. This was observed when “alkali was added to vigorously stirred suspension of 30 ml of styrene in an aqueous solution of 11 g of diazotized p-bromoaniline at 0°C” [27]. From the separated viscous organic layer, the authors isolated polystyrene with p-bromobenzene end groups and determined an average degree of poly­mer­i­za­tion of 22 [27]. Aliphatic azo-compounds have been in use at least since the late 1940s and quickly became quite popular sources of free radicals for poly­mer­i­za­tions in both organic media (azo-bis-alkylnitriles) and water (4-azo-bis-4-cyanopentanoic acid) because of their particular properties [28]. These compounds possess fairly good chemical stability during storage, first-order decomposition kinetics almost independent of reaction media, and the ability to act not only as thermal initiators but also as efficient photoinitiators (absorption in the near ultraviolet) [28–30]. Moreover, further chemical modification is quite easily possible, which is of special importance with respect to the topic of this chapter. The studies of Fritz Haber and others on the catalytic decomposition of hydrogen peroxide by both ferrous and ferric salts formed the basis for the development of redox initiation for radical poly­mer­i ­za­t ions [31]. The authors have shown that the reaction cycle combines a chain and a radical reaction, involving in its stages the radicals (HO· and HO2·) and the hydroxyl anion. Another important breakthrough was achieved at the ICI laboratories in Manchester in October 1940 with the extension of the principle of “reduction activation” to other peroxides [32]. It was found that poly­mer­i­za­tions initiated with persulfate could be improved in combination with hydroquinone, copper, bisulfite, or other reductants. Particularly for aqueous acrylonitrile poly­ mer­i­za­tion, the observations were made that the induction period in nearly all cases was shortened or even vanished, that the rate of poly­mer­i­za­tion, at least initially, was enhanced, and that both effects occurred frequently in an almost proportional fashion. This method, which nowadays is called redoxinitiation, enables one to conduct poly­mer­i­za­tions at low temperatures. In

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333

the decades since it has largely been used in both industrial and lab-scale production of poly­mer dispersions.

11.3 Specific Introduction The colloidal nature of emulsion poly­mer­i­za­tions and poly­mer dispersions is the origin for all pros and cons regarding their use and application. The basics of emulsion poly­mer­i­za­tion and poly­mer latexes are quite well understood [33–35] but still an object of ongoing refinements [36–38]. The huge number of small particles of an aqueous emulsion poly­mer­i­za­tion allows easy heat removal, the combination of hydrophilic and hydrophobic monomers in just a single poly­mer­i­za­tion step, and tailored modification of particle properties by subsequent monomer addition leading to layer-by-layer buildup of the desired particle morphology. The main drawback of emulsion polymers is the contamination of the desired poly­mer by auxiliary materials, mainly emulsifiers. Depending on the average particle size, the solids content, and the poly­ mer­i­za­tion procedure, the emulsifier content can be as high as 5 wt% relative to the amount of monomers. All emulsifiers for aqueous emulsion poly­mer­ i­za­tions are hydrophilic, and their presence in the final poly­mer increases the hydrophilicity during application. Moreover, low molecular weight emulsifiers are easily able to desorb or to migrate upon changing conditions. In latexes frequently this leads to undesired foaming. Migration of surfactant molecules is also an issue in the final application form of the poly­mer dispersion because they assemble in hydrophilic spots, forming entry sites for water molecules. Such effects contribute essentially to the failure of latex-based polymeric products such as protective coatings and are a strong driving force for the development of strategies to fix stabilizers in place [37,39]. Fixing the stabilizer in place is a compromise. The better alternative, the change in the properties of the surfactants from hydrophilic as needed during the poly­mer­ i­za­tion to hydrophobic as desirable for a nonlatex application of the poly­mer during the service life, seems obviously not attainable. In summary, the actual problem of an emulsion poly­mer is the stabilizing system. On the one hand, it should be optimized to preserve stability during the poly­mer­i­za­tion process. This requires optimized adsorption properties including a certain hydrophilicity and mobility. On the other hand, the final destination of most of the poly­mer latexes is the solid state with more or less hydrophobic properties. Clearly, these demands are not supported by optimized emulsifiers for aqueous emulsion poly­mer­i­za­tions. So, strategies have been developed during the last decades trying to improve the emulsifier efficiency regarding both contradicting requirements [39–45]. In order to keep the stabilizers in place, their chemical structure has been modified in various ways, allowing them to participate in the poly­mer­i­za­tion reaction

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either as monomer (so-called surfmers), as transfer agents (so-called transurfs), or as initiators (so-called inisurfs) [39]. These various functionalities allow covalent (permanent) binding to the poly­mer chains. Typically these reactive surfactants are based on low molecular weight emulsifiers. But polymeric reactive stabilizers also have been developed such as partly sulfonated polyolefins [45] belonging to the class of surfmers. Stabilizing and initiating properties can also be combined in polymers, offering a variety of clear advantages compared with only initiators or even surface active initiators. Surfactants for emulsion poly­mer­i­za­tion are “only” auxiliary materials facing strict cost requirements. Emulsifiers contribute between 5 and 10%, depending on the particular product, to the materials costs for latex production (cf. also the discussion in [37]). Reactive surfactants always have to compete with “classical” nonreactive standard emulsifiers. The improvements in the performance of the latex and the final poly­mer product must justify possibly higher costs of the reactive surfactants. Hence, synthesis of reactive surfactants for potential industrial applications should always be based on readily available raw materials. Studying the application of reactive surfactants is a matter not only of scientific curiosity but also of interest for application-oriented research, as the performance of poly­mer dispersions can be improved compared to similar dispersion prepared with conventional surfactants. An example of the application is given in [46]. The author showed that the overall performance of binder dispersions for industrial coatings could be improved when the nonreactive surfactant was replaced by a surfmer based on “easily” obtainable maleic acid esters. This chapter is exclusively devoted to initiators or initiating systems for aqueous emulsion poly­mer­i­za­tions that are able to act twofold in the course of the reaction. They must be able to efficiently start the poly­mer­i­za­tion and to stabilize a huge interfacial area; that is, they must allow the manufacture of poly­mer dispersions with high solids content and small particles. The chapter is organized in a way that first the role of hydrophilic initiators in aqueous emulsion poly­mer­i­za­tion is discussed, followed by considerations regarding the features of inisurfs and polymers as initiating species.

11.4 Role of Initiators in Aqueous Emulsion Polymerization In most industrial emulsion poly­mer­i­za­tions, water-soluble initiating systems are employed and radical generation takes place predominantly in the continuous aqueous phase via either thermal decomposition or redox activation [47]. Because the main monomers are hydrophobic, the poly­mer chain ends derived from primary radicals might be considered to be amphiphilic at least to a certain extent. The ability to stabilize latex particles depends

335

Surface Active Initiators

A:

R HO• << –OOC C• < –O3SO• < –O3S• R'

B:

C:

OH OH HO–(CH2–CH2–O)n–CH2 C• < x–(CH2–CH)n–X– C• H H Z–/+ +Z– R•

<

–Z– R•

Figure 11.1 Order of the stabilizing ability of a selection of initiating radicals applicable for aqueous heterophase poly­mer­i­za­t ion. Line A: end groups arising from low-molecular-weight inorganic initiators. Line B: end groups arising from polymeric radicals for starting aqueous heterophase poly­mer­i­za­t ion where X and Z–/+ denote an arbitrary terminal group and a charged group of a polyelectrolyte chain (either anionic or cationic), respectively. Line C: +Z–R and –Z–R denote arbitrary anionic and cationic radicals, respectively.

strongly on the chemical nature of initiating free radical and may change in the order as depicted in Figure 11.1. In general, under comparable conditions ionic end groups show a better ability to stabilize than nonionic ones, and polyelectrolyte chains perform better than nonionic hydrophilic polymers. The extraordinary stabilization potential of polyelectrolyte chains attached to colloidal particles was theoretically predicted by Pincus in 1991 [48] and later experimentally confirmed [49]. Among the ionic end groups, anionic groups tend to higher stability than cationic groups under identical conditions. This effect is understandable using Coehn’s rule [50], which summarizes experimental facts regarding induced charges upon contact between substances with different dielectric permittivity. Accordingly, the material with the lower permittivity, which is almost any material in comparison with water, gets a negative charge. Consequently, for aqueous heterophase poly­mer­i­za­tions, cationically charged compounds (stabilizers, latexes, etc.) tend to interact with the reactor material electrostatically. Emulsifier-free emulsion poly­mer­i­za­tions have been investigated since the 1930s. Remember, the first heterophase poly­mer­i­za­tion was carried out in the presence of stabilizing agents but in the absence of initiators. Because during the 1920s and early 1930s the number of commercialized emulsion polymers quite rapidly increased, the drawbacks of the stabilizers remaining in the polymeric products became evident. Thus, attempts were made to abandon the use of stabilizers during the poly­mer­i­za­tion [51–54]. Of course due to skipping over stabilizers, the whole poly­mer­i­za­tion process had to be newly adjusted in order to keep productivity (space-time yield) and other latex properties. In a comprehensive study it was shown that solids content as high as 33% has been reported for butadiene–styrene–acrylonitrile

