New Polymer Materials (Advances in Polymer Science,Vol.94)

94

Advances in Polymer Science

New Polymer Materials With contributions by B. Boutevin, Y. Ikada, M. Irie, Y.Tabata, T Takekoshi

With 59 Figures and 27 Tables

Springer-Verlag Berlin Heidelberg NewYork London Paris Tokyo Hong Kong

ISBN-3-540-51547-X Springer-Verlag Berlin Heidelberg New York ISBN-0-387-51547-X Springer-Verlag New York Berlin Heidelberg Library of Congress Catalog Card Number 61-642 This work is subject to copyright. All rights are reserved, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in other ways, and storage in data banks. Duplication of this publication or parts thereof is only permitted under the provisions of the German Copyright Law of September 9, 1965, in its version of June 24, 1985, and a copyright free must always be paid. Violations fall under the prosecution act of the German Copyright Law. © Springer-Verlag Berlin Heidelberg 1990 Printed in Germany The use of registered names, trademarks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. Bookbinding: Liideritz & Bauer, Berlin 2152/3020-543210 Printed on acid-free paper

Editors

Prof. Akihiro Abe, Tokyo Institute of Technology, Faculty of Engineering, Department of Polymer Chemistry, O-okayama, Meguro-ku, Tokyo 152, Japan Prof. Henri Benoit, CNRS, Centre de Recherches sur les Macromolecules, 6, rue Boussingault, 67083 Strasbourg Cedex, France Prof. Hans-Joachim Cantow, Institut ftir Makromolekulare Chemie der Universit~it, Stefan-Meier-Str. 31, 7800 Freiburg i. Br., FRG Prof. Paolo Corradini, Universith di Napoli, Dipartimento di Chimica, Via Mezzocannone 4, 80134 Napoli, Italy Prof. Karel Du~ek, Institute of Macromolecular Chemistry, Czechoslovak Academy of Sciences, 16206 Prague 616, (~SSR Prof. Sam Edwards, University of Cambridge, Department of Physics, Cavendish Laboratory, Madingley Road, Cambridge CB30HE, England Prof. Hiroshi Fujita, 35 Shimotakedono-cho, Shichiku, Kita-ku, Kyoto 603, Japan Prof. Gisela Henrici-Oliv6, 1332 Neal Road, Cantonment, Florida 32533, U.S.A. Prof. Dr. Hartwig H6cker, Deutsches Wollforschungs-Institut e. V. an der Technischen Hochschule Aachen, Veltmanplatz 8, 5100 Aachen, FRG Prof. Hans-Henning Kausch, Laboratoire de Polym6res, Ecole Polytechnique F6d6rale de Lausanne, 32, ch. de Bellerive, 1007 Lausanne, Switzerland Prof. Joseph P. Kennedy, Institute of Polymer Science. The University of Akron, Akron, Ohio 44325, U.S.A. Prof. Anthony Ledwith, Pilkington Brothers plc, R&D Laboratories, Lathom Ormskirk, Lancashire L40 5UF, U.K. Prof. Seizo Okamura, No. 24, Minamigoshi-Machi Okazaki, Sakyo-Ku, Kyoto 606, Japan Prof. Salvador 'Oliv6, 1332 Neal Road, Cantonment, Florida 32533, U.S.A. Prof. Charles G. Overberger, Department of Chemistry. The University of Michigan, Ann Arbor, Michigan 48 109, U.S.A. Prof. Helmut Ringsdorf, Institut ffir Organische Chemic, Johannes-GutenbergUniversit~it,J.-J.-Becher Weg 18-20, 6500 Mainz, FRG Prof. Takeo Saegusa, Department of Synthetic Chemistry, Faculty of Engineering, Kyoto University, Yoshida, Kyoto, Japan Prof. J. C. Salamone, University of Lowell, Department of Chemistry, College of Pure and Applied Science, One University Avenue, Lowell, MA 01854, U.S.A. Prof. John L. Schrag, University of Wisconsin, Department of Chemistry, 1101 University Avenue. Madison, Wisconsin 53706. U.S.A. Prof. John K. Stille, Department of Chemistry, Colorado State University, Fort Collins, Colorado 80523, U.S.A. Prof. Dr. G. Wegner, Max-Planck-Institut fiir Polymerforschung, Ackermannweg 10, Postfach 3148, 6500 Mainz, FRG

Prof. Dr. Giinther Heublein, 11.12. 1933--17. 7. 1989

Giinther Heublein Giinther Heublein, Professor of Organic Chemistry, FriedrichSchiller Universit/it Jena, died of cancer on July 17, 1989. Prof. Heublein studied Chemistry at the University of Jena where he also received his P h . D . in 1961 and Dr. sc. nat. in 1967. He worked under the guidance of Prof. Drefahl and started his scientific career with contributions to the stereochemistry of diastereomers, with investigations of the effect of EDA complexes in organic reactions, and the detection of reactive intermediates. In 1970, he entered the field of Polymer Chemistry and devoted his efforts to cationic polymerisation. This decission and the following period are characteristic of his attitude towards science: he always was eager to find the topics of current importance, ready to learn over and over again, and enthusiastic to perform thorough work in the selected field. Extensive investigations were made on the influence of donors and acceptors on the course of cationic polymerisation of vinyl monomers and the acceptor effect on molecular weight and copolymer composition. Research on the selective polymerisation of olefins from technical C4-fractions led to more than 20 patents which are applied in several countries. Prof. Heublein held the chair of Organic Chemistry from 1968. He was author or co-author of more than 300 scientific papers, of 4 books, and held more than 70 patents. He worked actively on many scientific commissions and was member of the International Steering Committee of the International Symposium on Cationic Polymerisation, the 7th of which took place with great success in Jena in 1985. From 1981 he was on the editorial board of the J. Macromol. Sci.-Chem.'and, f r o m 1983, one of the editors of Advances in Polymer Science. Those who knew him are grateful for the standards he set and keep alive the memory and name of a distinguished scientist and a good man. Gottfried G16ckner

Table of Contents

Polyimides T. Takekoshi

. . . . . . . . . . . . . . . . . . . . .

Photoresponsive Polymers M. Irie

. . . . . . . . . . . . . . . . . . . . . . .

27

Telechelic Oligomers by Radical Reactions B. B o u t e v i n

. . . . . . . . . . . . . . . . . . . . .

69

Phagocytosis of Polymer Microspheres by Macrophages Y. Tabata, Y. Ikada . . . . . . . . . . . . . . . . . .

107

Author Index Volumes 1-94

. . . . . . . . . . . . . .

143

. . . . . . . . . . . . . . . . . . . .

157

Subject Index .

Polyimides T o h r u Takekoshi General Electric, Corporate Research and Development, Schenectady, N Y 12301, USA

A survey of scientific and patent literature in the last 5-10 years is presented. The science and technology on polyimides have been rapidly diversified as minor but important cummulative technical breakthroughs have been made. Special emphasis is given to the area of processable polyimides and polyimide matrix resins for structural composites.

. . . . . . . . . . . . . . . . . . . . . . . . . . . . .

2

1 New Monomers . . . . . . . . . . . . . . . . . . . . . . . . . . 1.1 Diamines . . . . . . . . . . . . . . . . . . . . . . . . . . . 1.2 Dianhydride . . . . . . . . . . . . . . . . . . . . . . . . . .

2 2 6

2 Polyimides with Improved Proeessability . . . . . . . . . . . . . . . .

9

3 Crystalline Polyimides . . . . . . . . . . . . . . . . . . . . . . . .

11

4 Polyimides for Structural Composites . . . . . . . . . . . . 4.1 Acetylene Terminated Polyimides . . . . . . . . . . . . 4.2 PMR-15 . . . . . . . . . . . . . . . . . . . . . . . 4.3 Bismaleimides . . . . . . . . . . . . . . . . . . . . 4.4 Biphenylene Terminated Oligoimides . . . . . . . . . . 4.5 Polyimides with Benzocyclobutene Groups . . . . . . . .

. . . . . .

13 14 16 16 17

5 Polyimide Forms . . . . . . . . . . . . . . . . . . . . . . . . . .

19

6 Polyimides for Electronic Applications . . . . . . . . . . . . . . . . .

20

7 Polyimides with Other Specific Properties

. . . . . . . . . . . . . . .

21

. . . . . . . . . . . . . . . . . . . . . . . . . . . .

22

Introduction

8 Conclusion

9 Acknowledgement 10 References

. . . . . .

. . . . . .

. . . . . .

. . . . . .

13

. . . . . . . . . . . . . . . . . . . . . . . . .

22

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

22

Advances in Polymer Science 94 Springer-Verlag Berlin Heidelberg 1990

2

T. Takekoshi

Introduction Since the first commercialization of Kapton polyimide nearly three decades ago, an impressive number of new polyimides of unique properties have been introduced for various industrial and consumer product applications. Commercial and semi-commercial production of numerous new monomers have made it possible to explore seemingly infinite varieties of structurally different polyimides and copolyimides. As a result we seem to have a more finely tuned understanding of structure-property relationship necessary for a specific application. Research and development activities in new polyimides seem to be intensifying rather than reaching its maturity. In this article, recent advances in polyimides are reviewed in the area of scientific activity as well as commercial developments.

New Monomers One of the most important developments in the last decade was the increasing need for polyimides with various specific properties such as improved processability. New monomers were developed to meet such needs. New monomers as well as monomers which have become available recently because of new improved processes, are discussed below.

1.1 Diamines Bell et al. [I] synthesized an exhaustive number of position isomers of diaminodiphenylmethane (MDA), diaminodiphenyl ether (DDE) and diaminobenzophenone (DBP) and demonstrated that the meta linked diamines gave polyimides with markedly lower glass transition temperatures (Tg) than those ofpara-linked structures. Interestingly, ortho-linked structures were ineffective in decreasing Tg probably because of possible steric restriction imposed on the rotational freedom of main chains. Melt fusible LARC-TPI developed by NASA is based on this discovery and is composed of 3,3'-DBP and 3,3',4,4'-benzophenonetetracarboxylic dianhydride (BTDA). Diamines containing one or more stable linkages between aromatic rings such as - - O - - , - - S - - , - - 8 0 2 - , - - C O -N, --C(CH3)z--, and - - C ( C F 3 ) z - - , have been used to synthesize many tractable polyimides. Some of the standard procedures to prepare these diamines are described below. (a) Reaction of activated bishaloaromatic compounds and aminophenolates yields bis(aminophenoxy)arylene for example [2, 3].

2

H

Y

+

H2N~ - ~ - /

Z = - S O 2 - - , --CO--,

~

etc.

~

X = F, C1

"~-~-/'NHz

Polyimides

3

(b) Friedel-Crafts reaction of nitrobenzoyl chloride with nucleophilic aromatic ether gives bis(nitrobenzoyl)arylene ethers which can be readily reduced to the corresponding diamines [4].

Y = --O--,

--O--Ar--O--,

etc.

(c) Nucleophilic displacement reaction of 4-halonitrobenzene with various bisphenolates affords bis(4-nitrophenyl)arylene ethers which can be hydrogenated to the diamines [5].

20=~!

+ eo-Ar-O®

> Oz~O-Ar-O~NOz Hz > H 2 N ~ O _ A r _ O ~ H

z

Bis(3-aminophenyl)arytene ethers are useful monomers to prepare polyimides of lower Tg's. For example, 1,3-bis(3-aminophenoxy)benzene has been used as building blocks for various thermally processable PI systems. The compound was originaly synthesized by Fink [6] according to the following Ullmann synthesis under rather harsh conditions.

The improved synthetic method was reported [7] in which readily available m-dinitrobenzene was subjected to nitro-displacement reaction with various bisphenols. The resulting bis(3-nitrophenyl)arylene ethers were hydrogenated to afford bis(3aminophenyl)arylene ethers.

2

+ ®O-A r-O®

DMF Hz

r

Ortho or para activated nitro aromatic compounds have been known to undergo nitro-displacement reaction to form various ortho and para substituted aromatic ethers [8]. In the above case, the powerful electron withdrawing effect of one nitro group activated the other nitro group although they are meta to each other. Other meta substituted bis(aminophenyl)arylene ethers reported are 1,3-bis(3-amino-

4

T. Takekoshi

phenoxy)-5-chlorobenzene [9], 2,6-bis(3-aminophenoxy)pyridine [10], and 2,2-bis(aminophenoxy)biphenyls [1 t]. Also reported are diamines containing other heterocyclic rings such as 2,5-bis(4aminophenyl)pyrazine [12], 4,4'-diaminobipyridyl [13], N,N'-bis(4-aminophenyl)piperazine [14], and 2,5-bis(4-aminophenyl)-3,4-diphenylthiophene [15]. Perfluoroalkylene bridged diamines are described with increasing frequency, included in this group are 2,2-bis(3 or 4-aminophenyl)hexafluoropropane [16, 17] and 1,I-bis(4-aminophenyl)-l-phenyl-2,2,2-trifluoroethane [18, 19]. Polyimides derived from cycloalkylene bridged diamines such as 5-amino-3-(4aminophenyl)-l,l,3-trimethyldihydroindene [20] and bis-(3-aminophenoxy)spirobiindane [21] are reported to exhibit good thermal stability and processability. Diamines with bulky substituents such as phenyl have been used to increase the solubility of resulting polyimides [19, 22]. Other diamines listed in Table t, will be discussed in the following sections. TaMe 1. List of aromatic diamines

Diamine

References

B]

H'N~~z~H'

[2, 3]

[4] [53]

[6, 7]

[8]

H z ~

H2

H 2 ~

H2

[91

[lO]

[12]

Polyimides Table 1. continued Diamine

References

H 2 ~ H 2

[13] 114]

H 2 ~ H z

[15] [16, 17]

CF3"~,.-~-/

[18, 19]

F~

[9o1

H z ~ H 2

I2o]

Hz@~ H2

[21]

Hz~Hz

[22]

H z N ~

.

,

/'-'~

Hz

[49]

[5l]

[44] H

[58]

Hz

H3~

H., H2

H ~ CCH3 H3

Hz Hzf,,l.(( I)_I~IH z H~(~ CH~

[1 lO]

6

T. Takekoshi

1.2 Dianhydrides Generally, synthesis of dianhydrides is somewhat more complex than that of diamines and until recent time pyromellitic dianhydride (PMDA) and benzophenone-3,3',4,4'tetracarboxylic dianhydride (BTDA) had been the only commercially produced aromatic dianhydrides. Some of the significant commercial products developed recently, are Upilex by UBE Ind. and Ultem by General Electric. The former is based on biphenyl-3,Y,4,4'-tetracarboxylic dianhydride (BPDA) and the latter on 2,2bis[4-(3,4-dicarboxyphenoxy)phenyl]propane dianhydride or bisphenol A dianhydride (BPA-DA). BPDA is produced by oxidative coupling of inexpensive phthalic acid esters in the presence of palladium catalyst [23, 24].

~

OzR

O= Pd

OzR

Another process reported is based on dechloro coupling of 4-chlorophthalic acid salt in the presence of a palladium catalyst and sodium formate [25]. Synthesis of various ether containing dianhydrides, i.e. bis(ether anhydride)s was pioneered by Koton and Florinski [26] as shown by the following reaction scheme. 2 B

r•H3

H~C~O-Ar-O~ + HO-Ar-OH

H3 H

KOH/Cu >

H~ KMnO4

:>HO2C~-Ar HO=C-~-~

~ ' ~

O2H

~_../~C OzH

However, less than quantitative yields of reactions and difficulty in purification of the product hampered the practical use of this scheme. The same compounds can be prepared by "nitro displacement" of 3 or 4-nitrophthalimide with difunctional phenol salts. In this reaction, the nitro group is displaced and leaves as a nitrite ion [27]. The products bis(etherimide)s are hydrolyzed to the tetracarboxylic acids which are in turn converted to the dianhydrides [28].

>

It

-)-]-O-Ar-O-t-(-- / I

HO,CJ j

H

Bis(ether anhydride)s

Polymides

7

Similarly, nitro displacement of 4-nitrophthalimide with bissulfinates afforded bis(sulfoneimide)s from which bis(sulfoneanhydride)s were produced [29].

2 RN 1(~ ) I * eOzS-Ar-SOzE>

~o,

SOi-Ar--S

OcAr-S Nucleophilic displacement of hexafluorobenzene with 4-hydroxy-N-methylphthalimide followed by hydrolysis and cyclization gave tetrafluorophenylenedioxybis(phthalic anhydride) [30].

C H 3 ~ C H 3

O

)-

Field et al [31] reported synthesis of fused aromatic system dibenzoanthracenetetracarboxylic dianhydride by interesting photo-oxidative cyclization.

hu -Hz

Synthesis of trifunctional heteroaromatic anhydride was reported by Kanakarajan et al [32, 33]. Other dianhydrides listed ~n Table 2, will be discussed in the following sections.

T. Takekoshi

8

Table 2. List of dianhydrides Dianhydride

Reference

[23, 251

O•O-Ar-O• ~~'Oz-Ar-S~

[26, 28]

[291

[3ol

[31]

0

[32, 331

[44]

[45, 46]

Polyimides Table 2. continued Dianhydride

Reference

[471

[112, 114]

2 Polyimides with Improved Processability High performance characteristics of polyimides are represented by high mechanical strength and modulus, extraordinary non-flammability, excellent electrical properties and solvent resistance, as well as outstanding thermoxidative properties. However, extremely high glass transition temperatures of earlier polyimides associated with rigid fused heteroaromatic ring systems hampered development of various applications other than films and coatings in which the elegant two step polyamic acid process [34] was used. Researchers in the USSR [35] described earlier systematic observations that introduction of flexible linkages into polyimide main chains significantly lowered glass transition temperatures without greatly sacrificing thermal stability. However, a convenient and practical process to'synthesize such structures was not available until recent times. Nitro-displacement process developed at General Electric afforded a family of polyetherimides represented by Ultem 1000 resin whose structure is shown below.

-•N

H3

The polymer has a glass transition temperature of 217 °C and TGA weight loss of only 1% at 460 °C in air at a heating rate of 10 °C/min. Excellent melt stability over a wide process window is attributed to the completely imidized structure and stable chain end capping. Such control of the structure is attainable only by improved polymerization processes which are governed by procassability of the polymer itself. Polyetherimides (PEI) were synthesized from bis(ether anhydride)s described in the preceding chapter with various diamines. Because of excellent high temperature solubility and melt stability, PEI are excellent systems to demonstrate various alternative polycondensation processes applicable to the polyimide formation. PEI have been prepared by one-step high temperature solution polymerization in phenolic solvents [36] or

10

T. Takekoshi

in non-polar solvents [37] as well as solventless melt polymerization [38]. The polymerization has been also performed by amine-imide exchange [39] and ether-phenol exchange [40] reactions in melt condition. PEI can be also prepared by the nitrodisplacement reaction between bisphenol salts and bis(nitroimide)s in dipolar solvents [27, 41] as shown by the following equation.

~--~N-Ar--I~'~

+ eO-ArL'Oe

°

Upilex Type R by UBE Ind. is produced from BPDA and ODA. It is based on a unique combination of the new monomer synthesis described in the preceding section and one step high temperature solution polymerization in a phenolic solvent [42]. High quality films and fibers can be produced from the solution because a water forming reaction is not involved [43]. The polymers produced by such a process have a completely imidized structure and provide for superior properties than polymers prepared by solid state imidization ofpolyamic acids. For example long term oxidative and hydrolytic stabilities and retention of electrical properties are substantially better. One of the effective methods to improve the solubility is to introduce bulky nonpolar substituents onto polymer chains. Harris [44] prepared dianhydrides highly substituted with phenyl groups as shown below.

Ar+2

r

The polyimides derived from the dianhydrides had high Tg's of 238 to 466 °C and they were soluble in chlorinated hydrocarbon solvents. Because of their solubility, copolyimides containing the following acetylene substituted diamine monomers were readily prepared by homogeneous high temperature solution polycondensation in m-cresol.

~

C

H

Polyimides

11

Alston and Grants [19] described the structure-property relationship of polyimides derived from phenyl substituted monomers including the following dianhydride.

Woo [45] synthesized soluble polyimides with high Tg (225-285 °C) from 1,4phenylenebis[2-(2-alkylsuccinic anhydride)].

Teshirogi [46] also reported polyimides derived from the similar bis(succinic anhidride) and bis(glutaric anhydride) shown below.

Sillion et al [47] prepared polyimides containing benzhydrol groups by using the reduction product of benzophenonetetracarboxylic acid dimethyl ester shown below.

CH302C-~ ~~O2CH3 HOzC, ~.--~-J OH ~COzH The polyimides were soluble in dipolar solvents such as NMP. Interestingly, the polyimides were readily transformed to non-hydroxylated polymers via a redox disproportionation as illustrated below.

+ H20 Improvement of processability is also a key technology involved in melt processable linear crystalline polyimides, matrix resins for structural composites, and other new applications which will be discussed in the following sections.

3 Crystalline Polyimides Melt processable, crystalline, high temperature polymers such as polyetheretherketone (PEEK) have been developed for critical application areas where processability, chemical resistance and toughness are required. PEEK has been applied as thermo-

12

T. Takekoshi

plastic matrix resin in graphite fiber composites to impart high fracture toughness. Crystalline polyimides are expected to fit into similar areas of application with an additional advantage of having various process options. However, the majority of polyimides with high Tg are noncrystalline polymers. Polypyromellitimides such as Kapton generally show little crystallinity. The lack of significant crystatlinity may be primarily attributed to the immobility of rigid main chains at the process temperatures. The insertion of increased number of ether groups in the main chains improves such chain mobility as represented by decreased Tg. Earlier investigations indicated that some of these ether-containing polyimides showed crystallinity as shown below [35].

At:

Ar :

Recently St. Clairs [48] reported that polyimides prepared from a bis(ether anhydride) and p-phenylenediamine and benzidine were crystalline as shown below

Ar

=

Harris et al. [49] prepared a highly crystalline polyimides from oxybisphthalic anhydride and 1,2-bis(4-aminophenoxy)ethane as shown below.

i

--

1,2

Polyimides

13

However, melting temperatures of the above polyimides are well over 400 °C and expected to be difficult to process. More recently it has been shown that some of the polyetherimides derived from bis(ether anhydride)s and aromatic diamines containing more than one ether group show crystallinity and that their melting temperatures are in a range of 300 to 400 °C [36, 50]. Because of high symmetry and low Tg, polyphenylene sulfide has a great tendency to crystallize. Polyimides derived from aromatic diamines containing cummulative phenylene sulfide groups as shown below, were also found to crystallize in a moderate temperature range of 300 to 400 °C [51].

LARK-TPI developed by NASA is a melt procesable polyimide derived from BTDA and 3,3'-diaminobenzophenone and useful as a high temperature adhesive [1].

Characterization of this polyketoimide indicated that the properties of the sample varied according to annealing conditions because of partial crystallization [52]. Hergenrother et al [53] prepared diamines containing both ether and keto groups. Several polyimides derived from these diamines had melting temperatures of 350 to 440 °C.

4 Polyimides for Structural Composites 4.1 Acetylene Terminated Polyimides Thermid MC-600, a low melting oligoimide with acetylene end groups was first developed at the Hughes Aircraft Co. [54, 55] and is now produced by the National Starch and Chemical Corp. The structure is based on all m e t a linked diamine 1,3bis(3-aminophenoxy)benzene for better processability.

On heating, it cures by addition reaction with little off-gassing to give low void cured resins which have 315 °C service temperature. The reaction mechanism of the cross linking is complex. A part of the acetylene groups trimerize to form a benzene ring

14

T. Takekoshi

but the major part dimerize to form eneyne structure which is believe to cycloaromatize on further heating [56, 57].

Preformed eneyne could be built into linear polyimides using 1,4-bis(3-aminophenyl)1-buten-3-yne.

The polyimides crosslinked on heating at around 270 °C [58]. Thermid IP-600 series are the isoimide form of MC-600 whose structure is shown below.

Polyisoimides have better solubility and improved melt flow characteristics [59, 60]. The isoimide groups rearrange to imides on heating above 300 °C. Better processability is also achieved by substituting hexaffuoroisopropylidene-bis(phthalic anhydride) (6FDA) for BTDA, Thermid FA-700 [61-63]. Siloxane containing oligoimides with acetylene end groups were reported to exhibit good processability and good adhesive properties [64].

4.2 PMR-15 PMR-15 is a state of the art thermoset potyimide mainly used as a matrix resin for graphite fiber composites in the aerospace industry. It was originally developed at NASA [65] and represents Polymerization from Monomeric Reactants with a molecular weight of 1500. Composite prepregs are fabricated with a mixture containing dimethyl ester of benzophenonetetracarboxylic acid (BTDE), monomethyl ester of norbornenedicarboxylic acid (NE) and MDA in methanol. The chemistry of PMR-15 is illustrated in Fig. t. Usage of readily removable solvent and a wide process window make this resin the material of choice in aerospace application. However, the actual chemistry is complex and its quality control is difficult. Johnston et al. [66] showed that the intermediate amic acid was formed via anhydride which was formed by reverse cyclization of acid ester groups rather than direct ester aminolysis.

Polyimides

15

r O'H 1

L'-~-~O,CHd

+

L

n+1

HO2C~

~.,,~-'~CO:H

_t

A I-CH30H

A I "H:O I

A

/ i

+

n = ~'.o87

Crossllnked polymer Fig. I. PMR-15 polyimide resin system

One of the difficult problems is the analysis of the PMR-15 monomeric mixture for reliable quality control [67]. During the production of BTDE, excessive heating can produce some triester (BTTE). Lauber [68] demonstrated that the presence of BTTE led to final composites of inferior properties. More recently Roberts et al. [69, 70] developed a precise and sensitive HPLC method to analyze the PMR-15 momomer mixture. The results greatly helped to elucidate the complex chemical transformation of PMR-15 resin. Further increase of use-temperature up to 371 °C was achieved by use of thermally more stable diamines in place of MDA [71]. A new thermoset polyimide introduced by Ciba-Geigy is related to PMR-15. The oligomer is end capped with allylnorbornenedicarboxyl anhydride.

CI.~CI+C~''~

It is reported to have epoxy-like good processability and high reactivity [72-74].

16

T. Takekoshi

4.3 Bismaleimides Bismaleimide of MDA (Kerimid 601) was introduced by Rhone-Poulenc around 1970 [75]. The resin cures on heating via Michael addition of amino groups to maleimide unsaturations and polyaddition of the maleimide group itself. An attractive feature of bismaleimide resin (BMI) is its relatively low cure temperature. However, brittleness and micro crack formation in cured products are some of the problems attributed to very high cross link density. Another problem is a relatively high melting temperature of the uncured resin resulting in a narrow process window. Elimination of the solvent, thus hot melt application is used for some of the newer BMI resins. The brittleness can be improved by addition of rubbers (Compimid 453, Boots Technochemie) or with other components [76-79]. Effect of rubber toughened BMI resin was described by Shaw [80]. Bell et al [81] prepared bismaleimides from less toxic isomers of MDA. Attempts to make more processable BMI such as shown below, are found in much of the patent literature [82-84].

Process characteristics of various BMI resins are reviewed by Briscotl and Walton [85]. Difluoromaleimides showed improved thermal stability and ease of curing [86].

4.4 Biphenylene Terminated Oligoimides Stille et al. [87] introduced biphenylene as reactive end groups capable of being cured at elevated temperatures via an addition mechanism. When heated above 350 °C, biphenylene undergoes a thermal ring opening to form primarily its cyclic dimer, tetrabenzocyclooctatetraene.

Polyimides

17

In the presence of aromatic polymers, it reacts to form biphenylated aromatics as major products. Biphenylene end-capped polyimide oligomers were prepared using PMR technique and its curing poperties were investigated [88].

Ro,

The graphite composite fabricated from this resin and cured at 390 °C indicated that the molecular weight increased but crosslinking efficiency was low. The result was improved by use of a trifunctional amine to achieve increased crosstinking density. Biphenylene end groups were found to react at 350-400 °C with internal 1,2-diarylacetylene group to form phenanthrene crosslink [89].

The processability of the system was improved by using hexafluoropropylidene connecting groups such as 6FDA and 2,2-bis-[4-(4-aminophenoxy)phenyl]hexafluoropropane shown below [90].

Low molecular weight bisbiphenylene compounds were used as a plasticizer for various polymers including polyimides. The plasticized polymers were cured on heating [91].

4.5 Polyimides with BenzocyclobubeneGroups Benzocyclobutene (BCB) polymerizes at much lower temperatures of about 250 °C than the closely related biphenylene. The reaction undergoes electrocyclic ring opening to form o-xylylene which polymerizes to produce cyclic dimer and poly-o-xylylene [92].

18

T. Takekoshi

Tan and Arnold [92] synthesized bis(benzocyclobuteneimide)s of the following structures. ×=

The compounds cured thermally to form crosslinked polymers with 343 °C stability in air. The curing characteristics of oligoimides end-capped with aminobenzocyclobutene were also described [93]. o-Xylylene undergoes the Diels-Alder reaction with various dienophiles as shown below.

Monomers containing both BCB and acetylene groups were shown to undergo polyaddition via Diels-Alder cyclization [94].

Similarly, mixtures of imide oligomers containing BCB groups and those containing maleimide groups were shown to polymerize at moderate temperatures of 20t)-250 °C to give thermally stable polymers [95].

Potyimides

19

Mixtures of bisbenzocyclobutene and bismaleimide such as shown below were also polymerized to form stable polymers.

d~F3

v

The system provided for a wide process window and various crosslink densities according to the variation in the above monomer ratios [96]. Properties of mixtures containing benzocyclobutene end-capped oligoimides and bismaleimides were reported by Denny et al. [78]. Cyclopolymerization of bis(benzocyclobutene)s with other difunctional dienophiles such as aromatic biscyanates and bisacetylenes were also described [97]. A similar system, a p-xylylene dimer namely p-cyclophene was also explored for reactive end groups. Boldwin et al. [98] prepared oligoimides shown below.

The oligomer cured at significantly higher temperatures of 270--330 °C to give thermally stable resin.

5 Polyimide Foams The current polymer foam market is dominated by gas imbibed polystyrene, polyolefins and polyurethanes used in consumer products, packagings and construction markets. However, there is a growing market for high performance foam products. Insulation materials for aerospace, transportation and some construction industries are required to have higher temperature performance and non-flammability. In this respect polyimides are naturally the material of choice. Thermoplastic polyetherimide Ultem can be formulated with high temperature foaming agents such as 5-phenyldihydro-l,3,4-oxadiazinone to produce structural form products [99] by injection molding. PEI could be readily imbibed with various volatile organic compounds such as chlorinated hydrocarbons [100] and acetone [101].

20

T. Takekoshi

Polyimides have been prepared by the reaction of dianhydrides with diisocyanates. Carbon dioxide is the condensation byproduct in this reaction and serves as foaming gas [102-104].

O

Ar

+ OCN_Ar~NCO

~

Ar

Ar

+ CO2

With use of appropriate catalysts, mixtures of dianhydrides and diisocyanates were directly converted to rigid foam products without use of foaming agents [105, 106]. In situ formation of imide forms like the polyurethane process, was developed by Riccitietlo et al. [107]. The system contains a unique furfuryl alcohol-acid mixture which generates heat to initiate the isocyanate-anhydride reaction. An alternate process to produce polyimide foam is based •n PMR technique. A mixture containing diester of BTDA (BTDE) and diamines is heated in a closed mold. The imidization takes place with formation of methanol and water vapor which serve as foaming gas [108, 109].

6 Polyimides for Electronic Applications Polyimides including those already described above are used as insulators, passivation coatings, alpha particle barriers, planarization coatings and even as part of IC elements as interlayer dielectrics. Photo-imagable polyimides could be applied in microelectronic systems in the same manner as photoresists are used. Several systems developed are based on polyamic acids solution in which some of the carboxyt groups are derivatized to photo-sensitive groups. Some of the shortcomings are complex process steps, low photo sensitivity and most importantly the unstable shelf life of such polyamic acid solutions. In this review, the topics will be limited to some important basic technical progress reported recently. A unique photo-imagable polyimide, not intermediates but completely imidized form, was described by Pfeifer and Rhode [110]. The polyimides were prepared from BTDA and diamines whose ortho positions to the amino groups were extensively substituted with alkyl groups.

Tg = 384°C

Tg = 439°C

Importantly, a high degree of methyl substitution increased both solubility and Tg of the polyimides. Non-planner conformations and restricted rotational motion of the main chain are the probable cause of such effects. The polyimide solutions can be readily applied and have exellent film forming properties. Because of high Tg they are very stable under harsh processing conditions. In addition, the films showed high photo sensitivity and good contrast.

Polyimides

21

Another significant development is the recognition that certain polyimides exhibit very low values of the coefficient of linear thermal expansion (CLTE). In constructing electronic devices, matching CLTE of polyimides to those of substrate materials such as metals and ceramics is obviously important to avoid formation of serious internal stresses. Numata et al. [111] prepared polyimides from PMDA and BPDA with aromatic diamines which were composed of single or cummulative 1,4-phenylene and 2,5pyridinediyl structures. The polymers showed generally very low CLTE of below 2 x 10 -5 °C -1. One of these polyimides had a CLTE value of 4 x 10 -7 °C -1. Polyimides derived from 3,3",4,4"-tetracarboxy-p-terphenyl dianhydride were also shown to have very low CLTE [112, 113]. Upilex S Type which is primarily composed of BPDA and p-phenylenediamine was reported to have a very good dimensional stability and very low CLTE [114].

7 Polyimides with Other Specific Properties Earlier commercial polyimides derived from PMDA and BTDA are usually colored in deep yellow or yellowish orange. When two anhydride groups of diananhydrides are separated into two phthalic anhydride groups and linked together with sp3 carbon atom such as --C(CF3)2-- group or hetero atoms such as --O--, --S--, and --SO2--, they tend to produce polyimides of significantly lighter color. Quantitative comparison on degree of coloration is generally difficult because many factors cause coloration of polyimides other than the structure of polymer repeating units. The majority of dianhydrides are relatively difficult to purify to a colorless state. Most of the aromatic diamines are very sensitive to air oxidation and the purification by distillation is limited to those with low molecular weight. Because polyimide preparation usually involves a high temperature process exceeding 200 °C, it is difficult to prevent some oxidation of the amino group. In the case of BTDA, formation of an imino group may take place, particularly in the presence of an excess of diamine, by the reaction between the keto group and the amine.

Aromatic imines are usually intensely yellow. Other possible byproducts which may be formed in the polyimide system are the previously discussed isoimide and imideimine formed by the following reaction.

22

T. Takekoshi

Both isoimides and imideimines have a deep yellow color. Despite those difficulties, St. Clare et al. [115, 116] determined the qualitative relationship between the color of polyimides and the structures of diamines and dianhydrides from which they are derived. According to the above authors, bulky electron withdrawing groups such a s - - S O 2 - - , and --C(CF3)2 - and also m e t a linked aromatic ether structures in diamine moieties provided for light color and an increase in solubility. The effects were attributed to the reduced charge transfer interaction. However, simple disruption of conjugated unsaturation extending the imide groups may be considered as the major reason. According to our observation, the majority of polyetherimides which do not contain electron withdrawing groups were nearly colorless [36]. Polyimides with a low level of color are important in some critical applications such as lightweight flexible solar radiation reflectors, protective coating for solar cells, liquid crystal orientation films in LC display devices, LC light shutters, etc. Hasuda et al. [117, 118] described the construction of multi-layer thermal control structures for communication satellites. The outer layer was made of silvered Ultem 1000 polyetherimide film. The material was chosen because of good thermal radiation characteristics and a low solar radiation absorbance as well as excellent stability against solar radiation. Bilow et al. [ 17] described polyimides prepared from hexafluoroisopropylidene-4,4'-bis(phthalic anhydride) and 2,2'-bis(3-aminophenyl)propane as a protective coating for solar cells positioned in space. The coating has good transparency and exellent stability against heat, UV, and low energy particles. Recently, numerous patent disclosures have appeared in the area of colorless polyimides for LC alignment control films [119].

8 Conclusion The research and development efforts on polyimides have been intensified in recent years. Exploration of various new monomers and new synthetic methods as well as new polymer processes have made it possible to develop new applications in important high technology markets. Backed by high added value of new materials in sophisticated industrial societies, research and development activities in the field of polyimides seem destined to continue prospering.

9 Acknowledgement The author would like to express his sincere gratitude to Professor Charles G. Overberger of the University of Michigan for his support and encouragement.

10 References 1. Bell VL, Stump BL, Gager H (1975) J. Polym. Sci., Polym. Chem. Ed. 14:2275 2. Kawakami JH, Brode GL, KwiatokowskiGT, BedwinAW (1974)J. Polym. Sci, Polym.Chem. Ed. 12:565

Polyimides 3. 4. 5. 6. 7.