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Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

terpoly­mer­i­za­tion with redoxinitiation (potassium peroxodisulfate/sodium bisulfite) [54]. In general, emulsifier-free poly­mer­i­za­tions lead, under otherwise unchanged conditions, compared with poly­mer­i­za­tions in the presence of emulsifier to larger particles and to higher amounts of coagulum. The preceding results [54] with solids content of 33%, complete conversion, and an average particle size of 180 nm are exceptional. Of course, the outcome of emulsifier-free poly­mer­i­za­tion of hydrophobic monomers can be improved by the addition of water-soluble monomers, leading to amphiphilic copolymers contributing to particle stabilization (cf. [55–57]). These heterophase copoly­mer­i­za­tions, which bridge the gap to the application of surfmers, are an interesting topic in their own right but beyond the scope of this contribution. The stabilization of latex particles in emulsifier-free emulsion poly­mer­i­za­ tions with water-soluble, nonsurface active initiators is entirely due to hydrophilic end groups stemming from mainly three sources [58]: (1) The majority are former primary free radicals from initiator decomposition that have successfully started chain growth. (2) Some end groups arise from side oxidation reaction between the primary free radical and water molecules because after initiator decomposition the primary free radical is surrounded by much more water than monomer molecules. There is clear experimental evidence that water is not an inert solvent during emulsion poly­mer­i­za­tion. Sulfate ion radicals, hydroxyl radicals, and even carbon centered radicals can react with water and suffer side oxidation reactions [59,60]. (3) A few end groups are the result of reactions occurring at the particle water interface such as hydrolysis of sulfate groups or stepwise oxidation of hydroxyl groups via aldehyde to carboxylic acid groups. These experimental results prove that the reaction mechanism in the continuous aqueous phase is quite complex with important consequences for the whole poly­mer­i­za­tion process. For the first time ever, a comprehensive analysis of the by-products formed in the aqueous phase during stabilizer-free emulsion poly­mer­i­za­tion was accomplished in the course of attempts to develop a process for the emulsion poly­ mer­i­za­tion of ethylene at I.G. Farbenindustrie AG in Germany during the late 1930s and early 1940s [17]. The polyethylene dispersions contained the following component parts: alkylsulfates of very short to very high chain lengths, saturated and unsaturated fatty alcohols, glycols or glycol sulfates, and sulfonic acids. The colloidal and subsequently the kinetic conditions during surfactantfree emulsion poly­mer­i­za­tion (quite high initiator concentration and no additional stabilizer) favor larger particles and lower molecular weights than typically achieved with “complete recipes.” Under such conditions, special morphological features can be observed. The combination of a higher concentration of hydrophilic end groups and shorter poly­mer chains can lead to a mismatch between the particle volume (where the hydrophobic poly­mer chains are) and the particle surface (where the hydrophilic end groups are).

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Surface Active Initiators

This mismatch as discussed in [61] is the origin for the frequently observed anomalous morphologies of particles obtained in stabilizer-free emulsion poly­mer­i­za­tion [62–67]. Another general feature of free radical poly­mer­i­za­tions that is strongly related to the topic of this chapter is the so-called dead-end poly­mer­i­za­ tion. In classical free radical poly­mer­i­za­tion, the average lifetime of the radicals is much shorter than the time to accomplish complete monomer conversion. Thus, nonstop radical production is essential unless termination between radicals is hindered (cf. later discussion). Within the frame of the classical free radical poly­mer­i­za­tion mechanism, Equation (11.1) holds for the time-conversion curve [68] provided initiator decomposition is the sole source of radical generation, chain transfer is negligible, and primary radicals do not terminate. X(t) is the monomer conversion, t the poly­mer­i­za­tion time, I0 the initial initiator concentration, kd the decomposition rate constant of the initiator, f the efficiency of primary free initiator radicals to start chain growth, and kt the termination rate constant.

 f  − ln[1 − X (t)] = A ⋅ I01/2 ⋅ 1 − exp[−kd ⋅ t/2] with A = 2 ⋅ k p    kt ⋅ k d 

(

)

1/2

(11.1)

Now, for infinite time the monomer conversion X(t) reaches a limiting value Xlim, and Equation (11.2) can be used to estimate the initial initiator concentration that is connected with a certain limiting conversion.

 1 I0 =  − ln(1 − X lim )   A

(

)

2



(11.2)

Figure 11.2 is thought to convey an impression about the relation between the limiting conversion and the initial initiator concentration and how this relation is influenced by the particular kinetic constants. The numerical value of the lumped parameter A is for typical reaction rate constants greater than 1 and should decrease with temperature as the initiator decomposition has by far the highest activation free energy. According to the data of Figure 11.2, the higher the poly­mer­i­za­tion temperature the higher must be the starting initiator concentration in order to keep the limiting conversion high. The important conclusion from these considerations is that in order to reach high conversions, depletion of initiator must be avoided. From the industrial or commercial perspective of high space-time yields, the use of higher initiator concentration (possibly higher than actually needed) is favored because extinction of the poly­mer­i­za­tion must be avoided. In practice, I0 or the maximum rate of poly­mer­i­za­tion is determined by the limits of heat removal.

Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

1.2

101

1.0

100 10–1

Xlim

0.8

10–2

0.6

10–3

0.4

10–4

0.2

10–5

0.0 10–7 10–6 10–5 10–4 10–3 10–2 10–1 100 I0 (M)

A–2 (M)

338

10–6 101

102

10–7

Figure 11.2 Dead-end poly­mer­i­za­t ion: estimation of limiting conversion (Xlim) in dependence on the starting initiator concentration (I0) according to Equation (11.1) with the kinetic parameters taken from [69] for styrene bulk poly­mer­i­za­t ion initiated with 2,2-azobisisobutyronitrile at 60°C (kp = 260 l mol–1 s–1, kt = 1.2∙108 l mol–1 s–1, kd = 1.35∙10 –5 s–1, f = 1/2, A–2 = 1.1881∙10 –2) (solid line), and of the relation between I0 and A [Equation (11.2)] for Xlim = 0.9 and variable values of A (dashed line).

11.5 Initiation and Interfaces The concept of “initiation and interfaces” during aqueous heterophase poly­ mer­i­za­tions can be understood in at least three ways:





1. Emulsifiers containing functionalities allowing the generation of (primary) free radicals that are able to start chain growth. Such compounds are “classical” inisurfs and behave like surfactants showing surface activity and exhibiting a critical micelle concentration (CMC). 2. Initiating systems leading to end groups possessing high efficiency to stabilize polymeric particles. These initiators are not surface active but they must be soluble in the continuous aqueous phase. In essence, these developments represent advancements in the old field of emulsifier-free emulsion poly­mer­i­za­tion. 3. Formation of primary free radicals via reactions in the interfacial region between the monomer droplets or poly­mer particles and the aqueous phase or radical generation in adsorption layers. This happens with redox-initiator systems consisting of combinations of surface active or hydrophobic and hydrophilic components.

Both “inisurfs” and “advancements of emulsifier-free emulsion poly­mer­ i­za­tion” will be more thoroughly discussed. However, a few remarks are

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necessary regarding “radical generation in adsorption layers” because these reactions, in order to happen, inevitably need, in contrast to the former two, the presence of interfaces. Interfaces are places where, compared with homogeneous reaction sites, additional forces act.* These forces may induce and support unexpected reaction pathways. Studies on aqueous heterophase poly­mer­i­za­tions revealed some unusual reactions induced and influenced by interfacial effects. During the 1960s, Russian groups published a series of papers describing activated radical formation in adsorption layers. Specifically the authors investigated the influence of cationic surfactants (N-alkyl pyridinium salts) on the decomposition of cumene hydroperoxide [70] and benzoyl peroxide [71] during aqueous emulsion poly­mer­i­za­tion of styrene and methyl methacrylate, respectively. For cumene hydroperoxide, the authors observed in the presence of N-octadecyl pyridinium bromide a drastically increasing decomposition rate with increasing pH between 6 and 12 [70]. At pH of 7 the rate of styrene emulsion poly­mer­i­za­tion was the highest. It decreased again at higher pH due to too fast initiator decomposition (obviously dead-end poly­mer­i­za­tion occurred). A similar activation effect on the decomposition of benzoyl peroxide was observed for N-hexadecyl pyridinium at pH > 7 during the emulsion poly­mer­i­za­tion of methyl methacrylate at 20°C [71]. These results prove that N-alkyl pyridinium salts at basic pH not only behave as stabilizers during emulsion poly­mer­i­za­tion but also form with the hydrophobic organic peroxides an effective initiating system acting in the surfactant adsorption layer. Electron-withdrawing substituents in the pyridinium ring such as amide or methoxy groups change the behavior of the surfactants quite significantly [72]. At acidic pH, surfactants of this type (such as N-octadecyl nicotinic-acid amide or N-hexadecyloxymethylene pyridinium chloride) are able to initiate styrene poly­mer­i­za­tion without additional initiators. However, for the less nucleophilic methyl methacrylate as monomer, no poly­mer­i­za­tion was observed. Additionally, the rate of poly­mer­i­za­tion depends on both the nature of the substituents on the pyridinium ring and the pH-value [72]. Only recently, it was observed that miniemulsions of styrene, methyl methacrylate, butyl acrylate, and styrene/methyl methacrylate could be poly­mer­ized quite fast up to high conversion at 25°C in the absence of free radical initiators if the droplets were stabilized with common sulfate or sulfonate surfactants and L-ascorbic acid was also present in the aqueous phase [73]. This behavior was observed for sodium dodecyl sulfate and dodecyl benzene sulfonate as emulsifier but not for poly(vinyl alcohol) as sole stabilizer. The authors believe that “the radical-generation process is a surface phenomenon between the surfactant, adsorbed on the droplet surface, and L-ascorbic acid” [73]. *

Wolfgang Pauli stated, “The interface was invented by the devil”; and Lord Rayleigh said, “The surfaces of bodies are the field of very powerful forces of whose action we know but little” (cf. A. Zangwill, Physics at Surfaces, Cambridge: Cambridge University Press, 1988, p ix).

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These examples show that in the sense of Pauli and Lord Rutherford, “some interfacial forces influence somehow” the initiation of aqueous hetero­ phase poly­mer­i­za­tion. But even today little is known about the particular mechanism. The combination of hydrophobic with hydrophilic redox components is a unique possibility of aqueous heterophase poly­mer­i­za­tion. Indeed, interfaceredox reactions have been known as effective possibilities for starting the chain growth for decades. The so-called “emulsion redox system” was introduced to the public in the late 1940s [74–76]. However, it obviously goes back to studies carried out in Germany where this redox system was used for Buna S production [77]. This redox system involves organic peroxides as hydrophobic oxidant and an iron salt present as either ferric or ferrous ammonium sulfate to build up the redox cycle as sketched in Figure 11.3. The aqueous phase contains sorbose or other reducing sugars. Pyrophosphate and fatty acid bind the iron salts in the aqueous and monomer phase, respectively. A slightly modified procedure with cumene hydroperoxide as hydrophobic oxidant and ferrous sulfate/sodium metabisulfite as hydrophilic reductants was used to poly­mer­ize concentrated emulsions at room temperature [78]. Aqueous phase

(CH3 ( CH2 )16 C

O–)2/Fe2+

[P2O7]4–/Fe2+

O

OH

O

(2.) Droplet/particle (hydrophobic)

O C

O

O

O OH OH CH2OH

C OH

(1.) (CH3 ( CH2 )16 C

O–)3/Fe3+

[P2O7]4–/Fe3+

O

+ * Free radical Interfacial region

Figure 11.3 The emulsion redox cycle as discussed in [76]. Accordingly, initially most of the iron is bound as pyrophosphate complex in the aqueous phase. Sorbose reduces ferric to ferrous ion from which also a large portion remains as pyrophosphate complex in water. As the iron stearate salts are oil soluble, some amounts of both ferrous and ferric iron will be present in the oil phase (the amounts are determined by the corresponding partition equilibria) where the ferrous iron can react with benzoyl peroxide to form free radicals (*) and ferric iron. The ferric iron equilibrates again between the phases and the free radicals start the poly­mer­i­za­t ion. The net process is the reduction and decomposition of benzoyl peroxide by sorbose.

341

Surface Active Initiators

11.6 Surface Active Initiators—Inisurfs The aim of this section is not to review or to repeat in detail all the results that are accessible in the open literature but to discuss common features and to critically evaluate the inisurf concept. For details the reader is referred to the corresponding original papers and to a few reviews [39,79,80]. Figures 11.4–11.8 illustrate various types of inisurfs in the aforementioned sense; that is, these compounds are able to generate radicals, they are surface active, and they possess a critical micelle concentration. Note that this definition does not mean that the radicals generated upon decomposition must be necessarily surface active, and hence, it includes also nonsymmetrical compounds leading to two chemically different radicals. The general structural variety is rather limited due to the combination of the common thermo-labile azo- and peroxo-groups with ionic or nonionic surfactant moieties. The application of the various inisurfs in emulsion poly­mer­i­za­tions revealed some common features regardless of their specific chemical structure and the particular poly­mer­i­za­tion procedure. The evaluation of inisurfs in comparison with standard emulsion poly­mer­i­za­tion recipes is not as straightforward and easy as discussed later. The surface activity of inisurfs influences their properties very strongly. For instance, electron spin resonance studies revealed that the thermal decomposition of the inisurfs shown in Figure 11.6 distinctly depends on the chemical structure [87,89]. Compared with AIBN, which is the starting material for the synthesis, the inisurfs show

O

A:

O

CH3

n: 20 B:

CH3

C18H37 –O–(CH2–CH2–O)n–C–CH2–CH2–C–O–O–C–CH3

O O C18H37 –O–CH2–CH2–O–C–CH–––––––CH–C–O– n: 20 R1, R2 : H or CH3 R1 ≠ R2

CH2

R1 C

O

CH2

R2 C OC2H5 O OH

Figure 11.4 Unsymmetrical peroxo-inisurfs as developed and studied by Ivancev and Pavluchenko [81–84]. Upon decomposition, the inisurf of structure A releases one surface active radical and one tert-butoxy radical that is rather hydrophobic. The inisurfs of structure B decompose in one surface active radical and a highly mobile hydroxyl radical that can leave the adsorption layer and initiate poly­mer­i­za­t ion in the continuous aqueous phase. Structures A and B exhibit CMC at 2 × 10 –5 and 4 × 10 –6 M, respectively. (Reprinted from S. S. Ivanchev, V. N. Pavljuchenko, and N. A. Byrdina, Journal of Polymer Science, Part A: Polymer Chemistry 25: 47–62, 1987. With permission.)

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C2H5O CH3

H

H Z

O

CH3

H O

(CH2)n N C N R1 N C N C C N N C C N C N R1 N C N (CH2)n Z O H

O

CH3

H3C OC2H5

R1: residue of an aliphatic, or aromatic, or alicyclic diisocyanate

H n: 5–10

H Z:

O C O–

or SO3–

H O CH 3 N S (CH2 )n SO3– Z O C C N N C C O n: 10–16 S N CH3 CH3 Z Z: NH or O O H CH3

–O S 3

( CH2)n

Figure 11.5 Symmetrical azo-inisurfs as described in [85,86]. These inisurfs decompose into two surface active radicals. Latexes prepared with these inisurfs possess lower electrolyte content and show less foam formation compared with latexes made with classical emulsion poly­mer­i­za­t ion recipes using initiators and emulsifiers. The CMC of these inisurfs has not been determined.

CH3 A:

–O SO 3

O CH3 CH3 B:

–O SO 3

CH3

(CH2 CH2 O)n C C N N C C (O CH2 CH2)n OSO–3 H3C O

n: 4–20

CH3

( CH2 )n O C C N N C C O ( CH2 )n OSO–3 O CH3

H3C O

n: 10, 12, 16

Figure 11.6 Symmetrical ionic azo-inisurfs as described in [80,87–89]. The inisurfs of structure A are less surface active than the inisurfs of structure B that possess alkyl sulfate moieties. The CMC of these inisurfs depends strongly on the length of both the poly(ethylene glycol) (PEG) and the alkyl chain. For structure A with n = 4.5 (average molecular weight of the PEG about 200 g/mol), the CMC is 43 mM, and for the dodecane derivative of structure B (n = 12), the CMC is 0.32 mM [87].

by almost an order of magnitude lower 2fkd-values.* Moreover, the 2fkd­values for AIBN clearly decrease with increasing concentration, whereas the 2fkd-­values of the inisurfs show only very minor changes with the concentration. For the PEG inisurfs (Figure 11.6A, n = 4.5, PEGAS200) the 2fkdvalues decrease very slightly with increasing concentration below the CMC. The 2fkd-values of the alkyl chain inisurfs (Figure 11.6B, n = 10, DEDAS) are lower than that of PEG inisurfs (up to a factor of 3) and increase very slightly *

The 2fkd-value is a measure for the radical flux that was able to escape the solvent cage and reacted with the stable free radical employed for the electron spin resonance studies.

343

Surface Active Initiators

O CH3 A:

C9H19

O ( CH2

CH2

NC O

CN O CH3 B:

C9H19

O ( CH2

CH2

H3C

O )n C C N N C C ( O CH2 CH2)n O

C9H19

n = 30

CH3

O )n C C N N C CH3 CH3

CN

n = 30

Figure 11.7 Symmetrical (A) and nonsymmetrical (B) nonionic inisurfs as described in [90,91] prepared with the commercial surfactant Antarox CO-880 (ethoxylated nonylphenol ether) as precursor. The symmetrical compound leads to two surface active radicals, and the nonsymmetrical inisurfs decompose into one surface active and one nonsurface active, hydrophobic radical. The CMC for structures A and B is 2 × 10 –5 and 6.3 × 10 –4 M, respectively.

CH3 A:

–O S 3

(CH2)n O

H3C O

C C N N C C O (CH2)n O CH3

CH3

SO3–

n = 1–3 SO3–

H B:

H3C

(CH2)n C H2C SO3–

CH3

H3C O H

N C C N

N C C N

H O CH3

CH3

CH2 C (CH2)n CH3 H

n = 5, 7, 11, 13

Figure 11.8 Symmetrical ionic inisurfs as described in [92,93]. The compounds of structure B possess higher surface activity than the compounds of structure A. The CMC of structure A has not been determined. For inisurfs of structure B, the CMC depends on the alkyl chain length and decreases for n = 5, 7, 11, 14 from >40, over 4, and 1, to 0.3 mM, respectively [94].

with concentration above the CMC. Obviously, the surface activity, which is higher the lower the CMC, determines the decomposition of the azo-group. The 2fkd-values are lower the higher the surface activity under the particular conditions (Figure 11.9). AIBN in toluene shows no surface activity, and the surface activity of DEDAS in water is much higher than that of PEGAS200 according to the very different CMC values (the lower the CMC, the higher the surface activity). The CMC for PEGAS200 and DEDAS is 45 and 3.7 mM, respectively. The adsorption state of inisurfs influences not only the radical flux but also the activation free energy of the inisurfs’ decomposition. Lower activation free energies (by a factor between 3 and 10) have been measured for the symmetrical inisurfs of Figures 11.6 and 11.7A in water compared with that for AIBN determined in toluene [87,90]. Interestingly, the activation free energy

344

Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

1.2

2fkd (s–1) 106

1.0 0.8 0.6 0.4 0.2 0.0

AIBN

PEGAS200

DEDAS

Surface Activity Figure 11.9 Radical flux (2fkd) determined by electron spin resonance measurements during the thermal decomposition of various azo-initiators at 60°C via spin trapping with 4-­b enzoyl-­ 2,5-­bis(­d imethyl)-piperidine-N-oxide (for AIBN in toluene) and 4-hydroxy-2,5-bis(dimethyl)­piperidine-N-oxide (for PEGAS200 and DEDAS in water) [87]. The concentration of the initiators was 45.3, 42.1, and 44 mM for AIBN, PEGAS200, and DEDAS, respectively.

for the unsymmetrical inisurf of Figure 11.7B in water is almost similar to that for AIBN in toluene (130 kJ/mol). The generally lower activation free energy for the decomposition of inisurfs can be attributed quite convincingly to steric effects in the adsorbed state causing an additional strain to the azogroup due to the adsorbed surface active side chains. The association behavior of the inisurfs causes a higher primary radical recombination and a lower radical efficiency than typically observed for nonassociating initiators. Radical efficiencies (f-values) between 10 –2 and 10 –4 have been estimated for azo-inisurfs [90,91] and peroxo-inisurfs [82], for symmetrical and nonsymmetrical inisurfs [91], and not only in emulsion but also in solution poly­mer­i­za­tion [95]. Such low f-values do not necessarily lead to lower rates of poly­mer­i­za­tion as in the example of emulsifier-free methyl methacrylate emulsion poly­mer­i­za­tion and copoly­mer­i­za­tion with butyl acrylate [96]. The results of these experiments illustrate at least three important things. First, they nicely prove the inisurfs concept because they show that PEGAS200 really combines surfactant and initiator properties in a single molecule. Second, the experimental facts show how the specific conditions of emulsion poly­mer­i­za­tion modify the free radical poly­mer­i­za­tion kinetics because both the rate of poly­mer­i­za­tion and the average molecular weight is much higher if the inisurf PEGAS200 is used instead of potassium peroxodisulfate. This outcome, which is contradictory within the frame of classical free radical poly­mer­i­za­tion mechanism under homogeneous conditions, is, however, understandable under heterogeneous conditions where the average particle size dominates the kinetics. With the inisurf the average