23

Hergenrother PM, Watelyn NT, Havens SJ (1987) J. Polym. Sci., Part A, Polym. Chem. 25 : 1093 Schoenberg JE, Anderson SP (1983) US Pat. 4,405,770 to National Starch & Chem. Williams AL, Kinney RE, Bridger RF (1967) J. Org. Chem., 32:2501 Fink W (1968) Herv. Chim. Acta, 51 : 954 Jap. Pat. Disclosures 62-05035, 62-068817, 62-270636, Intl. Pat. 8701378 (1987) to Mitsui Toatsu 8. Takekoshi T (1987) Polymer J. 19:191 9. Ger. Pat. 3 429 903, Jap. Pat. Discl. 62-116 547 (1987) to Mit~ui Toatsu. 10. Jap. Pat. Discl. (1987) 62-116563 to Mitsui Toatsu. 11. Belg. Pat. (1977) 855653 to Ciba-Geigy. 12. Jap. Pat. Discl. (1987) 62-270623 to Daicel Chem. 13. Jap. Pat. Discl. (1986) 61-181828 to Hitachi. 14. Lee TB, Feld WA (1988) Am. Chem. Soc., Potym. Prepr. 29:2t4 15. Imai Y, Maldar, NV Kakimoto M (1984) J. Polym. Sci., Chem. Ed. 22:2189 16. Lau KSY, Landis AL, Kelleghan WJ, Beard CD (1982) J. Polym. Sci., Polym. Chem. Ed. 20: 2381 17. US Pat. 4,592,925 (1986) and 4,645,824 (1987) to Hughes Aircraft Co~ 18. Kray WD, Rosser RW (1977) J. Org. Chem. 42:1t86 19. Alston WB, Gratz RF (1987) In: Weber, WD, Gupta MR (eds) Recent advances in polyimide science and technology", Soc. Plast. Eng., p 1. 20. Cobuzzi CA, Chaudhari MA (1985) Natl. SAMPE Tech. Conf., 17:318 21. Jap. Pat. Discl. 62-050375 (1987) to Mitsui Toatsu 22. Gannett TP, Gibbs HH (1986) US Pat. 4,576,857 to Du Pont 23. Itatani H, Yoshimoto H (1973) J. Org. Chem., 38:76 24. Kajima M et al. (1973) J. Catalysis 29:92 25. Shoji F, Kataoka F (1986) Jap. Pat Discl. 61-167642 26. Koton MM, Florinski FS (1968) Zhur. Org. Khim. 4:774 27. Takekoshi T, Wirth JG, Heath DR, Kochanowski JE, Manello JS, Webber MJ (1980) J. Polym. Sci., Polym. Chem. Ed. 18:3069 28. Takekoshi T, Kochanowski JE, Manello JS (1985) J. Polym. Sci., Polym. Chem. Ed. 23:1759 29. Europ. Pat. 245729 (1987) to Bayer 30. USSR Pat. (1985), 1 100868 31. Fields EK, Wisenburg ML, Behrend SJ (1987) US Pat. 4,638,072 to Standard Oil (Indiana) 32. Kanakarayan K, Czarnik AW (1986) J. Org. Chem. 51:5241 33. Kanakarayan K, Czarnik AW (1988) Am. Chem. Soc., Polym. Prepr. 29:246 34. Sroog CE, Endrey AL, Abramo SV, Bert CE, Edwards WM, Olivier KL (1965) J. Polym. Sci. A3: 1373 35. Adrova NA, Bessenov MI, Laius LA, Rudakov AP (1970) Polyimides, Technomic, Stamford, CT (Progress in Materials Science Series, vol 7) 36. Takehoshi T, Kochanowski JE, Manello JS, Webber MJ (1986) J. Polym. Sci., Polym. Syrup. 74:93 37. Takekoshi T, Kochanowski JE (1976) US Pat. 3,991,004 to General Electric 38. Takekoshi T, Kochanowski JE (1974) US Pat. 3,803,085 to General Electric 39. Takekoshi T, Kochanowski JE (1974) US Pat. 3,850,885 to General Electric 40. Takekoshi T (1977) US Pat. 4,024,110 to General Electric 41. White DM, Takekoshi T, Williams FJ, Relies HM, Donahue PE, Klopfer HJ, Louks GR, Manello JS, Matthews RO, Schluenz RW (1981) J. Polym. Sci., Polym. Chem. Ed. 19:1635 42. Sasaki Y, Inoue H, Itatani H, Kashima M (1981) US Pat. 4,290,936 to UBE Ind 43. Yamane H (1985) Proceedings of Second International Conference on Polyimides, Soc. Plast. Eng., Ellenville, NY, Oct. 1985, p 86 44. Harris FW (1982)Proceedings from First Technical Conference on Polyimides, Soc. Plast. Eng., Ellenville, NY, Nov. 1982, p 1 45. Woo EP (1986) J. Polym. Sci., Part A, Polym. Chem. 24:2823 46. Teshirogi T (1987) J. Polym. Sci., Part A, Polym. Chem. 25:31 47. Quenneson M, Garapon J, Bartholin M, Sillion B, Verdet L, (1985) Proceedings of Second International Conference on Polyimides, Soc. Plast. Eng., Ellenville, NY, Oct. 1985, p 74 48. St. Clair TL, St. Clair AK (1977) J. Polym. Sci., Polym. Chem. Ed. 15:1529

24

T. Takekoshi

49. Harris FW, Karnavas AJ, Das S, Cucuras CN, Hergenrother PM (1986) Am. Chem. Soc., Polym. Mater. Sci. Eng., Prepr. 54:89 50. Takekoshi T, Anderson PP (1986) US Pat. 4,599,396 to General Electric 51. Takekoshi T, Anderson PP (1987) US Pat. 4,716,216 to General Electric 52. Burks HD, St. Clair, TL, Hou T (t986) SAMPE Quarterly 18:1 53. Hergenrother PM, Wakelyn NT, Havens SJ, (1987) J. Polym. Sci., Part A, Polym. Chem. 25: 1093 54. Bilow N, Landis AL, Miller LJ (1974) US Pat. 3,845,018 to Hughes Aircraft 55. Landis AL, Bitow N, Boschan RH, Lawrence RE, Aponyi TJ (1974) Am. Chem. Soc., Polym. Prepr 15 : 537 56. Hergenrother PM, Sykes GF, Young PR (1973) Am. Chem. Soc., Div. Pet. Chem., Prepr. 24: 243 57. Sefcik MD, Stejskal EO, McKay RA, Shaefer J (1979) Macromolecules 12:423 58. Reinhardt BA, Arnold FE (1981) J. Appl. Polym. Sci. 26:2679 59. Landis AL, Naselow AB (1982) Natl. SAMPE Tech. Conf. Ser. 14:236 60. Murray T, Tessier N (1986) 31st Intl. SAMPE Symp., Las Vegas, NM, Apr. 1986, p 693 61. Harris FW, Pamidimukkolas A, Gupta R, Das S, Wu T, Mock G (1984) J. Macromol. Sci., Chem., A21:1117 62. Capo DJ, Schoenberg J (1986) 18th Natl. SAMPE Tcch. Conf., Oct. 1986, Seatle, WA, p 710 63. Unroe MR, Reinhardt BA, Arnold FE (1985) Am. Chem. Soc., Polym. Prepr. 26:136 64. St. Clair TL, Maudgal S (1986) US Pat. 4,624,888 to NASA 65. Serafini T, Delvig P, Lightsey G (1972) J. Appl. Polym. Sci. 16:905 66. Johnston JC, Meador MAB, Alston WB (1987) J. Polym. Sci., Part A, Polym. Chem. Ed. 25: 2175 67. Lauber RW, Alston WB, Vannucci RD (1978) NASA Tech. Report 78~53 68. Lauber RW (1976) NASA TMX-73444 69. Roberts GD, Vannucci RD (1986) SAMPE J. 22:24 70. Roberts GD, Lauber RW (1987) J. Appl. Polym. Sci. 33:2893 71. Vannucci RD (1987) 32nd Intl. SAMPE Symp., Apr. 1987, p 602 72. Plastics World, Jan. 1988, p 64 73. Renner A, Eldin SH (1987) US Pat; 4,666,997 to Ciba-Geigy 74. Renner A (1987) US Pat. 4,667,003 to Ciba-Geigy 75. Mallet MAJ, Damory FP, (1974) Am. Chem. Soc., Div. Org. Coat. Plast. Chem., Prepr. 34:173 76. King J J, Chaudhari MA, Zahir SA (1984) Proceedings of 29th Natl. SAMPE Conf., 1984, p 392 77. Chaudhari MA, Galvin TJ, King JJ (1985) Proceedings of 30th Natl. SAMPE Conf., t985, p 735 78. Denny LA, Goldfab IJ, Farr MP (1987) Am. Chem. Soc., Div. Polym. Mater. Sci. Eng., Prepr. 56:656 79. Carduner KR, Chattha MS (1987) Am. Chem. Soc., Div. Polym. Mater. Sci. Eng., Prepr. 56: 660 80. Shaw SJ (1987) In: Weber WD, Gupta MR (eds) Recent advances in polyimide science and technology, Society of Plastics Engineers, Poughkeepsie, NY, p 290 81. Bell VL, Young PR (1986) J. Polym. Sci., Part A, Polym. Chem. 24:2647 82. Eur. Pat. 253891 (t986) to Mitsui Toatsu 83. Intl. Pat. 8700835 (1987) to AMOCO 84. Jap. Pat. Discl. 61-287938 (1986) to Mitsui Toatsu 85. Briscoll SB, Walton TC (1987) SAMPE J. 23:9 86. Green HE, Jones RJ, O'Rell MK (1979) US Pat. 4,173,700 87. Stille JK, Droske JP (1984) J. Macromol. Sci., Chem. A21 : 913 88. Takeichi T, Stille JK (1986) Macromol, 19:2093 89. Takeichi T, Stille JK (1986) Macromol. 19:2103 90. Takeichi T, Stille JK (1986) Macromol. 19:2108 91. Brand RA (1981) US Pat. 4,269,953 to General Dynamics 92. Tan L, Arnold FE (1985) Am. Chem. Soc., Polym. Prepr. 26:176 93. Denny LR, Soloski EJ (1988) Am. Chem. Soc., Polym. Prepr. 29:176 94. Tan L, Arnold FE (1985) Am. Chem. Sci., Polym. Prepr. 26:178 95. Tan L, Soloski EJ, Arnold FE, (1986) Am. Chem. Soc., Polym. Prepr. 27:240 96. Tan L, Soloski EJ, Arnold FE (1986) Am. Chem. Soc., Polym. Prepr. 27:453

Polyimides

25

97. Tan L, Soloski EJ, Arnold FE (1987) Am. Chem. Soc., Div. Polym. Mater. Sci. Eng., Prepr. 56: 650 98. Baldwin LJ, Meador MB, Meador MA (1988) Am. Chem. Soc., Polym. Prepr 29 : 236 99. Smearing RW, Floryan DE (1985) US Pat. 4,543,365 to General Electric 100. Krutchen CM, Wu P (1985) US Pat. 4,535,100 to Mobil Oil 101. Hoki T, Matsuki Y (1986) Eur. Pat. 186308 to Asahi Chem 102. Meyers RA (1969) J. Polym. Sci., Part A-l, 7:2757 103. Carleton PS, Farrissey WJ, Rose JS (1972) J. Appl. Polym. Sci. 16:2983 104. Alvino WM, Edelman LE (1975) J. Appl. Polym. Sci. 19:2961 105. Farrissey WJ, Rose JS, Carleton PS (1970) J. Appl. Polym. Sci. 14:1093 106. Riccitiello SR, Sawako PM (1979) US Pat. 4,177,333 to NASA 107. Hamermesh CL, Hogenson PA, Tun CY, Sawako PM, RiccitieUo R (1979) 1lth Natl. SAMPE Tech. Conf., 1979, p 574 108. Gagliai J (1980) US Pat. 4,241,193 to International Harvester 109. Lee R, Okey DW, Ferro GA (1985) US 4,535,099 to IMI-Tech Corp 110. Pfeifer J, Rohde O (1987) In: Weber WD, Gupta MR (eds) Recent advances in polyimide science and technology, Society of Plastics Engineers, Poughkepsie, NY, p 336 111. Numata S, Oohara S, Fujisaki K, Imaizumi J, Kinjo N (1986) J. Appl. Polym. Sci. 31 : 101 112. Eur. Pat. 247731 and Jap. Pat. Discl. 62-258338 (1987) to Hitachi Chemical 113. Jap. Pat. 61-18I 829 (1986) to Hitachi 114. High performance polymer films, Nikkei New Materials, Sept. 1986, p 21 115. St. Clair AK, St. Clair TL, Slemp WS, Ezzell KS (1985) Proceedings of Second International Conference on Polyimides, Ellenville, NY, Oct. 1985, p 333 116. St. Clair AK, St. Clair TL, (1986)Am. Chem. Soc. Div. Polym. Mater. Sci. Eng. 55:396 117. Ichino T, Sasaki S, Hasuda Y (1986) Denshi Tsushin Gakkai Ronbunshi, J 69-C: 199 118. Ichino T, Sasaki S, Hasuda Y (1987) US Pat. 4,666,760 to NTT 119. For example, Eur. Pat. (1986) 240249, Jap. Pat. Discl. (1987) 62-057421 to Nitto Electric, Jap. Pat. Discl. (1987) 62-231935-231937 to Canon, Eur. Pat. (1987) 234882 to Mitsui Toatsu

Editor: Ch. G. Overberger Received July 11, 1988

Photoresponsive Polymers Masahiro Irie Institute of Advanced Material Study, K y u s h u University, K a s u g a - K o e n 6-1, Kasuga, F u k u o k a 816, Japan

Several proposals for the construction of artificial photoresponsive polymer systems are reviewed. On photoirradiation, photoresponsive polymers change reversibly their physical and/or chemical properties, such as conformation, shape, surface wettability, membrane potential, membrane permeability, pH, solubility, sol-gel transition temperature, and phase separation temperature of polymer blends. The dynamics of the conformation changes detected with a time-resolved light scattering measuring system combined with a short laser pulse source is included in the discussion. Photoresponsive polymers are interesting practically as well as academically.

1 Introduction

. . . . . . . . . . . . . . . . . . . . . . . . . . . .

28

2 Photoeontrol of Polymer Conformation - - A Guiding Principle of Molecular Design of Photoresponsive Polymers . . . . . . . . . . . . . 2.1 Molecular Design . . . . . . . . . . . . . . . . . . . . . . . . 2.2 Dynamics of C o n f o r m a t i o n Changes . . . . . . . . . . . . . . . .

29 29 38

3 Photoeontrol of Physical and Chemical Properties of Polymers . . . . . . 3.1 Shape - - Macro-Size Effect . . . . . . . . . . . . . . . . . . . . 3.2 Surface Wettability . . . . . . . . . . . . . . . . . . . . . . 3.3 M e m b r a n e Potential . . . . . . . . . . . . . . . . . . . . . . 3.4 M e m b r a n e Permeability . . . . . . . . . . . . . . . . . . . . 3.5 p H . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . .

42 42 51 53 55 57

4 Photostimulated Phase Transition . . . . 4.1 A General View . . . . . . . . . . 4.2 Phase Separation o f Polymer Solutions 4.3 Sol-Gel Transition . . . . . . . . . 4.4 Miscibility of Polymer Blends . . . .

. . . . .

58 58 59 62 64

5 Acknowledgement . . . . . . . . . . . . . . . . . . . . . . . . . .

65

6 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

65

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . .

. . . . .

. . . . .

. . . . .

. . . . .

. . . . .

. . . . .

. . . . .

Advances in Polymer Science 94 © Springer-Verlag Berlin Heidelberg 1990

28

M. Irie

1 Introduction Biological systems have developed various kinds of photoactive organs to adapt themselves to the environmental electromagnetic radiation, sunlight. Plants, for example, have evolved photosynthesis systems to utilize the light as an energy source. At the same time, they have also developed systems which measure and respond to the light intensity and its duration, thereby seeking out optimum conditions for their life processes. These systems use light as information [1]. As in biological systems, light can be utilized in polymer chemistry not only as an energy source for polymer synthesis but also as an information source or a trigger for the reversible control of the physical and chemical properties of polymers. Biological photoresponsive processes consist of many complex biological reactions ranging from the capture of photons to photoresponsive behavior, such as phototropism or phototaxis [2]. Although we are yet unable to reconstruct the biological photoresponsive system as it is, it is worthwhile mimicking its processes and applying them to the molecular design of synthetic photoresponsive polymers, so that the physical and chemical properties can be changed reversibly by photoirradiation. The feature common to the biological photoresponsive systems is that they contain photochromic molecules embedded in biopolymer matrices to absorb light and use the photoisomerization for controlling the conformation and assembly of the biopolymers. The photoinduced structural changes of the biopotymers perturb subsequent biochemical reactions. As in biological systems, photoresponsive polymers consist of a photoreceptor, which contains photochromic molecules, and a functional part (see Fig. 1). At first, an optical signal is captured by the photochromic molecules and then the isomerization of the chromophores in the photoreceptor converts it to a chemical signal. The latter signal is transferred to the functional part via "a chemical circuit" and controls the polymer properties. The number of photochromic chromophores used in the biological systems is limited, while in the synthetic photoresponsive systems, the number of chromo-

I IPh°t°r°c°pt°rl

I

Fig. 1. The structure of a photoresponsivepolymer Table 1. Physical and chemicalproperties of photoresponsive polymerscontrolled by photoirradiation Solution

Solid

Viscosity pH Solubility Metal Ion Capture Capability

Membrane Potential Membrane Permeability Surface Wettability Shape Sol-Gel Transition Miscibility of PolymerBlends Tg

Photoresponsive Polymers

29

phores that can be used is virtually limitlesL Depending on the purpose, we can choose suitable chromophores from a great number of synthetic photochromic compounds. In addition, many aspects of polymer properties can be used for the functional part. Table 1 summarizes the properties so far reported to be photocontrolled reversibly. In the first part of this article, the fundamental idea for molecular design of photoresponsive polymers is described. The second part deals with several examples of photostimulated property changes of the photoresponsive polymers. In the third part, photostimulated phase transitions of photoresponsive polymer systems are discussed.

2 Photocontrol of Polymer Conformation -A Guiding Principle for Molecular Design of Photoresponsive Polymers 2.1 Molecular Design It is well known that many photosensitive molecules can be transformed under photoirradiation to other isomers, which return to the initial state either thermally or photochemically [3]. This reaction is schematically expressed as ]Iv

A~ ¸ ' B hvP,A

and referred to as photoisomerization. The chromophores capable of this reaction are called photochromic molecules. The photoreceptor of Figure 1 contains such molecules. Table 2 shows some typical photoisomerizations, which include (a) trans-cis isomerization, (b) zwitter ion formation (c) radical formation, (d) ionic dissociation, and (e) ring-formation and ring-cleavage. These isomerizations are always accompanied by certain changes in the physical and chemical properties of the chromophores, such as dipole moment and geometrical structure. These changes may induce the changes in the properties of the polymer in which the chromophores are incorporated. The conformation of polymers governs their various physico-chemical properties in solution. To begin with, we outline the guiding principle for designing polymers which change the conformation reversibly by photoirradiation, since they are relevant as a general model of photoresponsive polymers. Figure 2 illustrates several proposals to use photochromic chromophores as a tool for conformation changes. The first mechanism (1) was proposed for the first time by Lovrien [4] in 1967. If a polymer is in equilibrium interaction with some photoisomerizable low molecular weight chromophores, it may undergo a conformation change when irradiated with light, because the interaction between the polymer and the chromophores chantes. The example described by Lovrien is the mixture of poly(methacrylic acid) and chrysophenine G(1, CHP) in water. CHP changes

3O

M. lrie

Table 2. Photoisomerizations Type of reaction

Example

(a) Trans-cis isomerization N~N

%c c% (b) Zwitter ion formation

~ NR O 2 Ph

(c) Radical formation

-O

Ph

Ph

2 .~,'~>---Ph Ph Ph Ph Ph

Ph

H3 ? N H3

(d) Ionic dissociation

H3C~I ~*~--~N/CH3 H3C

CN

CH3

H:~

NC CN H3C~CH3

(e) Ring-formation and ring-cleavage

NC

H30--~ S~C~(~,.~S~...~--CH3

trans

form.

S,O3Na %

/.z/CH-~N,,~. ~ o.

SO3Na {I)

CN

H3C"-~ SC~H3S.,.~"'CH3

the hydrophobic property when the configuration changes from all

C2HsO~~--N~ ~

CHs

CN-

%

oct.,

to

c-t-c

31

Photoresponsive Polymers

~

3

I

hv:A

2o

~ h~,'.,%

2b

~

hv;A

5

h ls,'A

fi ~

htp',A hv'-2"A

~

Fig. 2. Schematic illustration of photostimulated conformation changes of polymer chains

Upon ultraviolet irradiation, trans CHP isomerized to the cis form (around 10~), and the aqueous solution viscosity decreased as much as 80 9/0. The conformation change was interpreted as follows. The anionic linear and planar all-trans CHP would attach itself to the hydrophobic poly(methacrylic acid) backbone, leading to an extended polymer conformation. In the cis form, azoMyes are much more hydrophilic. Consequently, the cis form was envisaged as binding less strongly so that the polymer chain would be less extended. In 1974, the above system was reexamined by Van der Veen and Prins [5]. They, however, did not observe the change in viscosity as much as Lovrien did. The reduced viscosity for 43 ~ cis CHP was only 5 ~ lower than the value for CHP completely converted to the trans form. It was concluded that the viscosity decrease reported by Lovrien had been caused by some impurity contained in the dye and/or the polymer. 1.9

-~

1.7 1.6

0.B5

Fig. 3. Photoinduced reversible conformation changes of HEMAVPy copolymer -- CHP complex in water at 30 °C [6]. (C)): reduced viscosity of 0.334 dl/g copolymer (HEMA content, 0.62); ( 0 ) : absorbance at 404 nm

0.75 t%

0.65 0.55 0

I I 1 20 rain 60

1 t I I 0 20 rain 60

I

I

0

8

I

I

16h24 Time

!

I

0

8

I

I

16h24

32

M. Irie

Being so attractive, efforts to confirm the photoregulation mechanism postulated by Lovrien were continued. In 1977, Negishi et al. [6] found a pronounced photostimulated viscosity change of an aqueous solution of 2-hydroxyethyl methacrylate (HEMA) -- N-vinylpyrrolidone (VPy) copolymer a and CHP or acid yellow 38 (2). The reduced viscosity reversibly decreased as much as 12%, as shown in Figure 3. The interaction between the polymer and CHP was sucessfully controlled by photoirradiation. The result suggested that the mechanism should strongly depend on the pair of polymer and dyes [7].

NaO3S

2 The second mechanism (2) utilizes the change induced in the intramolecular interaction between pendant groups by photoirradiation. The system reported for the first time is poly(methacrylic acid) with pendant azobenzene groups [4]. In an aqueous solution, the viscosity was found to increase by ultraviolet irradiation (Fig. 2(2 a). The trans to cis photoisomerization was considered to decrease the hydrophobic interaction between the azobenzene chromophores, allowing the polymer coil to expand. Mat6jka et al. [8] extended the study to styrene -- maleic anhydride copolymer with pendant azobenzene groups (3) and measured the photoresponsive behavior in less polar solvents.

( CH-CH--CH2--CHI i O| )x ( CHc=oI -- c=0CHI'"CH2~ ~-~_x o//C"o/C%o

I

!

OH NH

+ d

This copolymer exhibited a reversible photodecrease of the viscosity in 1,4-dioxane solution. A decrease of 24-30 % was found in the reduced viscosity after the solution was irradiated with ultraviolet light. In tetrahydrofuran, the viscosity decrease was 1-8 %. The contraction of the dimensions of the copolymer coil was explained as follows. Cis form azobenzene has a dipole moment of 3.t D, while the dipole moment of the trans form is less than 0.5 D. Therefore, the trans to cis isomerization induces strong dipoles in the pendant groups. These dipoles tend to orient in parallel and attract each other in less polar solvents, making compact coil conformations preferrable, as shown in Fig. 2(2)-b. In the dark, the viscosity of the copolymer

Photoresponsive Polymers

33

solution returned to the original value, though the process occurred much more slowly. The rate was 1/2.5 to 1/7 of the rate o f c i s to trans isomerization of the pendant azobenzene chromophores, which was measured by optical absorption. The discrepancy requires further examination of the postulated mechanism for the conformation change. Even when the azobenzene chromophores are incorporated into the polymer backbone, the dipole moment increase of azobenzene residues by photoirradiation can also induce a change in polymer chain conformation. The solution viscosity of poly(dimethylsiloxane) containing azobenzene residues in the main chain decreased upon ultraviolet irradiation, and the effect was attributed to the trans to cis photoisomerization [9]. The photodecrease of the viscosity depended on the polarity of the solvent. It was 24 ~ in non-polar heptane, but negligible in polar dichloroethane. In the mechanism (2), the driving force for conformation changes depends on solvent polarity. In aqueous solutions, a hydrophobic property change is effective to induce the conformation change, case a of Fig. 2, while in less polar solvents the dipole moment change becomes useful, case b. Polymer chain stacking owing to the aggregation of pendant merocyanine forms postulated for photoirradiated poly(spiropyran methacrylate) and poly(spiropyran acrylate) in benzene and toluene [10] may be classified into the mechanism (2). The third mechanism (3) is the simplest one. When trans-cis photoisomerizable chromophores are incorporated into the polymer backbone, the photoinduced configuration change of the chromophores is expected to induce a conformation change of the polymer chain. Azobenzene (4) is the most widely used as the trans-cis photoisomerizable photoreceptor molecule. It undergoes isomerization from the trans to the cis form under ultraviolet irradiation, while the cis form can return to the trans form either thermally or photochemically [11]. R

9

N

I

z,

N

1

R (z) 151 During the isomerization, azobenzene undergoes a large structural change. The distance between 4 and 4' carbons decreases from 9.0 to 5,5 A [12]. Table 3 summarizes the reported polymers having photoisomerizable unsaturated linkages in their backbones, mostly containing azobenzene groups, Polyamides with azobenzene groups in the backbone are among the earliest in which trans-cis isomerizabte chromophores were used to regulate the polymer conformation [13, 14]. The intrinsic viscosity [11]of polyamide (6) in polar N,N-dimethylacetamide was found to decrease from 1.22 to 0.5 dl/g upon ultraviolet irradiation

34

M. lrie

Table 3 Photoresponsive polymers with photoisomerizable unsaturated linkages in the polymer backbone Structure

Reference COOH

COOH 7

-"~N H~

N= N ~ N

HCO'-'~CH2"~mCO-)'gn

[14]

C•H3 k

CH3

C.H3

CH3

Ph

11

Ph

[19]

(410 > ~ > 350 nm) and to return to the initial value in 30 h in the dark at 20 °C (Fig. 4). The decrease is not due to the intramolecular dipole-dipole interaction, because the polarity of the solvent used was very high and the photo-effect was not observed for polymers with long flexible methylene chains. The slow recovery of the viscosity in the dark was accelerated by visible light irradiation (~. > 470 nm). When alternately irradiated with ultraviolet and visible light, the viscosity reversibly changed as much as 60 ~ (Fig. 5). Before photoirradiation, the polyamide has a rod-like conformation. The isomerization from the trans to the cis form kinks the polymer chain, resulting in a

Photoresponsive Polymers

35

1.5;

t~ 1.0

"~0 5

ii

............

0

0.2 0.4 Concentration,g/dr

i

Fig. 4; Viscosities of polyamide (6) in N,N-dimethylacetamide at 20 °C ( t ) in the dark before photoirradiation and (O) under irradiation with ultraviolet light (410 n m > 2 > 350 nm) [14]

0,6

1.0 8

~7 o.s a

1.2 "U

1.0

o" 0.8 0.6 b 0

i

50

i

t00 Time

i

150

i

200 min

Fig. 5. Changes in (Q) content of the trans azobenzene residues in polyamide (6) backbone and (©) viscosity of the polyamide in N,N-dimethylacetamide on alternate irradiation with ultraviolet (410 nm > 2 > 350 nm) and visible (2 > 470 nm) light at 20 °C [14]. Polymer concentration was 0.9 g/dl compact conformation and a decrease in the viscosity. The conformation changes from the compact form to the initially extended one by either heat or visible light irradiation, causing the viscosity to increase.

-~N~N~,N~N\N~N.

~----~ /'N'~--N\N----#N~N

36

M. Irie

Similar experiments were carried out for polyamides (8)and (9) by Blair et al. [15]. They, however, observed no decrease in intrinsic viscosity under ultraviolet irradiation, in contrast to the above case. But they found a small decrease in reduced viscosity at a high polymer concentration. The absence of the photodecrease in the viscosity is probably due to the inclusion of flexible piperazine segments in the polymer chain. Neckers et al. [16, 17, 18] demonstrated that polyureas with backbone azobenzene groups (t0) also underwent a photoviscosity effect when ultraviolet-irradiated. Stille et al. [19] reported that the intrinsic viscosity of potyquinoline (1/) with backbone stilbene groups in di-m-cresyl phosphate/m-cresol decreased as much as 24% under ultraviolet light. The decrease was ascribed to the trans to cis isomerization of the stilbene groups. Because of its simplicity the mechanism (3) has been widely applied to other polycondensation or potyaddition polymers. The fourth mechanism (4) invokes the electrostatic reptilsion between photogenerated charges as the driving force for conformation changes. Triphenylmethane leucoderivatives (12) have been used as photoreceptor molecules. The chromophore dissociates into an ion-pair under ultraviolet irradiation, generating an intensely green colored triphenylmethyl cation. The cation thermally recombines the counter anion as follows.

cH3,N N.3 R

CH3/

X

\CH3

hv

T X

12

13

The triphenylmethane leucohydroxide residues were incorporated into the pendant groups b y copolymerizing the vinyl derivative (12, R = C H = C H 2, X = O H ) with N,N-dimethylacrylamide [20]. Upon ultraviolet irradiation (X > 270 nm), the solution became deep green, and at the same time its reduced viscosity increased from 0.55 to 1.6 dl/g, as depicted in Fig. 6. After the light was shut, the viscosity returned to the initial value with a half-life of 3.1 min. The close correlation between the viscosity change and the absorption intensity at 620 nm implies that the electrostatic repulsion was responsible for the expansion of the polymer conformation. Formation of strong dipoles along the polymer chain and the intramolecular interaction of the dipoles with the polymer chain would also change the chain conformation, as expected by the fifth mechanism (5), This approach to induce con-

H3C CH3 H3C CH3

f~~j

/NO2

hv', & NO 2

-O

R

14

15

Photoresponsive Polymers / 0.4 ~ 4 ~ ~

37

Dark

Dark

/

E

0.3

E

o0.2 ~3

~0,1 A

0 ~1

1.5 "7 1.0

I

I

!

I

fLL

0.5 "b

i

.I

0

10

I

..........

I

20 30 Time

i

I

i

40min

Fig. 6. Changes of (A) absorption at 620 nm and (B) viscosity of poly(N,N-dimethylacrylamide) having pendant triphenylmethane leucohydroxide groups (9. l tool %) in methanol at 30 °C on exposure to ultraviolet light (2 > 270 rim) [20]. Polymer concentration was 0.06 g/dl

50

formation changes has used spirobenzopyran or azobenzene groups as photoreceptor molecules. Spirobenzopyran (14) is well known for undergoing under ultraviolet light irradiation a ring opening reaction leading to the formation of merocyanine having a strong dipole. This reaction can be reversed either thermally or photochemically. We can use the dipole moment change as a driving force for conformation changes of the polymer chain by incorporating spirobenzopyrans into the pendant groups. A typical example is poly(methyl methacrylate) with pendant spirobenzopyran groups [21]. Figure 7 shows its viscosity (the content of the pendant groups is

0.4

Cr~

-~ o.3 f

y

J

0.2 i

|

0.5 1.0 Concentration, g / d l

Fig. 7, Viscosities of poly(methyl methacrylate) having spirobenzopyran groups (13 mol%) at 30 °C: (A) in benzene (0) in the dark (O) under irradiation (2 > 310 nm); (B) in dichloroethane [21]

38

M. lrie

13 m o l e ~ ) in benzene in the dark as well as during the photoirradiation 0~ > 310 nm). The data for dichloroethane are also included to illustrate the viscosity behavior in polar solvents. In benzene, the intrinsic viscosity during irradiation is 17~ lower than the viscosity in the dark. The viscosity change in polar dichloroethane is only 1~o. The viscosity change decreases almost in parallel with increasing microscopic polarity of the solvents. These solvent effects suggest that the polymer chain shrinks mainly due to specific solvation of the photogenerated merocyanines by the poly(methyl methacrylate) ester groups. This intramolecular solvation competes with the solvation by solvents. The intramolecular attraction between the pendant merocyanine and the polymer chain overcomes the merocyanine -- solvents interaction, giving the polymer a more coiled conformation. The intramolecular dipole -- dipole interaction between pendant merocyanine groups in a polymer as suggested for poly(spiropyran methacrylate) and poly(spiropyran acrylate) [t0] is less likely to decrease viscosity for the following reasons: (1) the benzene viscosity of polystyrene having pendant spirobenzopyran groups showed no response to photoirradiation, and (2) the photodecrease of the benzene viscosity of the poly(methyl methacrylate) reached a maximum at a spirobenzopyran content as low as 17 mole %. Poly(methacrylic acid) with pendant spirobenzopyran groups also showed photostimulated conformation changes in methanol [22]. Visible light irradiation of the solution increased the viscosity, while ultraviolet light irradiation caused the solution viscosity to decrease. Alternate irradiation of visible and ultraviolet light brought about reversible viscosity changes with an amplitude as large as 40~, and it was possible to repeat the cyclic changes in viscosity many times. Photostimulated conformation changes observed for polypeptides with pendant azobenzene residues may also be classified as the mechanism (5) [23, 24]. We have described five mechanisms proposed so far for the induction of polymer conformation changes, along with some typical photoresponsive polymers. The photochromic reactions shown in Table 1 have been successfully utilized to induce the conformation changes. An optical signal is captured by the photochromic molecules and converts to chemical signals (geometrical structure and/or dipole moment changes) owing to the isomerization of the chromophores. The chemical signals are transferred to the polymer chain and eventually a change in polymer conformation comes about. This process is observed in common for photoresponsive polymers, and its underlying idea can be applied for controlling various properties of polymers.

2.2 Dynamics of Conformation Changes It is of particular interest to know how fast long polymer chains change their conformation in response to a short laser pulse. The dynamics of this process can be studied in photoresponsive polymers which undergo photostimulated conformation changes [25]. The isomerization of photochromic chromophores can be induced in less than 10 -8 s with a short laser pulse. The conformation change subsequent to it can be followed with a time resolved light scattering system combined with the short laser pulse source (Fig. 8).

PhotoresponsivePolymers

39

Ar ion laser t.__..~._~.,, ~ Sampleceil _ Shutter

~[ass fiber-

Photodetector

Monochrometer~

Anotyzing system

}

1

YAGlaser Fig. 8. Time-resolvedlight scattering measuring system combined with a short laser pulse

The Debye equation-Eq. (1)

K~ -

-

1 16za(s2) = -- + - sin 2(0/2) + 2A2

Ro M~

3Z~w

(1)

relates the light scattering intensity R 0 to the weight average molecular weight M w, the mean square radius of gyration (s2), and the second virial coefficient A2 of a polymer in dilute solution. Here, K = (2n2n2/NgL~) (dn/dc) z, c is the polymer mass concentration, no is the refractive index of the solvent, dn/dc is the specific refractive index increment, ko is the wavelength of the incident light and N A is the Avogadro constant. Expansion of the polymer coil leads to an increase in (s2), which decreases R 0. Polyamide (6) was irradiated with a single 20 ns flash (530 nm) in N,N-dimethytacetamide. The kinetics of the cis to trans isomerization of backbone azobenzene residues was followed by time resolved optical absorption, and the subsequent conformation change of the total polymer chain by time resolved light scattering. Before each laser experiment, the polymer was brought to a compact conformation by eontimaous ultraviolet irradiation, and then the unfolding process was traced by the laser flash photolysis method.

/

40

M. Irie

Figure 9 shows the oscillograms demonstrating the decrease and increase of optical absorption at 310 and 410 nm for polyamide (6) and the model compound (16) during and after the laser flash. oCONH~

N

COOH

16

Although a relatively slow relaxation process can be seen, we may say that the cis to trans isomerizations of both the polyamide and the model compound are complete in 100 ns. Figure 10 shows a typical oscilloscope trace illustrating the change in light scattering intensity during and after the laser flash. The decrease in light scattering intensity reflects the conformation change involving a decrease in (s2). The initial rapid increase in scattering intensity is due to a concurrent decrease in the optical absorption at 514nm, as depicted by oscillogram (b). For comparison, Fig. t0c shows an oscillogram illustrating the change in light scattering intensity observed on the model compound (•6). This trace only reflects changes in optical absorption and specific refractive index increment. These results indicate that the conformation change of the total polymer chain occurs in about 1 ms. Solvent quality changed the unfolding rat e of the polyamide coil. In good solvents, such as N,N-dimethylacetamide and N,N-dimethylformamide, the folding proceeded rather rapidly, whereas the unfolding was slow in poor solvents containing a miscible non-solvent. When the solvent quality was made poorer, the unfolding rate was retarded. Although solvent quality influences the relaxation time, we may say that the total polymer chain unfolds within the time interval from 0.5 to 1.1 ms.

Polyamide(6) .L

"h,: 31Onto

2my

a

5 0 ns -'1 I-

Model( 16 ) ,,,.,,

~,: 310 nrn

..L

2my T

Uo: 99mv

c

-I

50ns t-

Uo'- 6 8 m y

~, : 410 nm

.~ b

50ns q I-

_L 5 mv T

;~: 410 nrn f

.

.

.

.

50ns

.-.

Uo:109mv d

-t

t--

m

_L. 5mY

T Uo: 84 mv

Fig. 9a--d. Cis to trans isomerization of polyamide (6) and model compound (16) at 22 °C in N,Ndimethylacetamide (1.1 x 10 -2 g/dl) measured by optical absorption [25]. The oscillograms illustrate the decrease and increase of optical absorption at 310 nm (cis form) and 410 nm (trans form) during and after irradiation with 20 ns flash of 530 nm light

Photoresponsive Polymers a Polyamide(6)

41 L.S.

..L

2mY 500#s

~

b

Uo:6OmV

Polyamide(6)

0.A.

..L

5 mV == ~L__

T I

L

500#s ~ c

j

-

-

Uo:42 mV

Model(/6)

L.S.

.L

500#$

-4 l--

2 mV T

Uo: 46rnV

Fig. 10a-c. Chain unfolding and cis to trans isomerization of polyamide (6) in N,N-dimethylacetamidesolution (0.31 g/ dl) [25]. The oscillograms illustrate changes of fight scattering intensity (a, e) at 514nm and optical absorption at 514 nm (b) during and after 20 ns flash of 530 nm light. Traces a and b: polyamide (6); trace c: model compound (16)

The large difference in the response times for optical absorption and light scattering suggests a two step mechanism for the photostimulated unfolding process. During the isomerization of the backbone azobenzene residues, the total chain conformation maintains in the initial compact conformation. After the isomerization is completed, the conformation relaxes to a more stable extended conformation in 1 ms.

Compact Conformation 10 -7 s $ c i s - t r a n s isomerization Compact Conformation 10 -3 s + unfolding Extended Conformation

This scheme implies that the compact conformation having t r a n s azobenzene residues is a constrained form capable of storing a certain amount of strain energy. The strain energy causes coil expansion, and it is released during the unfolding process. The photostimulated conformation change of polystyrene with pendant azobenzene groups in cyclohexane has also been studied by the time-resolved light scattering technique [26].

42

Photoresponsive Polymers

3 Photocontrol of Physical and Chemical Properties of Polymers 3.1 Shape -- Macro-Size Effect It is possible to amplify the photostimulated conformation changes of polymer chains in solution to a macroscopic change in the size of gets or solids. The use of structural changes of photoisomerizable chromophores for the size change of polymer solids was proposed for the first time by Merian [27]. He studied a nylon filament fabric, 6 cm wide and 30 cm long, dyed with 15 mg/g azo-dye. After exposure to a xenon lamp at a distance of 30 cm, he found the dyed fabric shrank 0.33 m m (Fig. 11). Since this finding, many materials exhibiting photostimulated deformations have been reported. Polymer films mixed with low-molecular-weight photochromic compounds, such as nylon film-p-carotene [28], nylon film-~-cyanostilbene [28], and polystyrene - spirobenzopyran [29] were shown to undergo photostimulated reversible size changes.

c oz

co

NH ,< ~ NH

o~,.

Fig. I1. Contraction of fabric dyed with trans-cis photoisomerizable dye [27]

RI--OC 1 OH

0.4 [3

|

0

1

2

3

4

5 Time

6

7

8h9

Fig. 12. Photostimulated contraction of nylon film (A) in the presence of ~-cyanostilbene and (B) in the absence of the chromophore [28]

Photoresponsive Polymers

43

Figure 12 illustrates Blair's data on the mixed system nylon film-~-cyanostilbene

(17)[281. CN

c>i -o /

,x

17 When irradiated, this film contracts by 0.8 ~ , while in the dark it recovers to the initial length in about 4 h. Curve B is for a nylon film without ~-cyanostilbene under the same conditions and it displays no photo-shrinkage. A covalently bound photochromic chr0mophore is expected to give a more direct effect on the deformation of polymers. The systems studied were polyimide with backbone azobenzene groups [30], polyamide with backbone stilbene groups [31], polyquinoline with backbone stilbene groups [19], polytetrahydrofuran with backbone viologen groups [32], poly(ethyl acrylate) with spirobenzopyran [33, 34] or azobenzene groups [35] as cross-linking agents, and poly(n-butyl acrylate) with pendant azobenzene groups [36].

2.0

._J

1.0

0

t

Statl UV

t 1°

30

20

Slop

Time [min)

Fig. 13. Photomechanical behavior of poly(ethyl acrylate) cross-linked with spirobenzopyran groups [33]. Influence of temperature and stress time in min

O A III • V

Temperature

mm

Load, g

15 29.6 45 15 15

44.5 44 42 22 32.5

21.9 21.9 21,9 35.7 59.4

44

M. lrie

Among these systems, polyimide with azobenzene chromophores in the backbone was first studied by Agolini and Gay in 1970 [30]. They reported 0 . 5 ~ contraction of the polymer film at 200 °C taking place under ultraviolet irradiation. No correlation, however, was reported between the degree of isomerization and film contraction. At the high temperature they studied, the cis isomer content in the photostationary state would be very low, because a rapid thermal reverse reaction from the cis to the trans form should occur. Thus, the isomerization is not the sole origin of the contraction of the system. The most pronounced photo-contraction effect was observed for poly(ethyl acrylate) cross-linked with spirobenzopyran groups (18) [33]. This is shown in Fig. 13.

i

CH-CO2Et I 0 CH2

H2C--O--ICI --~--CH3 CH3

J~-..TX( 0 ~ (

[( )T X

~

CH2

+ I

I

H2C t

~

))'--NOzl

~H-CO2Et I

'

CH2 I

,N~

X 1( )1

lmNH( ))---~ CN3--C--C--O--CH 2

H~ CH-CO2Et i (is) Initially, it was assumed that the contraction is due to an entropy increase of the polymer chain associated with a higher flexibility of the open-ring merocyanine form than the parent ring-closed spiropyran. However, careful reexamination of the action spectrum of the contraction, i.e. the dependence of film shrinkage on the wavelength of irradiation, led to the unexpected finding that the contractio n spectrum closely fitted with the absorption spectrum of open-form merocyanine and that ultraviolet light causing the isomerization from the spirobenzopyran to the merocyanine form was very inefficient for film contraction. Thus, the film shrinkage appeared to be induced not by the photochemical isomerization of the spirobenzopyran to the merocyanine form, but by the increase in local temperature arising from a non-radiative transition of the photoexcited merocyanine.