Surface Active Initiators

345

particle size is smaller and, hence, the number of particles is much higher. Because the number of particles increases faster with decreasing particle size than the average number of radicals per particle decreases, the net effect on the rate of poly­mer­i­za­tion, which is proportional to the product of both, is an increase. On the other hand, the average particle size of 150 and 230 nm for PEGAS200 and potassium peroxodisulfate, respectively, is in a range where the monomer concentration per particle is almost independent of the size and the average number of radicals per particle increases with increasing size. This means that the lower average number of radicals per particles in the case of PEGAS200 causes lower termination probability and higher average molecular weight. Third, the kinetic considerations lead to the conclusion that the surface active radicals (generated by the decomposition of the adsorbed inisurfs) stay mainly adsorbed and either do primary radical recombination (leading to low f-values) or start the chain growth but terminate only to a minor extent. In a series of papers, Aslamazova investigated the influence of the chain length of inisurfs according to Figures 11.6A (PEG chain length) and 11.8B (alkyl chain length) on both the course of emulsion poly­mer­i­za­tion and on particle stability [94,97,98]. These results clearly reveal the influence of the stabilizing ability of the inisurfs on the course of the heterophase poly­mer­i­ za­tion because the colloid chemical properties of the particles and the poly­ mer­i­za­tion kinetics are strongly connected. The calculated barrier height of the overall interaction energy between the latex particles stabilized with both kinds of surface active end groups fits with the experimentally observed stability during the poly­mer­i­za­tion experiments [94,97]. The strong correlation between the surface activity of the inisurfs on the one hand and the rate of poly­mer­i­za­tion and the stability of the latex particles on the other hand is additionally influenced by the properties of the monomer. For both poly(methyl methacrylate) and polystyrene, it was found that the alkyl chain length of the inisurfs (Figure 11.8B) determines the zeta-potential, the hydrophilicity of the particle surfaces, and the colloidal stability of the dispersions. But the properties of the polymers also influence the stability of the latexes. It was shown that the more hydrophobic polystyrene particles possess a greater zeta-potential, and hence stronger repulsive forces exist between the polystyrene particles compared with the more hydrophilic poly(methyl methacrylate) [98]. In the whole field of heterophase poly­mer­i­za­tion, the number of studies and papers devoted to inisurfs is rather limited, and application of and working with inisurfs appears rather an exotic topic.* So, instead of a classical summary regarding the advantages of the application of inisurfs in emulsion poly­mer­i­za­tion, some general thoughts that might help the reader to understand this situation seem better suited to end this section. *

SciFinder lists less than 30 hits for the keyword “surface active initiators” but more than 70 for “surface active monomers” and more than 7,200 for “emulsion poly­mer­i­za­t ion.”

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Advanced Polymer Nanoparticles: Synthesis and Surface Modifications



1. The combination of two of the most important functions for emulsion poly­mer­i­za­tions (initiation and stabilization) in a single molecule is the most challenging task within the topic of reactive surfactants. The application of inisurfs instead of initiators and surfactants separately reduces the degrees of freedom for the experimenter to control and to modify both the poly­mer­i­za­tion process and the latex properties. This is the most significant intervention in the poly­mer­ i­za­tion process, which might be clarified by means of the general equation for rate of emulsion poly­mer­i­za­tion [Equation (11.3)]. In Equation (11.3), rp denotes the rate of poly­mer­i­za­tion, kp the propagation rate constant, CM the monomer concentration in the latex particle, n the average number of radicals per particle, and N the particle concentration.



rp = k p ⋅ CM ⋅ n ⋅ N

(11.3)

At given monomer conversion or solids content, N scales inversely with the third power of the particle diameter (N ∝ D –3), CM is a complex nonlinear function of D and increases with a power less than 1 (CM ∝ Dx, 0< × <1), and n increases also via a complex function with increasing particle size and additionally is directly proportional to the radical flux and inversely proportional to N. Despite the simplicity of Equation (11.3), the underlying dependencies are really complex, and hence the influence of changes in the recipes of emulsion poly­mer­i­za­tions is not easy to predict. This already holds for poly­ mer­i­za­tion recipes with classical emulsifiers and initiators where a change in the nature or the concentration of the stabilizer influences the particle size directly and subsequently also CM, n, N, and rp . Unintended effects on the rate of poly­mer­i­za­tion can be compensated for with changes in the initiating system. However, this possibility is lost with the application of inisurfs. Moreover, any change in the concentration of an inisurf acts much stronger on rp because the primary radical flux (2fkd) is changed simultaneously. 2. The ultimate goal of a drastic reduction in the content of free emulsifier in the final latexes cannot be achieved with inisurfs for at least two reasons. The first reason is the necessity, in order to avoid dead-end poly­mer­i­za­tion, to apply such a high concentration that un­decomposed inisurf remains at the end of the poly­mer­i­za­tion. The second reason is the low initiation efficiency or high primary radical recombination, which leads to “normal” nonreactive surfactant in the final dispersion. 3. Despite the insurmountable hurdles regarding the application of inisurfs to avoid the drawbacks caused by the presence of emulsifiers in emulsion polymers, the study of their behavior allows

Surface Active Initiators

347

deeper understanding of the mechanism of emulsion poly­mer­i­za­ tion. Emulsion poly­mer­i­za­tion with inisurfs is more than a scientific curiosity. Their application is useful for the synthesis of small-sized latexes with quite high solids content. After removing the free inisurfs via dialysis or ultrafiltration, the particles retain their stability. The advantage compared with “classical” emulsifier-free latexes is their smaller size and higher stability. This is especially valid for inisurfs as shown in Figure 11.8B because these structures are stable against hydrolysis that happens with ester linkages or sulfate end groups in aqueous media.

11.7 Polymers as Initiators for Emulsion Polymerization Polymers were the first auxiliary materials in the history of heterophase poly­ mer­i­za­tion. As mentioned in Section 11.2 “Historical Introduction,” naturally occurring polymers were used as stabilizers for aqueous heterophase poly­ mer­i­za­tion. About four decades later in Melville’s group at the University of Birmingham, hydrophobic polymers with peroxide end groups were the first polymeric initiators applied in emulsion poly­mer­i­za­tion [99]. The authors reported about new methods of preparing block copolymers including first reports on the synthesis of block copolymer latex particles by two methods. For the first method, the “dihydroperoxide method,” polystyrene with hydroperoxy end groups was prepared by bulk poly­mer­i­za­tion with 1,3-di(hydroperoxy-isopropyl)benzene at 50°C, freed from undecomposed initiator and fractionated via precipitation. Then, the polystyrene-initiator was dissolved in methyl methacrylate and emulsified in an aqueous emulsifier solution. The emulsion poly­mer­i­za­tion was initiated by the addition of ferrous ions according to an interface redox reaction at 0°C. The authors also described another method to prepare block copolymer dispersions, which they called the “emulsion method.” This method is based on the fact that long poly­mer radicals are effectively trapped inside latex particles. They cannot diffuse out of the particles, and termination is no longer occurring after the formation of primary free radicals is stopped. Vinyl acetate emulsion poly­mer­i­za­tion was initiated by γ-radiation and allowed to reach about 70% conversion before the γ-source was removed. Then, the latex was mixed with a methyl methacrylate emulsion and the poly­mer­i­za­tion was followed dilatometrically. Analysis of the final poly­mer revealed that the polymeric mixture contains large amounts of poly(vinyl acetate), a minor amount of poly(methyl methacrylate), and a considerable amount of block copolymer. Later both the “dihydroperoxide” and “emulsion” methods were combined by a group at the Slovak Technical University in Bratislava to make block copolymer latex particles [100,101]. In the first step, a normal emulsion

348

Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

poly­mer­i­za­tion of styrene was carried out at 35°C with polypropylene-hydro­ peroxide powder dispersed in the aqueous phase and triethylenetetramine as activator. After a certain time the polypropylene powder was separated from the polymerizing emulsion under inert conditions. Astonishingly, the emulsion poly­mer­i­za­tion of styrene could be completed in the absence of initiator and even more, freshly added methyl methacrylate could also be poly­mer­ized completely. These two sets of experiments might be considered as benchmarks in hetero­phase poly­mer­i­za­tion history because they prove that (1) polymeric initiators can be quite easily used, and (2) growing free radicals can survive in latex particles without significant termination. There is another redox couple of some interest for aqueous heterophase poly­mer­i­za­tion based on ceric ions. The ceric ion has been known since the 1950s as an efficient oxidant to generate polymerizable free radicals on hydroxyl groups containing reductants via a single electron transfer (cf. Figure 11.10A). Mino and Kaizerman prepared in this way graft copolymers with hydrophilic monomers onto poly(vinyl alcohol) and cellulose as polymeric reductants [102]. From these results it appears to be only a small step to using hydrophilic polymers to start aqueous emulsion poly­mer­i­za­ tions. Some early papers dealing with such experiments were published in 1991–1992 [103–105], where the authors describe emulsion poly­mer­i­za­tion of styrene using a dodecyl-PEG surfactant as reductant. The PEG ceric ion redox system seems to be ideally suited to carry out emulsion poly­mer­i­za­tion, as PEG-based stabilizers are frequently used in emulsion poly­mer­i­za­tion. Another possibility for starting emulsion poly­mer­i­za­tion with PEG-radicals

(

O ) CH2 n

(

. O ) CH n

OH + Ce4+

. O ) CH n

(

OH + Ce3+ + H+

A: O ) CH n OH

(

OH + monomer(s)

(co)polymer block

n: up to 22.000 H3C

CH3 B:

HO

(CH2

CH2

O)n C O

C CH3

N

N

C

C

H3C

O

(O

CH2

CH2)n

OH

n: 4–200 Figure 11.10 Initiation systems for radical poly­mer­i­za­t ions with poly(ethylene glycol) radicals. A: The PEGceric ion redox system. B: PEG-azo initiators of the PEGA type. The numbers of n refer to experimentally proven systems.

Surface Active Initiators

349

is the use of symmetrical PEG-azo initiators (cf. Figure 11.10B) as discussed in [106–108]. The use of nonionic PEGA initiators instead of ionic initiators in emulsion poly­mer­i­za­tions offers interesting possibilities to tune both the colloidal and polymeric properties of poly­mer dispersions. A comprehensive study with various kinds of anionic, cationic, and nonionic initiators including peroxodisulfate with different counter ions (ammonium and potassium) highlighted the role of the nature of the initiator. For example, in styrene emulsion poly­mer­i­za­tion (with monomer-to-water mass ratio of 1:4 at a given concentration of 1% with respect to monomer mass of either an anionic or a cationic surfactant), the replacement of ionic initiators (either anionic or cationic) by the nonionic PEGA200 leads to particles with considerably smaller size, polymers with higher molecular weight, and latexes with higher viscosity [109]. If the PEG molecular weight is above about 2000 g/mol, even surfactant-free emulsion poly­mer­i­za­tions without any charged ingredients are possible [106]. Prepared under such conditions the latexes consist entirely of block copolymer particles. The ceric ion redox route (Figure  11.10A) is quite versatile, as all kinds of hydrophilic polymers can be used. In order to start the poly­mer­i­za­tion most efficiently, the polymers should contain hydroxymethyl (methylol) end groups. Such hydrophilic polymers can be prepared by free radical poly­ mer­i­za­tion with PEGA initiators or 2,2-azobis(2-methyl-N-(2-hydroxyethyl) propionamide) (VA-086 from Wako), leading to the desired end groups. An interesting modification of the ceric ion redox route is the application of N-isopropyl acrylamide (NIPAM) as first monomer in the sequence of monomer additions at temperatures above the lower critical solution temperature (LCST) of polyNIPAM as described in [110–112]. It turned out that the procedure as sketched in Figure 11.11 is a flexible and robust method for preparing multiblock copolymers and/or multiblock copolymer latex particles by free radical heterophase poly­mer­i­za­tion. The key to understanding this procedure is the fact that only polymeric radicals participate in the reaction, which drastically reduces the probability of chain termination provided chain transfer to the monomer is of only minor importance. For NIPAM poly­mer­ i­za­tion initiated with the redox couple PEG-ceric ion, it is experimentally observed that, under optimized conditions, even when the PNIPAM blocks aggregate (at poly­mer­i­za­tion temperature above the LCST) the radicals do not terminate. This fact might be explained with the reasonable assumption that the diblock copolymers are fixed in place due to well-balanced hydrophilic and hydrophobic forces (cf. discussion in [113]). For these conditions, repeated restarts of poly­mer­i­za­tions have been observed upon sequential monomer additions. This behavior is supported by the experimental finding that the formation of primary polymeric radicals ceases shortly after ceric ion addition [112,114]. Obviously, the poly­mer­i­za­tion conditions with this redox couple meet the basic requirements for living radical poly­mer­i­za­tion regarding short initiation period and negligible probability of termination.

350

Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

&H &+ &H ²+&H

+2

7!/&67







+2













+2









+2

 

 +2





+2







+2 

+2





+2

+2 

& 2 1+

&+ & &+ +



&+

+2



31



+2

$0 ,3

+2

5

&+









&+ &+

+2 



+



,3 $0

31

+2 

&+







3$ 0



&+ &+ Q 5

31 ,



$0 ,3



31













+2

$0 ,3

31



& 2 1+ & &+



2+

+2







+2

Figure 11.11 Sketch of the ceric ion redox procedure for the block-by-block or layer-by-layer synthesis of block copolymer particles in aqueous phase free radical heterophase poly­mer­i­za­t ion. (1) Watersoluble poly­mer with methylol end groups. The redox reaction leads to radical formation at the terminal carbon (radical is denoted by the asterisk). (2) NIPAM addition and diblock copolymer formation. The diblock copolymer radicals aggregate if the poly­mer­i­za­t ion temperature is above the lower critical solution temperature (LCST) of the polyNIPAM block. The aggregation practically takes place without termination and leads to diblock copolymer radical particles. (3) Addition of a hydrophobic monomer leads to triblock copolymer particles with a hydrophobic core, a polyNIPAM middle block, and a polymeric stabilizer layer.

The procedure as sketched in Figure 11.11 allows the control of the morphology of the latex particles due to the sequential monomer addition, and the fixation of the radicals inside the particles’ secondary nucleation is excluded. An example of how the morphology of the latex particles (shown in Figure 11.12) can influence the morphology of a final product is shown in Figure 11.13. Here the final product is silica, which is obtained after calcination of various precursor poly­mer dispersions. After cleansing and lyophilization, these block copolymers can be easily redispersed again in distilled water as proven by the scanning electron microscopy (SEM) images of Figure  11.12. Because these particles contain a siloxane block, they can be converted via calcination (7 h at 550°C) into quartz. Interestingly, the morphology of the silica is determined by the molecular structure of the precursor block copolymers. It is either granular for the triblock copolymers A, C or porous for the quadriblock copolymers B, D. A crucial aspect to understanding this result is the specific behavior of the silane monomers as discussed in [113]. These silane monomers can react

351

Surface Active Initiators

A

B

C

D

Figure 11.12 SEM images showing four different block copolymer latex particles prepared with the PEGceric ion redox method (cf. Figure 11.11). The bars indicate 200 nm. The block sequence for the samples is (A) mono-methoxy-PEG-polyNIPAM-poly(vinyltriethoxysilane), (B) mono-methoxy-PEG-polyNIPAM-poly (butyl methacrylate)-poly(vinyltriethoxysilane), (C) mono-methoxy-PEG-polyNIPAM-poly(vinyltrimethoxysilane), and (D) mono-methoxy-PEGpolyNIPAM-poly(butyl methacrylate)-poly(vinyltrimethoxysilane). After poly­mer­i­za­tion the dispersions were cleansed via ultrafiltration, the solid was isolated via lyophilization, and finally the solid was redispersed in distilled water before the samples were prepared for SEM. (Images by Heike Runge and Rona Pitschke with a LEO1550 Gemini microscope operating at 3 kV.)

on two different pathways, that is, either radically via the double bond or via hydrolytic condensation. Also, the polyNIPAM block plays an important role in this particular reaction mechanism. First, the polyNIPAM block generates the heterogeneous reaction loci for the poly­mer­i­za­tion of the hydrophobic monomers; and second, it ensures that the hydrolytic condensation can take place because polyNIPAM above the LCST still contains about 30 w% of water [115,116]. Now, in dependence on the block copolymer structure before the silane monomer addition, the hydrolytic condensation proceeds either in the polyNIPAM core as in the case of the triblock copolymers C, A or in the

352

Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

A

B

C

D

Figure 11.13 SEM images of the calcined block copolymer particles shown in Figure 11.12 (calcination for 7 h at 550°C). The bars indicate 1 µm and 200 nm for images A,B and C,D, respectively. The block sequence for the samples before calcination were (A) mono-methoxy-PEG-polyNIPAMpoly(vinyltriethoxysilane), (B) mono-methoxy-PEG-polyNIPAM-poly (butyl methacrylate)poly(vinyltriethoxysilane), (C) mono-methoxy-PEG-polyNIPAM-poly(vinyltrimethoxysilane), and (D) mono-methoxy-PEG-polyNIPAM-poly(butyl methacrylate)-poly(vinyl­t ri­methoxy­ silane). (Images by Heike Runge and Rona Pitschke with a LEO1550 Gemini microscope operating at 3 kV.)

polyNIPAM shell region as in the case of quadriblock copolymers B, D. This scenario can explain the different morphology of the silica after calcination (cf. Figure 11.13). For the sake of completeness, it should be mentioned that in a similar approach to the ceric ion redox procedure (cf. Figure  11.11) the stabilizing poly­mer can be, even more precisely, built up via reversible addition-fragmentation chain transfer or other controlled poly­mer­i­za­tion techniques [117,118]. This procedure allows as well a sequential construction of the morphology of block copolymer particles and can also be applied for the encapsulation of inorganic materials [119].

Surface Active Initiators

353

11.8 Summary Due to the heterogeneous nature of aqueous heterophase polymerization the initiator system offers, compared with homogeneous polymerization, many more possibilities exist to control polymerization kinetics and to modify product properties. The initiator in aqueous emulsion poly­mer­i­za­tions can be present in all phases. It can be hydrophilic, hydrophobic, or surface active. Moreover, radicals can be generated specifically at hydrophobic-hydrophilic phase boundaries due to the local encounter of hydrophobic and hydrophilic reactants. The molecular weight of the primary radicals can vary over several orders of magnitude, influencing therewith the course of the poly­mer­i­ za­tion, the kinetics, and the properties of the latex particles specifically. Though certain expectations of particularly surface active initiators (inisurfs) regarding improvements of final product properties could not be fulfilled, recent developments of specifically polymeric initiators offer new possibilities. The initiating and stabilizing polymers can be either preformed or built up in situ and specifically tailored.