PhotoresponsivePolymers -~-

0.:3 - - L j

%

45 Z.2

-J-

~'l

_L

A

0.2

x

O.II

°°~~°

;~I{trons-~ds) =365 n m

)~2(cis_~.tco~sl=436 nm 0

~J

i 8, 12, 14, 2 '0 2 4 -28-#

4

I-I

o

i

600

Time {rain)

Fig. 14. Schematicrepresentation of the photomechanicaleffect induced in poly(ethylacrylate) network with azoaromatic cross-links upon irradiation [35] One example, which exceptionally exhibited a real photochemical contraction effect in the film state, is poly(ethyl acrylate) cross-linked with 4,4'-dimethacryloylaminoazobenzene studied by Eisenbach [35]. Figure 14 shows the data. The film contracts upon irradiation with ultraviolet light, which causes the trans to cis isomerization of the azobenzene chromophores, while it expands by irradiation with visible light, which induces the cis to trans isomerization. Both contraction and expansion are induced by photoirradiation. This finding indicates that the structural change of the cross-linking azobenzene chromophores in the polymer network is responsible for the contraction/expansion behavior. However, the observed contraction was very small, being only about 0.15-0.25 ~. In order to minimize the local heating effect, Prins et al. [37] proposed experimenting with solvent-swollen gels, in which rapid thermal conduction is supposed to suppress this unfavorable effect. The gel system used by Prins et al. was a mixture consisting of low molecular weight chrysophenin G(1) and a water-swollen gel of poty(2-hydroxyethyl methacrylate) (PHEMA) cross-linked with ethylene glycol dimethacrylate (1.1 w t ~ ) . Upon irradiation, the dye changed the configuration from all trans to the e-t-c form. The difference in the hydrophobic property of the two forms brough about a change in the intermolecular interaction between the dye and PHEMA. The increase in the hydrophilicity of the dye by the isomerization from all trans to the c-t-c form contracted the polymer gel, because this action liberated the hydrophilic dyes from the polymer chain to the surrounding solution.

I19

46

M. lric

A similar photo-effect on the swelling of cross-linked poly(methacrylic acid) (PMA) was observed in the presence of 4-phenylazophenyl trimethylammonium ions (19) [38]. An increased cis content of the chromophore by photoirradiation at a pH in the range of conformation unfolding of PMA led to an increased ionization and thus enhanced swelling. The conversion efficiency of light energy to mechanical work was calculated to be 3 x 10 -7. Even when a solvent-swollen gel is used, there remains the question as to the relative contribution of the local heating and the real photochemical reaction to the observed photo-shrinking. Mat6jka et al. [36, 39] carefully examined the contribution of the former to the photostimulated shrinkage of a maleic anhydride-styrene copolymer with covalently bound pendant azobenzene groups (MAH-STY-AAB) swollen in diethylphthalate. They measured the temperature of the gel by inserting a thermocouple into the gel along with the photo-generated force. The copolymer was irradiated at an elongation of 1.25 %. The irradiation caused a reversible increase in the force by 1% (Fig. 15). As seen in the figure, the force change rate is much faster than the isomerization reaction, and the response correlates well with the change in the temperature of the gel. The latter fact suggests that the decisive role played in the contraction process be the local heating due to light absorption, apparently not to the photoisomerization of the photochromic chromophores. When intensely photo-irradiated, the sample was heated by the absorption of radiation even under a careful thermostatic control. The rise in temperature inside the gel was determined to be 1.2 K. With an interference filter (X = 370 nm) it was possible to minimize the heating effect. The slow increase of the force as seen in Fig. 15(b) may be ascribable to the photochemical trans-cis isomerization, though the effect is less than 1~o.

---m.-

£1

0.474

299

0.47 0 t

I

1

)

1

298

I

LightDark Light Dark Light Dark .....

t

I

I

I

I

b 299

0.4?3

._-

298

0.470 0.026

t ,

" ~ ' ~ 0.02."

C

,,

Dark

Light I

1

0

25

I

I

50 t

75

I

100 min

Fig. 15a-c. Effects of radiation on retractive force f (in Newtons) at constant length of a sample of poly(MAH-STY-AAB) swollen in diethylphthalate and on temperature Ti inside the sample [36]. () for, f; (------) for T i. a . l = 1.25 without interference filter, b. t = 1.25 with interference filter, c. l = 1.05 without interference filter

Photoresponsive Polymers

47

The large heat effect observed even in the contraction of the solvent-swollen gel strongly suggests that many previous studies reporting to have observed photostimulated contractions have to be reexamined to check and evaluate the real photochemical effect. The following criteria may be useful to judge whether the effect is due to photochemistry or photoheating. (1) When the recovery rate of deformation in the dark after light is switched off is faster than the rate of thermal isomerization of the chromophores in the film, the contraction is due to photoheating. The recovery rate should always be slower than or almost equal to the rate ofisomerization even when the recovers is induced by photoirradiation, if the process is associated with the photochemical reaction of the chromophores. (2) At elongations l smaller than the inversion elongation llnv, the temperature increase causes the force to decrease, while at I larger than l~nv,an increase in the modulus with temperature causes the contraction force to increase. Therefore, photoheating should give rise to reverse effects depending on l. On the other hand, the photochemical effect is independent of I. If the photostimulated contraction depends on l, the contraction is due to photoheating. Photostimulated expansions observed for small elongation in polyamide film containing stilbene chromophores in the polymer backbone may be explained by the thermal effect [31]. The solution viscosity of this polymer decreased upon photostimulated trans-cis isomerization, while the film showed a decrease in force. In this system, the photoheating effect dominates the photochemical one. According to the above criteria, photostimulated deformations observed in a hydrogel by Ishihara et al. [40] may be ascribed to the photochemical effect. They prepared a gel of PHEMA with pendant azobenzene groups (20). CH3 I --~ CH2-- C - - ~

CH3 i CH^-- C ---~

C=O

C=O

o

o

I

I

1

I

CH, o.

o

c_O_\©

20

It was swollen in water, and then irradiated with ultraviolet light. Figure 16 shows the observed photoresponsive behavior. The gel swelling decreases by as much as 7 ~ in 1 h. Upon visible irradiation, "the gel again swells slowly in 10 h. The swelling rate is slower than the photoisomerization rate, and both the shrinking and swelling processes are induced by photoirradiation. These results support the view that the effect is photochemical. Although many systems showing photostimulated deformations have been reported, the deformations were limited to less than 10 ~. Small deformations make it difficult to judge whether the effect is due to photochemistry or photoheating. If the deformation is larger than 20 ~o, we may safely say that it is due to the photo-

4~

M. lrie

UV

14~

% 12

UV

I -o10

Vis

E

i Vis I

I

I,/~'

/

8

6

,,z

0

J

1

2

t

3 Time

s

4

I

h 5

Fig. 16. Photostimulated changes in the swelling degree of P H E M A having pendant azobenzene residues in water at 25 °C [40] UV: 2 = 350 ___ 50 nm; Vis: 2 > 470 nm

/A--. 10

chemical effect. One photo-deformable material of interest is poty-4-(N,N-dimethylamino)-N-r-D-glutamanilide, which displayed a dilaton amounting to 3 5 ~ in N,Ndimethylformamide when exposed to light in the presence of CBr4 [41]. This large deformation was due to the ionization of N,N-dimethylanilide groups. Although the system was irreversible and no attempt was made to make it reversible, such a pronounced effect is informative for the design of reversible photo-deformable polymers. We may infer from the studies on the conformation change in solution that the electrostatic repulsion between photogenerated charges is more effective for conformation changes than the trans-cis isomerization of unsaturated linkages. On due consideration, we decided to take advantage of electrostatic forces to obtain gels exhibiting large reversible deformations [42, 43]. Polyacrylamide gels containing a small amount of triphenylmethane leucohydroxide or leucocyanide groups (21) were prepared by free radical copolymerization of di(N,N-dimethylaniline)-4-vinylphenylmethane leucohydroxide (12, X = 0 H , R =

C=O I NH

I CH2 t

NH I

C=O

--~

CH2?H~ C=O I NH2

CH~

H3C)N,-~.-, H3C

1

~

/CH3 N. CH3 21

X = OH, CN

Photoresponsive Polymers

49

C H - - C H 2 ) or leucocyanide (12, X = C N , R = C H = C H 2 ) in dimethylsulfoxide in the presence of N,N-methylene-bisacrylamide. The gels were swollen to equilibrium by allowing them to stand in water overnight. Then the changes in their weight and dimensions induced by ultraviolet light were measured. A disk-shaped gel (10 mm in diameter and 2 m m in thickness) having 3.7 m o l % triphenylmethane leucohydroxide residues showed photostimulated reversible dilation in water. Figure 17 shows that upon ultraviolet irradiation (X > 270 nm), the gel swells and the weight increases by as much as 3 times its original weight in 1 h. The dilated gel contracts in the dark to its initial weight in 20 h. The cycles of dilation and contraction of the get were repeated several times. The gel having leucohydroxide residues swelled even in the dark when the aqueous solution became acidic, owing to the chemical ionization of the residues. In order to make the gel insensitive to pH changes, the hydroxide residues were replaced by cyanide groups. The weight of the leucocyanide gel remained constant in the range of p H 4-9. Figure 18 shows the photoresponsive behavior of the gel having 1.9 mole % leucocyanide residues in water. Upon ultraviolet irradiation, the gel weight increases as much as 18 times. In the dark, the gel contracts again slowly to the initial weight. Figure 19A and B show the rate of coloration at 660 nm and the gel expansion rate under continuous light irradiation. The triphenylmethyl cation is well known to have a very strong absorption at 622 nm. Upon ultraviolet irradiation, the color

t-.,--~,---+-Dark-~- ~

=I Dark-~-~

3

Fig. 17. Photostimulated dilation and contraction of polyacrylamide gel having pendant triphenylmethane leucohydroxide groups (3.7 mol %) with light of wavelength longer than 270 nm at 25 °C [43]. Wo is the weight before photoirradiation '

20

2

'

';z2() Time

~-~,--+--~

' 2'2 '

''iOh'

Dark - -

15

10

o

2'oh Time

Fig. 18. Photostimulated dilation and contraction of polyacrylamide gel containing 1.9 mole % pendant triphenylmethane leucocyanide groups with light of wavelength longer than 270 nm at 25 °C [43].Wo is the weight before photoirradiation

50

M. h'ic

1.0

t

*

~ ~ o ~

i

,

i

b

°---'~°~°-

~100 o

--o50 1

0 0

~

0

;

8'0

1;o 2;0

Fig. 19a, b. Photostimulated (a) color change and (b) dimension change of polyacrylamide gel containing 1.9mole% triphenylmethane leucocyanide groups in water [43]. 10is the initial diameter of the disk-shaped gel before photoirradiation

Time, rain

of the gel changes quickly from pale green to deep green in less than 3 rain and then remains almost constant. In the dark, the color returns to the initial pale green in several hours. The size of the gel, on the other hand, increases slowly and reaches the saturated value in about 2 h. The photostimulated dilation is 2.2 times. The slow response o f the size change in comparion with the color change indicates that the gel dilation is due not to the thermal effect but to the photochemical ionization. The formation o f charges, fixed cations and free anions, generates an osmotic pressure difference between the gel and the outer solution, and this osmotic effect is considered to be responsible for gel expansion. It is worthwhile to note that the gel expansion is suppressed by the addition of salts, such as NaC1 and KBr. N o photostimulated dilation was observed in the presence of 10 -2 M NaC1 or KBr for the gels having leucohydroxide or teucocyanide groups. The potyacrylamide gel described abobe is the first example showing a reversible deformation o f more than 100%. The effect is purely photochemical and reversible. However, this gel has a serious disadvatage in that the response time is slow. To improve this point the effect of electric field on the gel deformation was examined [44]. A rod-shaped polyacrylamide gel containing triphenylmethane leucocyanide groups (25 m m in length and 2 m m in section diameter) was prepared in a capillary tube. The gel rod was inserted between two parallel platinum electrodes in a small

Fig. 20. Photostimulated vibrational motion of a rod shaped polyacrylamide gel having 3.1 mol~ triphenylmethane leucocyanide groups under an alternating electric field (+0.8 v/cm, 0.5 Hz) in water in the presence of 4 x I0-4 M NaC1

PhotoresponsivePolymers

51

water pool (Teflon, 36 x 19 x 15 mm) and fixed at its one end on the pool wall. It vibrated in response to the alternating electric field (+8.5 V/cm, 0.5 Hz) under ultraviolet irradiation, as shown in Fig. 20.

3.2 Surface Wettability

Surface wettability is an important property of polymer solids and plays an important role in printing, dyeing and adhesion. This property depends on the surface free energy, which is expressed in terms of a sum of the dispersion energy and polar energy terms of the surface tension. These terms vary with the molecules which are attached to the polymer surface. If we introduce photoisomerizable chromophores, which change the polarity reversibly by photoirradiation, the surface wettability is expected to become photo-controlled. Figure 21 shows a wettability change measured by the contact angle of a water droplet on the surface ofa HEMA - - methacryloyl-2-hydroxyethyl-phenylazobenzene copolymer [45, 46]. The absorbance change at 325 nm, which gives information about the content of trans form azobenzene chromophores, is also included in the figure. The contact angle (cos 0) increases from 0.22 to 0.41 under ultraviolet irradiation, while it decreases to 0.22 with visible irradiation. At the same time, the absorbance decreases with ultraviolet irradiation, while it increases with visible irradiation. The close correlation between the contact angle and the absorbance at 325 nm indicates that the wettability change of the polymer surface is attributable to the structural change of the azobenzene chromophores. A wettability change was also observed when triphenylmethane leucohydroxide was introduced [47]. The contact angle with water of the surface of polystyrene having triphenylmethane leucohydroxide chromophores increased from 0.2 to 0.8. This increase in wettability is due to an enhanced hydrophilicity of the film surface brought about by ionic dissociation of the chromophores. 2-Hydroxytriphenylmethanol (22) is also an useful photochromic chromophore

I

0.4

'

1.1

E

c

t.o

"6 OJ

8 0.3

Fig. 21. Photoinduced change in (O) wettability and (O) absorb-

0.9

(3

o

0.2

I

0

I

'o.7

!

5 10 15min UV ir rodiation time I

I

I

I

0 5 10 rain 15 Vis irrodietTon time

ante of PHEMA film having pendant azobenzene groups [47].

UV:2 = 350 5:50 nm;Vis: 2 > 470 rim. Azobenzenecontent was 0.387

52

M. lric

to induce the surface wettability change [48]. The photochemical reaction of the chromophore is as follows:

÷

OH

22

H~o

0

23

Upon ultraviolet irradiation, the chromophore liberates water to a carbonyl group, which reverts to the hydroxyl group by reaction with water. According to the above reaction scheme, the surface polarity of poly(n-butyl methacrylate) with pendant 2-hydroxytriphenylmethanol is expected to decrease upon photoirradiation, if the chromophores are located in the surface region. Before photoirradiation, the contact angle (cos 0) of a water droplet at the polymer surface was about 0.1. After ultraviolet irradiation for 2 min, cos 0 decreased below --0.15, which indicates that the surface is highly hydrophobic. In the dark, the surface again became less hydrophobic. The decrease in cos 0 by photoirradiation was also observed for poly(n-butyl methacrylate) mixed with 2-hydroxytriphenylmethanol, though the increase of 0 was very small ( ~ 4 °) even at a content of 45 mol %. In addition, cos 0 after photoirradiation did not depend on the content, but stayed constant within experimental errors up to the content of 45 mol ~o. The marked difference in wettability behavior between the polymer having the chromophores in the pendant groups and the polymer mixed with the chromophores suggests the difference in the location of the chromophores in the polymers. A change in the hydrophilic nature of the polymer surface on irradiation of poly(p-phenylazoacrylanilide) (PAAn) or its copolymer with HEMA may be used to control the adsorption -- desorption behavior of proteins or organic substances onto the polymer [49]. Adsorption of lysozyme onto the copolymer ofp-phenylazoacrylanilide and HEMA was found to decrease from 4.6 eg to 1.8 cg per gram of adsorbent on ultraviolet irradiation, which induces .the isomerization from the trans to the cis form. The decrease in adsorption ability upon ultraviolet irradiation is explained by a reduction of the hydrophobic interaction between the protein and the polymer, which results from the appearance of hydrophilic cis-form azobenzene on the surface. Photostimulated changes in the adsorbance of a polymer may be utilized for adsorption chromatography [50]. Figure 22 is concerned with the adsorption of Cephalosporin C on a photoresponsive PAAn column, and the desorption by irradiation with ultraviolet light. When an aqueous solution of Cephatosporin C was passed through a column in the dark, the absorbance of the effluent did not differ from that of the solution. When it was irradiated with ultraviolet light, the absorbance of the effluent increased. This shows that Cephalosporin C was desorbed from the adsorbent as a result of hydrophobicity change. These findings suggest that isolation and purification of biomaterials be in principle possible by use of this adsorbent in systems in which water is the only solvent.

Photoresponsive Polymers

53

1.40

E

UV

~ 1.30 Fig. 22. Chromatography of Cephalosporin C on cross-linked polystyrene coated with PAAn at 25 °C [50]. Flow rate: 1 ml/min; fraction volume: 3 ml. Concentration of Cephalosporin C was 2 x 10-4 mol/L (0) in the dark; (O) during ultraviolet irradiation

u

1.20 " O O Q 0 m

< 1.10 I

.......

5

I

I

10 15 Fraction n u m b e r

.....

20

3.3 Membrane Potential Membrane characteristics, such as membrane potential and ion permeability, can be controlled by photoirradiation when photoisomerizable chromophores are incorporated into the membrane. The membrane can fabricate an organic-photosensor, which changes the potential in an on-off fashion when light irradiation is used as an input signal. Such an application of organic membranes is of considerable interest in connection with the development of molecular based electronic devices. The research was initiated by Kato et al. [51] in 1976, who used an acetyl cellulose film containing photochromic spirobenzopyran and phosphatidyl chloride. Figure 23 shows a schematic diagram of the apparatus used for the measurement of the membrane potential. The concentration ratio, T = C1/C2, of the electrolytes in compartments I and II is a parameter to vary the potential in the dark. In the dark before photoirradiation, the membrane exhibited a steady state potential difference Ato of --28 mv. The membrane potential shifted to --10 mv when the membrane was irradiated with ultraviolet light, and it reverted to the initial value upon visible irradiation. The change in the membrane potential was thus reversible. The potential change, AtOp - - AtOd, decreased with increasing salt concentration at constant 7- At high concentration, the membrane potential is determined mainly

I

E

L l IT

~M

I

Fig. 23. Experimental set-up for measuring light induced membrane potential change [51]. A, amplifier; B, recorder; E, saturated calomel electrode; L, light source; M, membrane; P, rubber packing; S, magnetic stirrer bar

54

M. trie

by the diffusion potential. On the other hand, the Donnan potential is important at low salt concentration. The light-induced potential change resulted from a change in charge density of the membrane, Donnan effect. Therefore, a significant potential change is induced at tow salt concentration. A similar photostimulated potential change was observed for a poly(methacrylic acid) membrane having pendant spirobenzopyran groups [52]. The membrane potential decreased by visible light irradiation in the low NaC1 concentration region ( < 5 x 10 -2 mol/1), while it increased in the higher NaC1 concentration region. The salt concentration dependence showed that the photoinduced potential change at higher concentration was caused by a change in the ion transport number resulting from the conformation change of the polymer chain, while the potential change at lower concentration was induced by the charge density change of the membrane due to the photoisomerization of spirobenzopyran groups, just as in the above mixed system. The photoinduced membrane potential change was also detected even in the absence of the ion concentration gradient between the two cell compartments. Anzai et al. [53, 54] prepared a poly(vinyl chloride) membrane containing spirobenzopyran with a long alkyl chain. The response of the membrane potential upon photoirradiation is shown in Fig. 24. When the membrane between two compartments I and II containing NaC1 solutions of the same concentration (1 mol/l) was irradiated with visible light from the side of compartment I, no membrane potential was detected. The potential increased as much as t00 mv upon ultraviolet irradiation. Visible irradiation brought the potential back to zero. The reversible on (positive potential)/off (zero potential) cycle was attained by use of ultraviolet/visible light switching as an input signal. Another interesting property of this membrane is that the polarity of the photoresponse in the membrane potential was reversed by irradiation from the side of compartment II, as shown in Fig. 24(B). The photoresponsive behavior is almost the same as that observed when irradiated from the side of compartment I, except for the polarity. This finding suggests that the surface potential at the membrane/solution interface facing the light source differ from that at the opposite interface, owing to the difference in charge density between the two membrane b

b b I(A)I

>

1

E 100 C

rl _7

-6 C

C

8 E

..Q

C

(8) I

o

-I00

C

a

a

3 rain

a

l

d

1

d

Fig. 24. Time responses of membrane potential across poly(vinyl chloride) membrane containing spirobenzopyran with a long alkyl chain upon UV and visible light irradiation [54]. NaC1 concentration in solution cl and ca:l M. a) UV irradiation from the side of cl ; b) visible irradiation from the side of c~; c) UV irradiation from the side of c2; d) visible irradiation from the side of c2

PhotoresponsivePolymers

55

surfaces. Photoirradiation gives a transient asymmetric membrane. As expected, prolonged ultraviolet irradiation reduced the potential. Membranes containing azobenzene-modified crown ether and crown ether linked spirobenzopyran also showed changes in the photostimulated membrane potential [55]. 2,3-Dipheuylindenone oxide was also effective in changing the membrane potential of poly(vinyl chloride) by photoirradiation [56].

3.4 Membrane Permeability Membrane permeability is khown to depend on the swelling degree of hydrophilic membranes through which water soluble solutes permeate [57]. This fact leads to the idea that the permeability can be photocontrolled by use of photodeformable polymer gels. Figure 25 shows time-permeation curves of proteins with various molecular weights for a PHEMA gel membrane with pendant azobenzene groups [58]. In the dark, the amounts of permeation of insulin, lysozyme and chymotripsin increase linearly with time. Albumin shows no permeation. The difference is probably due to the size of the proteins. Ultraviolet irradiation diminishes the permeation rate. In particular, the permeation of chymotripsin is completely suppressed. In Sect. 3.1, it was shown that the swelling degree of a polymer gel in water was decreased by ultraviolet irradiation and recovered to the original level by visible light irradiation. The photodecrease in the permeation rate of proteins is due to the decrease in the swelling degree of the polymer membrane. We tried to photocontrol water permeation through a porous poly(vinyl alcohol) membrane coated with the polyacrylamide gel containing triphenylmethane leucocyanide groups [59]. The photoresponsive behavior of the gel has already been described in Sect. 3.1. Figure 26 shows that the rate of water permeation through

I

x

30 E 20

Fig. 25. Permeation profiles of proteins through the PHEMA membrane having pendant azobenzene residues at 30 °C [58]. The arrows represent the UV irradiation to the membrane; (©) insulin, (O) lysozyme, (A) chymotripsin, (&) albumin

o

0

I00

200

Time, min

300

56

M. Irie

-~10 e" E :3

0

=,5 Ligh E r,

I

!

5

10 Time

?

I/~1

15

20 0

II~

I,

f

5 0 Time

5

1

I

10 15 Time

f

,

20

Fig. 26. Photo-effects on water permeation through a porous poly(vinyl alcohol) gel with triphenylmethane leucocyanide groups (content, 1.9 tool %). ( ~ ) an unmodified membrane; ( 0 ) a coated membrane in the dark; (O) a coated membrane under UV irradiation

an unmodified porous membrane is very fast, while the rate is markedly decreased when the membrane is coated with photoresponsive polyacrylamide. Upon irradiation with ultraviolet light the permeation rate increases by as much as 60 times, but in the dark it again decreases. Photostimulated size changes of the adsorbed polymer gel control the permeation of water. The addition of NaC1 to water quenched the photo-effect. This is because the salt suppresses the photostimulated swelling of the polymer gel. The transport property of poly(L-glutamic acid) membrane (24) was also photocontrolled by incorporating triphenylmethane leucoderivative, pararosaniline, groups [60]. The pararosaniline groups in the membrane dissociate into ion-pairs upon ultraviolet irradiation, yielding hydroxide ions. --NH-CH-CO--NH-CH-CO~NH-CH-CO--NH-CH-CO--

CO

CO

t

I

NH

NH

I

I

©

x_©+©_c'_ _x

©

COOH

--NH-CH-CO--NH-CH-CO--NH-CH-CO~NH-CH-CO--

CO

I

CO0-

H

CO

I 1

NH

hv

x_©_:_©_x!x_©_c_©_x,

OH I

.........

(2~:)

(25)

OH-- . . . . .

"J

X=NH;

Photoresponsive Polymers

57 Time

0

50

I

I

min

100 I

2.5 •r.d) 2.3

~ 2.1 x

1.9

n

t.7

0 a

5 Time

10rain Time 50

0

0.80

!

!

0.79 3=

0.78

0.77 b

!

I

0

5

I

,i

rain

100 !

Fig. 27a. Changes in the permeability coefficient of styrene glycol, P,, across a membranecomposedofpoly (L-glutamic acid) containing 15.5 mol % pararosaniline groups on UV irradiation and dark adaption at pH 8.6 and at 25 °C; b. changesin the degree of swelling, H, of the membrane on UV irradiation and dark adaption at pH 8.6 and at 15 °C [60]

lOmin

Time

The hydroxide ions accelerated acid dissociation of the neighboring L-glmamic acid moieties, which, in turn, changed the conformation of the polymer from the randam coil to a helix. Figure 27 shows the rate of styrene glycol permeation through a poly(L-glutamic acid) membrane with 15.5 mol% pararosaniline groups at pH 8.6 together with the swelling behavior. The rate increases by ultraviolet light irradiation. In the dark, the rate again decreases to the initial value. The permeation rate correlates closely With the swelling degree of the gel. The swelling degree is also consistent with the conformation response to light. These findings indicate that the photoinduced increase in the permeability of styrene glycol arises from the increase in the degree of swelling resulting from the conformation change of poly(L-glutamic acid). Photocontrol of the transport property was also studied for poly(L-glutamic acid) membrane with azobenzene-4-sulfonic acid residues [61].

3.5 pH Photocontrol of pH has been tried by use of poly(methacrylic acid) having spirobenzopyren pendant groups [62]. Figure 28 shows the response of pH of an aqueous solution of this polymer to visible light irradiation (~. > 470 nm). The pH increases

58

M. lrie .......

H

Dark t - - - - - 7,

='~=

Dark

---

7.4

3Z

7.3

I

I

I

0

10 rain

20

/]

i

/

t

I

1

2

3

4

Fig. 28. Response of pH of an aqueous solution of poly(methacrylicacid) having spirobenzopyran units (16 mol %) under visible irradiation (2 > 470 nm) and in the dark at 25 °C [62]. Concentration of the polymer was 0.08 g/dl

h Time

on exposure to the visible light, and returns to the initial value in the dark. The mechanism of the pH change is explained as follows. Hydrophobicity of the merocyanine is considered to be weaker than that of the spirobenzopyran because of its zwitter ionic structure. The increase of hydrophobicity due to the isomerization of the merocyanine to the spirobenzopyran form by visible light irradiation causes the polymer chain to contract. The conformation change of the polymer chain decreases the dissociation of the carboxylic acid residues in the pendant groups, giving rise to an increase in pH. The conformation change of polyamide with pendant azobenzene groups (6) in aqueous solution also induced a change in pH [14]. Ultraviolet irradiation caused the pH of an aqueous solution of the polyamide to decrease and visible irradiation returned the pH to the initial value.

4 Photostimulated Phase Transition 4.1 A General View Photoresponsive polymers so far described change their properties in proportion to the number of photons that they absorb. Thus, when they contain more photochromic chromophores, which undergo an isomerization by absorbing a definite number of photons depending on the quantum yield, their properties change more. To make a. sensitive photoresponsive polymer, i.e. one which responds more efficiently to a fewer photons, we have to introduce an amplification mechanism into the system. A convenient way to achieve this end is to utilize the phase transition of polymers. At a temperature close to the phase transition temperature, the system is in an unstable state, and hence a small perturbation may bring about a large effect on it. When such a system is perturbed by a photochromic reaction, the absorption of a few photons will induce a large property change. Figure 29 shows a schematic illustration of the photostimulated phase transition from the state X to the state Y. When the photochromic chromophores in the polymer

Photoresponsive Polymers Stote X

59

Potymer-B I

k2

% % %

Polymer-A I

State Y I

Ta

Fig. 29. Schematic illustration of photostimulated phase transition from the state X to the state Y

Tb Temperature

chain are A isomers, the polymer changes the state at a temperature of T,. We assume that the phase transition temperature will rise to Tb when A isomers convert to B isomers. Then, if the isomerizafion from the A to the B isomer can be induced by photoirradiation with light o f wavelength X, at temperature T(T~ < T < T ¢ , the state will change isothermally at T from Y to X by photoirradiation. In this system, a few photons can induce a marked change in such properties as phase separation in polymer solutions, gel-sol transition, and miscibility of polymer blends.

4.2 Phase Separation of Polymer Solutions Poly(N-isopropylacrylamide) in water has a lower critical temperature at 31 °C. Temperatures at which this system undergoes phase separation are expected to vary when photoisomerizable chromophores are introduced into the polymer. Such an

100

8O

60

Fig. 30. Transmittance changes at 750 nm of a 1% aqueous solution of poly(N-isopropylacrylamide) with pendant azobenzene groups (2.7 mol%) when heated at a rate of 2 °C/min. (O) before photoirradiation; (0) under photostationary state with ultraviolet irradiation (410nm > ,l > 350 nm)

u

a 40

E c-

~ 20

I--

15

20 25 Temperature (*C)

30

60

M. lrie

attempt was made by incorporating azobenzene chromophores into the pendant groups [63]. Figure 30 shows the transmittance change at 750 nm which occurred when a 1~o aqueous solution of poly(N-isopropylacrylamide) with 2 . 7 m o l e ~ pendant azobenzene groups was heated. In the dark before photoirradiation, the solution begins to be turbid at 18.5 °C and the transmittance decreases to one-half the initial value at 19.4 °C. Upon ultraviolet irradiation (410 n m > k > 350 nm), the phase separation temperature rises to 26.0 °C. Between 19.4 and 26.0 °C, ultraviolet irradiation solubilizes the polymer and the solution becomes transparent, while visible irradiation decreases the solubility of the polymer and leads to phase separation. The maximum difference in phase separation temperature was observed at a very small azobenzene content of 2.7 mol ~o. Below and above this content, the phase separation was not affected by photoirradiation. This fact indicates that the phase transition temperature depends on a subtle balance between the polymer's ability of hydrogen bond formation with water and the intermolecular hydropholic force. The isomerization of a small number of azobenzene chromophores (2-3 mol ~ ) effects the balance, resulting in an efficient phase separation. A large effect, a large turbidity change in this case, was induced by a small number of photons in the temperature range from 19.4 to 26.0 °C. Below 19.4 and above 26.0 °C, the photostimulated phase separation was not observed. These findings are consistent with the schematic illustration in Fig. 29. Similar phase separation was observed in theta solvents containing polymers with pendant photochromic chromophores. In a theta solvent, the interaction between the polymer and the solvent is in balance with intra- and inter-polymer interactions. The isomerization of the pendant chromophores alters this balance. The system studied was a cyclohexane solution of polystyrene with pendant azobenzene groups [64]. Cyclohexane becomes a theta solvent for polystyrene at 35 °C. Moderate molecular weight polystyrene (Mw = 5 x t04) with pendant azobenzene groups is soluble in

~100

~o

0 c-

ee°°°°°*

• ° e ° e ° l

•

e

• °Ooooeoolol

°eooooooooe

"~ ~0 E

8 20

~

0

I

100

I

l

~

200

t

300

~

l

400

500

Time(s)

Fig. 31. Changes in transmittance at 650 nm o f a cyclohexane solution containing polystyrene having pendant azobenzene groups (content, 6.1 mol ~ ) on alternate irradiation with ultraviolet (410 nm > 2 > 350 nm) and visible (2 > 470 nm) light at 30 °C [641

PhotoresponsivePolymers

61

this solvent at 30 °C. The solution became turbid upon ultraviolet irradiation (410 nm > ~ > 350 nm)..Prolonged irradiation caused the polymer to precipitate. The solution became transparent when irradiated with visible light (X > 470 nm). The photoresponsive behavior is shown in Fig. 31. The phase separation is ascribable to the isomerization of the pendant azobenzene groups. Introduction of non-polar trans form azobenzene chromophore into the pendant groups little affects the polymersolvent interaction, while the photogenerated cis form tends to decrease the polymersolvent interaction. Thus, upon ultraviolet irradiation, the polymer-solvent interaction decreases considerably until the polymer precipitates. The precipitation behavior of the polymer is interpreted by a photostimulated change of the critical miscibility temperature T¢. For polystyrene dissolved in cyclohexane, the polymer precipitates at temperature below T¢. According Fox and Flory [65], T~ depends on the molecular weight M as T¢

=

ToO -- b/M °'5)

(2)

where T o is the value of To for M = oe and b an empirical constant. We assume that T o and b change when the trans azobenzene groups convert to the cis form. Figure 32 shows a schematic illustration of the molecular weight dependence of Tc by plotting T¢ against M -°'s. First, we consider a mono-dispersed polystyrene of molecular weight M containing pendant azobenzene groups. When these groups are in the trans form, the polymer solution phase separates at t t, which corresponds to T~ of Fig. 29. The isomerization of the chromophores from the trans to the cis form causes the phase separation temperature to rise to t~, which corresponds to TB of Fig. 29. This means that phase separation of the solution is induced between t t and t¢ by ultraviolet irradiation, which causes the trans-cis isomerization. Next, we consider the phase separation of a poly-dispersed polystyrene with pendant azobenzne groups at constant temperature TM. With all azo groups in the trans configuration, any fractions of M < MT are soluble in cyclohexane at TM, but after photoirradiation, the fractions of M r < M < M.r become insoluble and

{¢

--

TM tt

....

Tm ....

C)

i----"~a~5

t

I. . . . .

t. . . . .

I I I

I I I

MT

M

"%.~T e (T)

I I i M-1/2

Mc

"~"

Fig. 32. Molecular weight (M) dependenceof critical miscible temperature, T,. Te(C) and Te(T) indicate the values of T¢ for polystyrene with cis and trans azobenzene groups at M = oo, respectively. See text for M, tt, te, TM,and Tm

62

M. Irie

J

e

/d IC

1b /

t

|

i

]5

i

t

°

k

i

i

20 25 Etution counts 1

106

I

I

105 10~ Molecu[er weight

30 I

Fig. 33. Irradiation time dependence of molecular weight distribution of insoluble polystyrene having azobenzene groups (content, 4.8 mol %) at 30 °C [64]. Irradiation time: (a) 10, (b) 20, (c) 40, (d) 60, and (e) 90 s. Concentration of the polymer was 0.08 g/dl

103

precipitate from the solution. Actually, irradiation here has the same effect as lowering the solution temperature from T M to Tin. The latter may be applied to fractionate the poly-dispersed polymers by photoirradiation. Figure 33 shows the photoirradiation time dependence of the molecular weight distributions of precipitated polymers. The fractions precipitated in the initial 10 s have the largest molecular weight ( M , = 7.1 x 104) and the smallest Mw/Mn (t.21). As time goes, the smaller molecular weight fractions succesively precipitate. The molecular weight (M,) of the fraction precipitate after 30 s is estimated to be 3.8 x 104. I f the phot~induced solubility change is large enough, the system can be used as a photoresist. Polystyrene with pendant spirobenzopyran groups was found to be useful as a negative type photoresist [66]. The photoresponsive behavior described above is quite efficient. Only 5 mol% azobenzene pendant groups were enough to cause the phase separation. In the system containing spirobenzopyran groups, the efficiency was much higher. The isomerization of 2molto spirobenzopyran chromophores in the pendant groups raised T~ considerably and led to phase separation.

4.3 Sol-Gel Transition The formation of a three dimensional infinite network in a polymer by a chemical or physical process leads to a gel. Polymer gels are classified into two types, irreversible and reversible. The latter are formed by cross-linking due to physical interaction between certain points on different polymer chains, and the sol-gel phase transition is induced by a change in temperature. At temperatures below Tgo~,

Photoresponsive Polymers

63

0 -I v

-2!

Fig. 34. Gel-sol transition of polystyrene (Mn = 1.5 × 104) with (O) 62% eis azobenzene and (@) 100% traps azobenzene groups in CS2 measured by the bail drop method [68]. Arrows indicate the gel melting temperature. The content of the azobenzene groups in the polymer was 10.5 tool% and the polymer concentration in CS2 was 200 g/1

-4

-o'o

50 ' Temp. (°C)

- 4'0

-30

the gelation temperature, the polymer solution stops flowing, while above Tg¢~ the gel melts to flow. Photoirradiation induces a reversible sol-gel phase transition in a polymer in which photoisomerizable chromophores are incorporated. The system so far reported is a CS2 solution of polystyrene with pendant azobenzene groups [67, 68]. Tgel can be conveniently determined by a ball drop method. A steel ball is placed on the top of the gel, and the temperature at which the depth-temperature curve begins to deviate from the horizontal line is taken as Tge~. Two CS2 solutions, one containing polystyrene with partially photoisomerized azobenzene groups (cis content, 6 2 ~ ) and the other containing polystyrene with 100% trans azobenzene groups, were placed in separate tubes, cooled to --78 °C, and allowed to stand for 5 h. Then a steel ball was placed on the top of each gel, and the temperature was raised at a slow rate of 0.5 °C/min. Figure 34 shows how the ball-sinking behavior of the two gels depends on temperature. The ball for the polystyrene gel having trans azobenzene groups begins to sink at --56 °C, whereas the ball for the gel having partially cis azobenzene groups still remains on the top at this temperature. For the latter the ball begins to fall at --47 °C. This Tge~ reverted to --56 °C, when the gel was irradiated for 20 min with visible light at --78 °C, prior to raising the temperature. This behavior can be attributed to the action of visible light which converts the pendant groups from the cis to the trans form. The above finding indicates that the gel-sol transition can be induced isothermally between --56 and --47 °C by changing the irradiation wavelength. Ultraviolet irradiation (400 nm > ~. > 310 nm) converts the sol to the gel state, whereas visible irradiation (L > 450 nm) induces the transition from the gel to the sol state. In fact, a reversible gel-sol transition was observed at --52 °C.

sol ~

~'2

400 n m >

gel kl > 310 nm, ~-z > 450 nm

64

M, Irie

The formation of a photo-reversible gel is explained as follows. The azobenzene groups in the surface region of the polymer coil help the coil overlap. When they change to a more polar cis form, the interactions are strengthened. The change in the interpolymer interactions is responsible for the change in the gel melting temperature.

4.4 Miscibility of Polymer Blends Miscibility of polymer blends is an attractive subject from both scientific and industrial view points. Recently, several attempts have been reported to make immiscible pairs of polymers miscible at room temperature by incorporating a third component. Pearce et al. [69] observed that the immiscible pair of polystyrene and poly(n-butyl methacrylate) became miscible when only 1.8 mot % hydroxy groups were introduced into polystyrene. It was also shown that the cloud point temperature of poly(methyl vinyl ether), PMVE, blended with deuterated polystyrene is 40 °C higher than the temperature of the blend with undeuterated polystyrene [70]. These demonstrate that small changes in polymer properties alter miscibility markedly. This is expected because the miscibility, or the phase separation of polymer mixtures, depends on a subtle balance of inter- and intra-molecular interactions. With the incorporation of photoisomerizable chromophores into one of the paired polymers, we should be able to control the miscibility of the polymer blends by photoirradiation. This prediction was confirmed for PMVE blended with polystyrene having pendant stilbene groups (26) [71].

,,

26

hv

•

27

Stilbene isomerizes from the trans to the cis form when irradiated with ultraviolet light (400 n m > ~. > 300 rim). The photogenerated cis form returns to the trans form by irradiation with light of 254 nm. Thermal isomerization from the cis to the trans form is negligible, even at 200 °C. Figure 35 shows the temperature dependence of the inverse intensity of light transmitted through PMVE blended with polystyrene having either all trans or partially cis pendant stilbene groups (cis content, 25 mol%). Both blends are transparent at room temperature. When heated from room temperature at a rate of 5 °C/min, the blend containing cis stilbene groups turns optically opalescent at 78 °C, while the blend containing trans stilbene groups still remains transparent at that temperature. The latter turns opalescent at 101 °C. The cloud point temperature of the blend containing 0.25 cis fraction is 23 °C lower than that of the blend containing all trans stilbene groups. Although the molecular basis of the miscibility change is not yet fully understood, the interaction between phenyl rings and C O C H 3 groups is considered to play an important role. Probably, the introduction of bulky stilbene pendant groups perturbs the efficient packing of PMVE with polystyrene, causing the the phase separation

Photoresponsive Polymers

65

50

!

_~ 30

J/

"E:

o/

/

0

j/

10 t

I

I

I

I

70

80

90

I00

II0

120

T/°C

Fig. 35. Temperature dependence of the inverse of the transmittance fight, 1/Tr, after passage through blend of PMVE with polystyrene having (O) all trans stilbene groups and ( ~ ) partially cis stilbene groups (cis content, 0.25) [71]. Content of the stilbene groups in the copolymer was 15.2 m o l ~ temperature to lower. Conversion o f the stilbene groups from the trans to the cis form further decreases the cloud point temperature. D u r i n g the isomerization, the molecule change the geometry from p l a n a r to "propeller-shaped". Thus, the molecular volume increases by the isomerization. The expansion o f the molecular Volume will decrease the intermolecular interaction forces between the phenyl rings a n d C O C H 3 groups, thus bringing a b o u t a decrease in the cloud p o i n t temperature.

5 Acknowledgement The a u t h o r wishes to thank Professor K. H a y a s h i o f O s a k a University for continuous encouragement. H e is deeply indebted to Professor W. Schnabel o f the H a h n Meitner Institute for his stimulating contributions to the laser experiments o f Sect. 2.2. H e is also grateful to Emeritus Professor H. F u j i t a o f O s a k a University for critically inspecting the manuscript a n d giving invaluable comments. He also thanks all o f his co-workers for their devoted contributions.

6 References 1. 2. 3. 4. 5. 6.

Montagnoli G, Erlanger BF (1983) Molecular models of photoresponsiveness, Plenum Etzold H (1965) Planta 64:254 Brown GH ~,971) Photochromism, Wiley-Interscience Lovrien R (1967) Proc. Nat. Acad. Sei. 57:236 Van der Veen G, Prins W (1974) Photochem. Photobiol. 19:191 Negishi N, Takahashi M, lwazawa A, Matsuyama K, Shinohara I: Nippon Kagaku Kaishi 1977: 1035 7. Negishi N, Ishihara K, Shinohara I (1982) J. Polym. Sci., Chem. Ed. 20:1907 8. Mat~jka L, Dn~ek K (1981) Makromol. Chem. 182:3223 9. Irie M, Suzuki T (1987) Makromol. Chem. Rapid Commun. 8:607 10. Goldburt E, Shvartsman F, Fishman S, Kronganz V (1984) Macromolecules 17:1225 11. Zimmerman G, Chow L, Paik U (1958) J. Am. Chem. Soc. 80:3528 12. Hampson GC, Robertson JM: J. Chem. Soc. 1941:409 13. Irie M, Hayashi K (1979) J. Macromol. Sci., Chem. A13:511

66 14. 15. 16. 17. 18. 19. 20. 21. 22. 23. 24.

25. 26. 27. 28. 29. 30. 31. 32. 33. 34. 35. 36. 37. 38. 39. 40. 41. 42. 43. 44. 45. 46. 47. 48. 49. 50. 51. 52. 53. 54. 55. 56. 57. 58. 59. 60. 61. 62. 63.

M. hie trie M, Hirano K, Hashimoto S, Hayashi K (t981) Macromolecules 14:262 Blair HS, Pogue HI, Riordan JE (t980) Polymer 21:1195 Kumar GS, DePra P, Neckers DC (1984) Macromolecules 17:1912 Kumar GS, DePra P, Zhang K, Neckers DC (1984) Macromolecules 17:2463 Kumar GS, Savariar C, Sattran M, Neckers DC (1985) Macromolecules 18:1525 Zimmerman EK, Stitle JK (1985) Macromolecules 14:1246 Irie M, Hosoda M (1985) Makromol. Chem. Rapid Commun. 6:533 Irie M, Menju A, Hayashi K (1981) Macromolecules 12:1176 Menju A, Hayashi K, Irie M (1981) Macromolecules 14:755 Ueno A, Osa T (1980) Yuki Gosei Kagaku 38:267 a. Ciardelli F, Cartini C, Salaro R, Altomare A, Pieroni O, Houben JL, Fiss A (1984) Pure Appl. Chem. 56:329 b. Fissi A, Pieroni O, Ciardelli F (1987) Biopolymer 26:1993 Irie M, Schnabel W (1983) Maeromolecules 14:1246 Irie M, Schnabel W (1985) Macromolecules 18:394 Merian E (1966) Text. Res. J. 36:612 Blair HS, Law TK (1980) Polymer 21 : 1475 Blair HS, Pogue HI (1982) Polymer 23:779 Agolini F, Gay FP (1970) Macromolecules 3:349 Osada Y, Katsumura K, Inoue K (1981) Makromol. Chem. Rapid Commun. 2:47 Kohjiya S, Hashimoto T, Yamashita S, Irie M: Chem. Lett. 1985:1479 Smets G, Evans G (1973) Pure Appl. Chem. Macromol. Chem. 8:357 Smets G, Breaken J, Irie M (1978) Pure Appl. Chem. 50:845 Eisenbach CD (1980) Polymer 21 : 1175 Mat~jka L, Ilavsky M, Du~ek K, Wiehterle O (1981) Polymer 22:1511 Van der Veen G, Prins W (1971) Nature Phys. Sci. 230:70 Chuang JC, de Sorgo M, Prins W (t973) J. Mechanoehem. Cell. Motility 2:105 Mat~jka L, Du~ek K, Ilavsk~, M (1979) Potym. Bull. 1 : 659 Ishihara K, Hamada N, Kato S, Shinohara I (1984) J. Polym, Sci. Chem. Ed., 22:121 Aviram A (1978) Macromolecules 11:1275 Irie M, Kungwatchakun D (1984) Makromol. Chem. Rapid Commun. 5:829 Irie M, Kungwatchakun D (1986) Macromolecules t9:2476 Irie M (1986) Macromolecules t9:2890 Ishihara K, Okazaki A, Negishi N, Shinohara I, Okano T, Kataoka K, Sakurai Y (1982) J. Appl. Polym. Sci. 27:239 a. Ishihara K, Kato S, Shinohara I (1983) J. Appl. Polym. Sei. 28:1321 b. Negishi N, Tsunemitsu K, Shinohara I (1981) Polym. J. 13:411 Ishihara K, Hamada N, Kato S, Shinohara I (1983) J. Polym. Sci., Chem. Ed., 21: 155I Irie M, Iga R (1987) Makromol. Chem. Rapid Commun. 8:569 Negishi N, Ishihara K, Shinohara I, Okano I, Kataoka K, Sakurai Y, Akaike T: Chem. Lett. 1981 : 681 Negishi N, Ishihara K, Shinohara t, Okano T, Kataoka K, Sakurai Y (198t) Makromol. Chem. Rapid Commun. 2:95 Kato S, Aizawa M, Suzuki S (1976) J. Membrane. Sci. 1 : 289 Irie M, Menju A, Hayashi K: Nippon Kagaku Kaishi 1984:227 Anzai J, Sasaki H, Ueno A, Osa T: Chem. Lett. 1985:1443 Anzai J, Sasaki H, Ueno A, Osa T (1986) Makromot. Chem. Rapid Commun. 7:133 Anzai J, Sasaki H, Ueno A, Osa T: J. Chem. Soc. Chem. Commun. I983:1045 Sasaki H, Ueno A, Anzai J, Osa T (1986) Bull. Chem. Soc. Jpn. 59:1953 a. Yasuda H, Lamaze CE, Peterlin A (1971) J. Polym. Sci. A-2, 9:1117 b. Zentner GM, Cardinal JR, Kim SW (1978) J. Pharm. Sci. 67:1352 Ishihara K, Shinohara I (1984) Potym. Sci., Polym. Lett. Ed. 22:515 Irie M, Kungwatchakun D: to be published. Sato M, Kinoshita T, Takizawa A, Tsujita Y (I988) Polym. J. 20:729 Sato M, Kinoshita T, Takizawa A, Tsujita Y (1988) Polym. J. 20:761 Irie M, Hayashi K, Menju A ('1981) Polym. Photochemistry 1:233 Kungwatchakun D, Irie M (1988) Makromol. Chem. Rapid Commun. 9:243

Photoresponsive Polymers 64. 65. 66. 67. 68. 69. 70. 71.

Irie M, Tanaka H (1983) Macromolecules 16:210 Fox TG, Flory PJ (1951) J. Am. Chem. Soc. 73: 1909, 1915 Irie M, Iwayanagi T, Taniguchi Y (1985) Macromolecules 18:2418 Irie M, lga R (1985) Makromol. Chem. Rapid Commun. 6:403 Irie M, Iga R (1986) Macromolecules 19:2480 Pearce EM, Kwei TK, Min BY (1984) J. Makromol. Sci. Chem. 21 : 1481 Halary JL, Ubrich JM, Monnerie L, Yang H, Stein RS (1985) Polymer Commun. 21 : 73 Irie M, Iga R (1986) Makromol. Chem. Rapid Commun. 7:751

Edited by H. Fujita Received June 8, 1989

67

Telechelic Oligomers by Radical Reactions B. B o u t e v i n E c o l e N a t i o n a l e S u p e r i e u r e de C h i m i e de M o n t p e l l i e r L a b o r a t o i r e de C h i m i e A p p l i q u e e U R A D 11930 C N R S / F r a n c e , 8 R u e E c o l e N o r m a l e , M o n t p e l l i e r / F r a n c e

The synthesis of telechelic oligomers by a radical reaction can be carried out either by functional initiators or by telomerization. This review describes the different methods of synthesis used to obtain these oligomers. First, we mention the preparation and use of the functional diazoic initiators, functional peresters, hydrogen peroxide, hybrid initiators (which contain two kinds of labile groups) and macromolecular polyinitiators. Then, new initiators disubstituted (tetraphenyl ethanes or thiurams functional or not) which are real precursors of living oligomers are described. In each case, the kinetical data (decomposition rate constants and efficiency) are provided. In the second part, surveys concerning telechelic telomers are mentioned. The different telogens used and their known transfer-constants are supplied: aliphatic and aromatic disulfides, disubstituted benzoyl disulfides, functional xanthogens and polyhalogenated compounds. Also novel monoaddition reactions of functional monomers onto both end groups of dithiols and ditrichtoromethyl compounds are summarized.

1 Introduction

. . . . . . . . . . . . . . . . . . . . . . . . . . .

2 Synthesis of Tdechelic Oligomers by Radical Initiation

71

. . . . . . . . . .

71

2.1 F u n c t i o n a l I n i t i a t o r . . . . . . . . . . . . . . . . . . . . . . . 2.2 T e l o m e r i z a t i o n . . . . . . . . . . . . . . . . . . . . . . . . .

71 72

3 0 l i g o m e r i z a t i o n s by Functional Initiators . . . . . . . . . . . . . . . . 3.1 T e r m i n a t i o n R e a c t i o n o f V a r i o u s M o n o m e r s . . . . . . . . . . . . 3.2 Efficiency o f t h e I n i t i a t o r . . . . . . . . . . . . . . . . . . . . . 3.3 D e a d - e n d P o l y m e r i z a t i o n . . . . . . . . . . . . . . . . . . . . 3.4 D i a z o i c C o m p o u n d s . . . . . . . . . . . . . . . . . . . . . . . 3.5 O x y g e n a t e d C o m p o u n d s . . . . . . . . . . . . . . . . . . . . . 3.6 H y d r o g e n P e r o x i d e . . . . . . . . . . . . . . . . . . . . . . . 3.7 T e t r a a l k y l t h i u r a m Disulfides . . . . . . . . . . . . . . . . . . . 3.8 D i s u b s t i t u t e d T e t r a p h e n y l E t h a n e s . . . . . . . . . . . . . . . . .

73 73 74 75 76 79 83 86 89

4 Telomerization . . . . . . . . . . . . . . . . . . . . . . . . . . .

91 91 93 94 96

4.1 4.2 4.3 4.4

Disulfides . . . . . . . . . . . . A c i d Disulfides . . . . . . . . . . Xanthogens . . . . . . . . . . . . The Uses of Halogenated Telogens .

. . . .

. . . .

. . . .

. . . .

. . . .

. . . .

. . . .

. . . .

. . . .

. . . .

. . . .

. . . .

. . . .

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. . . . .

Advances in Polymer Science 94 © Springer-Verlag Berlin Heidelberg 1990

70

B. Boutevin 4.5 The Use of Non-conjugated Dienes . . . . . . . . . . . . . . . . 4.6 The Uses of C o m p o u n d s which Exhibit CC13 end groups . . . . . . . 4.7 Synthesis of Tetechelic Products by R h o d i u m Catalysis . . . . . . . .

98 99 100

5 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

102

6 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

102

TelechelicOligomersby Radical Reactions

71

1 Introduction The synthesis of telechelic oligomers has been brought up in numerous genera1 publications. There are four main ways of synthesis: -- polymerization by condensation or polyaddition; -oxidative cleavages of polymers; -ionic polymerizations; -- radical polymerizations. This paper deals with this last method. Yet, the publications are quite general and deal with these four topics without giving a complete overall review. Furthermore, they are spaced in the time from the seventies up to now. Lastly, they are either general or very specific (for instance they mention topics such as dienes, functionality or molecular distribution). With reference to the general reviews of particular note are the surveys carried out by Brossas et al. [1] (about 100 references), then Athey [2, 3] (roughly 50 references), Barentsevich [4] (66 references) and finally those published in 1987 by Heitz [5, 6] and Brosse et al. [7] (76 and 260 references, respectively). For specific papers on oligomers prepared from dienes, special mention is made to French's [8] and Schnecko's [9] works (126 and 68 references respectively). Then, we can mention a special study by Entelis [10, 11] based on the functionality and the molecular distribution of telechetic polymers. Before going into the methods for radical reactions it most be said that polycondensation or polyaddition have led to more industrial preparation. In this connection epoxy resins, the polyurethanes obtained from prepolymers and, more recently, more specialized polymers such as the PEBAC (ATOCHEM), amid-ether or polyimids (KHERIMIDE from RHONE POULENC must be mentioned). Moreover, it is interesting to note that the ionic methods (cationic or anionic ones) have not produced industrial products (except dihydroxy poly (dimethyl siloxanes), poly (tetrahydrofuranes)) but they have facilitated theoretical studies both on the analytical aspects and the materials we can obtain. In this paper we are going to the syntheses of telechelic oligomers by the radical method. Such a topic has already been studied very often. In this field of research, there are two main parts for the obtaining of such oligomers: -the use of functional initiators, -the telomerization.

2 Synthesis of Telechelic Oligomers by Radical Initiation 2.1

Functional

Initiator

Generally, this initiator is symbolized by G - - A - - A - - G where G represents the functional group and A the part of the molecule which is cleaved by heat or radiation: G-A-A-G

0o~hv 2 GA'

G A ' + M --~ GAM' " ~ G - A - ( M ) ~ + t

(1) (2)

72

B. Boutevin

The above reactions represent the initiation and propagation steps. The two last steps determine whether the oligomer will be telechelic or not. Termination :

combina~

GA(M)2. AG

(3 a)

2 GA(M).

(3 b)

GA(M)~~ td~oPnra~.P-o%r~

The combination step itself gives the telechelic compound; however, there is a lack of knowledge about both the last steps. Heitz [4] gave interesting data on this topic. Transfer:

GA-(M)~ + XY --. GA-(M). Y + X"

(4)

Using a functional Y lads to the telechelic compound but generally one of both end groups of XY is not functional and in this case, it does not produce the difunctionality of the oligomer.

2.2 Telomerization The initiator A 2 is not necessarily functional, but in this case, the telogen is difunctional or may be potentially functional: G - - T - - T - - G A 2 ~ 2 A"

(5)

A" + G T T G --. ATG + GT"

(6)

G T ' + M ~ GTM" 2_~ GT(M)~+I

(7t

As previously, these reactions above correspond to the initiation and propagation steps. As for the termination and transfer steps, the latter one is mainly favored. Actually, the G T T G compound has been chosen since it reacts quite easily with radicals in the middle: GT(M). + G T - T G ~ GT(M)nTG + GT

(8)

If the termination occurs by recombination, we obtain the difunctionality; on the other hand, every disproportionation diminishes this last characteristic. Furthermore, we might expect the difunctional telomers to exhibit molecular weights much lower than those of the telechelic oligomers obtained with the difunctional initiators without the transfer step. Thus, in both cases, the disproportionation adversely effects the obtaining of the difunctional compound.

Telechelic Oligomers by Radical Reactions

73

30ligomerizations by Functional Initiators We can distinguish three main categories of functional initiators: - - diazoic compounds, - - hydrogen peroxide, - - oxygenated substances. Each of them is quite wide and several regroupings can be expected. Hydrogen peroxide is rather close to the third variety but its reactivity and its solubility in water show that such reactant represents, itself, a unique category for its industrial applications. Before studying each series of initiator, we should mention again that difunctionalization is connected with the way the radicals can recombine. Thus, we will study first the behavior of different monomers to the reaction of termination.

3.1 Termination Reaction of Various Monomers Bamford and Tipper [12] gave the results gathered in Table 1 for the termination step. Table 1. Percent of recombination (p) of various monomers at 25 °C Monomers

P

Styrene p CI styrene p OCH3 styrene Methyl/ethyl acrylate Methyl/ethyl methacrylate Acrylonitrile Methacrylonitrile

100 100 81 100 33 100 35

As regards styrene, several authors [13] found 80% instead of 100%. Heitz [5] noticed that the reactivity of the intermediate radical takes an important part. Actually, if it is primary, it tends to be very reactive and attacks either the polymer (especially at high conversion rate) and this leads to trifunctional compounds, or reacts with the solvent (monofunctional species), or reacts with the initiator (telechelic compound). Heitz and Guth [14] showed that the functionality of the product resulting from the addition of ethylene onto AIBN in tertiobutanol is 1.7. The reactivity of the primary radicals allows one to predict t.8 [15] but we must consider that the transfer is an important step. When methanol is used as solvent, the amount of product obtained by transfer is 10 % and with benzene it reaches 20 %. With reference to vinyl acetate, few data have been given but Brosse et al. [7] described the synthesis of oligomers the molecular weights of which are Mn = 500 to 4,000. They mentioned that the initiation with H202 leads to a polymer with a Mn

74

B. Boutevin

which depends upon the vinyl acetate concentration, and the functionality is 2 anyway [16]. For butene, Brosse et al. [17] gave the following series: 1-butene > 2-butene > isobutene The molecular weights Mn are below 1,000 and their functionality varies between 2 and 4. This lack of reactivity explains why these monomers are mostly used in copolymerization. As for fluorinated monomers, Rice et al. [18] noticed that the termination of H 2 C = C F 2 and F z C = C F - - C F 3 occurs by recombination. Besides this parameter which depends on the recombination or the disproportionation of macromolecular radicals, we must consider, in the case of telechelic oligomers, the reactions with primary radicals obtained from the direct decomposition of the initiator:

GA(M)~, + AG"

~GA(M). AG [GA(M). H + AG(minus H)

(9a) (9b)

Besides, it is natural that in those reactions where we are seeking to obtain low molecular weights, we must use a higher initiator concentration with reference to the M A Y O equation and consequently the reactional mixture is rich in AG' radicals. Thus, we must consider those reactions (of termination of macroradical with primary radical (Eq. (9)) which have not necessarily the same reactivity ratio, as the termination of two macroradicals. And this makes it often possible to obtain telechelic oligomers for monomers which give a non-negligible amount of disproportionation reactions in traditional polymerization. The price of the difunctional initiator is also a crucial parameter. Actually this is the most expensive compound and it is essential that it is entirely used. Thus, in classical polymerization, we are seeking to use an important initiator amount in order to obtain a high conversion rate in the monomer. On the other hand, when we prepare a telechelic oligomer, the initiator must be consumed completely and this leads to two control parameters: -- the efficiency of the initiator on one hand, and - - on the other hand, the kinetical conditions to use up completely the functional initiators. 3.2 Efficiency o f the Initiator

The different reactions involved are Kd

R 2 ---~ 2R" K¢

(10)

R" + M - - ~ RM'

(11)

R" + R" Ki, R2(inactivated product)

(12)

Telechelic Oligomers by Radical Reactions

75

The efficiency can be written according to/the following formula: f=

K~(R') (M) K~(R') (M) + K~(R') z

=

(M) (M) + Kffk~(R')

(13)

Such an equation shows easily that the initiators are more active at high monomer concentrations. Moad et al. [19] studied the change of the effeciency with the monomer concentration and from the obtained curve, they found: K e

K--T"(R') = 10 The crucial igoint is the determination of f. Heitz [5] suggested a new relation : f =

A(M) e/2(DPn)~.m A(I2)

(t4)

where A(M) and A(I2) are the monomers and initiators consumptions and e represents the functionality of the oligomers. Determining e is also difficult and this is true for all the types of polymerizations. Heitz [4] suggested the formula: DPn e = 2 - 2 DPno

(15)

where D P and DP----orepresent the real and without transfer values of DP~.

3.3 Dead end Polymerization Tobolski [20, 21] showed that log (M)° - K(I2)lo/2 ( 1 - e(-Kdt)/2) (M) with

(16)

2 Kpf 1/2 K - K1/21z- t/2

d X~Te

By assuming that the initiator is consumed faster than the monomer, (Izo0 = 0 and (M)o~ is determined from the equation: log

(M)o (M)~o

-- K(12)~/2

(i7)

Knowing K permits the calculation of (M)~o. With reference to the volume contractions in the polymerization of high monomer concentration, Tobotski gave more elaborated equations [21] which are still widely used.

76

B. Boutevin

The term involving the energy, EpEgU2ETeU2 directs the polymer decomposition rate, whereas E a directs that of the initiator. In most cases, 20 < E a < 40 Kcal/mol; 25 < Eve N 5 Kcal/mol and 6,5 < Ep < _ 8 Kcal/mol and it is easy to show that an increase of the temperature favors more the initiator-decomposition than the monomer-disappearance. Practically, we control the temperature in order to obtain a faster initiator decomposition than that of the monomer and the time is calculated to be greater than 10 initiator half-lives. 3.4 Diazoic Compounds

The synthesis is that from Strecker; R

\

R

C=O + H2N-NH 2 ~

CHf

N

C=N-N=C

CN R

C-NH-NH-C CHf

~ C H 3 Hnr

R

\CH 3

CHf

HCN R C N

/

CN

CN

R-C-N=N-C-R [ [ CH 3 CHs

The most commun diazoic compound is AIBN ( R = C H a ) but CH3COCH2CH2R (R---CO2H , CH2OH ) can be used as a starting material and then th~ corresponding products are [5]: ~H3

~H3

CN - C - N = N - C - C N CH 2

1 I ~H2

CH2

J I ~H2

R

R

From AIBN, we can prepare another series of diazoic initiators: O AIBN + ROH

CH31

|CHs

O

.~

R = CH3, (CH2) n - O H Therefore, we have two series of diazoic compounds the nomenclature of which has been remarkably described by Brosse et al. [7]: - - The xx'-azobis (x cyano-alkanol) and, - - The di (x-hydroxyalkyl)-2,2'-azobisisobutyrate.

77

Telechelic Oligomers by Radical Reactions

A wide range of products are potentially available and their applications are numerous. Table 2 gives kinetic oata (K a, activation energy etc...). It is interesting to note recent or innovating work in this area. First, Ghatge et al. [23] obtained a diazo initiator which is a precursor ofisocyanate according to the following reactions:

~N HO2C-(CH2)2-~-N=N~CO2H

+ 2N(Et)3

CH 3

CN + Et3NHOzC-(CH2) 2- ~ -N=N~

CO 2H

/

CH3 o O O CN , H II I EtOC-Cl_loocE t - O - C - O - C - ( C H z ) z - ( ~ - N = N ~ O E t CH3 O

CN

O

-2 to 0°C, N 3 - C - ( C H 2 ) / - CI- N = N ~ C N CH 3

3

This is noteworthy since the azide leads to an isocyanate during the thermal polymerization. O Jl

CN i

CN J

N3C-(CH2)2-~-N=N

~N 3 + nM ~

OC=N-(CH2)2-~-(M)n

CH 3

CH3

In the same way, Heitz's works [25, 26] are also interesting. ~H3

~H3

CH3

CH 3

N C - C - ( S t y ) . - C . - C N H2/co H2N_CH2_t_(Sty) _~._CH2_NH 2 CH 3

~H 3

CH 3

l CH3

1 240 ° C/30' h, HO2C-

~H 3 2

CH 3

+

-(StY)n- - C O 2 H CH 3

CH 3

78

B. Boutevin

~H3 O C = N - C H 2 - C - (Sty).- C - C H z - N=CO ~Hs

2 COC12;

CH 3

a) C1-O-OEt/NET3

b, N~N3

CH 3

CH3 1

~H3

CH 3

CH 3

... O C = N - C - ( S t y ) . - C - N = C O

Table 2, Kinetical parameters of several diazoic functional initiators Solvent

I05 • Kd (T °C)

Ref,

E KJ/

mol

~ H3 @H

CH3-C-N=N-

[81

16.0 (80)

CN

~ H3 HO-(CH3)3-C. - N = N -

0.78

[31

130

0.72

[3]

4.6 (70) 9.0 (80)

130 --

0.68 --

[3] [81

Et

8.3 (80)

120

MeOH

4.6 (95)

127

acetone

4.3 (80)

acetone

4.5 (70)

acetone H20

crN

~

H3 Br-(CH2)a-~-N=NCN CH 3 HO2C-(CHz)z- + - N = N CN

~ H3 R-O-C-C-N=N-

If

I

[3]

O CH 3 CH 3 O

0.70

[3]

CH 3

~ H3

Toluene

HO-CH2CH2-O~-~-N=NO CH 3

20 (80)

1.6 (60)

130

2.0 (80) 2.0 (80)

125 130

[25] Dioxane DMF

TelechelicOligomersby RadicalReactions

79

These surveys permit the obtaining of telechelic diisocyanates and diamines, unknown so far. The side-reactions must also be considered with diazoic derivatives:

~H3 NC-C I f CH

~H3 C-CN I CH 3

coupling

CH 3. AIBN ---* NC-~" CH 3~ " ~

~ H3

/CN

N C - ~ - H + H2C=C CH3 ~CH3

disproportionation

~ H3 CH-C-N=C=C I I CH 3 CH 3

H3 ~ H3 NC-C C I I CH 3 CN

~ H3 C-CN I CH 3

trimer

The coupling was already observed in 1950 by Bicker et al. [28]. On the other hand, the transfer constant to the polymer is always low since the cyanoisopropyl radical has a rather weak reactivity.

3.5 Oxygenated Compounds As Heitz mentioned, the problem is more complex with the peracids: O

tl

O

II

R-CO-O-C-R. O R - C / / O O%C-R -* 2 R - C / / M_~ polymer \O--O / [ \O _CO2 " 2 R. ~

polymer

80

B. Boutevin

when R is aliphatic, the R" radical is mainly produced and when R is an acyl group, there is a mixture of O - C O " and O'. Therefore, two series of polymeric products can be obtained. O O This also occurs for the dicarbonates tl t1 which lose a CO 2 RO-C-O-O-C-OR molecule and the RO" radicals initiate the polymerization (except for R = t-But and perhaps for R = cyclohexyl [29]). Furthermore, these authors showed that the reactivity of the RO' radical was much weaker than that of the RO--CO' group; this was observed from the 14C tracing of the carbonyl group. However, few functional oxygenated compounds were mentioned except by some teams. In 1962, the Thiokol Company [30] developed the synthesis of dicarboxylic polybutadienes from functional peresters prepared, according to Clover and Houghton, [31] as indicated in the following scheme:

/R. O=C\o/C=O 10 to 20°C

2h

+ H202

, HO2C- R-CO-O2-

OC- R-CO2H

Thus, 70 ~o of the initiators lose a C O 2 molecule when added on to the monomer. We can note the particularly interesting kinetical study carried out by continuously adding both the initiator and the monomer in order to obtain an expected average molecular weight (all was calculated by computer). The patent is for the synthesis and processing, and this needs to be elaborated. Rice and Sandberg [18] suggested another interesting survey, using fluorinated compounds:

CIOC--(CF2)3--COC1+ R O H

~ RO2C--(CF2)3--COCt

NaOH/n20 ,, R O z C - ( C F z ) 3 - C O - O O - C O - ( C F z ) 3 - C O 2 R H202

VDF/nFP, RO2C_(CFz)3_(CH2CF2)n_(CF 2_~ F)p_(CF2)3_CO2 R CF3 functional copotymer Mn = 3,000 Barentsevich et al. [4] suggested a series of initiators listed in Table 3. It is possible to introduce CO2H o r CC13 as end groups that can be changed. We present the results obtained with polyfunctional oxygenated or nitrogenous initiators. Ivanchev [36] proposed a rationalization of particular functional initiators. More recently, Simionescu et al. [37] have written a complete review the synthesis of initiators di- and polyfunctional.

Telechelic Oligomers by Radical Reactions

81

First, we list the traditional initiators whose reactivity decreases in tim series: O

II

O

O

II

II

ROCO-OCOR

O

O

II

II

> RCO-OCR > RCO-OR > RO-OR > RO-OH > (R3E--O)2-where E = Si, B, Sn

Table 3. Kinetical characteristics of the oxygenated initiators Product

Solvent

l0s Kd (T °C)

EaKJ/ moL

f

Ref.

Acetone Toluene

4.8 (70) 0.8 (70)

105

093 --

[33]

CCI3-O-C~ O O-

Toluene

0.5 (70)

--

0.90

[34]

O HO2C_(CH2)2_C// \ O-

BuOH DMF Acetone

0.6 (90) 1.6 (70) 4.3 (70)

104 ---

0.20 ---

I4]

--

--

[35]

//O C1CH2-~-C\o-

[32]

Otl CH3_O_C_ O_

H20

Then, the polyfunctional initiators are classified into three parts: • X-R-OO-R-Y • H2C=CH

\

RO-O-R' • -(R"-O-O-R").where X and Y represent the functional groups, R a divalent group, R' an alkyl group a n d R " an alkylene one. This first class has previously been discussed. In the second type of monomer, the m o n o m e r must exhibit a lateral group labile thermically. F o r instance, Ivanchev proposed that /CHs H2C=C \CO2-CH2-CH2-OOBu.

82

B. Boutevin Furthermore, azoic compounds [37] can be used such as:

H2C=CH-O-N=N-C-CH

3

These monomers are precursors of graft polymers and curing agents. The third part is composed of bi-initiators which contain a number of limited labile groups on perfectly defined organic molecules. For instance, is azo-peroxy, peroxy-peroxy and azo-carbonate the two functions are cleaved at different temperatures and this enables one to add labile end-groups in the polymers. They then can be further used to prepare block copolymers. Table 4 lists several examples o f such products with their kinetical characteristics. O O With II I1 lvanchev et al. [39] prepared adpolydispersed (R-OO-C-(CHz)z-CO ~ polymer with a functionality of 1.50-1.85. They obtained 50 ~o of bifunctional, 38 ~o of monofunctional and 12 ~o of a mixture composed of tri- and tetrafunctional products. The functionality and the yield depend upon the experimental procedure, i.e. the higher the temperature, the lower the functionality.

Table 4. Kineticat characteristics of potyfunctional initiators Product

Solvent

c//O ROO-C-CH2-

• Et

'\O-

10s Kd 6.7 (80)

EKJ/mol (T °C)

• Et

14.0 (80)

126.5

3.5 (t lo)

158.8

R-O0-C-O-C\ o~H3 //O R-N=N-C. -(CH2)3-C\ I OCH3

~ H3 CN

0.4

[401

0.4

[411

t.9 (63) p O CI

--

[421

-

[42l

--

[42]

1.9 (73) a 1.9 (45) p OCl

O

~H3 R - O - O - ,C,-(CHz)2-C, - N = N 11 I O CN a = azo; p = peroxy

Ref.

--

3.7(110) 156.3

~O

f

1.9 (73) a

12.5 (80) a 0 CI 3.6 (80) p

Telechelic Oligomers by Radical Reactions

83

Lastly, this third group also contains macromolecular poly-initiators which have been developed for a long time by A. E. Woodwards and G. Smets [43]. The principle of the reaction is the polymerization of a monomer (M,) with the phtaloyle peroxide - - ( O O O C - - O - - C O - - O - - C O - - O - - C O ) --. The obtained homopolymer still exhibits perester groups which the authors used for initiating polymerization of a second monomer (M2) and for obtaining multiblock copolymers. The different M1/M 2 monomers blends used were Styrene/MMA, Sty/VaC and Sty/N-vinylpyrolidone. Ivanchev used the polyperesters: --(OC--(CH2h--CO--OO--CO--(CH2)6 - C 0 - 0 - 0 ) I8

In the same way, Matsushima et al. [44] prepared block copolymers from styrene, vinylacetate, vinylchloride and acrylic monomers with the following initiators: -- (CO-- (CH 2)4- CO2 - - (CH2 CH2 Oh -- C O - - (CH 2)4-- CO--OO)s.3

Finally, Heitz [45] recently synthesized polyesters which had azo groups: .CI/OH

AIBN + H O - R - O H

0to-5°C

~H3

~H3

, HO-R-O-(CO-~-N=N-~-CO2RO).CH 3

H

CH 3

3.6 Hydrogen Peroxide This peroxide is certainly the most used initiator for different reasons, its price, its solubility in water and a reaction temperature lower than 50 °C. Brosse et al. [7] have proposed the most complete review, by far. From the Fenton's reagent [46] H202/FeSO,, HaO 2 + Fe2+ ~ F e 3+ + H O -

+HO',

in an aqueous middle, a radical is generated and is able to initiate a polymerization. Furthermore, Fe a ÷ is also able to decompose H202: H202 + Fe 3+ ~ F e 2+ + H ÷ + H O O " H O O ' ~ 0 2 "q- H' These redox systems have been prepared either in aqueous medium or in an organic system (HCIOJH202 or BF3/etherate/H202). We can add an alcohol to the system and the mechanism is as follows: H202 + Fe 2 + ~ Fe 3 + + O H - + HO" HO" + H - - R - - O H ~ H20 + HO--R" HOR" + mM ~ HOR(M)n ~ HO--(M)2n--OH

84

B. Boutevin

The yield depends upon the nature of alcohol. tBuOH > nBuOH > iPrOH > EtOH However, t-120 2 is not used only with a redox system but directly as a peroxide H 2 0 2 ~ 2 HO'. Because of its particular solubility and that of the nonomers, a co-solvant has also been used (very often an alcohol). Generally this solvent induces secondary effects according to the solubility of the polymer in the alcohol:

Solubility not soluble

{

Product

Example

rich in H202 : oligomer (O)

diene

rich in M : polymer (P) 1 type of product

soluble

/ Mn = 500 (O) /

VAC

Mn 1,500-11,000(P) (Mn 500-4,000)

The different parameters which influence the reaction, the oligomer/polymer ~ratio essentially and the molecular weight Mn are the temperature, the nature of the alcohol, and the monomer and hydrogen peroxide concentrations. Moreover, the lower the monomer concentration, the lower is the molecular weight Mn. The most interesting case concerns the poly(butadiene) hydroxytelechelic (PBHT) and deals with the repartition of the hydroxy groups in the chain and the nature of the chain (1-2, 1 4 c/s and trans). As for the nature of the hydroxy groups, the PHAM's N M R study on the polymerization of butadiene in 2-butanol [44] is of special interest. Table 5.

HO-H2C \ ( HO-H2CN__ --\ or - C -

HO-HzC\=/

Mn=500

Mn=2,800

56 30 10

35 46 19

IL

CH-CHzOH unidentified

4

functionality (~/o) Conversion (~o) Barentsevich [4] confirmed and explained the 1-2 nature of the first base unit, even in the case of initiation by ( C I - - C H 2 - - O - - C O - - O ) 2 and this came from the allylic radical of butadiene. R - C H 2 - ( C H == CH .... CH2).

Telechelic Oligomers by Radical Reactions

85

If R = OH or ~CH2C1, the conjugation is decreasing and we obtain more 1-2 bonds. However, this effect disappears when the chain length increases. With reference to the functionality, it is generally greater than 2 for the polydienes. Heitz [5], who carefully studied the radical's reactivity, showed that the HO' radical is very reactive and it is able to initiate side reactions. This may explain the functionality in the range of 2.2 to 2.3 and also the presence of mono-, di- and trifunctional compounds although the difunctional ones are more numerous at a low conversion rate. Schnecko [9] confirmed these results and gave an interesting graph from Falkova's survey [48]. This shows that the HO" radical has been added onto the butadiene by making first a 1,2 base unit but the propagation is rather a 1,4 type. Thus, for low Mn, the 1,2 bond amount is greater than for high Mn. Furthermore, the HO" radical reacts with the growing-chain and leads to the trifunctional products. Moreover transfer reactions to solvents, initiators and other compounds lead to monofunctional compounds. However, functionality, greater then two, is obtained, so we observe that trifunctional compounds favoured over monofunctional ones. 100 % 80

.'= 60 tO

"6 g ~0

I.L

20

0

I

I

i

I

20

&O

60

80

% ~00

Conversion

Finally, Brosse [7] showed that the functionality depends upon Mn. It remains constant between 1,000 and 4,000 and then it increases up to 5 or 7 when Mn varies between 4,000 and 10,000 [49]. From a kinetical point of view, it is interesting to notice the transfer constants to the initiator and to the alcohols [50] at 120 °C for the different monomers: butadiene (B), isoprene (I) and vinvlacetate (VAc) listed in Table 6. The transfer constant decreases in the following series of solvent [7]: M e O H > E t O H > nPrOH > iPrOH The dienes might be copolymerized with numerous monomers such as styrene in most cases and also p-bromostyrene [51], some acrylates [52] and acrylonitrile for instance.