References

1. Ottewill, R. H. 1983. Introduction. In Surfactants, ed. T. F. Tadros, 1–18. London: Academic Press. 2. Hancock, R. I. 1983. Macromolecular surfactants. In Surfactants, ed. T. F. Tadros, 287–321. London: Academic Press. 3. White, J. L. 1999. Pioneering poly­mer industry developments. Bayer and the first synthetic rubber. International Polymer Processing 14:114. 4. DRP 254672 Gottlob, K. 1912. Verfahren zur Darstellung von künstlichem Kautschuk. 5. Kern, W. 1948. Influence of molecular oxygen on the poly­mer­iz­ a­tion of unsaturated compounds. Die Makromolekulare Chemie 1:199–208. 6. Staudinger, H., and L. Lautenschlager. 1931. Highly poly­mer­ized compounds. LI. Polymerization and autoxidation. Justus Liebigs Annalen der Chemie 488:1–8. 7. DRP 265325 1912. Verfahren zur Verbesserung der durch die Polymerisation von Butadien und seinen Homologen erhältlichen Substanzen. 8. DRP 281688 1914. Verfahren zur Herstellung technisch wertvoller Produkte aus organischen Vinylestern. 9. Lautenschläger, L. 1913. Autoxydation und Polymerisation ungesättigter Kohlenwasserstoffe. PhD diss., TH Karlsruhe. 10. Engler, C., and J. Weissberg. 1904. Kritische Studien über die Vorgänge der Autoxydation. Braunschweig: Vieweg und Sohn.

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Index Page numbers in italics indicatefiguresai tables. block copolymers and, 23-25,24 as controlled radical polymerization method, 99, 200, 202 CRP in miniemulsion and, 222 A fluctuation effect and, 264,282 AB diblock copolymer, 98, 172 in miniemulsion, 19-20,108-109 ABC triblock copolymers, 120,220,123 onion-like morphology and, 46,46 Activator generated by electron overview of, 2, 20,11-15,24 transfer atom transfer radical photo-induced, 226-227,228 polymerization. See AGET ATRP polymer-coated silica particles and, Activator regenerated by electron 228-230,229 transfer atom transfer radical surfactant-free polymerization and, polymerization. See ARGET ATRP 309-324 Activators, ATRP and, 108 thermo-responsive nanoparticles Active periods, 265 and, 201 Addition of monomers, 21-22 Azo-compounds, 332 Adsorption, 210-214 Adsorption layers, radical generation in, 338-339 B AFM (atomic force microscopy), 54 Batch addition of monomers, 21-22 AGET ATRP (activator generated by Batch gradient copolymerization, 103 electron transfer ATRP), 10,20, BCPs (brush-core particles). See Core108-109,111,112 brush-type nanoparticles Aggregation. See Coagulum Benzoyl peroxide, 13,15 AIBN (azobisisobutyronitrile), 13-14,14, Bessel function, 290 15,19 Bifunctional alkoxyamine, 23,23 Aliphatic azo-compounds, 331 Bimodal morphology, 7,8 Alkoxyamines, 11,13 Biocompatibility, 185 Amine functional groups, 119 Biphasic materials, 187,188-189 Amphiphilic copolymers, 99,113-114, Block copolymers. See also Diblock 117-118 copolymers; Triblock copolymers Amphiphilicity, 73,74,207-208 AGET ATRP and, 109 Anisotropic particles, 63,64,73-76, 74, eerie ion redox system and, 349-350 75,86,88-89 controlled radical polymerization ARGET ATRP (activator regenerated by and, 98,100-101,106-107,220 electron transfer ATRP), 10,10,109 conventional pH-responsive micelles Aspect ratio, 80-81 and, 172-177,274 Atomic force microscopy (AFM), 54 self-assembly of, 113,114 ATRP (atom transfer radical Block polymers. See Diblock polymers; polymerization). See also AGET Triblock polymers ATRP; ARGET ATRP; Reverse Blown film process, 83-86,84 ATRP ID stretching, 79-81 2D stretching, 83-86,84

361

362

Body-centered cubic (BCC) packing structure, 239 BPH (benzophenone), 229 BPOEA (2-(2-bromopropiononyloxy)) ethyl acrylate, 311-324 Branched copolymers, 182-183,183,187 Brush structures, 239-249,241. See also Core-brush-type nanoparticles Bubble expansion, 84,85 Buna S, 340 Butyl acrylate, 23 C

Capillary instability, 50 Carbodiimide-mediated cross-linking, 178 Carboxylic acid, 119 Catalysis, 186,331-332 Cationic surfactants, 15 Ceric ions, 348-352,348,350 Cetyl alcohol, 18-19 Chain transfer agents (CTA) distributing chain growth period and, 266 inverted core-shell particle formation and, 41,42 microemulsion polymerization and, 155-160,156,157 overview of, 14,19 RAFT and, 134,140,141,142,143-144, 145,151-152 Characterization of core-shell particles, 52-54 Chelation, 209 Click reactions, 178 Clonazepam, 201 CLRP (controlled/living radical polymerization). See also CRP degenerative transfer polymerization and, 282-293 fundamental distribution in, 293-297 molecular weight distribution and, 293-302 origin of livingness in, 265-267,266 overview of, 264,302-303 RAFT and, 282-293,298-302 rate of polymerization and, 267-295 SFRP, ATRP and, 268-282,297-298

Index

Clustering, 33 CMC. See Critical micelle concentration Coagulum ATRP and, 15 controlled radical polymerization in heterogenous media and, 106 CRP and, 118 emulsifier-free polymerization and, 313,336 NMPand,ll RAFT and, 15 surface-initiated ATRP and, 229 surfactant-free polymerization and, 313 thermo-responsive nanoparticles and, 206-207,207 Coehn's rule, 335 Cold-stage holders, 52-53 Colloidal crystals, 62-63,81,86-87, 246-249,248,249 Colloidal instability, 107,308,314 Color materials, structural, 239-249,248 Compartmentalization, 104,268 Compatibilizing agents, 42,43 Compression, nonspherical particles and, 78,86-87,88 Confetti-like morphology, 48 Constant rate period, 18 Contaminants, 307,333 Contrast, 53 Controlled polymerization. See Living polymerization methods Controlled radical polymerization. See CRP Controlled/living radical polymerization. See CLRP Conventional emulsion polymerization. See Emulsion polymerization Conversion stage, 6-7, 7 Copolymer particle latexes, 22 Copolymers. See also Specific types branched pH-responsive, 182-183, 183,187 emulsion polymerization and, 7,22 generation of, 20-24,21 microemulsion polymerization and, 138-139 Copper compounds, 13-15 Copper ligand complex, 12-13,14

Index

Core cross-linking, 117-119 Core-brush-type nanoparticles, 224-235, 227,232,232,233,234,235,243,246 Core-corona morphology, 224 Core-shell (CS) particles characterization of, 52-54 dispersion polymerization and, 47-48 emulsion polymerization and, 20-25, 25,35-43,39,40,43 equilibrium morphologies of, 30-33, 32 with hydrophilic shell and hydrophobic core, 21,21 microemulsion polymerization and, 47 miniemulsion polymerization and, 43-46,45,46 nonequilibrium morphologies of, 30^31,33-35,34 other methods for formation of, 49-50,52 overview of, 29-30 photofunctional, 242-243,244,245 pH-responsive polymer nanoparticles and, 273,175,342 suspension polymerization and, 48-49,49,50 thermo-responsive nanoparticles and, 200-201 Costabilizers, 18-19,44 Critical micelle concentration (CMC) emulsion polymerization and, 2,3,3, 35-36,38,44 inisurfs and, 338,342,342-343,343 microemulsion polymerization and, 105 Cross-linked core particles (CCPs), 240-242 Cross-linker level, 70,71-73,116 Cross-linking applications of nanoparticles from, 121-123,122 core-brush-type nanoparticles and, 224,225-227,226,227,230 equilibrium morphologies and, 32 functionalization of micelles and, 121 nonequilibrium morphologies and, 33-34

363

pH-responsive polymer nanoparticles and, 177-179, 275 reversible, 123 of self-assembly structures, 115-120, 226, 227,118,119,120 shape control and, 70,71-73 surfactant-free polymerization and, 321-323 swelling and, 181 thermo-responsive nanoparticles and, 200-202,205,208,209 CRP (controlled radical polymerization). See also CLRP block copolymers and, 98,100-101 gradient copolymers and, 103 graft copolymers and, 98,101-103, 202 in heterogeneous media, 104-113, 220, 222, 222 overview of, 98-100, 200 star copolymers and, 98,103,204 CTA. See Chain transfer agents CuBr2 ligand complex, 12-13, 24 Cumene hydroperoxide, 339 D DC-mediated living radical polymerization, 225,230-235,232, 232,233,234,235,239 Deactivator complex, 12-13. See also CuBr2 ligand complex Deactivators, 100 Dead chains, 99,296-297,337,338 Defoaming, 189 Degenerative transfer (DT) polymerization, 20,264,282-293 Degradation, acid-triggered, 175-176, 276 Diblock copolymers eerie ion redox system and, 349-350, 350 controlled radical polymerization and, 98 core cross-linked, 116, 227 pH-responsive, 172,184 schizophrenic, 174-175 self-assembly of, 181,224 Diblock polymers, 16, 27,23,46

364

Dichloromethane, 50 Differential scanning calorimetry (DSC), 52,54 Dihydroperoxide method, 347 Dipole interactions, 76 Disks, intervertebral, 186 Dispersion polymerization, 47-48, 76-78,77,224 Dithioester groups, 15 Dodecyl trimethyl ammonium bromide, 15 Dormancy, 99 Droplet nucleation, 16 Droplet polymerization principle, 16 Drug delivery, 121,185-186,201,209-210 DT. See Degenerative transfer polymerization E EGDMA (ethylene glycol dimethacrylate), 33 Egg-like morphology, 48 EHMA (2-ethylhexyl methacrylate), 76-78,77 Elastic films, 79 Elastic-driven phase separation, 68-69 Elastomers, 80-81 Embedding, 53,79 Emulsifier-free polymerization. See Surfactant-free polymerization Emulsion copolymerization, 225-227, 226,227 Emulsion engineering, 187-188,188 Emulsion polymerization. See also Seeded, macro-, micro-, and miniemulsion polymerization controlled polymerization and, 9-16 generation of copolymer or core-shell particles by, 20-25,22,23,24,25, 35-43,39,40,43 history of, 330-333 latex and, 62 nonspherical particles and, 64 nucleation in, 4,5,16-18 overview of, 1-8,333-334 role of initiators in, 334-338 surfactants and, 307 Emulsion redox system, 340,340