86

B. Boutevin

6. Various transfer constants for the polymerization of dienes and vinylaeetate initiated by thermally decomposed hydrogen peroxide

Table

Monomer

C~o n

C~¢ntanol

C.2oz

B

0.3

--

I VAc

5 x 10 -4 10-3

1.6 --

0.190 0.215 0.300

×

10 -6

Two other types of compounds must be added to this kind of functional initiators although the scientific community does not regard them as initiators. These are: S

S

II

tl

R2N-C-S-S-C-NR

z and

R(I)2C--C(I)2R

3.7 Tetraalkylthiuram Disulfides The tetraalkylthiuram disulfides were mentioned for the first time by Tobolsky et al. [53]. We can find them classified in the Polymer Handbook [54] as "disulfides (bis dialkylthiocarbanoyle)". In 1955 Tobolski [53] noticed that the thiocarbamate disulfides could be as reactive as benzoyl peroxide. However, when the initiator concentration increased, they e~hibited a retarding behavior and such as effect was more important for M M A than for styrene. In the same way, in 1955 Otsu et al. [55] showed that the compounds: R

R

\N-C-(S)

.,/ r~

-C-N /

II

II

S

S

\D,

"~

where n = 1,2 and R = O ; R ' - C H 3 ; 4 ; C2H5; R = R ' = e t h y l e n e oxide are excellent thermal initiators and photochemical sensibilizers of styrene and MMA, but they are inefficient for acrylonitrile, vinylidene chloride and vinylacetate. It can be seen that for R = R ' = M e the inhibiting or retarding effect is more important. However, Japanese researchers, because of their interest is such initiators investigated a lot in 1960 [56] and 1982 [57]. Otsu [56] prepared triblock copolymers VAc--S--VAc as follows: Et\ Et

~ S /2

//Et\ q~

Et/

"~

~

;

,]2

After precipitation of polystyrene in methanol (called TPSt) the further reaction was carried out photochemically at 30 °C in benzene. TPSt + VAc - ~ (VAc)p-(S).-(VAc)p-

Telechelic Oligomers by Radical Reactions

87

The triblock copolymer was then hydrolyzed. The oligostyrene exhibited between 170 and 430 base units for an initiator-monomer ratio ranging from 5 x 10 - 3 (yield = 37%) to 2 x t0 -2 (yield = 47%). The average VAc number in the end-blocks was 650. Moreover, the authors showed that 75 % of PVAc was in the triblock copolymer and 25 % in the PVAc homopolymeL The authors attributed such reactivity to the intermediates radicals: Et2N-~-S's + "(Sty). [ --~ T.PSt

or

Et2N-~" + 'S(Sty). S The --(Sty). and --(Sty) --S" radicals are more reactive than others because (Et2N~S)2 S does not lead to any product with VAc either by thermal or photochemical initiation. In 1982, Konishi [57] performed the same synthesis by using H 2 C = C H - - C O - NH--C(CH3)2CHzSO3H (called ASO3H ) as monomer for the block copolymerization with T--PSt which had a DPn 150. The photochemical block copolymerization (with Hg) in methylene chloride with triethylamine led to the results listed in Table 7. Table 7. Reactants and products amounts for the blockcopolymerization of T.PSt with ASO3H T.PSt

ASO3H

%

%

50.0 60.0 66.5

50.0 40.0 33.5

%

homo PS

inter-

Block 1

Block 2

34 (30)~ 41 (35)~ 35 (38)"

0 3 (48)a 9 (60)a

mediate 94 90 96

19.3 9.5 3.7

47.0 46.5 52.3

a designatesthe ASO3H% in the copolymer Such products were precursors for biological semipermeable membranes. Table 8 lists several kinetical constants of these xanthogcns. Recently, a new team investigated the use of functional thiuram [62, 63]; Clouet et al. studied the polymerization of MMA with: C2H5 \N_C_S_S_C_N -C2H: ~ ~ A

C2H 5

/ \C2H4-OH

[64]

88

B, Boutevin

and they pointed outthe efficiency of such compounds as both transfer ager/ts and initiators (Table 9).

Table 8. Transfer constants of xanthogen for MMA or styrene Monomer

T (°C)

Cr

Ref.

MMA Me\

/ Me N-C-SS-C-N Me/ ~ ~ \Me

70

O.Ol15

[53]

20

5.500 (hv)

[58]

60

0.080(hv)

[58]

/Me O-C-S-C-N

S MeN /Me N-C-S-S-C-N

Me/

~

~

Et\ /N-C-SS-C-N Et ~ ]IS

\Me

60

1.110

[591

70

0.0114

80

0.568

80 95 95 115 115 130 130

0,620 0,780 0.860 0.939 1.035 0.984 1.150

[53] [60] [61] [611 [60] [60] [611 [60] [61]

60

0.724

[59]

60

1.750

[59]

/Et \Et

/Et N-C-SS-C-N Et / ~ ~ \0

TabLe 9, Kinetical parameters of A T (°C)

CT,

106xKi~

60 70 85 95

0.230 0.265 0.350 0.455

0.53 4.41 26.00 48.50

a K~ = 2 • f. K d (constant Of decomposition of common initiators)

TelechelicOligomersby Radical Reactions

89

Furthermore, the authors noticed that the DPn increased with the monomerconversion-rate since the initiator decomposed very quickly. The products exhibited very good thermal properties; actually at 300 °C the oligomers were still stable because of the absence of double bonds obtained in traditional radical polymerization of MMA. The authors also prepared polymers which exhibited phosphonated end-groups from thiuram [65]: S

I

S

H

(CzH 50)2-p. - N - C H 2 C H z - N - I~-S- S - C - N - C H 2 C H 2 - N

II i

I

O CH 3

CH3

I

~'-(OC2Hs)2

[

CH 3

CH30

The initiators were synthesized in two steps: H - N - C H z C H z N]- H I + CI-~-(OEt)2 c~c!a, H - N - C z H a - N I[ CH 3

CH 3

O

CH 3

~-(OEt)2

CH 3 0

(B) CHCI 3

(B) + CS2 + 12 ~

thiuram

The polymerizations of MMA and styrene were also studied and the authors obtained polymers whose molecular weights were 2,000 to 40,000 by varying the initiator/monomer molar ratio. Finally, Clouet et al. [66] prepared "polymeric iniferters", precursors of multiblock copolymers. The compounds:

R

-×

R

"×

were condensed with CS2 and led to poly(phosphonamides) linked by thiuram bridges, thermically labile, used for initiating the polymerization of MMA and styrene [67].

3.8 Disubstituted Tetraphenyl Ethanes In t955, Pierson et al. [68] studied the influence of

I

I

CN CN

90

B. Boutevin

on the polymerization of styrene. After 17 h at 50 °C, the conversion rate was 4.5 ~o and the transfer constant was determined (C T = 2.8). But the low yield value showed that these compounds exhibited the same behavior as both transfer agent and inhibitor of polymerization. Mayo et al. [69] noticed that (I)3C--C~3 played the same role. According to these authors these compounds did not play any role in the emulsion polymerization of butadiene and this explained why such research had been given up for 20 years. C. Braun and Bledzki [70--72] contributed greatly to the development of these investigations. M M A and styrene were mainly studied and three initiators were used:

T?

~-C-C-~

J L

R R

where R represents CN or O ~ or OSi(Me)3 groups. The products obtained exhibited the following structure:

?

T

R

R

where4 < n < 300

Their syntheses were carried out in two steps in the temperature range 80 to 100 °C: first, the oligomers were prepared and then the molecular weight increased with an increase of the conversion rate or by decreasing the initiator concentration. With M M A [73, 74] the authors showed that the telechelic oligomers from MMA were able to be cleaved between the two last carbon atoms and this was carried out from the model molecules:

?

~H3

(b-C-CH2-C-R CN

CO2Me

(1)l ~H3 and

(I)-C--C- R

t

with R = H, CHa, C2H5

I

CN COEMe

Such a product facilitated the preparation of diblockcopolymer [71 ] in a temperature range of 60 to 100 °C and these compounds can also be used as curing agents of saturated polyesters [61]. With styrene, the oligomers cannot be cleaved whereas with the a-methylstyrene [75] such a cleavage is possible from 50 °C. These products along with the M M A or the styrene lead to diblockcopolymers and we can regard these oligomers as living polymers: in this case the monomer used in the first step has to be the m-substituted one. So far, no classical functional oligomer (diacids, diols etc...) has been prepared by such a reaction.

Telechelic Oligomers by Radical Reactions

91

4 Telomerization F o u r main methods o f telomerization can be suggested as leading to difunctionat compounds but in each case it is essential to use an initiator which is either a generator o f free radicals or a redox catalyst. The first two methods deal with the telomerization o f a non-functional m o n o m e r with a functional telogen (first method) or a telogen which can be further modified in order to exhibit the functional group (second method). The two last methods consist o f performing the monoaddition on b o t h sides o f the chain extremity o f a non-conjugated diene (third method) with a functional telogen or on a telogen with a functional monomers (four method). We are going to study each o f these methods.

4.1 Disulfides They are used the most. The first investigations were carried out by Costanza and Pierson [68, 76] on styrene with aromatic disulfides especially. These authors showed that the aliphatic disulfides are not very reactive even though the aliphatic R - - S H thiols are very good transfer agents. F o r instance, the transfer constant of B u - - S - - S - Bu is 1.54x 10 -3 at 55 °C [77] and 6.80× 10 -3 at 99 °C [78]. For the activated disulfides (Table I0): (R-O-~-CH2-S~-2, O whatever the nonomer, the corresponding values are rather low but the results obtained from the literature do not allow us to form a conclusion, they are only regarded as interesting transfer agents to use. The results from the aromatic disulfides on both styrene (Table 11) and M M A (Table 12), on which Japanese teams performed a lot o f investigations, are move interesting. We can try to interpret their results although the authors thenselves did not do that. The transfer constant seems to be slightly influenced by the nature o f the substituent in the para position, whatever its inductive effect.

Table 10. Comparison between the transfer constants of non-aromatic disulfides with various monomers Disulfide

R

Monomer T (°C)

Cx

Ref.

RO2C--(CH2)lo-- SS--(CH2)lo--CO2R R O 2 C CH 2 SS CH 2 CO2R

Et Et Et Et Et Et Et Me

Styrene VAc VAc MMA Styrene Styrene Styrene Styrene

0.005 0.0132 1.5 0.00065 0.0005 0.015 0.2 0.1

[76] [79] [80] [79] [76] [79] [78] [80]

50 60 60 60 50 60 99 99

92

B. Boutevin

On the other hand, if the substituents is in the ortho position, the more the group donates electrons, the higher the transfer constant. The Thiokol Corporation [83] used another disulfide which exhibits acid end groups :

HO2C-CH2- - ~ S -

S--~CH2-CO 2H

Finally, Okano et al. [84] have recently prepared an aromatic disulfide with isocyanate end group according to the reaction: O 2 N - @ - C I + Na2S ~ H 2 N - O - S - N a + H202) H 2 N _ O _ S _ S _ O _ N H l)

z

HCl ) O = C = N - O - S - S - O - N = C = O

2) COCI2

This disulfide has been used in photopolymerization of styrene in bulk or in the presence of T H F and the degrees of polymerization are in the range o f 20 to 130 for telogen/monomer ratio o f 0.1 to 0.01 and for m o n o m e r conversion rate o f 20-30 %. Table 11. Transfer constants to the styrene of monosubstituted aromatic disulfides [68, 76]

/CH 3 (0.22) (0.11} CH3--~)-S

(O.09)

.CH2-C02H (0.005) ~SCH2Br {1) /CH2CI (1.3)

/CH20H (0.58) HOH2C----S-O~

(0.24) H2N~ k / - ~ S (0.21) RNH/lk--"/

/NH2(3) -

(0.18) C H 3 0 - - ~ S -

(0.2z,) RO-C-HN II 0 (0.11) Et 02~ CO2Et(0.005) /~CO2H (0.01) (0.17) H02CJ-x~S (Q~)--S- (0.06)

--CH2--S--(0.02)

93

Telechelic Oligomers by Radical Reactions

Table 12. Transfer constants to the MMA of substituted phenyl disulfides ( x 104) at 50 and 60 °C [81]

Disulfides

T (°C)

(~S)z (p CH 3-~S)2 (p Br--~S)~ (p Ct--OS)2

~p o c u ~ - - . s h

50

60

38 31 46 72

85 44 98 117

44

(p NO 2-~S)2 NO2--OS)2 (EtOzC--CHz--S)2 (~_CHz--S)2

52

127 176 ---

198 508 6.5 a 62.7 b

a Ref. [79]; b Ref. [82]

In 1986, Akemi et al. [85] carried out the same synthesis and obtained triblock cotelomers as previous researchers - - the monomers used where firstly HEA/S/HEA and secondly FA/S/FA (where FA is fluoroacrylates). In the second case, medical applications (antitrombogenic compounds) were developed. Several surveys on disulfides with fluorinated monomers [86, 87] should also be mentioned, Thus, Yacubovich et al. [87] added tetrafluoroethylene OSS~ according to the following scheme:

~-S--S--~ + C2F4 +

O-S-C2F4-S-O

A2

I ~-S-C2F~-S~ 60"/, t~-S--(C2F4)2- S~ 17*I. .~

(I)--S--C2F4H

,..,,,,.~CFv.. L' ~ S j C F 2

5*•, 5 */.

~Ae20 0 - S O 2 - C 2 F 4 - S O 2 - 0

Sharp et al. [86] carried out the photochemical reaction of non-functional disulfides on different molecules: C H a - - S - - S - - C H 3 + H2C --- CF 2 -~ C H 3 - - S - - C H 2 - - C F 2 - - S C H 3 C 6 F s - - S - - S - - C 6 F 5 + H2C = CH 2 ~ C6Fs--S--C2H4--SC6F 5

4.2 Acid Disulfides The acid disulfides exhibit the structure:

O O Few studies on acid disulfides have been performed, whatever the functionality of these telogens. Tables 13 and 14 sum up their basic transfer constants to M M A and Styrene.

B. Boutevin

94 TaMe 13. Transfer constants to the MMA of substituted benzoyl disulfides at 60 °C (according to Tsuda and Otsu) [88] Disulfides

Cr ( × 104)

(qb--CO--S)z (p CH3--q~--CO--S)z (p B --dP--CO--S)2 (p CH30--~--CO--S)2 (p CN--~--CO--S)2 (p NO2--dP--CO--S)2

10.0 11.0 16.7 14.6 290.0 694.0

Table 14. Transfer constants to the styrene of substituted benzoyl disulfides Disulfides

T (°C)

CT ( × 104)

Ref.

((I) CO--S--)2

50 60 60 99 60 60 60 60 60 60

50 107 36 1,100 96 46 745 t96 3,190 6,650

[68] [89] [88] [78] [88] [88] [88] [88] [88] [88]

60

3,400

[68]

60

61,000

[59]

(CH30--~--CO--S)2 (CH3--~--CO--S)2 (Br--~--CO--S)2 (CI--~--CO--S)2 (CN--q)--CO--S)2 (NO2--q~--CO--S)2

( [~co-s-)-(O/--AN--C - S)2 k__/ S

4.3 Xanthogens Their transfer constants are very high (1 < CT < 20). These telogens have been studied since 1955 and there are several publications on this subject. First several authors planned their use as initiators for thermal o r photochemical polymerization for different monomers. Thu s, Otsu [55] c o m p a r e d the activity o f these xanthogens, sulfides, disulfides and thiuram with several monomers - - M M A , S., A . N . , VAc, VDC. The results allowed him to classify products as telogens and not as functional initiators. In the same way, these surveys showed that they are photoinitiators without having retarding or inhibiting effects as are observed for several disulfides.

Telechelic Oligomers by Radical Reactions

95

Furthermore, Pierson et al. [76] determined the transfer constants of diene disulfides and among them the Dixie:

o CH3

S

O

/

CH3

O

At 50 °C, in presence of styrene, the transfer constant is C T = 5.3. It is a very high value and such a reactant is regarded as a good transfer agent. In the same period of time, some non-functional xanthogens were studied and the corresponding transfer constants were determined (Table 15). Basically, the monomers were the styrene or the butadiene/styrene mixture. The objectives were to synthesize new elastomers and to study the curing or the vulcanization by different agents. Fokina et al. [90] studied the modification of xanthogens according to the reaction: RO-C-S-S-C-OR

II

S

LI

+ nM --* R O - C - S - ( M ) . - S - C - O R

Ir

S

S

II

S

NH3 HS_(M)n_SH CICH2CH2OH , . , HOCH2CH2S-(M).-SCH2CH2OH with M is St, Isoprene, Divinyl benzene DVB, or St/DVB and St/Butyl ( ~ S between 5 and 10%) 103 < M n

<3x103.

The products were then cured and the elastomers studied. In the same period of time, Uraneck et al. [91] studied the emulsion copolymerization of butadiene (B) and styrene (S) with Dixie, but the most interesting topic dealt with the hydrolysis of the xanthogen: RO-C-S-(B).-(S)p-S-C-

II

S

Ii

OR

S

either with H 2 N - - N H 2 or with N H a at 70 °C. The SH amount was determined by amperometric titration with NOaAg. The hydrolysis was a first-order function about the xanthogen but after two hours, the hydrolysis reached a plateau at 75 ~o, whereas with N H 3 this normally decreased if 20 times more ammoniac was required in this reaction. In a second step the authors compared the properties of the elastomers cured at various curing rates and they showed that such SBR and dithiol exhibited the same mechanical properties even if 6 times less curing agent was added in the dithiol than in the SBR. Furthermore, the authors studied the functionality and they compared these products to the counterparts obtained by ionic reaction. Therefore, in order to synthesize dithiols the authors preferred using the ionic method, but no obtain diols the radical method.

96

B. Boutevin

In 1975, Csontos [92] working for the Goodrich Company, also studied the emulsion copolymerization of a mixture composed of two monomers M 1 and M z with xanthogens and he investigated the hydrolysis of the xanthogen into the dithiol. M 1 was partially soluble in water (greater than 0.2%) e.g. various acrylates, VAc, allylic monomers, acrylonitrile and vinylchtoride. Whereas M 2 was insoluble in water (less than 0.2%) e.g. butadiene, isoprene, styrene, long chained acrylates. By using rates of about 10~o by weight of xanthogen to the overall ratio of monomers, they obtained copolymers the average molecular weights Mn of which were between 103 and 104 (the Mn were determined by the titration of either the sulfur atom of the xanthogens or the SH end-group by iodine). The copol)~aer may be dried under vacuum at 90 °C in order to avoid the coagulation. The obtaining of the dithiol can be carried out either by basic hydrolysis (KOH/ EtOH or NHR~) but such a reaction lasts a long time, or by pyrolysis under vacuum at 120 °C (the problem of metals has been brought up because of curing after drying if coagulation has been performed. In this case A12(SO4)3 is the best one). The most recent studies were developed by the De Soto Company [93, 94] in 1985 and the applications dealt with paints and coatings, for instance, the patent [84] mentions high solid resin coating, soluble liquid or low viscous products with a functionality greater or equal to 2 (as telechelic) and easy to cure. The company synthesized an original difunctional xanthogen : HO-C4H8-O-~-SS

S-~-O-C4Hs-OH S

which reacted with one or several monomers and led to telechelic polymers the Mn of which varied between 1,000 and 10,000. An interesting monomer for increasing the functionality can be the 2-hydroxy ethyl acrylate. All the monomers are quoted and of special interest are the vinylchloride, the vinylidenechloride and the acrylics. The curing reaction can be performed by a polyisocyanate and the hexamethylol melamine. The second patent [94] does not give furthe.r information about the synthesis but describes an application of these products -- UV curing of coatings for optical fibers. Telechelics diols are used as coreagents for cationic polymerization of epoxy resins. Such coatings are composed of: -- a polyepoxy which can be U.V. cured, - - a photoinitiator -- amine salt from Crivello, - - a polyalcohol which is the xanthogen they prepared. They greatly improved (10 to 40%) the softness of this varnish compared to that of a photocured one. In Table 15 we give kinetical data about the xanthogens. 4.4 The Uses of Halogenated Telogens

The halogenated compounds CmHxClrBr z enable one to obtain products which exhibit halogenated end groups (these are telechelic) although an end-group change can be usually performed. But this is not always the case as Csontos [98, 99] showed in 1973.

Telechelic Oligomers by Radical Reactions

97

Table 15. Transfer constants of xanthates Xanthate/monomer

T (°C)

CT

Ref.

Styrene R = CH(CH3h

50 99

5.30 7,50

[76] [78]

5 5 5 5 5 5 5

16.43 8.43 4.42 2.83 2.42 1.65 0.74

[95] [95] [95] [95] [95] [95] [95]

Butadiene-Styrene R = CH s Et n Pr i Pr n Bu i Bu hex R = i Pr

--5

50

1.18

[96]

9.73

[97]

Low-molecular-weight oligomers (10,000 to 20,000) with 75~o conversion rate have been synthesized photochemically from BrCCI2--CH2Br with an acrylate blend (Ethyl and butyl). The vulcanization at t 50 °C by diamines leads to elastomers (125 to 200 ~ strain). Other interesting telogens are available: CCI~, CClsBr, CBr 4, CH2C12, CH2Br 2 and C13C--CO2R. In 1974 Starks [10(3] published a very interesting review on this topic. In our laboratory, more than one hundred papers have been published concerning the telomerization on both the synthetic (monomers, telogens and catalysts listed in Table 16) and kinetical aspects. Actually, the chemical change of the halogenated groups is difficult since side reactions (especially elimination) m a y occur. A m o n g the successful cases, we mention the following series of reactions [101]: F2C = CFC1 + CC14 ~ CC13--(CF2CFC1)n--C1

A1CI3..~.ClsC__(CF2__CFC1)n 1-CF2CC13 CC14 ol~um ~ C 1 C O _ ( C F 2 C F C I ) n _ I _ C F 2 C O C 1 In the same way, aminoacids were prepared in two steps from telomers of ethylene with ClaCBr [102]: CI3C-(C2H4),-Br ~ HO2C-(CzH4)n-Br

NH3, H O 2 C _ ( C z H 4 ) n _ N H 2

We can conclude that if a m o n o m e r leads to a stable chain telomer such a method is useful, otherwise it is not interesting. Furthermore, the diversity is general and this might be a reason why the uses of aminoacids did not lead to interesting applications.

98

B. Boutevin

Table 16. Monomers, telogens and catalysts used in telomerization Monomer

Telogen

Catalyst

DPn

Ref.

CF 2 = CFC1

CC14

Redox FeCI3/benzoine

1-20

[ 103]

CF2CFCI

CCI 3Br

BzzO 2

1- 10

[ 104]

CH2=CHC1

CCt3--CO2--R

AIBN

t03 < M n < 104

[105]

CH 2 --CCI 2

CCI 4

FeC13/benzoine

1-5

[106]

CH 2 = C H C O 2 R EG, glycydile

CC13--CO2H

FeCla/benzoine CuCI 2

1-100

[107]

CH2 = C H ~-~

CC13--POC12

FeCI 3

1-3

[108; 109]

//A/

CCI 4

FeCI 3

1-I00

[I 10]

CH 2 = C H O A c

CC14

AIBN

1-20

[111 ; 112l

H2C=CHOAc

HCCI2--CO2R

AIBN

1-10

[113]

4.5 The U s e o f N o n - C o n j u g a t e d Dienes Several non-conjugated dienes can react in a double addition with functional telogen as we note in Table 17. Redox catalysts have been used. The advantage of such syntheses lies on the obtaining of a perfectly monodispersed product for rather low molecular weights and this leads to well-defined structured materials.

Table 17. Possible telomerization of non-conjugated dienes with functional tetogens Monomer

Telogen

Ref.

CH 2 = C H - - ( C H 2 ) x - - C H = CH 2

CC14 CC13CO2R

[114] [115]

[116]

X = 1,2,4;6

CH 2 = C H - - C o H 4 - - C H = C H 2

CH 2 = C(CH3)--CO2--(CH 2 - - C H 2 - O ) . - C O CH 2 = C (CH3) n=l--4 CH 2 = C H - - C H 2 - - O - - C H 2 - - C H = CH 2

2-

CC13POC12 C13CCH2CHC1CH2OCOCH 3 CCt~ CC13CO 2R CCI3POC12 CCI, CC13- CO2R CC1 a POC12 CCI 4

[ 117] [116] [ 118] [ 115] [ 117] [119] [ 115] [ 117] [114]

TelechelicOtigomersby Radical Reactions

99

4.6 The Uses of Compounds which Exhibit CC! 3 End Groups Several methods are available to synthesize products which have two CC½ groups: -- by direct telomerization of HzC=CCI z [106] or F2C=CC ½ [120] with CC14: CC14 + H2C=CC12 cu2+} C13C-(CH2CC12)n-C1 CC14 + F2C=CC12 cu2+, CC13_(CF2CCt2)n_C1

-- by chemical change as previously mentioned: CC13_(CF2CFC1) _C1

AICI3~,CCI3_(CF2CFC1)n _I_CF2CCI3

-- by addition of CCh onto non-conjugated dienes (Table 17). We studied the bistelomerization of various functional monomers with these a,coditrichloromethyl telogens and the results have been summed up in Table 18. The same remark as mentioned previously can be made about the monodispersity. However, the most important target concerns the activation of the CCl3-groups, When a --CF 2 - or a carbonyl group is located in the ~ position about them, the bistelomerization is favored and a telechelic compound may be obtianed. But for a methylene group in ~, the activation is poor and we obtain a blend of mono and difunctional compounds even with very reactive catalysts and long reaction times. Such a blend is sometimes difficult to seigarate. The use of very selective catalysts such as RuC½(PPh3) 3 does not improve the reaction yield [120]. Radical initiation is possible and, in this case, dithiols must be used. An example of such a reaction has been known for about 20 years. This led to the production by the 3 M company of a product, whose trademark is Seotchguard, for textiles. The synthesis is the following [1261: H S - (CH 2CH2CO2-(CH 2CH zO).- COCH2CH2S)p- H + H2C=CH-CO2-C2H,t-C6FI 3 H-(V H-CH2),-~S-CH2H 4CO2-(C2H40).- COC2H4S~-(CH 2- ~H)p- H CO2R F

RFO2 C

with 3 < n < t00 1 < p < 500

We carried out this reaction on siliconated chained dithiols with MMA and we obtained the triblockcopolymers [ 127]: ~H3

~H3

~H3

H - ( M M A ) v - S - C 3 H 6 - S , i - O-(Si-O)~ - O - ~ i - C 3 H r - S - ( M M A ) p - H ~)CH 3 CH3

OCH 3

100

B, Boutevin

Table 18. Bistelomerization o f several functional m o n o m e r s with ditrichloromethyl telogens Telogen

Monomer

Remark

Ref.

CC13 --(CH~CCl2) .-CC13

CH 2= CH--CH z - O A c

[ 116]

CCI3_(CF2_CFC1).

CH2 = CH--CH2--OAc

monofunctional mainly mono/difunctional blend difunctional difunctional

CFz -CC13

CH 2 = CH 2 CCI3_CH _CHC1--CH2-.CH2OAc CH2=CHC1

CH2OAc

[120][121] [ 122] [123]

Of

or

low

CCI3--CHz--CHCt CO 2 R CCI3--CO 2 R and CCls CO2--CH2--CH2--CO2CCI3

CH 2 = CH--CO~ R CH z =CH--(CH2)s--CO2Me or CH2=CH (CH2)s--CO2CH2CHzOH

yield

[ 124]

difunctional

[ 125]

or

CH 2 = CH--(CI | 2 ) 9 - - OH

More recently, we performed this method for the obtaining of macromolecular monodispersed diols with two thiols [128]: HS--CH2CH2--S--CH2CH2--SH CH2CH 2 - S H

and

HS--CH2CH2--O--CH2CH2--O--

and various alcohols HzC = C H - - ( C H 2 ) 9 - - O H H2C = CH--(CH2) 8 - C O 2 - ( C H 2 ) x - O H H2C = CH--(CHE)a-- CONH--(CH2)y-- OH with x = 2, 4, 6, 12 and y = 2,3. and we obtained a series of diols having molecular weights between 500 and 1,000. Thus, the radical initiator with thiols gives more interesting results than those obtained from the redox catalysis with ditrichloromethyled groups. Finally, an original method to obtain telechelic polydienes is also possible - - it can be associated to the telomerization of allylic alcohol with butadiene.

4.7 Synthesis of Telechelic Products by Rhodium Catalysis The catalyst is composed of a blend of Rh(NO3) 3 and an alkaline metal in presence of an allylic derivative. The authors studied the butadiene as monomer mainly [129]. Using an alkaline metal as cocatalyst comes from the necessity to neutralize the acid formed by the reaction of Rh(NO2) 3 to the alcohol. R - - C H 2 O H + RhX 3 --, H R h X 2 + R - - C H O + HX In the presence of allylic alcohol [120], the reaction is as follows:

[from 64]

TelechelicOligomersby RadicalReactions

101

2 / / \ / O H + n ~X~ HO CH 2 .O \CH/ \ C H z - ( C H 2 - C H = C H - C H 2 ) . - CH2CHzC~ 1 H CH 3\ C H / / CH "-.CH2-(CH2-CH=CH-CH2)"- CHzCH2CL//O 2

H

In is interesting to note the selectivity of this reaction since 100~ of 1,4-trans compound has been obtained. Furthermore, the functionalities are the following: fc=o= 1 and 0 < f o n ~ 1 When the temperature decreases, the functionality (OH group) is reaches 1. The molecular weights Mn are in the range of 300 to 500 and other allylic derivatives such as allyl chloride, bromide or cyanide can be used. Moreover, the authors showed that besides 1, another product which exhibited double bond was obtained: H z C = ~ - ( C H 2 - C H = C H - CHz).-CH2CH2-C~ O ~H20 H

H

The mechanism proposed is the following:

~x~/Ol-I

+

Na

(~ .~,

L H - R h (.,¢ %N~,,/

Rh{N03)3

+ NctN03

H H

The allylic complex becomes a compler in presence of butadiene:

H--

~

H-Rh/~/H

H--Rh

.~.

Rh +

0

/ HO'¢(~/v nt~¢"v

transfer

H

hybrid

B. Boutevin

102 In the same way, with allyl chloride and butadiene we can obtain [130] Ct

5 Conclusion As has been mentioned, radical initiation has greatly contributed to the search for new telechelic polymers either by the use o f functional initiators or by telomerization. In b o t h cases, besides the methods known from 1955, recent surveys have been investigated and, several applications have been found. However, such reactions require, from the synthetic point o f view, the obtaining o f new initiators and telogens and from the kinetical point o f view, very selective reactives which have a very high reactivity (great transfer constant value). These new systems open up applications such as the difunctional compounds (used in polycondensation) which exhibit new reactive groups (amine or isocyanate) o r the "pseudo living p o l y m e r s " which are able to initiate new polymerizations for obtaining triblockcopolymers. However, the results are still scattered and some errors remain in kinetics, even in text books. Furthermore, the lack o f d a t a prevents a more rational use o f the radical polymerization for the obtaining o f telechelic oligomers from the most commonly used monomers.

6 References 1. 2. 3. 4. 5. 6. 7.

Brossas J (1974) Infchimie 128:185 Athey RD Jr (1982) J. of Coatings technology 54:47 Athey RD Jr (1974) Progress. in Org. Coatings 7:289 Barentsevich YN, Ivanchev SS (1983) Polym. Sci. USSR 25:2341 Heitz W (1978) Makromol. Chem. Macromol. Symp. 10/11 : 297 Heitz W (1986) Angew. Makromol. Chem. 145-6:37 Brosse JC, Derouet D, Epaillard F, Soutif JC, Legay G, Dusek K (1987) Advances in Polym. Sci. 289 : 167 8. French DM (1969) Rubber Chem. Technol. 42:71 9. Schnecko H, Degler G, Dongowski H, Caspari R, Angerer R, Ng TS (t978) Die Angew. Makrotool. Chem. 70:9 10. Entelis SG, Advances in Polym. Sci. 1986:129 11. Romanov AK, Vyevreinov V, Entelis SG (1986) Polym. Sei. USSR, 28:t381 12. Bamford H, Tipper CF (1976) Comprehensive chemical kinetics vol 14a Free radical polymerization. Elsevier, Amsterdam 13. Berger KC (1975) Makromol. chem. 176:3575 14. Gutz W, Heitz W (1976) Makromol. Chem. 177: 3159 15. Terry JO, Futrew JH (1967) Can. J. Chem. 45:2325 16. Pinazzi CP, Brosse JC (1976) Makromol Chem. 177:2861 17. Brosse JC, Pinazzi CP, Legay G (1976) Makromol. Chem. 177:2877 18. Rice DE, Sanberg CL (1971) Polym. Prepr. Amer. Chem. Soc., 12: 396. Chem. Abst. 78:302853 19. Moad G, Rizzardo E, Solomon D, Johns S (1984) Makromol. Chem. Rapid, Comm. 5:793 20. Tobolsky AV (1958) J. Amer. Chem. Soc. 80:5927

Telechelic Oligomers by Radical Reactions

103

21. Tobolsky AV, Rogers CE, Brickman RD (1960) J. Amer. Chem. Soc, 82:1277 22. Huceste H, Baysal BM (1987) Makromol Chem. 188 : 495 23. Idage BB, Vernakar SP, Ghatge ND (1983) J. Polym. Sci. Polym. Chem. Ed. 4:307 24. Ghatge ND, Vernekar SP, Wadgaonkar PP (1983) Makromol./Chem. Rapid. Comm. 4:307 25. Konter W, Bomer B, Kohler KH, Heitz W (1981) Makromol. Chem. 182:2619 26. Guth W, Heitz W (1976) Macromol. Chem. 177:1835 27. Merck Patent GMBM; French Patent 2, 120, 809 (20/12/71) 28. Bickel AF, Waters WA (1950) Rec. Trav. Chim., (The Netherlands) 69:1490 29. Razuvaez GA (1965) Dokl. Akad. Nauk. USSR. 161 : 614 (Chem. Abst. 63:1869 h) 30. Thiokol. Corp. Brit. Patent. 957 652 17/09/62 31. Glover C, Houghton M (1904) J. Amer. Chem. Soc. 32:431 32. Pronin BN, Barentsevich YEN (1977) Polym. Sci USSR 19 (7): 1950 33. Haas HC, Schuler NW, Kolesinki HS (1967) J. Polym. Sci., A1 : 2964 34. Barentsevich YN, (1982) Kanchuk I Rezina 5:20 35. Anderson WS (t968) Polymer. Prepr. nts. 9:773 36. Ivanchev SS (1978) Polym. Sci. USSR 20:2157 37. Simionescu CrI, Comanita E, Pastra Vanu M, Dumitriu S (1986) Prog. Polym. Sci. 12 (1): 1 38. Kerber R, Nuyken O, Durn M (1978) Makromol. Chem. 179 (7): 1803 39. Ivanchev SS, Artamunova TM, Belov IB, Nasonova TP, Kuznetsov VI (1979) Vysokomol. Soed. B25 : 426 40. Galibei VI, Ivanchev SS (1970) Zh Organ. Khim. 6:1585 41. Galibei VI, Ivanchev SS (1974) Zh Organ. Khim. 44:1630 42. Sheppard CS, Bafford RA, Macleay RE (1970) Fr. Pat. 1905915., Chem. Abst. 72:13201 43. Woodwards AE, Smets G (1955) J. of Polym. Sci. XVII: 51 44. Matsushima M, Komai T, Nakayama M, ger. often 2,948,152 (12/05/80) Chem. Abst. 93: 115 246X 45. Heitz W, Latterkamp M, Oppenheimer CH, Anand PS (1983)ACS. Symposium. Series. 212: 337 46. Fenton HJH (1984) J. Chem. Soc. 65:899 47. Fages G, Pham QT (1979) Makromol. Chem. 180:2435 48. Falkova OS, VahievVI, Shlyakhter RA, Avanesova KM, Korolkova MD, Spirin YL (1975) Sint. Khi. Polim. 15:16 (Chem. Abst. 83: 98031) 49. Dusek K (1986) Adv. Polym. Sci 78/79: XXX 50. Brosse JC (1978) Makromol. Chem. 179:79 51. Nae HN, Vofsi D (1985) J. of Applied. Polym. Sci. 30:1893 52. Reed SF (1977)J. Potym. Sci. (Potym. Chem. Ed) 15:3079 53. Ferington TE, Tobolsky AV (1955) J. Amer. Chem. Soc, 77:4510 54. Brandup J, Immergut EH (1975) Polymer handbook, 2"a Edition; Wiley, N.Y.) 55. Otsu T, Nayatani K, Muto I, Imai T (1958) J. Chem. Soc. Japan, 62:142 56. Imoto M, Otsu T, Yonezawa J (1960) Makromol. Chem. 36:93 57. Konishi H, Shinogawa Y, Azuma A, Okano T, Kiji J (1982) Makromol. Chem. 183 (12): 2941 58. Okawara M, Nakai T, Imoto E, Kogio Kagaku Masshi 69: 973 59. Otsu T, Nayatani K (1955) Makromol. Chem. 27:149 60. Beniska J, Staudner E (1967) J. Polym. Sci C16:1301 61. Staudner E, Beniska J, Europ. Polym. J. Suppl. 1969:537 62. Clouet G, Nair CP, French Patent No. 8, 805, 178 (19/04/88) (Norsolor S.A.) 63. Clouet G, Nair CPR, French Patent No. 8, 805,179 (19/04/88) (Norsolor S.A.) 64. Nair CPR, Clouet G, Chaumont P (1988) J. Poly. Sci. Polym. Chem. Ed (to be published) 65. Nair CPR, Clouet G (1988) Makromol. Chem. Rapid Commun. (to be published) 66. Nair CPR, Clouet G, Brossas J (1988) J. Macromol. Sci. Chem. ; A 25 (9): 1089 67. Nair CPR, Clouet G (1988) (to be published) 68. Constanza AJ, Coleman RJ, Pierson RM, Marvec CS, King C (1955) J. of Polym. Sci. 17:319 69. Mayo FR, Gregg RA (1948) J. Amer. Chem. Soc. 70:1284 70. Bledzki A (1983) Kunststoffe 73 (3): 156 71. Braun D (1986) Makromol. Chem. (Makromol. Symp). 4:41 72. Bledzki A, Braun D (1986) Makromol. Chem. 187:2599 73. Bledzki A, Braun D, Tretner lrI (1985) Makromol. Chem. 186:2491

t04 74. 75. 76. 77. 78. 79. 80. 81. 82. 83. 84. 85. 86. 87. 88. 89. 90. 91. 92. 93. 94. 95. 96. 97. 98. 99. 100. 101. 102. 103. 104. 105. 106. 107. 108. 109. 1 I0. 111. 112. 113. 1t4. 115. 116. 117. 118. 119. 120. 12t. 122. 123. 124. 125. 126. 127. 128.

B. Boutevin Bledzki A, Pol. Patent 129 973 (28/02/85) Chem. Abst 107: 78463a Btedzki A, Braun D (1986) Polymer Bulletin t6 (1): 19 Pierson RM, Costanza A J, Weinstein AH (1955) J. of Polym. Sci. XVII: 221 Miller LA, Stannett V (1969) J. Polym. Sci. A1 7:3159 Dinaburg VA, Vansheidt AA (1954) Zh. Obshch. Khim. 24:840 Clarke JT, Howard RO, Stockmayer WH (1961) Makromol. Chem., 44/46:427 Stockmayer WH, Howard RO, Clark JT (1953) J. Amer. Chem. Soc. 75:1756 Otsu T, Kinoshita Y, Imoto M (1964) MakromoI. Chem. 73:225 Tsuda K, Kobayashi S, Otsu T (1965) Bull. Chem. Soc. Japan, 38:1517 Thiokol Corp (1964) Brit. P. 945,713 Okano T, Katayama M, Shinohala I (I978) J. of Applied Polym. Sci. 22:369 Akemi H, Aoyagi T, Shinohara I (1986) Makromol. Chem. 187:1627 Sharp DWA, Miguel HT (1978) Israel Journal of Chem. 17:144 Yacubovich A, Zaitseva EL, Rozantseva TV, Chicherina II (1970) Zh. Org. Chem. 6 (4): 886 (Chem Abt 73 : 25 893p) Tsuda K, Otsu T (1966) Bull. Chem. Soc. Japan. 39:2206 Pryor WA, Pickering TL (t962) J. Amer. Chem. Soc. 84:2705 Fokina TA, Apukhtina NP, Skii ALK, Nelson KN, Solodovnikova GS (1966) Vysokomol. Soyed. 8 (12) 2197 Uraneck CA, Hsieh HL, Sonnefeld RJ (1969) J. of Applied Polym. Sci. 13:149 Csontos AA U.S. Patent. No 3, 862, 975 (28/01/75) Zimmerman JM, Krajewski JJ, Noren GK Europ. Patent. Appt. No 0, t61,502 (13/04/85) Bishop TE, Pasternack G, Zimmerman JM, Europ. Patent. Appl. No 0, 162, 304 (20/04/85) Vaclaveck V (1967) J. Appl. Polym. Sci. 11 : 1881 Kamenar S (1960) Chem. Zvesti 14: 525; (1961) Chem. 133:493 Vaclaveck V (1960) Chem. Prumysl 10:103 Csontos AA, U.S. Patent 3, 730, 862 (01/05/73) Csontos AA U.S. Patent 3, 775, 276 (27/05/73) Starks CM (I974) Free radicals telomerization. Academic, New York Boutevin B, Pietrasanta Y (1975) Europ. Polym. J. 12:225 Joyce RM, Hanford WE, Harmon J (t948) J. Amer. Chem. Soc. 70:2529 Boutevin B, Pietrasanta (t973) Tetrahedron Letters 12:887 Boutevin B, Cals J, Pietrasanta Y (1975) European Polym. J., 12:225 Boutevin B, Pietrasanta Y, Taha M (1982) t83:2977 Belbachir M, Boutevin B, Pietrasanta Y, Rigal G (1984) Makromol. Chem. 185:1583 Boutevin B, Maliszewicz, Pietrasanta Y (1982) Makromol Chem., 183:2333 Corallo M (1977) Ph D thesis, Montpellier Rosin M, Assher M (1975) J. Org. Chem. 40:3298 Anthoine JC, Boutevin B, Vernet JL (1978) Tetrahedron letters 23:2003 Asahara T, Makishima T (1966) Kogyo Kagaku Zasshi 69: 2173 (Chem. Abst. 66: 85207) Sideris A (1978) Ph D thesis, Montpellier Bertrais H, Boutevin B, Maliszewicz M, Vernet JL (1982) Europ. Polym. J. 18:791 Coratlo M, Pietrasanta Y (1976) Tetrahedron 32:2295 Boutevin B, Dongala EB and Pietrasanta Y (1977) Europ. Polym. J., 13 : 939 Ameduri B (1988) Ph D thesis, Montpellier Corallo M, Pietrasanta Y (1977) Phosphorous and Sulfur 3:359 Corallo M, Pietrasanta Y (1976) C.R. Acad Sci (C) 283:187 Corallo M, Pietrasanta Y (1976) Tetrahedron Letters 26:2251 Ameduri B, Boutevin B, Lecrom C, Pietrasanta Y (I988) Makromol Chem. (to be published) Battais A, Boutevin B, Hugon JP, Pietrasanta Y (1986) J. of Fluorine Chem. 16:397 Boutevin B, Pietrasanta Y (ATOCHEM) French Patent No 8, 801,882 (17/02/87) Boutevin B, Dongata EB, Pietrasanta Y (t977) European Polym. J. 13:929 Boutevin B, Dongala EB, Pietrasanta Y (1977) European Polym J. t3:935 Battais A, Boutevin B, Pietrasanta Y, el Sakraf (1982) Makromol. Chem. 183:2359 Minesota Mining and Manif Fr Patent No 1562070 (24/01/68) Pietrasanta Y, Fleury E, Boutevin B, Sarraf L (1986) Polym. Bul. 15:107 Boutevin B, El Idrissi A, Parisi JP (1988) Makromol Chem., (to be published)

Telechelic Oligomers by Radical Reactions 129. Heitz W, Arlt K, Mehnert W (1976) Makromol Chem. 177 (5): 1625 130. Arlt K, Heitz W (1979) Makromol. Chem. 12:41

Editor: H-J Cantow Received June 29, 1989

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Phagocytosis of Polymer Microspheres by Macrophages Yasuhiko T a b a t a and Yoshito Ikada Research Center for Medical Polymers and Biomaterials, K y o t o University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606, Japan

This article reviews the phagocytosis of polymer microspheres by macrophages with respect to the size and the surface characteristics of the microspheres. Since few investigations have been carried out using well-characterized polymer microspheres, the authors have emphasized own experimental results. The findings provide useful information on the development of polymer microspheres as carriers for drug delivery systems.