Index

Encapsulation, 89,209-214,230-235,231, 232,233,234,235 End-capping, 200,335,335 End-functionalized amphiphilic copolymers, 117-118 Engler, C., 331 Equilibrium morphologies of core-shell particles, 30-33,32 Extended segregation effect, 276-277, 277 F Feed rate, core-shell morphology and, 38,39,40 Ferromagnetic nanoparticles, 199 Field emission scanning electron microscopy (FESEM), 54 Films, 79-81 Hooded addition, 21-22 Flowchart, 34 Fluctuation effect, 264,280-281,281 Flying saucer-shape, 85-86,86 Food contact, 19 Forced gradient copolymerization, 103 Free energy, 32-33,65,66-68, 67, 343-344 Functionalization, 121 G

Glass transition temperature (Tg), 37,64, 76-78,82 Glazed doughnut shape, 90 Gold nanoparticles, 230 Golf ball shape, 78 Gottlob, Kurt, 62,330 Gradient copolymers, 103,112-113 Gradients, 7-8 Graft copolymers eerie ion redox system and, 348 controlled radical polymerization and, 2,98,101-103, 202,112 cross-linking and, 118 self-assembly of, 113,114,115,118 surface-tailoring and, 224,229 "Grafting from" approach, 202,102, 224-227,228,234-235,235,246,250

Index

"Grafting onto" approach, 102,253-255, 254 "Grafting through" approach, 102, 250-253 H Haber, Fritz, 332 Half-moon morphology, 31-32 Hard templates, self-assembly in, 91-92 Health hazards, 19 Heavy metals, 210-214 HEMA(2-hydroxyethylmethacrylate), 230-231 Hemisphere morphology, 31-32,33 Heterogeneous media, controlled radical polymerization in, 104-113,120, 222, 112 Heterogeneous nucleation, 4,5 Heterophase polymerization, defined, 329 Hexadecane, 18-19,78 Hollow ellipsoids, 81 Homogeneous nucleation, 4,5,8,9 Hybrid polymer particles, 44,202,229, 235-239,236,237 Hydrocarbon solvents, 77-78 Hydrogen peroxide, 331,347 Hydrophilic domains, 171 Hydrophilic polymers, 2 Hydrophobic polymers, 2,16 Hydrophobic-hydrophilic interface, cross-linking at, 119 Hyperbranched polystyrene, 224

365

interfaces and, 338-340,340 inverted core-shell particle formation and, 41 miniemulsion polymerization and, 16 organotellurium-based, 225 polymers as, 347-352,348,350,351, 352 RAFT and, 16,100 role of in aqueous emulsion polymerization, 334-338 surface active, 334,338,341-347,342, 343 Intellectual materials, 197-198 Interfaces, 338-340,340 Interfacial tension, 30-32,32,34,35,42, 63 Intermediate termination (IT) model, 283-285,284,291-293 Interpenetrating polymer networks (IPNs), 65-66 Inverse micelles, 114,115 Inverse miniemulsion polymerization, 2,18 Inverted core-shell (ICS) morphology, 31,36,41-43,43 Ion-capture property, 209-210,210 IR spectroscopy, 52,54 IT model, 283-285,284,291-293

J Janus morphology, 31-32,74 K

I Impurities, 307,333 Indirect ID deformation, 81 Inhibition periods, 108,140-141 Inifeters, 224 Inisurfs, 334,338,341-347,342, 343 Initiators. See also Inisurfs absence of, 22 ATRPand,12,23,14 coating of silica particles and, 229 core-shell morphology and, 37-39, 38,39 emulsion polymerization and, 4 history of, 331-332

Kinetics. See also Rate of polymerization inisurfs and, 343-346 of phase separation, 68-69 of RAFT, 144-153,145,150,151,153 of surfactant-free emulsion polymerization, 336-337 L Latex. See also Rubber latex controlled radical polymerization in heterogenous media and, 106 particle size and, 161-163, 262 surface-functionalized, 183-184

366

Lauryl methacrylate, 11.12,13 Lautenschlager, Ludwig, 331 Lipophobes, 18 Liquefaction, 81-82,82 Liquid marbles, 189 Living polymerization methods, 9-10, 10,19,22-23,223-225. See also Specific methods Livingness, 265-266 Long life-ization. See Radical long lifeization process Lower critical solution temperature (LCST), 198-200,349 M M2feedcopolymerization, 103 Macroemulsion polymerization. See Emulsion polymerization Macroinitiators, 230-235 Magnetic properties, 75,76,199 Marbles, liquid, 189 MCV effect. See Monomerconcentration-variation effect Methanol:water ratio, 78 Methyl methacrylate. See MMA Micellar catalysis, 186 Micelles conventional pH-responsive, 172-177, 173,174,176 cross-linked pH-responsive, 177-179, 178 Microdisks, 85,85 Microemulsion copolymerization, 138-140. See also Heterogeneous media Microemulsion polymerization core-shell particles and, 47 in heterogeneous media, 105 molecular weight, polydispersity and, 153-160,254,156,157,158,160 overview of, 105,134-136 particle size and, 161-163,162 RAFT, kinetics of, 144-153,145,150, 151,153 thermo-responsive nanoparticles and, 200-201 uncontrolled, 135-140

Index

Microgel particles, pH-responsive, 179-181,180 Micron-size monodisperse particles, 224 Microscopy, 52-54 Microstructure, aqueous solubility and, 137 Migration, nonequilibrium morphologies and, 33 Miktoarm star copolymers, 98,103,113, 114,120 Miniemulsion polymerization complex nanoparticles synthesized by CRP in, 110-113, HI, 112 controlled radical polymerization and, 107-113,110, HI, 112 core-shell particles and, 43-46,45,46 in heterogeneous media, 105 overview of, 2,9-20,18,20,104-105 stabilizers and, 339 Minimum interfacial energy, 30-31,63 MMA (methyl methacrylate), 226-227. See also PNIPAAm-MAA copolymer nanoparticles Molecular weight emulsion polymerization and, 2-3 equilibrium morphologies and, 32 RAFT microemulsion polymerization and, 153-160,154, 156,157,158,160 Molecular weight distribution (MWD) profiles, 264,293-302,300 Monomer-concentration-variation (MCV) effect, 264,286-291,299 Monomeric costabilizers, 19 Monomenpolymer swelling ratio, 70 Monomodal morphology, 8 Monte Carlo (MC) simulation method, 264,272,272,281-282,286-291,287, 288,289,290 Morgan model, 143,145-147,151 Morphology. See also Surface morphology; Specific morphologies aqueous solubility and, 137 control of, 30 of copolymer particles, 21 of core-shell particles, 30-35,32,34 nonspherical particles and, 69-70 surfactant-free polymerization and, 312-313,320,321,336-337

367

Index

Morton equation, 70 MPS, 74-75 Multimodal morphology, 7,8 Multiple addition microemulsion polymerization, 139 Multiplets, 69,71, 72 Multistep polymerization, 70-73, 72 MWD profiles. See Molecular weight distribution profiles Myristyl trimethyl ammonium bromide, 15 N Nanocapsules, 44-45,45,46 Nanocarriers, 121 Nanogels, pH-responsive, 181 Nanoprecipitation, 15-16,49,106 Nanoreactors, 186 Negative staining, 53 NIPAM (N-isopropyl acrylamide), 349-352,350,352,352 Nitroxide-capped polymer chains, 19 NMP (nitroxide-mediated polymerization) as controlled radical polymerization method, 99-100,200,101 CRP in miniemulsion and, 112 nitroxide-capped polymer chains in, 19 overview of, 2,10,11,12,13 second-generation, 109 surface modification of silica particles by, 253-255,254 NMR (nuclear magnetic resonance), 52,54 Nonequilibrium morphologies, of coreshell particles, 30-31,33-35,34 Nonspherical particles compression and, 78,86-87,88 overview of, 62-64,92 phase separation, seeded emulsion polymerization and, 64-76,65,67, 68,72, 74, 75 self-assembly and, 87-92,91 solvent evaporation, seeded dispersion polymerization and, 76-78, 77 stretching and, 78-86,79,82,83,84, 85,86

Nuclear magnetic resonance (NMR), 52,54 Nucleation aqueous solubility and, 137 emulsion polymerization and, 4,5, 16-18,104-105 heterogeneous, 4,5 homogeneous, 5,8,9 miniemulsion polymerization and, 18 NMP and, 11 secondary, 22 surfactant-free polymerization and, 308-309,309,311,322-323 O

Occluded morphology, 31-32 One-dimensional (ID) stretching, 79-81 Onion-like morphology, 45-46,46 Opals, 239 Orange-peel morphology, 7,8 Organic halides, 11-12 Organic peroxides, 331 Osmium tetraoxide (OsOJ, 53 Ostwald ripening, 16 Oxygen, radical polymerization and, 330 Ozonides, 331 P Packing behavior, 90 Partially engulfed morphology, 31-32 Particle formation interval, 4-6,6 Particle size control of, 224 inisurfs and, 344-345 molecular weight distribution and, 299-302,300 polymerization rate and, 264,275 polymerization technology and, 30, 35,43,47 RAFT and, 161-163,162 shape control and, 70 surfactant concentration and, 308, 310,312 thermo-responsive nanoparticles and, 205-208,207,208,209, 212-213,213

368

Particle size distribution (PSD) emulsion polymerization and, 104, 112 pH-responsive polymer nanoparticles and, 183 RAFT microemulsion polymerization and, 161 surfactant-free polymerization and, 242-243 thermo-responsive nanoparticles and, 200,205,206 Pauli, Wolfgang, 339-340 PBuA, 41 PDEAM (poly(N,N-diethylacrylamide)), 198-199 PDI. See Polydispersity index PEG-ceric ion redox system, 348-352, 349 PEHMA, 76-78, 77 PEI, 73-74 Permeability, 202-203 Permittivity, 335 Peroxides, 13,15,331,339,347 Persistent radical effect (PRE), 100,266 Persulfate, 331-332 Phase separation aqueous solubility and, 137 nonequilibrium morphologies and, 33,34-35 nonspherical particle formation and, 64-76,65,67, 68,72, 74, 75 Phase transitions, 198-199,202-203,205 Phosphotungstic acid (PTA) staining, 53 Photo-cross-linking, 201-202 Photofunctional polymers (PFD), 235-236,236,238-239,240 Photonic bandgaps, 63 Photonic crystals, 239-249 Photopolymerization, 224 pH-responsive polymer nanoparticles. SeePRPN pKa,171 Planar morphology, 7,8 PMMA (poly(methyl methacrylate)) seeds, 38-39,40,43,239 PNIPAAm nanoparticles, 198-205,203, 204,205