1 Abbreviations . . . . . . . . . . . . . . . . . . . . . . . . . . . .

108

2 introduction

110

3

Polymer Mierospheres Used in Phagocytosis Studies . . . . . . . . . . . 3.1

111 111 113 116 116 117

Phagocytosis of Polymer Microspheres In Vitro . . . . . . . . . . . . .

118 118 122 122 123 123 127 131

4. t 4.2

4.3

Nondegradable Polymer Microspheres . . . . 3.1.1 . Polystyrene Microspheres . . . . . . . 3.1.2 Other Microspheres . . . . . . . . . Biodegradable Polymer Microspheres . . . . 3.2.1 Synthetic Polymer Microspheres . . . . 3.2.2 Protein Microspheres . . . . . . . .

. . . . . .

. . . . . .

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. . . . . .

. . . . . .

. . . . . .

. . . . . .

111 . . . . . .

3.2

4

. . . . . . . . . . . . . . . . . . . . . . . . . . . .

Biochemistry of Phagocytosis . . . . . . . . . . . . . . . . . Factors Regulating Phagocytosis of Polymer Microspheres . . . . . 4.2.1 Microsphere Size . . . . . . . . . . . . . . . . . . . 4.2.2 Surface Charge . . . . . . . . . . . . . . . . . . . . 4.2.3 Surface Hydrophobicity . . . . . . . . . . . . . . . . 4.2.4 Proteins and Other Additives . , . . . . . . . . . . . . Degradation of Polymer Microspheres in the Cell . . . . . . . .

. . . . . .

5

Phagocytosis of Polymer Mierospheres In Vivo

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6

Concluding Remarks . . . . . . . . . . . . . . . . . . . . . . . .

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7

References

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1 Abbreviations Polymers and Proteins poly(vinyl alcohol) PVA PE polyethylene polypropylene PP polytetrafluoroethylene PTFE PET poly(ethylene terephthalate) poly(methyt methacrylate) PMMA poly(N-hydroxyethyl-L-glutamine) PHEG polyacrylamide PAAm carboxymethyl cellulose CMC poly(vinyl pyrrolidone) PVP poly(L-lactic acid) PLLA poly(D,L-tactic acid) PDLLA poly(glycolic acid) PGA copolymer of L-lactic acid and glycolic acid PGLA bovine serum albumin BSA bovine immunoglobulin G IgG human plasma fibronectin FN Microspheres Cell-OH cellulose Cell-CM cellulose having the carboxymethyl group Cell-SE cellulose having the sulfoethyl group CelI-DEAE cellulose having the diethylaminoethyl group Cell-DEAE(Me) .cellulose having the methyl quanternary salt of DEAE CelI-NH2 cellulose having the primary amino group Cell-C a cellulose grafted with methyl chain Cell-C2 cellulose grafted with ethyl chain Cell-C3 cellulose grafted with n-propyl chain Ceil-C4 cellulose grafted with n-butyl chain Cell-C6 cellulose grafted with n-hexyl chain cellulose grafted with n-octyl chain Cell-C8 cellulose grafted with n-decyl chain Celt-Clo cellulose grafted with n-dodecyl chain Cell-Clz cellulose grafted with n-hexadecyl chain Cell-C16 Cell-C18. cellulose grafted with n-octadecyl chain Cell-qb cellulose grafted with phenyl chain Cell-O cellulose grafted with cyclohexyl chain CelI-g-BSA cellulose grafted with BSA Cell-g-IgG cellulose grafted with IgG Cell-g-FN cellulose grafted with FN Cell-g-Tuft. cellulose grafted with tuftsin Cell-g-Gel. cellulose grafted with gelatin

Phagocytosisof PolymerMicrospheresby Macrophages Miscellaneous phosphate-buffered saline solution (pH 7.4) PBS PBS(+) PBS-containing Ca 2+ and Mg 2+ ions cyanogen bromide CNBr fetal calf serum FCS mononuclear phagocyte system MPS M~ macrophage scanning electron microscopy SEM transmission electron microscopy TEM

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2 Introduction When a foreign substance comes in contact with the human body, the system initiates its host defense mechanisms involving what may be called the inflammatory response. For instance, the presence of foreign materials causes acute inflammatory changes, evokes an immune reaction, or is associated with infiltrate of cells predominantly of the mononuclear phagocyte after an acute inflammatory reaction. It is the macrophage that is the most important cell in the mononuclear phagocyte system (MPS) which plays a major role in all these kinds of inflammation. Mononuclear phagocytes are all derived from bone marrow precursors, which circulate first as monocytes before entering tissues under physiological or inflammatory conditions, where they mature into macrophages [1]. Inflammatory giant cells, commonly seen in areas of chronic inflammation, are also derived from the macrophage following appropriate environmental stimuli. Functionally, macrophages are a rather diverse group of cells, operating at many levels in their response to invading foreign materials. Moreover, macrophages are important ill the development and regulation of the immune response, together with lymphocytes, since macrophages can behave as accessory cells to facilitate the progression of immune functions and as suppressor cells, thereby limiting the extent of host responses to a particular stimulus. In addition, macrophages play a role in the host resistance against attack by parasites, tumors, and a wide variety of microorganisms. During the maturation of these host responses, macrophages respond to mediators released by the other leukocytes or they themselves release the soluble mediators which have primary or secondary effects on the development of host response patterns. Polymer materials have been widely used in medicine as artificial organs, surgical devices, and to assist drug delivery, since most of them are nontoxic, available with a wide variety of properties, and can be readily fabricated into many forms: microspheres, fibers, textiles, films, tubes, and molded products. In addition, their surface can be modified physically, chemically, and biochemicalty, in contrast with metals and ceramics. Surface properties have significant influences on the development of host response patterns. Since the inflammatory responses on polymer materials in the body are inevitable events, it is indispensable to investigate interactions between the polymer materials and the living system in order to develop biocompatible polymers which are actually applicable for clinical medicines. As described above, the macrophage is the most important cells playing a central role in the host defense mechanisms. The cell ingests the foreign material if it is small enough to be internalized into the phagocytic cell or differentiates into a multinucleate foreign-body giant cell by its self-fusion if the foreign material is much larger in size than itself. Roughly speaking, biomedical polymers can be divided into two categories. One is the bioinert polymer which should not be recognized as foreign by the defense system. The other is the bioactive polymer which should elicit a reaction. This classification system is best illustrated using the example of a polymer applied to drug delivery systems. Most types of microspheres tend to be rapidly cleared from body fluids by the cells of the mononuclear phagocyte system (MPS). This has an important consequence, because microspheres can easily be targeted to liver and, to a lesser extent, to spleen and bone marrow. This is advantageous in imaging these organs and in trying to achieve a slow release of carrier-entrapped drugs within these organs.

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However, if localization of microspheres in other sites is required, their normal rapid MPS-mediated clearance must be prevented. As macrophages play an important role in MPS-mediated clearance of microspheres in this way, the investigation on interactions between the microspheres and the macrophage is unavoidable for a development research of the polymer carriers to be applicable to the drug delivery systems. If a drug becomes effective only when internalized into phagocytic cells, the drugmicrosphere composite must have a size susceptible to phagocytosis and a surface structure which is readily recognized by the cells as a target to ingest. On the contrary, if phagocytosis of the drug must be avoided, the microspheres should have a surface to which the defense system is quite indifferent. This article describes macrophage phagocytosis of polymer microspheres for the purpose of a deeper understanding of the polymer interaction with phagocytic cells. The provided information should contribute to the development of polymeric biomaterials, especially of polymer carriers applicable for drug delivery systems.

3 Polymer Microspheres Used in Phagocytosis Studies It has been demonstrated that the size and the surface properties of the particles play an important role in phagocytosis [2-6]. However, the particles employed are mostly fixed to commercial latexes, bacteria, pollen, and carbon microspheres. Therefore, it is extremely difficult to study the effects of the size and the particle surface on phagocytosis. To understand the detailed phagocytosis behavior of macrophages (Mqb), the use of well-characterized microspheres is highly desirable. In this connection, synthetic polymer microspheres are the most suited for this purpose, not only because their size is widely controlled with ease, but also because they are amenable to the surface modifications through which we can prepare microspheres with different surface natures starting from the same material. Moreover, biodegradable microspheres can be prepared by selecting appropriate polymer materials.

3.1 NondegradablePolymerMicrospheres 3.1.1 Polystyrene Microspheres The most widely used particles in cell biology are polystyrene microspheres, generally called latex. They have the advantage of uniform size, nontoxicity, high stability, and commercial availability in various forms. For special purposes, monodispersed latex particles can be prepared in the laboratory by using emulsion polymerization with or without surfactants [7-9]. Single-step polymerization yields particles smaller than 5.2 ~tm [10], while two-step or seed polymerization gives larger grains [11-13]. Polymer microspheres with monodispersed distribution in size are much perferable for phagocytosis assays, because the size dominantly governs phagocytosis of the microspheres by Mdp. In addition, the microspheres should be prepared without any surfactants to exclude the influence of the soap molecules adsorbed onto the surface. on phagocytosis of the microspheres. We have synthesized monodispersed polystyrene microspheres by soap-free emulsion polymerization of styrene at 70 °C for 30 hr using potassium persulfate as a initiator [14]. The widely different diameters of the

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microspheres were obtained by changing the monomer and initiator concentrations in the microsphere synthesis. However, it was difficult to prepare monodispersed microspheres with a diameter larger than 2 lam by this method. Much bigger microspheres can be obtained by the use of seeded-growth procedure [9, 11-13]. However, in many seeded-growth syntheses, new nucleation frequently occurs leading to a new set of particles and thus to a bimodal, or even broader, distribution [15] in addition to the growth of the seed particles. Other microspheres than polystyrene with a marked distribution in size are also available for the study of phagocytosis; among them are microspheres from poly(methyl methacrylate) (PMMA), poly(vinyl toluence), poly(vinyl acetate), and polyacrolein, but these are little used in phagocytosis research. Monodispersed polyacrolein microspheres with a large diameter [16] were used to prepare microspheres with a similar surface to polystyrene. When aldehyd~ groups of the microspheres are reacted with aniline, we can introduce the phenyl groups into the microspheres through Schiff base formation. Introduction of the phenyl groups onto the surface of polyacrolein microspheres can be confirmed by measuring the zeta potential of phenylated

Fig. 1. SEM photographs of polystyrene (Pst) and phenylated polyacrolein (PPA) microspheres of different sizes; (1) Pst 0.46 lam, (2) PPA 0.80 ~tm,(3) Pst 0.91 ~tm,(4) Pst, 1.73 gm, (5) PPA 2.30 lain, and (6) PPA 4.60 I~m

Phagocytosisof PolymerMicrospheresby Macrophages

113

microspheres, because it should have an almost same surface as that of polystyrene microspheres. Any morphological change does not take place during the phenylation reaction. SEM photographs of the phenylated polyacrolein microspheres of different sizes are shown in Fig. 1, together with those of polystyrene microspheres. As can be seen, both of the microspheres are almost monodispersed in size, regardless of their diameters. 3.1.2 Other Microspheres Phagocytosis of microspheres by Mqb is greatly influenced by the physicochemical properties of the microsphere surface, especially by the surface charge and the hydro-

Carbodiimide

Method

K

~

R"

f

I

N

II

COOH

~_ ( ~ _ !

c

II

0 !H PROTEIN-NH~ -

N

~

0 II C-NH-PROTEIN

CNBr A c t i v a t i o n OH

+

0 RqNH-~-NH_R~"

Method

CNBr =_~O-C~N

OH

....~

O\

C=NH

_J-OH

PROTEIN......... -NH2 -- ~ 0 ~ Glutaraldehyde

-II ..... NH

0/

C=N-PROTEINpH 8-9

~

~O-CONH-PROTEIN ~._.~--OH

Method

~NH20HC-(CH2)3-CH, ~-N=CH-(CH2)3-CHO PROTEIN-NH2 _

~

--N=CH- (CH~) 3-CH=N-PROTEI N

Fig. 2. Various coupling methods of proteins to polymer microspheres having surface functional groups

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Y. Tabata and Y. Ikada

phobicity. Until now, most of the research on phagocytosis has been carried out using polystyrene latex beads [17-19]. It is, however, very difficult to modify the surface of this material. Such modifications would provide microspheres having a different surface nature but the same microsphere size. The extent of microsphere phagocytosis is supposed to depend on the surface properties if the size is kept constant. Various monodispersed polymer microspheres having surface functional groups are prepared [20-23] and the nature and density of the functional groups can be changed by varying the initiator in emulsion polymerization, by copolymerizing with ionic monomers or by subsequent chemical transformation. Some microspheres have surface functional groups, such as carboxyl, hydroxyl, or amino groups, available to surface modification of microspheres. Among many coupling reactions of proteins to functional microspheres, the common methods are shown in Fig. 2. Marumoto et at. [22] have reported the coupling reaction of immunoglobulin G (IgG) to polymer microspheres having carboxyl groups by using both CNBr activation and carbodiimide methods (Fig. 3). These monodispersed microspheres have been utilized extensively in therapeutic and diagnostic applications [24], but few investigations have been reported on their application to phagocytosis study.

+HOOC-prot ein cT~--CONH(CH2)7NH2 ~ C O N H ( C H 2 ) 7 N H C O - p r o t e i n 'oH

oH

.~7--_COOH O/H~O~ +H2N-protein ~--CONH(CH2)sCOOH ~---CONH(CHz)sCONH-protein OH OH H O O C _ ~ OH "OH

+CNBr

+H2N-protein __

HOOC---O:C=NH NH

II HOOC--O--O--C--NH--protein

Fig. 3. Coupling reaction of proteins to functional polymer microspheres

Cellulose is very useful as the starting material of microspheres for phagocytosis study, because this hydrophilic but water-insoluble polymer can be chemically modified with ease. Cellulose microspheres are generally regenerated by the alkaline saponification of the cellulose triacetate microspheres which can be prepared by the solvent evaporation method [25] from the O/W emulsion of methylene chloride of cellulose triacetate. The size of the cellulose microspheres can be changed by the input power of sonication at emulsification. For instance, we can obtain cellulose microspheres with an average diameter of 1.5 gin, which is a size very susceptible to Mqb phagocytosis as will be described later. The resulting cellulose microspheres can be crosslinked with epichlorohydrin [26]. The chemical modification of the crosslinked

Phagocytosisof PolymerMicrospheresby Macrophages

115

cellulose microspheres is carried out by etherification of alkali-cellulose [25-28]. Carboxymethyl cellulose (Cell-CM) and sulfoethyl cellulose (Cell-SE) microspheres with negative surfaces can also be prepared from the cellulose microspheres. Diethylaminoethyl cellulose (CelI-DEAE) and its quanternary ammonium salt, CeI1-DEAE(Me) microspheres with positive surfaces, as well as benzyl cellulose microspheres with phenyl groups are also obtained by surface modification of cellulose microspheres. Primary amino groups (Cell-NHz) can be introduced to the cellulose microspheres using the conventional CNBr activation method [29]. The microspheres mentioned above are all spherical and no change of the diameter and aggregation of the microspheres takes place during the reaction of surface modification. The surface charge of every microsphere can be determined by electrophoresis. For instance, the zeta potentials of our cellulose triacetate, Cell-OH, crosslinked Cell-OH, Cell-CM, Cell-SE, CeI1-NH2, CelI-DEAE, Cell-DEAE(Me), and benzyl cellulose microspheres were --19.9, --2.7, --2.7, --17.1, --20.9, +4.6, + 14.2, + 15.1, and --65.2 mV, respectively. This result indicates that anionic and cationic microspheres with the same average diameter but different surface charges can be prepared by this method. The surface hydrophobicity of microspheres is one of the main factors regulating phagocytosis of microspheres by Md~. Microspheres having different hydrophobicities can be prepared by conversion of the hydrophilic surface of cellulose microspheres into a hydrophobic one by allowing alkyl amines of different carbon numbers or aromatic and cycloaliphatic amines to link to the cellulose microspheres using the CNBr activation method [30], which is widely used in Sepharose gel preparation for

Fig. 4. SEM photographs of modifiedcellulosicmicrospheres; (1) Cell-OH, (2) CelI-C6, (3) Cell-Cl2, (4) Cell-Cts, (5) Cell-qb,and (6) Cell-O microspheres

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Y. Tabata and Y. Ikada

hydrophobic chromatography [31-33]. A similar reaction of the surface modification is applicable to a sizable regenerated cellulose film which may be used as a reference material to estimate the surface reaction much easier than the tiny cellulose microspheres. The contact angles of the film surfaces increase with reaction time and become higher as the carbon number of aliphatic amines increases. Moreover, the modified cellulose microspheres have almost the same zeta potentials as the modified cellulose films, clearly indicating that the surfaces of microspheres are chemically covered with the hydrocarbon chains, similar to the films. SEM observation demonstrated that the surface modification produces cellulose microspheres with a graded water wettabilities of the surface but the same size distrubition without any change in microsphere size during the reaction, as shown in Fig. 4. Coupling reactions of various proteins to the cellulose microspheres can be conducted by the CNBr activation method [29]. The proteins employed are bovine serum albumin (BSA), bovine immunoglobulin G(IgG), gelatin, tuftsin, and human serum fibronection (FN).

3.2 BiodegradablePolymer Microspheres Recently, much attention has been paid to polymer carriers for the sustained release of various drugs and targeting of therapeutic or diagnostic agents to their site of action. However, when administered into the body, nondegradable polymer microspheres such as polystyrene and cellulosic microspheres, undergo neither digestion nor metabolization in vivo, resulting in a lasting influence on the living environment. Consequently, employment of biodegradable microspheres is preferable as carriers for drug delivery systems in order to avoid accumulation of foreign materials in the body. 3.2.1 Synthetic Polymer Microspheres Poly(L-lactic acid) (PLLA), poly(D, L-lactic acid) (PDLLA), poly(glycotic acid) (PGA), and their copolymers (PGLA) are synthetic biodegradable polymers. Microsphere preparations have been used as carrier materials for the controlled release of a wide variety of drugs [34-40]. Ali of these polylactides are synthesized by polycondensation of the respective monomer acid or by ring-opening polymerization of the respective lactide. The weight-average molecular weight of polymers can be controlled from 1,000 to 10,000 by changing the extent of reduced pressure in potycondensation. The content of L-lactic acid in PGLA copolymers is almost the same as that in the monomer feed for polymerization [41]. Polymers with higher molecular weights are obtainable by ring-opening polymerization of lactide and/or glycolide which are produced by depolymerization of the corresponding polymers. PLLA and PGLA microspheres are generally prepared by the solvent evaporation method [42]. The size of the microspheres can be regulated by changing the input power of sonication in emulsification (Fig. 5). The degradation rate of the resulting microspheres, and thereby the release rate of drugs contained in the microspheres, can be controlled over a wide range by altering the molecular weight and the monomer composition of polymers constituting microspheres. Another kind of synthetic biodegradable microspheres used for Mqb phagocytosis are polyalkylcyanoacrylate nanoparticles with a diameter smaller than 0.3 gin. They

Phagocytosis of Polymer Microspheresby Macrophages

1t 7

are prepared by adding the alkylcyanoacrylate monomers to an aqueous solution with or without surfactants at various pH values ranging from 2 to 4 under vigorous stirring [43]. The degradation rate of the microspheres is dependent upon the length of alkyl chains of alkylcyanoacrylate monomers used and increases with the increasing alkyl chain length.

Fig. 5. SEM photographs of PLLA microspheres with different sizes. The diameter is smaller than 2 ~tm (1), from 2 to 5 ~tm (2), and larger than 5 ~tm (3), respectively

3.2.2 Protein Microscpheres The protein which is most widely used as a microsphere material is serum albumin from bovine, human, or other appropriate species. There are two basic methods for the production of albumin microspheres. One is either thermal denaturation at an elevated temperature from 95 °C to 170 °C or chemical crosslinking in vegetable oil or organic solvent emulsions [44]. The latter method which is claimed to produce "hydrophilic" microspheres [45], depends on chemical crosslinking in a water-in-organic solvent emulsion using concentrated polymer solutions as the dispersing phase. The other is simple one-step preparation either involving thermal denaturation of protein aerosol in gas medium [46] or an aerosol step followed by denaturation in oil [47]. The size of albumin microspheres prepared by these methods ranges from 0.2 to 100 tam in diameter. Gelatin has been commonly utilized for microencapsulation, such as complex coacervation [48], simple coacervation [49], emulsification [50], and its modified emulsification [51-53]. Since the heat denaturation method described above cannot be applied for the microsphere preparation of gelatin (denatured collagen), the microsphere requires stabilization by chemical crosslinking. Glutaraldehyde is one of the best known crosslinking reagents of proteins, and numerous investigators have reported the crosslinking of collagen with glutaraldehyde [54-56]. Crosslinking of gelatin microspheres is carried out by an addition of glutaratdehyde in the organic phase after generating a water-in-organic solution emulsion to avoid aggregation in the microsphere preparation [57]. According to this method, the shape of microspheres is invariably spherical (Fig. 6) and the size can be widely changed by selecting the appropriate input power of sonication in emulsification. In addition, the extent of gelatin crosslinking can be controlled by changing the amount of glutaraldehyde

118

Y. Tabata and Y. tkada

Fig. 6. A SEM photograph of gelatin microspheres crosslinked with glutaraldehvde

"~ 100

-7.

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Fig. 7. In vitro degradation profiles of gelatin microspheres crosslinked with glutaraldehyde in concentrations of 1.33 (1), 0.71 (2), 0.28 (3), 0.14 (4), 0.05 (5), and 0.03 mg/mg gelatin (6). (open mark, in PBS ( +)-containing collagenase; solid mark. in PBS)

Time ( d o y )

added, resulting in the satisfactory regulation o f microspbere degradation as shown in Fig. 7.

4 Phagocytosis of Polymer Microspheres In Vitro 4.1 Biochemistry of Phagocytosis The ingestion o f foreign materials by cells was first clearly described by Metchnik o f f [59] though it had been mentioned by several earlier workers. The term o f phago-

Phagocytosisof PolymerMicrospheresby Macrophages

119

cytosis initially meant the ingestion of solid foreign materials by cells. More recently it has been realized that there a number of ways in which cells may take in materials. As long ago as 1931, Lewis showed that M~ in tissue culture would take in microscopically visible droplets prepared from the culture fluid. This is so-called pinocytosis. Not tong after the introduction of the electron microscope it became apparent that ingestion is also seen for tiny vesicles of 0.1 ~tm or less in a diameter. This has been given several names of which perhaps the best is micropinocytosis. The general aspect on uptake of substances by cells has been reviewed by Jacques [59]. According to that review, Mdp are quantitatively superior in endocytic capacity to other types of cells in the body, and it is an assigned task of Md~ to ingest a wide variety of substances which have invaded into the living system. Endocytosis is the process of internalization of extracellular materials within an invagination of the plasmalemma through various pathways illustrated in Fig. 8. The endocytic activity has always been divided into two categories: phagocytosis, or eating, and pinocytosis, or drinking. The term phagocytosis is used to describe the internalization of large particles, such as those visible by light microscopy, mostly some viruses and bacteria. Uptake occurs by close apposition of a segment of plasma membrane to the particle's surface, exclusing most, if not all, of the surrounding fluid. The term pinocytosis is used to describe the vesicular uptake of everything else, including insoluble particles (lipoproteins, ferritin, colloids, immune complex), soluble macromolecules (enzymes, hormones, antibodies, toxins), fluids, and lowmolecular-weight solutes. It is likely that these materials are all interiorized in vesicles with electron-lucent contents, and it is assumed that extracellular fluids are included in the contents. Although these are not indentical in cellular processes, they have much

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Fig. 8. Schematicdiagramillustratingvariouspathwaysof endocytosis;(1) phagocytosis,(2) receptormediated phagocytosis,(3) pinoeytosis,and (4) receptor-mediatedpinocytosis

120

Y. Tabata and Y. Ikada

in common, such as requirement fdr an energy source (ATP) and for physiologic temperature. The phenomenon of phagocytosis seen in living cells in tissue culture or in a rabbit's ear chamber is dramatic. The M~) which have been moving with flapping ruffles at their leading edge, push out processes towards a particulate substance and rapidly flow around it. The process of ingestion may take only a few minutes. Once ingested, the material may be totally digested, or may persist in the form of an indigestable residue, may actually fill up the cell, and if toxic may kill the cell. Another less common form of phagocytosis occures when the particle is too large for one cell to ingest. In this case, several cells flow around it and form a capsule. Early literature on phagocytosis was reviewed by Mudd et al. [60], Berry and Spies [61], and Hirsh [62]. The events of phagocytosis are considered to take place in three subsequent stages; attachment, ingestion, and digestion of the particles. The attachment of particles to the plasma membrane is a prerequisite for interiorization and leads to a localized perturbation of the membrane beneath the attachment site. This is characterized morphologically by the aggregation of actin-like filaments, associated with the formation of pseudopods that enclose the particle. However, it is not clear at present how a cell recognizes a particle as being foreign, though the presence of specific surface receptors has been postulated. The membrane of Mqb contains the receptors specific for the Fc fragment of IgG and for third component of complements [63, 64]. There is no doubt that these receptors mediate the specific binding between Mq~ and molecules or particles bearing the corresponding ligands. The phagocytosis of nonantigenic particles, such as latexes and powdered carbons, cannot be always linked with the need for specific receptors or opsonizing factors. The phagocytic cells have a capability on the cell surface to recognize foreign materials by their surface properties. In the beginning of the 1820s, Fenn and Mudd [65, 66] investigated the response of cells to foreign bodies in terms of surface tension effects. Mudd et al. [60] pointed out the similarity between the way in which a phagocyte spreads on a surface and the way in which it spreads on a particle (phagocytosis).

6 6

1

0

7 ~// 0

Fig. 9. Effect of the interfacial free energyYlw of surfaces against water on L cell adhesion to conventional polymer films at 4 °C (O) and 37 °C (0). Film material: 1. PE, 2. PP, 3. PTFE, 5. PET, 6. PMMA, 7. nylon, 9. PVA, and 10. cellulose

2

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40 ~w, e r g ' c m -2

60

Phagocytosisof Polymer Microspheres by Macrophages

121

Many invextigators [67-70] have also demonstrated the attachment of cells to foreign bodies. It would appear that the attachment is a physicochemical reaction rather than an active energy-dependent biological reaction. For instance, the adhesion phenomena of L cells to conventional polymer films in aqueous media may be discussed on the basis of adhesion work of films with cells in water, provided that only dispersive and polar forces are operative in adhesion (Fig. 9). The attachment of a particle to the cell bearing surface receptors for ligands on the particle surface generally occurs independently of temperature [71] and the expenditure of metabolic energy. Robinovitch [72] demonstrated that the attachment of aldehyde-fixed erythrocytes to M~ was less dependent on temperature and did not require divalent cations or serum in contrast to ingestion which was reduced at lower temperatures and by some metabolic inhibitors. Once a particle is attached to a cell surface, the formation of a phagosome is triggered so that the particle is internalized and transported to the inside of the cell membrane [73]. A common feature seems to be that the engulfing plasma membrane which surrounds the particles during their entry to Mqb by phagocytosis is very closely apposed to the surface of the particle, so that very little fluid may enter the inside with the particle. For the receptor-mediated phagocytosis, it seems apparent that the receptors on the cell surface successively interact with the ligands disposed around the particles, "zipping" the plasma membrane shut around the particles as summarized by Silverstein et al. [74]. The actual mechanism of the cytoplasmic movements involved in the ingestion phase ofphagocytosis is obscure, but the action ofcytoskeleton system is clearly attributed to the ingestion phase [75, 76]. The cytoplasm immediately beneath the area of the particle-associated plasma membrane is devoid of organelles,. and has been termed the hyaline cortex. It contains a network consisting of actin microfilaments. The actin binding protein and myosin are also concentrated into this region [77]. When small particles impinge on the surface of M~, they are swept by active ruffling movements of the cell membrane into vacuoles which then pass deep into the cell. When the size of the materials to be phagocytosed is larger than Md~, the process of the ingestion is somewhat different. Mqb become very closely apposed to the foreign substances and adherent to one another by tightly interlocking cell processes. The cytoplasma next to the substances is entirely ectoplasmic and free of organelles, leading to the formation of the hyaline cortex. During the particle ingestion, phagocytes show an increase in cyanide-insensitive O z consumption, a markedly increased production of hydrogen peroxide and superoxide radical, and stimulation of the oxidation of glucose via the pentose phosphate shunt [78]. Most workers agree that this burst of oxidative activity results from the activation of a plasma-membrane-linked N A D H [79] or NADPH [80] oxidase that converts 02 to hydrogen peroxide via superoxide anions [81] and that hydrogen peroxide drives the hexose phosphate shunt. The stimulation of the pentose phosphate shunt is probably related to the need for the synthesis of a new cell membrane. Reduced NADP is required for the synthesis of fatty acids which are essential components of the cell membrane required for phagocytosis. This need for N A D P H is probably fulfilled, therefore, by the stimulation of the hexose monophosphate shunt. After ingestion of the vesicle which forms around the phagocytosed particle, the phagosome fuses with one or more lysosomes to form a secondary lysosome or phagolysosome. The hydrolytic enzymes contained in the lysosome are thus discharged

t 22

Y, Tabata and Y. Ikada

into the enlarged vacuole to degrade the contents. The lysosome is a membranous bag of hydrolytic enzymes to be used for the controlled intracetlular digestion of ingested materials. The lysosomal enzymes of M~ have been studied by Cohn and Wiener [82]. Approximately 40 enzymes are now known to be contained in lysosomes. They are all hydrolytic enzymes, including proteases, nucleases, glucosidases, lipases, phospholipases, phosphatases, and sulfatases. In addition, all are acid hydrolases, optimally active near pH 5 as it is maintained within this organelte. The newly formed phagosome is acidified rapidly and this process is initiated prior to fusion with lysosomes although the two processes are linked closely in time [83, 84]. The acidic environment within phagolysosomes gives rise to the dissociation of ligand-receptor complexes, degradation of ligands and receptors, and retrieval of receptors and membrane constituents by recycling [85].

4.2 Factors Regulating Phagocytosis of Polymer Microspheres 4.2.1 Microsphere Size The dependence of M~ phagocytosis on the size of microspheres was examined using monodispersed polystyrene and monodispersed phenylated polyacolein microspheres. There is no straightforward method for evaluating Mq~ phagocytosis, especially when comparison is to be made using microspheres of different sizes. One may evaluate the extent of phagocytosis by either the number or the volume of the total microspheres which a Mqb has phagocytosed. Thus, the number or the volume of the microspheres was measured when a fixed number or a fixed volume per M~b was given. Figure 10 illustrates the result when the microsphere number is fixed. Clearly, the number of

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2

3

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Fig. 10. Influence of the size on phagocytosis of microspheres by Md~; (©) polystyrene and (0) phenylated polyacrolein microspheres

Phagocytosis of Polymer Microspheres by Macrophages

123

microspheres phagocytosed per Mqb has a maximum at a diameter between 1.0 and 2.0 gm. The number of microspheres with a small diameter was larger than that with a larger diameter, when the volume added to Mqb was fixed. However, the percentage of the number of phagocytosed microspheres to that of the microspheres added became maximal in a diameter range between 1.0 and 2.0 t~m. Kawaguchi et al. [86] reported that the particles with a diameter between 0.4 and 1.0 lam were the most easily ingested by leukocytes, when the volume added was fixed. Moreover, it was demonstrated that the largest uptake by leukocytes was for particles with a diameter ranging 0.3 to 2.6 tam [87]. It seems that Mqb may have the ability to recognize the size of foreign materials attached to them, but the reason is at present undefined. In addition, the polystyrene microspheres with a diameter of 2.1 rtm and the phenylated polyacrolein microspheres with a diameter of 2.3 p.m were ingested to a similar extent, indicating that M ~ phagocytosis was not governed by the bulk property of microspheres, but merely by the surface property of microspheres. 4.2.2 Surface Charge [14] Figure 11 gives the relationship between the zeta potential of microspheres and the number of modified cellulose microspheres phagocytosed by one Mqb. The microspheres have the same average diameter of 1.5 pm but different surface charges as described in Sect. 3.1.2. It is seen that the phagocytosis is enhanced as the absolute value of zeta potentials increases for both the negatively charged and the positively charged surfaces. It is interesting to point out that the lowest phagocytosis is realized for the surface with a zeta potential of zero. It seems that the negatively charged membrane of Md~ and the preser~ce of divalent cations like Ca z÷ and Mg z ÷ in the culture medium are closely related to the dependence of phagocytosis on the zeta potential of the charged microspheres. 10 = 8 ¢..)

Fig. 11. Effect of the surface charge on phagocytosis of modified cellulosic mierospheres by M~; (1) CeII-OH, (2) crosslinked Cell-OH, (3) CeU-CM, (4) Cell-SE, (5) CeI1-NH2, (6) CelI-DEAE, (7) Cell-DEAE (Me), (8) cellulose triacetate, and (9) benzyl cellulose microspheres

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10

20

Zeta potential (mV)

4.2.3 Surface Hydrophobicity Most of the investigations on phagocytosis of foreign particles have demonstrated that the uptake of the particles by the phagocytic cells is largely influenced by the

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Y. Tabata and Y. Ikada

physicochemical properties o f the particle surface, especially its hydrophobicity [3, 5, 6, 18, 88-91]. In general, an increase in h y d r o p h o b i c i t y o f a particle surface leads to an enhanced uptake, unless the surface is very strongly hydrophobic. Van Oss et al. [88] have'shown that bacteria with a higher contact angle than that o f neutrophits were readily phagocytosed by them and that those with a lower contact angle were phagocytosed to a much lesser extent by neutrophils (Table 1). It is likely that phagocytosis o f microspheres by M ~ takes place through at least two steps, attachment and ingestion, as described earlier. The first event m a y be d o m i n a t e d by a c o m m o n physicochemical process, while the second event must involve a series o f biological reactions.

Table 1. Degree of Phagocytosis and Contact Angles of a Number of Bacteria Organism

Average number of bacteria phagocytized per neutrophil

Contact angle + < 1°

Brucella abortus Neisseria gonorrhoeae Listeria monocytogenes (rough form) Staphylococcus epidermidis Escherichia coli, type 07 Aerobacter aerogenes Streptococcus pyogenes a Salmonella typhimurium Streptococcus durans Paracolobactrum arizonae Staphylococcus aureus ~ Hemophilus influenzae (rough form) Shigella flexneri

1.83 +_ 0.26 1.88 + 0.30 2.10 _ 0.36 2.48 + 0.39 2.20 + 0.38 2.04 _+ 0.33 2.08 _+ 0.28 1.40 + 0.22 2.10 _+ 0.31 1.56 _+ 0.28 1.55 +_ 0.25 1.55 ___0125 1.01 _ 0.19

27.0 ° 26.7° 26.5° 24.5 ° 23.0 ° 21.5° 21.3° 20.2 ° 20.0° 19.0° 18.7° 18.6° 18.1 ° (17.5°-18.5°) b 17.3° 17.2° 17.0° 17.0° 16.5°

(Human neutrophils) Diplococcus pneumoniae, type unknown Escherichia coli, type 0111 Diplococcus pneumoniae, type I Klebsiella pneumoniae Staphylococcus aureus, type Smith

0.83 0.60 0.48 0.38 0.23

-4- 0.19 ± 0.19 + 0.12 _ 0.11 + 0.07

These two organisms frequently have a lower contact angle, but upon reculturing with a view to the measurement of their phagocytosis, their contact angle tends to increase. The higher contact angle is given here because that is the one they manifested at the time of the phagoeytosis test. b The contact angles of peripheral human neutrophils from different donors tend to vary between these values.

The modified cellulose microspheres with different water wettabilities were added to M~b in order to study the dependence o f the hydrophobicity on Mdp phagocytosis. Figure 12 indicates that there is definitely an optimal surface hydrophobicity for the microspheres to be phagocytosed. In addition, as shown in Figure 12, the number o f b i o d e g r a d a b l e P L L A and P G L A microspheres phagocytosed also obey the observed dependence o f microsphere hydrophobicity on Md~ phagocytosis, indicating that Mdp phagocytosis is n o t governed by the bulk properties o f microspheres such as the degradability o f microspheres themselves, but by the surface properties o f microspheres.