Index

PNIPAAm-MAA copolymer nanoparticles, 202-205,203,204, 205,207,210-214,212,213 PNIPAM. See PNIPAAm PNVCL (poly (N-vinylcaprolactam)), 198-199 Polydispersity index (PDI) controlled radical polymerization and, 102,103 nitroxide-mediated polymerization and, 106 RAFT microemulsion polymerization and, 106,153-160, 154,156,157,158,160 Polyelectrolytes, 175,335 Polyion complexation, 178 Polymer brushes. See Core-brush-type nanoparticles Polymeric stabilizers, 18-19 Polymerization rate. See Rate of polymerization Polymerization-driven phase separation, 68-69 Polystyrene, 48,224 Polyvinyl alcohol (PVA)films,79-81 Positive staining, 53 PRPN (pH-responsive polymer nanoparticles) applications of, 185-189,188 branched copolymers, 182-183,183, 187 conventional micelles, 172-177, 273, 174,176 cross-linked micelles, 177-179,178 microgels, 179-181,180 overview of, 169-171,170,189-190 with pH-responsive surfaces, 183-184 swelling and, 204 PSD. See Particle size distribution Pseudo-initiation, 269,269-270 Pseudo-termination, 269,269-270,276 PS/PMMA seeds, 38-39,40,43 PS/PVAc core-shell latexes, 38-39,40, 42-43 PTA staining. See Phosphotungstic acid staining PYAc/PBuA, 41

Index

369

RAFT and, 108,140-141,298-302 SFRP, ATRP and, 268-282,297-298 Radical long life-ization process time fraction of active radical period overview of, 265-266,302-303 and, 266 SF model and, 285,286 Reactivity, emulsion polymerization SFRP as example of, 268-282 and, 7-8,21 single-molecule-concentration effect Redox reactions, 332,340,348-352,349, and, 271-274 350. See also Emulsion redox Radical penetration, theory of, 34-35 system Radical polymerization. See Controlled Redoxinitiation, 332 radical polymerization Reducing agents, 108-109 Radical segregation, 275-278 Reduction activation, 331-332 Radicals, 4,11,16. See also Persistent Responsive double block copolymers, radical effect 172 RAFT (reversible additionRetardation, intermediate termination fragmentation chain transfer) model and, 291-293 in bulk, 282-285 Reverse ATRP (atom transfer radical controlled radical polymerization polymerization), 10,10 and, 108 Reversible addition-fragmentation as controlled radical polymerization chain transfer polymerization. See method, 99,101,102-103 RAFT core-shell functional particles and, Reversible cross-linking, 121 25,25 Reversible termination, 10,11,265 CRP in miniemulsion and, 112 Reversible transfer, 10 in dispersed systems, 285-293 R-groups, 103,140-141,142 kinetics of, 144-153, 145, ISO, 151,153 ROMP, 113 mechanism of, 143-144 ROP, 113 microemulsion polymerization and, Rubber latex, 62 134-135 Ruthenium tetroxide (Ru04), 53 in miniemulsion, 20 Rutherford scattering, 53 molecular weight, polydispersity and, 153-160,154,156,157,158,160 monomer-concentration-variation s effect and, 264 Scanning electron microscopy (SEM), 54 overview of, 2,10,15-16,17,140-142, Schizophrenic diblock copolymers, 141,142 174-175,178 particle size and, 161-163,162 SCM. See Shell cross-linked micelles stabilizing polymers and, 352 Secondary nucleation, 22 surface modification by, 249-253,251, Sectioning, 53 252 Seeded dispersion polymerization, Rate of polymerization. See also Kinetics 76-78 emulsion vs. miniemulsion nonspherical particle formation and, polymerization and, 18 77 fundamental distribution and, Seeded emulsion polymerization. See 293-297 also Nanoprecipitation overview of, 267-268 ATRP and, 15 RAFT, DT and, 282-293 core-shell morphology and, 36-39,48

370

NMPand,ll nonspherical particle formation and, 64-76,65,67,68,72, 74, 75 particle morphology and, 47-48 RAFT and, 25 Seeding, 65-66,106 Segregation effect, 275-277 Self-assembly colloidal crystals and, 62-63 complex copolymer particles and, 99 of copolymers, nanostructures via, 114-115 of core shell polymer micelles, 173 cross-linking in, 115-123, 226, 227, 118,119,120 in heterogeneous media, 106-107 nonspherical particles and, 87-92, 92 pH-responsive nanogels and, 181 synthesis of amphiphilic copolymers by, 113-114 SEM. See Scanning electron microscopy Semibatch addition of monomers, 21-22 Semicontinuous microemulsion polymerization, 139-140 SF model. See Slow-fragmentation model SFRP (stable free-radical mediated polymerization) in bulk as long life-ization process, 268-271 in dispersed systems, 272-282 fluctuation effect and, 264,281-282 Shearing energy, 18 Shell cross-linked micelles (SCM), 177-179,178,185-186 Shell cross-linking, 117-119,177-179,178 Shirasu porous glass membrane (SPG) emulsification, 49-50 Shot addition, 316-320 Silanol (Si-OH), 228 Silica nanoparticles coated with high-density brushes, 228-230,229 encapsulated, 230-235,232,232,233, 234,235 hybrid, 235-239,236,237

Index

NMRP for modification of, 253-255, 254 RAFT polymerization for modification of, 239-249,252,252 Siloxane (Si-O-Si), 228 Simultaneous reverse and normal initiation atom transfer radical polymerization. See SR&NI ATRP Single-molecule-concentration (SMC) theory, 271-274,302 Slow-fragmentation (SF) model, 284-286 Smart materials, 197-198. See also PRPN; Thermo-responsive particles SMC effect. See Single-moleculeconcentration theory Snowman-like morphology, 31-32,48 Soft templates, self-assembly in, 87-90, 88 Solubility, 136-137,139,155-160, 256 Solvents, 76-78 SPG emulsification, 48-49 Spheres per droplet, 90 SPM particles, 230-235,232,232,233, 234,235 Spontaneous gradient copolymerization, 103 SR&NI ATRP, 109,113 Stabilization, 187,189,334-335,335, 345-347. See also Costabilizers Staining, 53 Star copolymers, 98,103,204,112,113, 114 Starved addition, 22 Staudiger, Hermann, 331 Stimuli-responsive polymers, 197-198. See also PRPN; Thermo-responsive particles Stirring. See Suspension polymerization Strathclyde approach to branched polymers, 182-183,183 Strawberry morphology, 7,8,314,324, 320,322 Stretching, 78-86, 79,82,83,84,85,86 Structured latex particles, 22-23 Styrene, 23,15,20,313-324,349 Styrene-co-N-isopropylacrylamide, 8,9 Superficial area, 41

371

Index

Surface charge, 307,335 Surface crater morphology, 7,8 Surface energy, 114 Surface morphology. See also Morphology brush structures, structural color materials and, 239-249,241 emulsion polymerization and, 7-8, 8,9 encapsulation by polymer brushes and, 230-235 high-density polymer brush coating and, 228-230 NMRP for modification of, 253-255, 254 photofunctional polymers, colloid crystals and, 235-239 pH-responsive, 183-184 radical initiating sites on surface and, 225-228 RAFT polymerization for modification of, 239-249,251,252 Surface properties, role of, 90 Surface tension, 3 Surface-functionalized polymer latexes, 183-184 Surfactant effect, 205,205 Surfactant-free polymerization advances in, 338 ATRP and, 309-324 nucleation in, 308-309,309 overview of, 307-308,335-336 Surfactants ATRP and, 14-15,20 emulsion polymerization and, 2-3, 3,16 migration of, 333 miniemulsion polymerization, 43-44 reactive, 334 role of, 307 thermo-responsive nanoparticles and, 207-208,208 Surfmers, 334 Suspension polymerization, 48-49,49, 50 Swelling, 65-66,75,137,170,170-171, 179-181,204

T TEM. See Transmission electron microscopy Temperature. See also Thermoresponsive particles ATRP and, 11-12 core-shell morphology and, 37,41, 47-48 modified stretching and, 81-82 NMPand,ll shape control and, 70 Templates, self-assembly in, 87-92,88,91 TEMPO nitroxide (2,2,6,6-tetramethyl-lpiperidinoxyl), 11,19,20 Termination, 11,99,100,100,276-277. See also Reversible termination Tetradecane, 78 Tg (glass transition temperature), 37,64, 76-78 Thermodynamics, 66-68,67 Thermoplastics, 80 Thermo-responsive particles applications of, 208-214 overview of, 197-200,214 size control and, 205-208,207,208, 209 synthesis and characterization of, 200-205,203,204,205 Toluene, 82 Toxicity, 178 Transfer, reversible, 10 Transfer agents. See Chain transfer agents Transition metals, 13 Transmission electron microscopy (TEM), 52-53 Transurfs, 334 Trapping agents, 265-266,266,269,271, 273-274,277-282,275 Triblock copolymers, 22-23,178, 185-186,350-351 Triblock polymers, 17,47,113-114, 120-123,177 Trithiocarbonates, 16 Two-dimensional (2D) stretching, 83-86, 84

372

U Upper critical solution temperature (UCST), 198-199 Uranyl acetate (UAc) staining, 53

Index

Volatility, 18-19 Volume, 170-171 W Water-in-oil-in-water (W/O/W) emulsion polymerization, 50

V

X

Van der Waals attraction, 90 VBDC (4-vinylbenzyl N,Ndiethyldithiocarbamate), 224-. 230,232,232,236,242,255 Viscoelastic deformation, 80 Viscosity, 33,44-45

Xanthates, 25,25 Z Z-groups, 103,140-141, 242 Zigzag configuration, 76