Phagocytosis of Polymer Microspheres by Macrophages

125

A similar dependence of surface wettability on cell adhesion was also found for the adhesion of bacteria onto fiat films of different hydrophobicities [92, 93]. Physical phenomena associated with the cell surface, such as cell adhesion and phagocytosis, may be characterized as being dominated by surface free energies, which are the relevant thermodynamic potentials for these processes [6]. The calculation of a change in the free energy (AFnet) during phagocytosis of the modified rnicrospheres demonstrated that phagocytosis increased with the increasing negative free energy

12 lO ¢D

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d

Z .*'S o~ cO.

ba

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20

30 /,0 50 60 Contact angle (deg)

70

80

Fig. 12. Effect of the contact angle on phagocytosis of modified cellulosic microspheres by Mqb; (1) Cell-OH, (2) Cell-C1, (3) Ceil-C2, (4) Ceil-C3, (5) Cell-C4, (6) Cell-C6, (7) CelI-Cs (8) Cell-Clo, (9) Cell-C12,(10) CelI-Ct6,(11) Cell-Cts, (12)Cell-alp,(13)Cell-O, (A) PLLA, and (A) PGLA microspheres 12

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Y. Tabata and Y. lkada

change, in agreement with the thermodynamic expectation (Figure 13). This indicates that the engulfing process in phagocytosis may essentially be explained by the interfacial free energy effects. The relationship between phagocytosis of the microspheres and their zeta potentials is shown in Figure 14. Phagocytosis takes place more markedly with the increasing

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Phagocytosis of Polymer Microspheres by Macrophages

127

negative zeta potentials of the microsphere surface, suggesting that the interaction of the M~ with the mtcrosphere surface in the cell culture medium is substantially governed by electrostatic forces. Divalent cations in the culture medium would be localized between the two substances to reduce the free energy of the total system. As can be seen in Figure 15, where the addition of EDTA to the system is given, reduction of the phagocytosis is observed only in the region of high negative values of zeta potentials of the microspheres. This result implies that bridging is formed between the microspheres and the cells through divalent cationic ions in the culture medium. It may be concluded that the van der Waals interaction is the most important for the attachment of microspheres to Mqb followed by internalization of the microspheres, and that there is an optimal hydrophobicity for the surface ofmicrospheres susceptible to phagocytosis, regardless of the biodegradable nature of microspheres themselves. 4.2.4 Proteins and Other Additives M~b phagocytosis is greatl3~ affected by the presence of various proteins contained in serum. It is well known that some specific proteins remarkably enhance the phagocytosis of particles. This phenomenon is called opsonization [94, 95], Most popular proteins among those responsible for opsonization, i.e., opsonins, are immunological proteins like immunoglobulin G [96, 97] and the third component of complements (C3b) [98]. A tetrapeptide "hormone", tuftsin stimulates phagocytosis by non-specifically binding to immunoglobulin [99]. In addition, it is known that methylated albumin [6, 100], fibronectin [t01, I02], Hageman factor (clotting factor XII) [6], fibrinogen or fibrin [6], and macrophage migration inhibition factor [6, 103] are other plasma components possessing opsonizing potential. Table 2 summarizes the results of Md~ phagocytosis of cellulose microspheres whose surfaces were grafted with various protein molecules, together with the microspheres not grafted or modified by coulping with a n-hexyl (C6) chain, as well as polystyrene microspheres. In addition, the effect of fetal calf serum (FCS) added to M~ cultures Table

2. Phagocytosis of Protein-Grafted Cellulose Microspheres by Macrophages

Microspheres FCS(--)

Polystyrenec Ceil-OH Ceil-C6 CeU-g-BSA Cell-g-IgG CelI-g-FN Cell-g-Tuft. Cell-g-Gel.

FCS(+~FCS(--)~

FCS(+)

Microsphere No./Cell

Ratiob

Microsphere No./Cell

Ratiob

5.88 0.40 7.02 0.25 9.24 8.41 6.71 7.31

14.70 1.00 17.55 0.63 23.15 21.03 16.78 t8.28

2.16 0.33 3.57 0.26 10.08 8.71 6.79 11.29

6.55 1.00 10.82 0.79 30.55 26.39 20.58 34.21

0.37 0.83 0.51 1.04 1.09 1.04 1.01 1.54

Ratio of the number of microspheresphagocytosedin the presenceof FCS to that in the absence of FCS b Ratio to the number of Cell-OH microspheresphagocytosed c Diameter is 1.73 pm

128

Y. Tabata and Y. lkada

on phagocytosis is also given. Several interesting features can be seen in the results. First, the cellulose microspheres grafted with BSA undergoes the least phagocytosis, irrespective of the presence of FCS. The next least phagocytosis is observed for the original microspheres of cellulose. In contrast, the surface modification with C6 chains greatly enhances Md~ phagocytosis, almost to a similar level as the polystyrene microspheres. Second, the M~b phagocytosis is remarkably accelerated by surface grafting of the cellulose microspheres with other proteins than BSA. Third, an addition of FCS to the culture medium increases the uptake of gelatin-grafted cellulose microspheres to a remarkable extent, whereas the added FCS decreases the phagocytosis for microspheres having a hydrophobic surface, such as C6-coupted cellulose and polystyrene microspheres. The effect of FCS addition can be seen much more distinctly in Figure 16, where the number of microspheres phagocytosed is plotted against the FCS concentration of the medium for some typical microspberes. The results obviously confirm the findings demonstrated in Table 2. Phagocytosis of the original and the BSA-grafted cellulose is insignificant and hardly influenced by the presence of FCS, while the addition of FCS apparently increasqs the phagocytosis for the gelatin-grafted cellulose, in marked contrast with that for the C6-coupled microspheres. 14

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20

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As is well known, protein adsorption generally takes place onto the foreign surfaces, especially when they are moderately hydrophobic. It is likely that protein dessorption also depends on the hydrophobicity of the surface to which the protein has been adsorbed. Presumably, the more strongly the protein is adsorbed, the less readily it may be desorbed. In this connection, the surface of C6-coupled cellulose microspheres is hydrophobic and is strongly adsorbed by proteins and also highly resistant

Phagocytosis of Polymer Microspheres by Macrophages

129

against protein desorption. The effect of protein precoating on the Md~ phagocytosis of the C6-coupled cellulose microspheres in the presence of FCS is shown in Figure 17. One prominent change is observed for IgG and BSA; the former increases the phagocytosis, while the latter decreases it with the increasing concentration at precoating. This trend is similar to that found for protein-grafted microspheres, indicating that the proteins must be adsorbed onto the surface of C6-coupled microspheres, apparently as firmly as covalently grafted. The other striking finding in Figure 17 is that gelatin precoating remarkably promotes microsphere phagocytosis, compared with opsonic proteins such as IgG and FN. In addition, a similar trend mentioned above 20

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(z~) IgG, (A) FN, (0) BSA, ([3) Tuftsin, and (1) none

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Y. Tabata and Y, Ikada

was also observed when biodegradable PLLA, PGA, and PGLA microspheres were used for Mqb phagocytosis, as shown in Figure 18. The above results can be explained in terms of the surface hydrophobicity of microspheres and opsonization, regardless of the degradability of microspheres themselves. Theres is no reason to suspect that the resistance of the virgin cellulose microspheres against phagocytosis is due to its low hydrophobicity (high hydrophilicity). BSA has neither the opsonizing ability nor the propensity to alter the hydrophobicity of the cellulose, and consequently does not increase phagocytosis when grafted to the cellulose surface. Polystyrene, C6-coupled, PLLA, PGLA, and PGA microspheres with a very hydrophobic surface will be preferably coated by albumin, the most abundant protein in FCS, leading to suppressed phagocytosis when placed in the medium containing FCS. Besides, Table 3 demonstrates that lowering the hydrophobicity of the microsphere surfaces by precoating with non-proteinaceous macromolecules, such as PVA, dextran, PAAm, CMC, and PVP, led to a reduction in Md~ phagocytosis.

Table 3. Influence of Macromolecule Precoating of PLLA Microspheres on Phagocytosisby Macrophages Macromolecles~ for precoating

Contact angle (deg)

Microsphere No./Cell FCS(--)

Microsphere No./Cell FCS(+)

FCS(+)/FCS(--)

None BSA IgG FN Tuftsin Gelatin PVA Dextran PAAm PHEG CMC PVP

72.5 26.2 24.5 20.8 34.6 22.4 20.5 25.5 26.5 28.6 24.5 32.4

3.68 1.57 6.24 4.48 3.55 3.90 0.48 2.09 1.31 2.74 2.34 2.79

2.50 1.46 6.25 4.74 3.59 9.23 0.39 1.88 1.17 2.44 1.98 2.34

0.68 0.93 1.00 1.06 1.01 2.37 0.81 0.90 0.89 0.89 0.85 0.84

a The concentration of macromoteculesfor precoating is 0,15 mg/ml

The exception is the microspheres modified with gelatin, regardless of the mode of surface binding, that is, either covalen{ly grafting or physical coating. FN and other cell-adhesive proteins contained in serum may dominantly be bound to the gelatin microsphere surface due to the bioaffinity of gelatin, Gudwicz et al. [104] and other investigators [105] have demonstrated that Mqb phagocytosis of gelatin-coated latex particles enhanced with the increased amount of F N (Clg) added (Table 4). Consequently, the opsonizing ability of gelatin must be more strongly enhanced in the presence than in the absence of FCS. In addition to the opsonic ability, gelatin has the inherent propensity to M ~ phagocytosis. A superior nature of gelatin susceptible to ingestion by M~b has been demonstrated for the microspheres prepared from gelatin, and we succeeded in very effective delivery of some drugs into M~b using the gelatin

Phagocytosis of Polymer Microspheres by Macrophages

131

microspheres [57, 106]. Beside, it is a p p a r e n t that the F C S addition has no remarked effect in M ~ phagocytosis o f the microspheres grafted or precoated with other proteins than gelatin, denoting that these surfaces are not b o u n d by any serum proteins in FCS, in contrast to the microspheres without grafting.

Table4, Uptake of Preopsonized Gelatin-coated Latex Particles by Peritoneal Macrophages Preincubation additions*

Uptake by macrophages +

None Heparin, 10 U/ml Clg, 22 pg/ml Clg + heparin

cpm of 1251/t00 fag pl otein 420 + 50 422 ___ 51 846 + 43 1.049 + 108

* g-Ltx* (I00 ktg)was incubated with the specified additions for 15 min at 37 °C in 1.0 ml of KRB. The preopsonized latex was centrifuged, washed twice, and resuspended to a 1.0-ml volume in DMEM before adding precoated particles to the monolayers. + 1.0 ml of preopsonized g-Ltx* in DMEM was added to PM monolayers (2 × 106 cells/dish) containing 10 U/ml of heparin and incubated for 2 h at 37 °C. After incubation, monolayers were washed twice with PBS and treated with trypsin (100 lag/ml) for 30 min at 37 °C to minimize cell surface binding of latex particles. 4.3 Degradation of

Polymer Microspheres in the C e l l

As described above, p o l y m e r microspheres are ingested by M ~ in phagocytic vacuoles (phagosomes) that fuse them with lvsosomes to form phagolysosomes, where the

Fig. 19. A TEM photograph with arrows showing PGA microspheres in the macrophage after 2 hr incubation. The microspheres are incorporated into cytoplasmic phagolysosome

Fig. 20A-F. SEM photographs of M~ phagocytosing PGLA and PLLA microspheres; A Md~ before phagocytosing PGLA microspheres, B Mqb phagocytosing PGLA microspheres after 2 hr incubation, C Mqb having completely phagocytosing PGLA microspheres after 6 hr incubation, D M~ with

the phagocytosing PGLA microspheres gradually being degraded in the interior of the Md? after 4 days incubation, E M~b with the entirely degraded PGLA microspheres after 7 days incubation, and F Mqb with phagocytosed PLLA microspheres after 7 days incubation

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ingested microspheres are exposed to the attack by various hydrolytic enzymes of the lysosomes to degrade. However, for the nondegradable polystyrene microspheres, the resistance of the microspheres to the lysosomal enzymes led to their intact presence within the cells and the lysosomat vesicles without exocytosis [107]. Uptake of biodegradable PGA microspheres within the cytoplasm of Md? was similar to that seen when the polystyrene microspheres were identified in M~b cytoplasm. Incorporation of the phagocytosed microspheres into cytoplasmic phagolysosomes was observed by transmission electron microscopy [103] (Figure 19). The use of the Md~ culture system is an effective method for studying the process of microsphere phagocytosis and evaluating the time course of microsphere degradation in the cells, when combined with electron microscopic techniques. Figure 20 shows SEM photographs of the mode of degradation of PGLA microspheres with the passage of culture time. Figure 20A shows the M~b before incubation with the microspheres, and Figures 20B to 20E show the Mdp incubated with the microspheres for 2 hr, 6 hr, 4 days, and 7 days, respectively. It is apparent that the microspheres were well phagocytosed by M~b within 6 hr. Then, the contour of the microspheres in the Mqb gradually disappeared with increaring incubation time. After 7 days, no microspheres were observed in the cells. In addition, phase-contrast microscopic observation more clearly confirmed that the disappearance of PGLA microspheres inside the M~ is not due to exocytosis but due to degradation. On the contrary, microspheres prepared from PLLA with a weight-average molecular weight higher than that of PGLA, still remained in the cell even after 7 days, as shown in Figure 20F. When the release of a fluorescent dye from the PGLA microspheres in Mdp was observed by fluorescence microscopy, the microspheres ingested by Mdp was found to have a clear contour and the dye occupied the space inside the cell except for the celt nucleus after 4-hr incubation. The contour of the microspheres in the cell gradually disappeared and the dye in the microspheres diffused out into all of the internal space of the cell within the incubation time, resulting in the whole staining of the cell by the fluorescent dye. These results

lOO o

E

"E

"5 E

80

D

o

~,~ 60 Qa . C t/1 Q,.e I/I

o~ .~_ ~

40

E~ -E

20

~._~ 1 2 incubation time

3

(day)

Fig. 21. Degradation profiles in M~bof gelatin microspherescrosslinked with glutaraldehydein concentrations of 1.33 (O), 0.7t (O), 0.28 (A.), 0.14 (&), 0.05 (D), and 0.03 mg/mg gelatin (m)

Phagocytosisof PolymerMicrospheresby Macrophages

135

indicate that the phagocytosed microspheres were gradually degraded in the interior of Mqb during the incubation time, leading to a slow release of the substance incorporated in the microspheres in the cells. The behavior of microsphere degradation in Mqb could be regulated by changing the molecular properties of PLLA- and PGLAconstituting microspheres, similarly to that of the microspheres in vitro [41]. The gelatin microspheres were not degraded by the simple hydrolysis without enzymes, different from PLLA and PGLA microspheres, but digested in Mdp after being phagocytosed. The degradation profiles of the microspheres in M~ are shown in Figure 21. It is abvious that the microspheres phagocytosed were gradually degraded in the cells within the incubation time. The rate of degradation could be controlled by changing the extent of crosslinking of the microspheres with glutaraldehyde in the preparation [109], similarly to the in vitro degradation of the microspheres with collagenase as shown in Figure 7.

5 Phagocytosis of Polymer Microspheres In Vivo Studies in vivo on Mqb phagocytosis have generally concentrated on the ability of mononuclear phagocyte system (MPS), such as monocytes, lung, liver, and spleen Md~, to clear substances introduced into the circulation. The in vivo behavior of most types of polymer microspheres is profoundly affected by their interaction with the cells of MPS, which has been excellently reviewed by Edman et al. [110] and by Douglas et al. [111]. The cells belonging to the MPS have a variety of important biological functions [112], but for our purpose, we will focus on their abilities in removing microspheres from the bloodstream. The natural functions of the MPS cells probably involve the removal of protein aggregates derived from tissue destruction and repair, clearance of senescent erythrocytes, and removal of invading bacteria, fungi, and viruses. However, the MPS cells are also highly efficient in removing foreign particles including polymer microspheres, injected for therapeutic and diagnostic purposes. The cells can often take up polymer microspheres by apparently nonspecific phagocytosis [113], A variety of methods have been used for microsphere formation including nondegradable polystyrene, poly(methyl methacrylate) (PMMA), and polyacrylamide (PAAm) microspheres, as well as PLLA, PGA, PGLA, polycyanoacrylate, starch, and protein microspheres, which would be more likely to be fully biodegradable [42, 110]. Measurable amounts of polystyrene [107] and PAAm microspheres [I10] persist in the tissue for many weeks after administration. It seems likely, however, that PGA [108] and protein microspheres [110] may be degraded in vivo in a period of days. The size is one of the important factors influencing the distribution and fate of microspheres after intravenous (i.v.) injection, regardless of the nature of microsphere matrix, such as its degradability. Large microspheres with a diameter larger than about 7 ~tm are mainly cleared by simple entrapment or filtration, usually in the lung capillary bed [114], while below this size but larger than 100 nm the microspheres will normally pass through the lung without being trapped or taken up by alveolar Mff and accumulate in the liver and the spleen. Some histological studies revealed that microspheres of 3 to 5 lam were found consistently in vascular channels, Kupffer

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Y. Tabata and Y. Ikada

cells, and the sinusoids of the liver and spleen, and bone marrow with Mdp, while microspheres of 12 gm in a diameter were found predominantly in the capillaries of the alveolar walls and occasionally free in the alveolar lumina in the lung [115-117]. Microspheres smaller than I00 nm have the possibility of leaving the systemic circulation through fenestrations in the cells lining the blood vessels. These fenestrations have different sizes'depending on the capillary beds. The capillary endothel[um of pancreas, intestines, and kidney has fenestrations of 50-60 nm while that of the liver, spleen, and bone marrow has fenestrations of about 100 nm. There is a suggestion that capillaries in inflammatory regions may have greater permeability [118]. Although alteration of surface characteristics of polymer microspheres can lead to a significant change in clearance kinetics, eventual uptake by the MPS still usually ensues. The uptake of the microspheres by the Mqb residing at liver, spleen, and bone marrow is governed mainly by the physicochemical properties of the microsphere surface, such as surface charge and hydrophobicity [6, 119], similarly to that observed from in vitro experiments. Microspheres with hydrophobic surfaces will be removed from the circulation rapidly, while those with more hydrophilic surfaces would be expected to remain in circulation for longer periods of time [6]. Microspheres with a hydrophobic surface such as polystyrene microspheres are normally taken up by the MPS cells of the liver and spleen after i.v. injection [107, 110, 111, 119]. This rapid and efficient removal is a result of two interrelated processes; the first is the coating of the microspheres by blood components, such as IgG, complements, and FN (opsonization) that render them recognizable by Mff. The second is the adhesion of the microspheres to the surface of Mdp and their subsequent engulfment. In an attempt to avoid the rapid clearance by Mdo, the microspheres are often coated with hydrophilic macromolecular materials to give a hydrophitic surface. This may give rise to a minimum uptake by Mqb. Coating of microspheres with negative and positive macromolecules can also alter organ uptake considerably, as reported by Wilkins and Myers [120], who found that the positively charged gelatin-coated polystyrene microspheres

Polystyrene nanopartic[es Activity at different sites eight days after i.v.-administration

8° F 70 ~60

~5~

~50

5 34

-6 "54O

"53

[ ] Uncoated latex [ ] Coated latex System I [ ] Coated latex System ]t

"6 30

2 10 Lung

Heart

Kidney

Spleen

Liver

Carcass

Fig. 22. Distribution of uncoated and Poloxamer 188- (system I) and Poloxamer 338- (system II) coated polystyrene particles (50 nm) in various organs 8 days after intravenous administration

Phagocytosis of Polymer Microspheres by Macrophages

137

of 1.305 gm diameter accumulated initially in the lung and later in the spteen, while negatively charges gelatin-coated microspheres were found in liver and spleen, Jeppsson and Rossner [121] and Gery [122] have studied emulsion systems and demonstrated that non-ionic surfactants of the Pluronic (Poloxamer) series could modify the kinetics of their clearance. Ilium and Davis [123-125] showed that the blood clearance and organ distribution of polystyrene microspheres of 1.27 Jam and 50 nm in diameters could be altered when Poloxamer 338 and 188 were used as the coating agents. Coating of the microspheres with the surfactant gave rise to a significant increase of the number of microspheres reaching the lung and a corresponding reduction in the quantity reaching the liver. The reduced uptake of the coated microspheres in the liver is related directly to the physicochemical properties of the adsorbed Poloxamer layer. It is known that the complement system is activated when it comes in contact with synthetic polymer surfaces and that certain complement components can be taken up rapidly [126]. Microspheres coated with the complement proteins will be cleared rapidly by liver and spleen. As shown in Figure 22, the coating of the microspheres with Poloxamer 338 reduces or even eliminates the uptake of the opsonic materials and the subsequent phagocytic engulfment by the Kupffer cells in liver is minimized [125]. Another approach is the incorporation of carbohydrate residues onto the microsphere surfaces. A variety of cells are known to have lectin-like cell surface receptors [127]. It has already been demonstrated that the incorporation of carbohydrate residues into liposomes leads to a change of their clearance characteristics [128-130]. However, such an attempt has not yet been made for polymer microspheres. In principle, one can introduce appropriate ligands which recognize cell surface receptors onto the microspheres to obtain important changes in the clearance and distribution of the microspheres.

6 Concluding Remarks One of the important objectives in current drug therapies is the selective delivery of drugs and diagnostic agents to a specific target site or organ in the body. This would result in a reduction of unwanted side effects and adverse reactions and thereby allow the use of highly bioactive but toxic chemicals that cannot be employed at present because of unselective distribution in the body. For example, the agents used in cancer chemotherapy that show an activity against neoplastic tissues also have action against normal tissues. Greater selectivity and a consequent increase in the therapeutic index would be of considerable benefit. Drug targeting may be achieved with use of a wide variety of drug carriers including macromolecules and cells as well as colloidal particles. Different types of colloidal systems, such as liposomes, emulsions, and polymer microspheres, have been reported in the literature. Colloids have the advantage of being able to entrap relatively large amounts of pharmacological agents and are relatively easy to prepare. Injection of active agents incorporated in carrier microspheres into the blood stream often has a great advantage over the injection of the agents themselves. However, once they come in the blood, the fate of any microsphere is determined by the MPS cells which clear such materials rapidly in liver, spleen, or bone marrow. Therefore, it is essential to

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understand how this clearance is mediated. The understanding will allow manipulation o f b o t h microspheres and host so as to enhance or prevent MPS-mediated b l o o d clearance and to achieve its objective o f providing tissue selectivity for drug delivery. This review dealt with the phagocytosis of polymer microspheres by MOP, which are main cells o f M P S playing the most i m p o r t a n t role in the clearance and disposition o f microspheres injected into the body. The uptake of the microspheres by MOp is mainly governed by the physicochemical characteristics of the microspheres: especially their size, surface charge, and surface hydrophobicity, regardless o f the degradability o f microspheres themselves. These results are provided on the basis of in vitro experiments and cannot be necessarily extrapolated to the in-vivo mutual action of the microspheres to MOp. However, they will provide information useful for the fate and distribution of microspheres injected into the body, and a guidance for the development o f polymer microspheres for drug targeting.

7 References 1. Carr I (1973) The Macrophage: A Review of Ultrastructure and Function, Academic Press, London, New York 2. North RJ (1970) Semin. Hematol. 7:161 3. Cohn ZA (1970) in: van Furth R (ed) Monouuctear Phagocytes, Blackwetl Scientific Publications, Oxford, p 121 4. Griffin FM Jr, Griffin JA, Leider JE, Silverstein SC (1975) J. Exp, Med. 142:1263 5. StosseI TP (1975) Semin. Hematol. 12:83 6. van Oss CJ (1975) Phagocytic Engulfment and Cell Adhesiveness, Marcel Dekker, New York, Basel 7. Kotera A, Furusawa K, Takeda Y (1970) Kolloid-Z. u Z. Polymere 239:677 8. Goodwin JW, Hearn J, Ho CC, Ottewilt RH (1974) Colloid and Polym. Sci. 252:464 9. Hearn J, Ottewill RH, Shaw JN (1970) Br. Polym. J. 2:116 10. Almog Y, Reich S, Levy M (1982) Br. Polym. J. 14:131 11. Chung-li Y, Goodwin JW, Ottewill RE (1976) Prog. Colloid and Polym. Sci. 60:173 12. Goodwin JW, Ottewill RH, Pelton R, Vianllo G, Yates DE (1978) Br. Polym. J. 10:173 13. Ugelstad J, Kaggerung KH, Hansen FK, Berge A (1979) Makrom. Chem. 180:737 14. Tabata Y, Ikada Y (1988) Biomateriats 9:356 15. Matsumoto T, Okubo M, Imai T (1974) Kobunshi-Ronbunshu 31 : 576 16. Margel S (1985) Methods Enzymol 112:165 t7. Walter H, Krob EJ, Garza R (1968) Biochim. Biophys. Acta 165:507 18. van Oss CJ (1978) Annu. Rev. Microbiol. 32:19 19. Capo CP, Bongrand P, Benoliel AM, Depieds R (1979) Immunology 36:501 20. Rembraum A, Yen SPS, Cheong E, Wallace S, Molday RS, Gordon IL, Dreyer WJ (1976) Macromolecules 9: 328 21. Bhattacharyya BR, Halpern BD (1977) Polymer News 4:107 22. Marumoto K, Suzuta T, Noguchi H, Uchida Y (1978) Polymer 19:867 23. Kawaguchi H, Hoshino H, Amagasa H, Ohtsuka Y (1984) J. Colloid Interface Sci 97:465 24. Suzuta T (1983) in: Bruck SD (ed) Controlled Drug Delivery, Clinical Applications, Vol II, CRC Press, Florida, p 149 25. Matsumoto K, Hirayama C, Motozato Y (1981) Chem. Soc. Japan t2:1890 26. Mckelvey JB, Benerite RR, Berni RJ, Burgis BG (1963) J. Appi. Polym. Sci. 7:1371 27. Peterson EA, Sober HA (1956) J. Am. Chem. Soc. 20:751 28. Peska J, Stamberg J, Hradil J (1986) Angew. Makrom. Chem. 53:73 29. March SC, Parikh I, Cuatrecasas P (1974) Annl. Biochem. 60:149 30. Tabata Y, Ikada Y (1989) J, Colloid Interface Sci 127:132 31. Cuatrecasas P (1970) J. Biol, Chem. 245:3059

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Editor: S. Okamura Received April 18, 1989

Author Index Volumes 1-94

Allegra, G. and Bassi, L W.: Isomorphism in Synthetic Macromolecular Systems. Vol. 6, pp. 549--574 Andrade, J. D., Hlady, V.: Protein Adsorption and Materials Biocompability: A. Tutorial Review and Suggested Hypothesis. Vol. 79, pp. 1-63. Andreis, M. and Koenig, J. L.: Application of NMR to Crosslinked Polymer Systems. Vol. 89, pp. 69-160. Andrews, E. H. : Molecular Fracture in Polymers. Vol. 27, pp. 1-66. Anufrieva, E. V. and Gotlib, Yu. Ya.: Investigation of Polymers in Solution by Polarized Luminescence. Vol. 40, pp. 1-68. Apicella, A. and Nicolais, L. : Effect of Water on the Properties of Epoxy Matrix and Composite. Vol. 72, pp. 69-78. Apicella, A., Nicolais, L. and de Cataldis, C.: Characterization of the Morphological Fine Structure of Commercial Thermosetting Resins Through Hygrothermal Experiments. Vol. 66, pp. 189-208. Argon, A. S., Cohen, R. E., Gebizlioglu, O. S. and Schwier, C.: Crazing in Block Copolymers and Blends. ~ol. 52/53, pp. 275-334. Argon, A. S. and Cohen, R. E.: Crazing and Toughness of Block Copolymers and Blends. Vol. 91/92, pp. 301-352. Aronhime, M. T., Gillham, J. K.: Time-Temperature Transformation (TTI') Cure Diagram of Thermosetting Polymeric Systems. Vol. 78, pp. 81-112. Arridge, R. C. and Barham, P. J.: Polymer Elasticity. Discrete and Continuum Models: Vol. 46, pp. 67-117. Aseeva, R. M., Zaikov, G. E.: Flammability of Polymeric Materials. Vol. 70, pp. 171-230. Ayrey, G. : The Use of Isotopes in Polymer Analysis. Vol. 6, pp. 128-148.

B(issler, H.: Photopolymerization of Diacetylenes. Vol. 63, pp. 1-48. Baldwin, R. L.: Sedimentation of High Polymers. Vol. 1, pp. 451-511. Bascom, W. D.: The Wettability of Polymer Surfaces and the Spreading of Polymer Liquids. Vol. 85, pp. 89-124. Balta-Calleja, F. J. : Microhardness Relating to Crystalline Polymers. Vol. 66, pp. 117-148. Barb~, P. C., Cecchin, G. and Noristi, L.: The Catalytic System Ti-Complex/MgC12. Vol. 81, pp. 1-83. Barton, J. M. : The Application of Differential Scanning Calorimetry (DSC) to the Study of Epoxy Resins Curing Reactions. Vol. 72, pp. 111-154. Ballauff, M. and Wolf, B. A.: Thermodynamically Induced Shear Degradation. Vol. 84, pp. 1-31. Basedow, A. M. and Ebert, K.: Ultrasonic Degradation of Polymers in Solution. Vol. 22, pp. 83-148. Batz, H.-G..~ Polymeric Drugs. Vol. 23, pp. 25-53. Baur, H. see Wunderlich, B.: Vol. 87, pp. 1-121. Bell, J. P. see Schmidt, R. G. : Vol. 75, pp. 33-72. Bekturo~, E. A. and Bimendina, L. A.: Interpolymer Complexes. Vol. 41, pp. 99-147. Berger, L. L. see Kramer, E. J. : Vol. 91/92, pp. 1-68. Bergsma, F. and Kruissink, Ch. A.: Ion-Exchange Membranes. Vol. 2, pp. 307-362. Berlin, AI. AI., Volfson, S. A., and Enikolopian , N. S.: Kinetic of Polymerization Processes. Vol. 38, pp. 89-149 .

144

Author Index Volumes 1-94

Berry, G. C. and Fox, T. G.: The Viscosity of Polymers and Their Concentrated Solutions. Vol. 5, pp. 261-357. Bevington, J. C. : Isotopic Methods in Polymer Chemistry. Vol. 2, pp. 1-17. Beylen, M. van, Bywater, S., Smets, G., Szwarc, M., and Worsfold, D. or.: Developments in Anionic Polymerization -- A Critical Review. Vol. 86, pp. 87-143. Bhuiyan, A. L. : Some Problems Encountered with Degradation Mechanisms of Addition Polymers. Vol. 47, pp. 1~55. Billingham, N. C. and Calvert, P. D.: Electrically Conducting Polymers -- A Polymer Science Viewpoint. Vol. 90, pp. 1-104. Bird, R. B., Warner, Jr., H. R., and Evans, D. C. : Kinetik Theory and Rheology of Dumbbell Suspension with Brownian Motion. Vol. 8, pp. 1-90. Biswas, M. and Maity, C. : Molecular Sieves as Polymerization Catalysts. Vol. 31, pp. 47-88. Biswas, M., Packirisamy, S.: Synthetic Ion-Exchange Resins. Vol. 70, pp. 71-118. Block, H.: The Nature and Application of Electrical Phenomena in Polymers. Vol. 33, pp. 93-167. Bodor, G.: X-ray Line Shape Analysis. A. Means for the Characterization of Crystalline Polymers. Vol. 67, pp. 165-194. B6hm, L. L., Chmeli~, M., L6hr, G., Schmitt, B. J. and Schulz, G. V.: Zust/inde und Reaktionen des Carbanions bei der anionischen Polymerisation des Styrols. Vol. 9, pp. 145. B6lke, P. see Hallpap, P. : Vol. 86, pp. 175-236. Bormashenko, E. Yu. : see Fridman. M.L. : Vol. 93, pp. 81-136. Boutevin, B.: Telechelic Oligomers by Radical Reactions. Vol. 94, pp. 69-106. Bout, F.: Transient Relaxation Mechanisms in Elongated Melts and Rubbers Investigated by Small Angle Neutron Scattering. Vol. 82, pp. 47-103. Bovey, F. A. and Tiers, G. V. D.: The High Resolution Nuclear Magnetic Resonance Spectroscopy of Polymers. Vol. 3, pp. 139-195. Braun, J.-M. and Guilett, J. E.: Study of Polymers by Inverse Gas Chromatography. Vol. 21, pp. 107-145. Breitenbach, J. W., Olaj, O. F. und Sommer, F. : Polymerisationsanregung durch Elektrolyse. Vol. 9, pp. 47-227. Bresler, S. E. and Kazbekov, E. N.: Macroradical Reactivity Studied by Electron Spin Resonance. Vol. 3, pp. 688-711. Brosse, J.-C., Derouet, D., Epaillard, F., Soutif, J.-C., Legeay, G. and Dugek, K.: Hydroxyl-Terminated Polymers Obtained by Free Radical Polymerization. Synthesis, Characterization, and Applications. Vol. 81, pp. 167-224. Bucknall, C. B. : Fracture and Failure of Multiphase Polymers and Polymer Composites. Vol. 27, pp. 121-148. Burchard, W. : Static and Dynamic Light Scatterir/g from Branched Polymers and Biopolymers. Vol. 48, pp. 1-124. Bywater, S. : Polymerization Initiated by Lithium and Its Compounds. Vol. 4, pp. 66-110. Bywater, S. : Preparation and Properties of Star-branched Polymers. Vol. 30, pp. 89-116. Bywater, S. see Beylen, M. van: Vol. 86, pp. 87-143. Calvert, P. D. see Billingham, N. C. : Vol. 90, pp. 1-104. Candau, S., Bastide, J. und Delsanti, M. : Structural. Elastic and Dynamic Properties of Swollen Polymer Networks. Vol. 44, pp. 27-72. Carrick, W. L.: The Mechanism of Olefin Polymerization by Ziegler-Natta Catalysts. Vol. 12, pp. 65-86. Casale, A. and Porter, R. S. : Mechanical Synthesis of Block and Graft Copolymers. Vol. 17, pp. 1-7"1. Cecchin, G. see Barb6, P. C.: Vol. 81, pp. 1-83. Cerf, R.: La dynamique des solutions de macromolecules dans un champ de vitresses. Vol. 1, pp. 382--450. Cesca, S., Priola, A. and Bruzzone, M.: Synthesis and Modification of Polymers Containing a System of Conjugated Double Bonds. Vol. 32, pp. 1-67. ChMlini, E., Solaro, R., Galli, G. and Ledwith, A. : Optically Active Synthetic Polymers Containing Pendant Carbazolyl Groups. Vol. 62, pp. 143-170. Cicchetti, O.: Mechanisms of Oxidative Photodegradation and of UV Stabilization of Polyolefins. Vol. 7, pp. 70-112.

Author Index Volumes 1-94

145

Clark, A. 11. and Ross-Murphy, SI B.: Structural and Mechanical Properties of Biopolymer Gels. Vol. 83, pp. 57-193. Clark, D. T.: ESCA Applied to Polymers. Vol. 24, pp. 125-188. Cohen, R. E. see Argon, A. S.: Vol. 91/92, pp. 301-352. Colemann, Jr., L. E. and Meinhardt, N. A.: Polymerization Reactions of Vinyl Ketones. Vol. 1, pp. 159-179. Comper, IV. D. and Preston, B. N.: Rapid Polymer Transport in Concentrated Solutions. Vol. 55, pp. 105-152. Corner, T. : Free Radical Polymerization -- The Synthesis of Graft Copolymers. Vol. 62, pp. 95-142. Crescenzi, V.: Some Recent Studies of Polyelectrolyte Solutions. Vol. 5, pp. 358-386. Crivello, J. V.: Cationic Polymerization -- Iodonium and Sulfonium Salt Photoinitiators, Vol. 62, pp. 1-48.

Dave, R. see Kardos, J. L.: Vol. 80, pp. 101-123. Davydov, B. E. and Krentsel, B. A.: Progress in the Chemistry of Polyconjugated Systems. Vol. 25, pp. 1-46. Derouet, F. see Brosse, J.-C. : Vol. 81, pp. 167-224. Dettenmaier, M. : Intrinsic Crazes in Polycarbonate Phenomenology and Molecular Interpretation of a New Phenomenon. Vol. 52/53, pp. 57-104. Dettenmaier, M. and Leberger, D.: Crazing of Polymer-Diluent Mixtures. Vol. 91/92, pp. 119--136. Diaz, A. F., Rubinson, J. F., and Mark, H. B., Jr. : Electrochemistry and Electrode Applications of Electroactive/Conductive Polymers. Vol. 84, pp. 113-140. Dobb, M. G. and Mclntyre, J. E.: Properties and Applications of Liquid-Crystalline Main-Chain Polymers. Vol. 60/61, pp. 61-98. D6ll, W. : Optical Interference Measurements and Fracture Mechanics Analysis of Crack Tip Craze Zones. Vol. 52/53, pp. 105-168. D6ll, W. and K~ncz6l, L. : Micromechanics of Fracture under Static and Fatigue Loading: Optical Interferometry of Crack Tip Craze Zones. Vol. 91/92, pp. 137-214. Doi, Y. see Keii, T.: Vol. 73/74, pp. 201-248. Dole, M. : Calorimetric Studies of States and Transitions in Solid High Polymers. Vol. 2, pp. 221-274. Donnet, J. B., Vidal A. : Carbon Black-Surface Properties and Interactions with Elastomers. Vol. 76, pp. 103-128. Dorn, K., Hupfer, B., and Ringsdorf, H.: Polymeric Monolayers and Liposomes as Models for Biomembranes How to Bridge the Gap Between Polymer Science and Membrane Biology? Vol. 64, pp. 1-54. Dreyfuss, P. and Dreyfuss, M, P.: Polytetrahydrofuran. Vol. 4, pp. 528-590. Drobnik, J. and Rypd?ek, F. : Soluble Synthetic Polymers in Biological Systems. Vol. 57, pp. 1 50. Dr6scher, M.: Solid State Extrusion of Semicrystalline Copolymers. Vol. 47, pp. 120-138. Dudukovid, M. P. see Kardos, J. L. : Vol. 80, pp. 101-123. Drzal, L. T. : The Interphase in Epoxy Composites. Vol. 75, pp. 1-32. Dujek, K. : Network Formation in Curing of Epoxy Resins. Vol. 78, pp. 1-58. Du~ek, KI and Prins, W. : Structure and Elasticity of Non-Crystalline Polymer Networks. Vol. 6, pp. 1-t02. Du~ek, K. see Brosse, J.-C. : Vol. 81, pp. 167--224. Duncan, R. and Kope?ek, J. : Soluble Synthetic Polymers as Potential Drug Carriers. Vol. 57, pp. 51-101.

Eastham, A. M.: Some Aspects of the Polymerization of Cyclic Ethers. Vol. 2, pp. 18-50. Ehrlich, P. and Mortimer, G. A. : Fundamentals of the Free-Radical Polymerization of Ethylene. Vol. 7, pp. 386-448. Eisenberg, A. : Ionic Forces in Polymers. Vol. 5, pp. 59-112. Eiss, N. S. Jr. see Yorkgitis, E. M. : Vol. 72, pp. 79-110. Elias, H.-G., Bareiss, R. und Watterson, J. G. : Mittelwerte des Molekulargewichts und anderer Eigenschaften. Vol. 11, pp. 111-204. Eisner, G., Riekel, Ch. and Zachmann, H. G. : Synchrotron Radiation Physics. Vol. 67 pp. 1--58.

146

Author Index Volumes 1-94

Elyashevich, G. K. : Thermodynamics and Kinetics of Orientational Crystallization of Flexible-

Chain Polymers. Vol. 43, pp. 207-246. Enkelmann, II.: Structural Aspects of the Topochemical Polymerization of Diacetylenes. Vol. 63,

pp. 91-136. Entelis, S. G., Evreinov, V. V., Gorshkov, A. 1I. : Functionally and Molecular Weight Distribution of

Telchelic Polymers. Vol. 76, pp. 129-175. Epaillard, F. see Brosse, J.-C.: Vol. 81, pp. 167-224. Evreinov, II. V. see Entelis, S. G. : Vol. 76, pp. 129-175. Ferruti, P. and B'arbucci, R. : Linear Amino Polymers: Synthesis, Protonation and Complex Forma-

tion. Vol. 58, pp. 55-92. Finkelmann, H. and Rehage, G. : Liquid Crystal Side-Chain Polymers. Vol. 60/61, pp. 99--172. Fischer, H.: Freie Radikale w/ihrend der Polymerisation, nachgewiesen und identifiziert durch

Elektronenspinresonanz. Vol. 5, pp. 463-530. Flory, P. J. : Molecular Theory of Liquid Crystals. Vol. 59, pp. 1-36. Ford, IV. T. and Tomoi, M. : Polymer-Supported Phase Transfer Catalysts Reaction Mechanisms.

Vol. 55, pp. 49-104. Fradet, A. and Mardchal, E. : Kinetics and Mechanisms of Polyesterifications. I. Reactions of Diols

with Diacids. Vol. 43, pp. 51-144. Franta, E. see Rempp, P.: Vol. 86, pp. 145-173. Franz, G. : Polysaccharides in Pharmacy. Vol. 76, pp. 1-30. Fridman, M. L. and Sevruk, V. D. : Extension of Molten Polymers. Vol. 93, pp. 140. Fridman, M. L. and Peshkovsky, S. L.: Molding of Polymers under Conditions of Vibration Effects.

Vol. 93, pp. 41-80. Fridman, M. L., Petrosyan, A . ~ . , Levin, V. S. and Bormashenko, E. Yu. : Fundamentals of Low-

Pressure Moulding of Polymer Pastes (Plastlsols) a/fd Thermoplastic Materials. Vol. 93, pp. 81-136. Fridman, M. L. see Tunkel, V. I.: Vol. 93, pp. 137-174. Friedrich, K. : Crazes and Shear Bands in Semi-Crystalline Thermoplastics. Vol. 52/53, pp. 225-274. Fujita, 11. : Diffusion in Polymer-Diluent Systems. Vol. 3, pp. 147. Funke, W. : Uber die Strukturaufkl/irung vernetzter Makromolekiile, insbesondere vernetzter Poly-

esterharze, mit chemischen Methoden. Vol. 4, pp. 157-235. Furukawa, H. see Kamon, T.: Vol. 80, pp. 173-202. Gal'braikh, L. S. and Rigovin, Z. A.: Chemical Transformation of Cellulose. Vol. 14, pp. 87-130. Galli, G. see ChieUini, E. : Vol. 62, pp. 143-170. Gallot, B. R. M.: Preparation and Study of Block Copolymers with Ordered Structures, Vol. 29;

pp. 85-156. Gandini, A.: The Behaviour of Furan Derivatives in Polymerization Reactions. Vol. 25, pp. 47-96. Gandini, A. and Cheradame, H.: Cationic Polymerization. Initiation with Alkenyl Monomers.

Vol. 34/35, pp. 1-289. Geckeler, K., Pillai, V. N. R., and Mutter, M. : Applications of Soluble Polymeric Supports. Vol. 39,

pp. 65-94. Gerrens, H. : Kinetik der Emulsionspolymerisation. Vol. 1, pp. 234-328. Ghiggino, K. P., Roberts, A. J. and Phillips, D. : Time-Resolved Fluorescence Techniques in Polymer

and Biopolymer Studies. Vol. 40, pp. 69-167. Gillham, J. K. see Aronhime, M. T.: Vol. 78, pp. 81-112. Glrckner, G. : Analysis of Compositional and Structural Heterogeneitis of Polymer by Non-Exclusion

HPLC. Vol. 79, pp. 159-214. Godovsky, Y. K. : Thermomechanics of Polymers. Vol. 76, pp. 31 102. Godovsky, Yu. K. and Papkov, V. S.: Thermotropic Mesophases in Element-Organic Polymers.

Vol. 88, pp. 129-180. Goethals, E. J.: The Formation of Cyclic Oligomers in the Cationic Polymerization of Heterocycles.

Vol. 23, pp. 103-130. Gorshkov, A. V. see Entelis, S. G.: Vol. 76, 129-175. Griiger, H. see Kulicke, W.-M. : Vol. 89, pp. 1-68. Graessley, IV. "W.: The Etanglement Concept in Polymer Rheology. Vol. 16, pp. 1-179.

Author Index Volumes 1-94

147

Graessley, W. W. : Entagled Linear, Branched and Network Polymer Systems. Molecular Theories. Vol. 47, pp. 67-117. Grebowicz, J. see Wun.derlich, B. :Vol. 60/61, pp. 1-60. Grebowicz, J. see Wunderlich, B. : Vol. 87, pp. 1-121. Greschner, G. S. : Phase Distribution Chromatography. Possibilities and Limitations. Vol. 73/74, pp. 1-62. Hagihara, V., Sonogashira, K. and Takahashi, S. : Linear Polymers Containing Transition Metals in the Main Chain. Vol. 41, pp. 149-179. Hallpap, P., B6lke, M., and Heublein, G. : Elucidation of Cationic Polymerization Mechanism by Means of Quantum Chemical Methods. Vol. 86, pp. 175-236. Hasegawa, M.: Four-Center Photopolymerization in the Crystalline State. Vol. 42, pp. 1-49. Hatano, M.: Induced Circular Dichroism in Biopolymer-Dye System. Vol. 77, pp. 1-121. Hay, A. S. : Aromatic Polyethers. Vol. 4, pp. 496-527. Hara, M. see Saner, J. A.: Vot. 91/92, pp. 69-118. Hayakawa, R. and Wada, Y.: Piezoelectricity and Related Properties of Polymer Films. Vol. 11, pp. 1-55. Heidemann, E. and Roth, W. : Synthesis and Investigation of Collagen Model Peptides. Vol. 43, pp. 145-205. Heinrich, G., Straube, E., and Helmis, G.: Rubber Elasticity of Polymer Networks: Theories. Vol. 84, pp. 33-87. Heitz, IV. : PolYmeric Reagents. Polymer Design, Scope, and Limitations. Vol. 23, pp. 1-23. Helfferich, F. : Ionenaustausch. Vol. 1, pp. 32%381. Helmis, G. see Heinrich, G. : Vol. 84, pp. 33-87. Hendra, P. J. : Laser-Raman Spectra of Polymers. Vol. 6, pp. 151-169. Hendrix, ,1. : Position Sensitive "X-ray Detectors". Vol. 67, pp. 59-98. Henrici-Olivd, G. and Olivd, S. : Oligomerization of Ethylene with Soluble Transition-Metal Catalysts. pp. 496-577. Henrici-Olivd, G. und Olive, S. : Koordinative Polymerisation an 16slichen Ubergangsmetall-Katalysatoren. Vol. 6, pp. 421-472. Henrici-Oliv~, G. and Olivd, S. : Oligomerization of Ethylene with Soluble Transition-Metal Catalysts. Vol. 15, pp. 1-30. Henrici-Oliv~, G. and Olivd, S. : Molecular Intercations and Macroscopic Properties of Polyacrylonitrile and Model Substances. Vol. 32, pp. 123-152. Henrici-Oliv~, G. and Olive, S.: The Chemistry of Carbon Fiber Formation from Polyacrylonitrile. Vol. 51, pp. 1-60. Hermans, Jr., J., Lohr, D. and Ferro, D. : Treatment of the Folding and Unfolding of Protein Molecules in Solution According to a Lattic Model. Vol. 9, pp. 229-283. Herz, J.-E. see Rempp, P.: Vol. 86, pp. 145-173. Heublein, G. see Hallpap, P. : Vol. 86, pp. 175-236. Higashimura, T. and Sawamoto, M. : Living Polymerization and Selective Dimerization : Two Extremes of the Polymer Synthesis by Cationic Polymerization. Vol. 62, pp. 49-94. Higashimura, T. see Masuda, T.: Vol. 81, pp. 121-166. Hlady, V. see Andrade, J. D. : Vol. 79, pp. 1-63. Hoffman, A. S. : Ionizing Radiation and Gas Plasma (or Glow) Discharge Treatments for Preparation of Novel Polymeric Biomaterials. Vol. 57, pp. 141-157. Holzmiiller, W. : Molecular Mobility, Deformation and Relaxation Processes in Polymers. Vol. 26, pp. 1-62. Hori, Y. see Kashiwabara, H. : Vol. 82, pp. 141-207. Horie, K. and Mita, L : Reactions and Photodynamics in Polymer Solids. Vol. 88, pp. 77--128. Hutchinson, J. and Ledwith, A.: Photoinitiation of Vinyl Polymerization by Aromatic Carbonyl Compounds. Vol. 14, pp. 49-86. lizuka, E.: Properties of Liquid Crystals of Polypeptides: with Stress on the Electromagnetic Orientation. Vol. 20, pp. 79-107. Ikada, Y.: Characterization of Graft Copolymers. Vol. 29, pp. 47-84. lkada, Y.: Blood-Compatible Polymers. Vol. 57, pp. 103-140.

148

Author Index Volumes 1-94

Ikada, Y. see Tabata, Y. : Vol. 94, pp. 107-142. lmanishi, Y.: Synthese, Conformation, and Reactions of Cyclic Peptides. Vol. 20, pp. 1-77. Inagaki, H. : Polymer Separation and Characterization by Thin-Layer Chromatography. Vol. 24, pp. 189-237. lnoue, S.: Asymmetric Reactions of Synthetic Polypeptides. Vol. 21, pp. 77-106. Irie, M. : Photoresponsive Polymers. Vol. 94, pp. 27-68. Ise, N.: Polymerizations under an Electric Field. Vol. 6, pp. 347-376. Ise, N.: The Mean Activity Coefficient of Polyelectrolytes in Aqueous Solutions and Its Related Properties. Vol. 7, pp. 536-593. lsihara, A. : Irreversible Processes in Solutions of Chain Polymers. Vol. 5, pp. 531-567. Isihara, A. : Intramolecular Statistics of a Flexible Chain Molecule. Vol. 7, pp. 449476. lsihara, A. and Guth, E. : Theory of Dilute Macromolecular Solutions. Vol. 5, pp. 233-260. lshikawa, M. see Narisawa, I. : Vol. 91/92, pp. 353-392. lwatsuki, S. : Polymerization of Quinodimethane Compounds. Vol. 58, pp. 93 120.

Janeschitz-Kriegl, H. : Flow Birefrigence of Elastico-Viscous Polymer Systems. Vol. 6, pp. 170-318. Jenkins, R. and Porter, R. S.: Unpertubed Dimensions of Stereoregular Polymers. Vol. 36, pp. 1-20. Jenngins, B. R. : Electro-Optic Methods for Characterizing Macromolecules in Dilute Solution. Vol. 22, pp. 61~81. Johnston, D. S. : Macrozwitterion Polymerization. Vol. 42, pp. 51-106.

Kamachi, M.: Influence of Solvent on Free Radical Polymerization of Vinyl Compounds. Vol. 38, pp. 55-87. Kamachi, M.: ESR Studies on Radical Polymerization. Vol. 82, pp. 207-277. Kamide, K. and Saito, M. : Cellulose and Cellulose Derivatives: Recent Advances in Physical Chemistry. Vol. 83, pp. 1-57. Kamon, T., Furukawa, H. : Curing Mechanisms and Mechanical Properties of Cured Epoxy Resins. Vol. 80, pp. 173-202. Kaneda, A. see Kinjo, N. : Vol. 88, pp. 148. Kaneko, M. and W6hrle, D.: Polymer-Coated Electrodes: New Materials for Science and Industry. Vol. 84, pp. 141-228. Kaneko, M. and Yamada, A. : Solar Energy Conversion by Functional Polymers. Vol. 55, pp. 148. Kardos, J. L., Dudukovid, M. P., Dave, R.: Void Growth and Resin Transport During Processing of Thermosetting -- Matrix Composites. Vol. 80, pp. 101-123. Kashiwabara, H., Shimada, S., Hori, Y. and Sakaguchi, M.: ESR Application to Polymer Physics -Molecular Motion in Solid Matrix in which Free Radicals are Trapped. Vol. 82, pp. 141-207. Kawabata, S. and Kawai, H.: Strain Energy Density Functions of Rubber Vulcanizates from Biaxial Extension. Vol. 24, pp. 89-124. Keii, T., Doi, Y.: Synthesis of "Living" Polyolefins with Soluble Ziegler-Natta Catalysts and Application to Block Copolymerization. Vol. 73/74, pp. 201-248. Kelley, F. N. see LeMay, J. D.: Vol. 78, pp. 113-148. Kennedy, J. P. and Chou, T.: PolyOsobutylene-co-~-Pinene): A New Sulfur Vulcanizable, Ozone Resistant Elastomer by Cationic Isomerization Copolymerization. Vol. 21, pp. 1-39. Kennedy, J. P. and Delvaux, J. M.: Synthesis, Characterization and Morphology of Poly(butadieneg-Styrene). Vol. 38, pp. 141-163. Kennedy, J. P. and Gillham, J. K. : Cationic Polymerization of Olefins with Alkylaluminium Initiators. Vol. 10, pp. 1-33. Kennedy, J. P. and Johnston, J. E.: The Cationic Isomerization Polymerization of 3-Methyl-l-butene and 4-Methyl-l-pentene. Vol. 19, pp. 57-95. Kennedy, or. P. and Langer, Jr., A. W. : Recent Advances in Cationic Polymerization. Vol. 3, pp. 508-580. Kennedy, J. P. and Otsu, T.: Polymerization with Isomerization of Monomer Preceding Propagation. Vol. 7, pp. 369-385. Kennedy, J. P. and Rengaehary, S. : Correlation Between Cationic Model and Polymerization Reactions of Olefins. Vol. 14, pp. 148.

Author Index Volumes 1-94

149

Kennedy, J. P. and Trivedi, P. D.: Cationic Olefin Polymerization Using Alkyl Halide -- AlkylAluminium Initiator Systems. I. Reactivity Studies. II. Molecular Weight Studies. Vol. 28, pp. 83-151. Kennedy, J. P., Chang, V. S. C. and Guyot, A.: Carbocationic Synthesis and Characterizatioh of Polyolefins with Si-H and Si-C1 Head Groups. Vol. 43, pp. 1-50. Khoklov, A. R. and Grosberg, A. Yu. : Statistical Theory of Polymeric Lyotropic Liquid Crystals. Vol. 41, pp. 53--97. Kinjo, N., Ogata, M., Nishi, K. and Kaneda, A.: Epoxy Molding Compounds as Encapsulation Materials for Microelectronic Devices. Vol. 88, pp. 1--48. Kinloch, A. J. : Mechanics and Mechanisms of Fracture of Thermosetting Epoxy Polymers. Vol. 72, pp. 45--68. Kissin, Yu. V.: Structures of Copolymers of High Olefins. Vol. 15, pp. 91--155. Kitagawa, T. and Miyazawa, T.: Neutron Scattering and Normal Vibrations of Polymers. Vol. 9, pp. 335--414. Kitamaru, R. and Horii, F. : NMR Approach to the Phase Structure of Linear Polyethylene. Vol. 26, pp. 139--180. Klosinski, P., Penczek, S. : Teichoic Acids and Their Models: Membrane Biopolymers with Polyphosphate Backbones. Synthesis, Structure and Properties. Vol. 79, pp. 139--157. Kloosterboer, J. G. : Network Formation by Chain Crosslinking Photopolymerization and its Applications in Electronics. Vol. 84, pp. 1--62. Knappe, W. : Warmeleitung in Polymeren. Vol. 7, pp. 477--535. Koenik, J. L. see Mertzel, E. Vol. 75, pp. 73--112. Koenig, J. L. :Fourier Transforms Infrared Spectroscopy of Polymers, Vol. 54, pp. 87--154. Koenig, J. L. see Andreis, M. Vol. 89, pp. 69--160. K6ncz6l, L. see D611, W. : Vol. 91/92, pp. 137-214. K6tter, M. see Kulicke, W.-M. Vol. 89, pp. 1 68. Kola~ik, J. : Secondary Relaxations in Glassy Polymers : Hydrophilic Polymethacrylates and Polyacrylates: Vol. 46, pp. 119--161. Kong, E. S. W.: Physical Aging in Epoxy Matrices and Composites. Vol. 80, pp. 125--171. Koningsveld, R. : Preparative and Analytical Aspects of Polymer Fractionation. Vol. 7. Kosyanchuk, L. F. see Lipatov, Yu. S. : Vol. 88, pp. 49--76. Kovacs, A. J. : Transition vitreuse dans les polymers amorphes. Etude ph6nom6nologique. Vol. 3, pp. 394--507. Krgissig, H. A. :Graft Co-Polymerization of Cellulose and Its Derivates. Vol. 4, pp. 111--156. Kramer, E. J. : Microscopic and Molecular Fundamentals of Crazing. Vol. 52/53, pp. 1--56. Kramer, E. J. and Berger, L. L. : Fundamental Processes of Craze Growth and Fracture. Vol. 91/92, pp. 1-68. Kraus, G. : Reinforcement of Elastomers by Carbon Black. Vol. 8, pp. 155--237. Kratochvila, J. see Mejzlik, J. : Vol. 81, pp. 83--120. Kreutz, W. and Welte, W. : A General Theory for the Evaluation of X-Ray Diagrams of Biomembranes and Other Lamellar Systems. Vol. 30, pp. 161--225. Krimm, S. : Infrared Spectra of High Polymers. Vol. 2, pp. 51--72. Kuhn, W., Ramel, A., Waiters, D. H: Ebner, G. and Kuhn, H. J.: The Production of Mechanical Energy from Different Forms of Chemical Energy with Homogeneous and Cross-Striated High Polymer Systems. Vol. 1, pp. 540--592. Kulicke, W.-M., K6tter, M. and Griiger, H.: Drag Reduction Phenomenon with Special Emphasis on Homogeneous Polymer Solutions. Vol. 89, pp. 1--68. Kunitake, T. and Okahata, Y.." Catalytic Hydrolysis by Synthetic Polymers. Vol. 20, pp. 159--221. Kurata, M. and Stockmayer, W. H.: Intrinsic Viscosities and Unperturbed Dimensions of Long Chain Molecules. Vol. 3, pp. 196--312. Kurimura, Y.: Macromolecule-Metal Complexes -- Reactions and Molecular Recognition. Vol. 90, pp. 105--138. Leberger, D. see Dettenmaier, M. : Vol. 91/92, pp. 119-136. Ledwith, A. and Sherrington, D. C.: Stable Organic Cation Salts: Ion Pair Equilibria and Use in Cationic Polymerization. Vol. 19, pp. 1--56. Ledwith, A. see Chiellini, E. Vol. 62, pp. 143--170.

150

Author Index Volumes 1-94

Lee, C.-D. S. and Daly, W . H . : Mercaptan-Containing Polymers. Vol. 15, pp. 61--90. Legeay, G. see Brosse, J.-C.: Vol. 81, pp. 167--224. LeMay, J. D., Kelley, F. N. : Structure and Ultimate Properties of Epoxy Resins. Vol. 78, pp. 113-- 148. Lesn6, M. see Mejzlik, J. :Vol. 81, pp. 83--120. Levin, V. S. see Fridman, M. L. : Vol. 93, pp. 81-136. Lindberg, J. J. and Hortling, B.: Cross Polarization -- Magic Angle Spinning N M R Studies of Carbohydrates and Aromatic Polymers. Vol. 66, pp. 1--22. Lipatov, Y. S. : Relacation and Viscoelastic Properties of Heterogeneous Polymeric Compositions. Vol. 22, pp. 1--59. Lipatov, Y. S. : The Iso-Free-Volume State and Glass Transitions in Amorphous Polymers : New Development of the Theory. Vol. 26, pp. 63--104. Lipatov, Yu. S., Lipatova, T. E. and Kosyanchuk, L. F.: Synthesis and Structure of Macromolecular Topological Compounds. Vol. 88, pp. 49--76. Lipatova, T. E. : Medical Polymer Adhesives. Vol. 79, pp. 65--93. Lipatova, T. E. see Lipatov, Yu. S. : Vol. 88, pp. 49--76. Litmanovich, A. A. see Papisov, J. M. : Vol. 90, pp. 139--180. Lohse, F., Zweifel, H. : Photocrosslinking of Epoxy Resins. Vol. 78, pp. 59--80. Lusto~, J. and Va~g, F. : Anionic Copolymerization of Cyclic Ethers with Cyclic Anhydrides. Vol. 56, pp. 91--133.

Madec, J.-P. and Mar~chal, E.: Kinetics and Mechanisms of Polyesterifications. II. Reactions of Diacids with Diepoxides. Vol. 71, pp. 153--228. Mano, E. B. and Coutinho, F. M. B. : Grafting on Polyamides. Vol. 19, pp. 97--116. MarOchal, E. see Madec, J.-P. Vol. 71, pp. 153--228. Mark, H. B., Jr. see Diaz, A. F.: Vol. 84, pp. 113--140. Mark, J. E. : The Use of Model Polymer Networks to Elucidate Molecular Aspects of Rubberlike Elasticity. Vol. 44, pp. 1--26. Mark, J. E. see Queslel, J. P. Vol. 71, pp. 229-248. Maser, F., Bode, K., Pillai, V. N. R. and Mutter, M.: Conformational Studies on Model Peptides. Their Contribution to Synthetic, Structural and Functional Innovations on Proteins. Vol. 65, pp. 177--214. Masuda, T. and Higashimura, T.: Polyacetylenes with Substituents : Their Synthesis and Properties. Vol. 81, pp. 121--166. McGrath, J. E. see Yilg6r, I. : Vol. 86, pp. 1--86. McGrath, J. E. see Yorkgitis, E. M. Vol. 72, pp~ 79--110. Mclntyre, J. E. see Dobb, M. G. Vol. 60/61, pp. 61--98. Meerwall v., E. D.: Self-Diffusion in Polymer Systems. Measured with Field-Gradient Spin Echo NMR Methods, Vol. 54, pp. 1--29. Mejzlik, J., Lesn5, M. and Kratochvila, J.: Determination of the Number of Active Centers in ZieglerNatta Polymerizations of Olefins. Vol. 81, pp. 83--120. Mengoli, G. : Feasibility of Polymer Film Coating Through Electrointiated Polymerization in Aqueous Medium. Vol. 33, pp. 1--31. Mertzel, E., Koenik, J. L.: Application of FT-IR and N M R to Epoxy Resins. Vol. 75, pp. 73--112. Meyerhoff, G. : Die viscosimetrische Molekulargewichtsbestimmung von Polymeren. Vol. 3, pp. 59-105. Millich, F.: Rigid Rods and the Characterization of Polysocyanides. Vol. 19, pp. 117-- 141. Mita, L see Horie, K.: Vol. 88, pp. 77--128. M61ler, M. : Cross Polarization -- Magic Angle Sample Spinning N M R Studies. With Respect to the Rotational Isomeric States of Saturated Chain Molecules. Vol. 66, pp. 59--80. M6ller, M. see Wunderlich, B. : Vol. 87, pp. 1--121. Morawetz, H. : Specific Ion Binding by Polyelectrolytes. Vol. 1, pp. 1--34. Morgan, R . J . : Structure-Property Relations of Epoxies Used as Composite Matrices. Vol. 72, pp. 1--44. Morin, B. P., Breusova, L P. and Rogovin, Z. A.: Structural and Chemical Modifications of Cellulose by Graft Copolymerization. Vol. 42, pp. 139--166. Mulvaney, J. E., Oversberger, C. C. and Schiller, A. M. : Anionic Polymerization. Vol. 3, pp. 106-- 138.

Author Index Volumes 1-94

151

Nakase, Y4 Kurijama, L and Odafima, A.: Analysis of the Fine Structure of Poly(Oxymethylene) Prepared by Radiation-Induced Polymerization in the Solid State. Vol. 65, pp. 79--134. Narisawa, L and Ishikawa, M. : Crazing in Semicrystalline Thermoplastics. Vol. 91/92, pp. 353-392. Neuse, E. : Aromatic Polybenzimidazoles. Syntheses, Properties, and Applications. Vol. 47, pp. 1--42. Nicolais, L. see Apicella, A. Vol. 72, pp. 69--78. Nishi, K. see Kinjo, N. : Vol. 88, pp. 1--48. Noristi, L. see Barbr, P. C. : Vol. 81, pp. 1--83. Nuyken, 0., Weidner, R.: Graft and Block Copolymers via Polymeric Azo Initiators. Vol. 73/74, pp. 145--200. Ober, Ch. K., Jin, J.-L and Lenz, R. W. : Liquid Crystal Polymers with Flexible Spacers in the Main Chain. Vol. 59, pp. 103--146. Ogata, M. see Kinjo, N. : Vol. 88, pp. 1--48. Okubo, T. and Ise, N.: Synthetic Polyelectrolytes as Models of Nucleic Acids and Esterases. Vol. 25, pp.d35--181. Oleinik, E. F. : Epoxy-Aromatic Amine Networks in the Glassy State Structure and Properties. Vol. 80, pp. 49--99. Osaki, K. : Viscoelastic Properties of Dilute Polymer Solutions. Vol. 1Z pp. 1--64. Osada, Y.: Conversion of Chemiral Into Mechanical Energy by Synthetic Polymers (Chemomechanical Systems). Vol. 82, pp. 1--47. Oster, G. and Nishijima, Y.: Fluorescence Methods in Polymer Science. Vol. 3, pp. 313--331. Otsu, T. see Sato, T. Vol. 71, pp. 41--78. Overberger, C. G. and Moore, J. A.: Ladder Polymers. Vol. 7, pp. 113--150. Packirisamy, S. see Biswas, M. Vol. 70, pp. 71--118. Papisov, J. M. and Litmanovich, A. A. : Molecular ,,Recognition" in Interpolymer Interactions and Matrix Polymerization. Vol. 90, pp. 139--180. Papkov, S. P. : Liquid Crystalline Order in Solutions of Rigid-Chain Polymers. Vol. 59, pp. 75--102, Papkov, V. S. see Godovsky, Yu. K.: Vol. 88, pp. 129--180. Patat, F., Killmann, E. und Schiebener, C. : Die Absorption yon Makromolekiilen aus L6sung. Vol. 3, pp. 332--393. Patterson, G. D. : Photon Correlation Spectroscopy of Bulk Polymers. Vol. 48, pp. 125--159. Penczek, S., Kubisa, P. and Matyjaszewski, K.: Cationic Ring-Opening Polymerization of Heterocyclic Monomers. Vol. 37, pp. 1--149. Penczek, S., Kubisa, P. and Matyjaszewski, K.: Cationic Ring-Opening Polymerization; 2. Synthetic Applications. Vol. 68/69, pp. 1--298. Penezek, S. see Klosinski, P.: Vol. 79, pp. 139--157. Peshkovslcy, S. L. see Fridman, M. L.: Vol. 93, pp. 41-80. Petieolas, W. L. : Inelastic Laser Light Scattering from Biological and Synthetic Polymers. Vol. 9, pp. 285--333. Petropoulos, J. H. : Membranes with Non-Homogeneous Sorption Properties. Vol. 64, pp. 85--134. Petrosyan, A. Z. see Fridman, M. L.: Vol. 93, pp. 81 136. Pino, P. : Optically Active Addition Polymers. Vol. 4, pp. 393--456. Pitha, J.: Physiological Activities of Synthetic Analogs of Polynucleotides. Vol. 50, pp. 1--16. PlatO, N. A. and Noak, O. V. : A Theoretical Consideration of the Kinetics and Statistics of Reactions of Functional Groups of Macromolecules. Vol. 31, pp. 133--173. Plat6, N.A., Valuer, L. I.: Heparin-Containing Polymeric Materials. Vol. 79, pp. 95--138. PlatO, N. A. see Shibaev, V. P. Vol. 60/61, pp. 173--252. Pleseh, P. H. : The Propagation Rate-Constants in Cationic Polymerisations. Vol. 8, pp. 137--154. Porod, G.: Anwendung und Ergebnisse der Rrntgenkleinwinkelstreuung in festen Hochpolymeren. Vol. 2, pp. 363--400. Pospi~il, J. : Transformations of Phenolic Antioxidants and the Role of Their Products in the LongTerm Properties of Polyolefins. Vol. 36, pp. 69--133. Postelnek, W., Coleman, L. E., and Lovelaee, A. M. : Fluorine-Containing Polymers. I. Fluorinated Vinyl Polymers with Functional Groups, Condensation Polymers, and St~crene Polymers. Vol. 1, pp. 75--113.

152

Author Index Volumes 1-94

Queslef. J. P. and Mark, J. E. : Molecular Interpretation of the Moduli of Elastomeric Polymer Net-

works of Know Structure. Vol. 65, pp. 135--176. Queslel, J . P . and Mark, J. E: : Swelling Equilibrium Studies of Elastomeric Network Structures.

Vol. 71, pp. 229--248. Rehage, G. see Finkelmann, H. Vol. 60/61, pp. 99--172, Rempp, P. F. and Franta, E. : Macromonomers : Synthesis, Characterization and Applications. Vol. 58,

pp. 1--54. Rempp, P., Herz, or. and Borchard, W.: Model Networks. Vol. 26, pp. 107--137. Rempp, P., Franta, E., and Herz, J.-E. : Macromolecular Engineering by Anionic Methods. Vol. 86,

pp. 145--173. Richards, Rigbi, Z . : Rigby, D. Roe, R.-J.

R. W.: Small Angle Neutron Scattering from Block Copolymers. Vol. 71, pp. 1--40.

Reinforcement of Rubber by Carbon Black. Vol. 36, pp. 21--68. see Roe, R.-J.: Vol. 82, pp. 103 141. and Rigby, D. : Phase Relations and Miscibility in Polymer Blends Containing Copolymers. Vol. 82, pp. 103--141. '"~ Rogovin, Z . A . and Gabrielyan, G. A. : Chemical Modifications of Fibre Forming Polymers and Copolymers of AcrYlonitrile. igol. 25, pp. 97-- 134. Roha,. M. : Ionic Factors in Steric Control. Vol. 4, pp. 353--392. Roha, M.." The Chemistry of Coordinate Polymerization of Dienes. Vol. 1, pp. 512 539. Ross-Murphy, S. B. see Clark, A. H.: Vol. 83, pp. 57--193. Rostami, S. see Walsh, D. J. Vol. 70, pp. 119--170. Rozengerk, v. A. : Linetics, Thermodynamics and Mechanism of Reactions of Epoxy Oligomers with Amines. Vol. 75, pp. 113--166. Rubinson, J. F. see Diaz, A. F.: Vol. 84, pp. 113--140. Safford, G. J. and Naumann, A. W. : Low Frequency Motions in Polymers as Measured by Neutron

Inelastic Scattering. Vol. 5, pp. 1--27. Sakaguchi, M. see Kashiwabara, H. : Vol. 82, pp. 141--207. Saito, M. see Kamide, K.: Vol. 83, pp. 1--57. Sato, T. and Otsu, 7".: Formation of Living Propagating Radicals in Microspheres and Their Use

in the Synthesis of Block Copolymers. Vol. 71, pp. 41--78. Sauer, J. A. and Chen, C. C. : Crazing and Fatigue Behavior in One and Two Phase Glassy Polymers.

Vol. 52/53, pp. 169--224. Sauer, J. A. and Hara, M. : Effect of Molecular Variables on Crazing and Fatigue of Polymers. Vol.

91192, pp. 69-118. Sawamoto, M. see Higashimura, T. Vol. 62, pp. 49--94. Schirrer, R. : Optical Interferometry: Running Crack-Tip Morphologies and Craze Material Properties.

Vol. 91/92, pp. 215-262. Schrnidt, R. G., Bell, J. P. : Epoxy Adhesion to Metals. Vol. 75, pp. 33--72. Sehuerch, C. : The Chemical Synthesis and Properties of Polysaccharides of Biomedical Interest.

Vol. 10, pp. 173--194. Schulz, R. C. und Kaiser, E. : Synthese und Eigenschaften yon optisch aktiven Polymeren. Vol. 4,

pp. 236--315. Seanor, D. A.: Charge Transfer in Polymers. Vol. 4, pp. 317--352. Semerak, S. N. and Frank, C. W.: Photophysics of Excimer Formation in Aryl Vinyl Polymers,

Vol. 54, pp. 31--85. Seidl, J., Malinsk~, J., Dugek, K. und Heitz, W.: Makropor6se Styrol-Divinylbenzol-Copolymere

und ihre Verwendung in der Chromatographie und zur Darstellung yon Ionenaustauschern. Vol. 5, pp. 113--213. Semjonow, V. : Schmelzviskosit~iten hochpolymerer Stoffe. Vol. 5, pp. 387--450. Semlyen, J. A. : Ring-Chain Equilibria and the Conformations of Polymer Chains. V01. 21, pp. 41 --75. Sen, A.: The Copolymerization of Carbon Monoxide with Olefms. Vol. 73/74, pp. 125--144. Senturia, S. D., Sheppard, N. F. Jr.: Dielectric Analysis of Thermoset Cure. Vol. 80, pp. 1--47. Sevruk, V. D. see Fridman, M. L. : Vol. 93, pp. 1--40. Sharkey, W. H. : Polymerizations Through the Carbon-Sulphur Double Bond. Vol. 17, pp. 73--103. Sheppard, N. F. Jr. see Senturia, S. D. : Vol. 80, pp. 1 47.

Author Index Volumes 1-94

153

Shibaev, V.P. and PlatO, N. A.: Thermotropic Liquid-Crystalline Polymers with Mesogenic Side

Groups. Vol. 60/61, pp. 173--252. Shimada, S. see Kashiwabara, H. : Vol. 82, pp. 141--207. Shimidzu, T.: Cooperative Actions in the Nucleophile-Containing Polymers. Vol. 23, pp. 55--102. Shutov, F. A.: Foamed Polymers Based on Reactive Oligomers, Vol. 39, pp. 1--64. Shutov, F. A. : Foamed Polymers. Cellular Structure and Properties. Vol. 51, pp. 155--218. Shutov, F. A.: Syntactic Polymer Foams. Vol. 73/74, pp. 63--124. Siesler, H. W.: Rheo-Optical Fourier-Transform Infrared Spectroscopy: Vibrational Spectra and

Mechanical Properties of Polymers. Vol. 65, pp. 1--78. Silvestri, G., Gambino, S., and Fi!ardi, G. : Electrochemical Production of Initiators for Polymeri-

zation Processes.Vol. 38, pp. 27--54. Sixl, H.: Spectroscopy of the Intermediate States of the Solid State Polymerization Reaction in

Diacetylene Crystals. Vol. 63, pp. 49--90. Slichter, W. P. : The Study of High Polymers by Nuclear Magnetic Resonance. Vol. 1, pp. 35--74. Small, P. A. : Long-Chain Branching in Polymers. Vol. 18. Smets, G.: Block and Graft Copolymers. Vol. 2, pp. 173--220. Smets, G. : Photochromic Phenomena in the Solid Phase. Vol. 50, pp. 17--44. Smets, G. see Beylen, M. van: Vol. 86, pp. 87--143. Sohma, J. and Sakaguchi, M. : ESR Studies on Polymer Radicals Produced by Mechanical Destruction

and Their Reactivity. Vol. 20, pp. 109--158. Solaro, R. see Chiellini, E. Vol. 62, pp. 143--170. Sotobayashi, H. und Springer, J.: Oligomere in verdiinnten L6sungen. Vol. 6, pp. 473--548. Soutif, J.-C. see Brosse, J.-C. :Vol. 81, pp. 167--224. Sperati, C. A. and Starkweather, Jr., H. W. : Fluorine-Containing Polymers. II. Polytetrafluoroethy-

lene. Vol. 2, pp. 465--495. Spiertz, E. J. see Vollenbroek, F. A.: Vol. 84, pp. 85--112. Spiess, H. W.:Deuteron N M R - A new Toolf0r Studying Chain Mobility and Orientation in

Polymers. Vol. 66, pp. 23--58. Sprung, M. M. : Recent Progress in Silicone Chemistry. I. Hydrolysis of Reactive Silane Intermediates, "

Vol. 2, pp. 442--464.

Stahl, E. and Briiderle, V.: Polymer Analysis by Thermofractography. Vol. 30, pp. 1--88. Stannett, V. T., Koros, W. J., Paul, D. R., Lonsdale, H. K., and Baker, R. W. : Recent Advances in

Membrane Science and Technology. Vol. 32, pp. 69--121. Staverman, A. J.. Properties of Phantom Networks and Real Networks. Voll 44, pp. 73--102. Stauffer, D., Coniglio, A. and Adam, M. : Gelation and Critical Phenomena. Vol. 44, pp. 103--158. Stille, J. K.: Diels-Alder Polymerization. Vol. 3, pp. 48--58. Stolka, M. and Pai, D. : Polymers with Photoconductive Properties. Vot. 29, pp. 1--45. Straube, E. see Heinrich, G. : Vol. 84, pp. 33 87. Stuhrmann, H. : Resonance Scattering in Macromolecular Structure Research. Vol. 67, pp. 123--164. Subramanian, R. V. : Electroinitiated Polymerization on Electrodes. Vol. 33, pp. 35--58. Sumitomo, H. and Hashimoto, K. : Polyamides as Barrier Materials. Vol. 64, pp. 55--84. Sumitomo, H. and Okada, M. : Ring-Opening Polymerization of Bicyclic Acetals, Oxalactone, and

Oxalactam. Vol. 28, pp. 47--82. Szegr, L. : Modified Polyethylene Terephthalate Fibers. Vol. 31, pp. 89--131. Szwarc, M. : Termination of Anionic Polymerization. Vol. 2, pp. 275--306. Szwarc, M. : The Kinetics and Mechanism of N-carboxy-~-amino-acid Anhydride (NCA) Polymeri-

zation to Poly-amino Acids. V01.4, pp. 1--65. Szwarc, M. : Thermodynamics of Polymerization with Special Emphasis on Living Polymers. Vol. 4,

pp. 457--495. Szwarc, M. : Living Polymers and Mechanisms of Anionic Polymerization. Vol. 49, pp. 1--175. Szwarc, M. see Beylen, M. van: Vol. 86, pp. 87--143. Tabata, Y. and Ikada, Y.: Phagocytosis of Polymer Microspheres by Macrophages. Vol. 94, pp.

107--142. Takahashi, A. and Kawaguchi, M. : The Structure of Macromolecules Adsorbed on Interfaces. Vol. 46,

pp. 1--65. Takekoshi, T. : Polyimides. Vol. 94, pp. 1--26.

154

Author Indes Volumes 1-94

Takemori, M. T.: Competition Between Crazing and Shear Flow During Fatigue. Vol. 91/92, pp.

263-300. Takemoto, K. and Inaki, Y.: Synthetic Nucleic Acid Analogs. Preparation and Interactions. Vol. 41,

pp. 1--51. Tani, H. : Stereospecific Polymerization of Aldehydes and Epoxides. Vol. 11, pp. 57--110. Tate, B. E. : Polymerization of Itaconic Acid and Derivatives. Vol. 5, pp. 214--232. Tazuke, S. : Photosensitized Charge Transfer Polymerization. Vol. 6, pp. 321--346. Teramoto, A. and Fujita, H. : Conformation-dependet Properties of Synthetic Polypeptides in the

Helix-Coil Transition Region. Vol. 18, pp. 65--149. Theoea'ris, P. S. : The Mesophase and its Influence on the Mechanical Behvior of Composites. Vol. 66,

pp: 149--188. Thomas, W. M.: Mechanismus of Acrylonitrile Polymerization. Vol. 2, pp. 401--441. Tieke, B. : Polymerization of Butadiene and Butadiyne (Diacetylene) Derivatives in Layer Structures.

Vol. 71, pp. 79--152. Tobolsky, A. V. and DuPr~, D. B.: Macromolecular Relaxation in the Damped Torsional Oscillator

and Statistical Segment Models. Vol. 6, pp. 103--127. Tosi, C. and Ciampelli, F.: Applications of Infrared Spectroscopy to Ethylene-Propylene Copolymers.

Vol. 12, pp. 87--130. Tosi, C.: Sequence Distribution in Copolymers: Numerical Tables. Vol. 5, pp. 451--462. Tran, C. see Yorkgitis, E. M. Vol. 72, pp. 79--110. Tsuchida, E. and Nishide, H. : Polymer-Metal Complexes and Their Catalytic Activity. Vol. 24,

pp. 1--87. Tsuji, K. : ESR Study of Photodegradation of Polymers. Vol. 12, pp. 131--190. Tsvetkov, V. and Andreeva, L. : Flow and Electric Birefringence in Rigid-Chain Polymer Solutions.

Vol. 39, pp. 95--207. Tunkel, V. 1. and Fridman, M. L. : Granulated Thermosetting Materials (Aminoplasts) -- Techno-

logy. Vol. 93, pp. 137--174. Tuzar, Z., Kratochvil, P., and Bohdaneck~, M . : Dilute Solution Properties of Aliphatic Polyamides.

Vol. 30, pp. 117--159. Uematsu, I. and Uematsu, Y. : Polypeptide Liquid Crystals. Vol. 59, pp. 37--74. Valuer, L. L see Platr, N. A.: Vol. 79, pp. 95--138. Valvassori, A. and Sartori, G, : Present Status of the Multicomponent Copolymerization Theory.

Vol. 5, pp. 28--58. Vidal, A. see Donnet, J. B. Vol. 76, pp. 103--128. Viovy, J. L. and Monnerie, L. : Fluorescence Anisotropy Technique Using Synchrotron Radiation

as a Powerful Means for Studying the Orientation Correlation Functions of Polymer Chains. Vol. 67, pp. 99--122. Voigt-Martin, L : Use of Transmission Electron Microscopy to Obtain Quantitative Information About Polymers. Vol. 67, pp. 195--218. Vollenbroek, F. A. and Spiertz, E. J. : Photoresist Systems for Microlithography. Vol. 84, pp. 85-- 112. Voorn, M. J. : Phase Separation in Polymer Solutions. Vol. 1, pp. 192--233. Walsh, D.J., Rostami, S.: The .Miscibility of High Polymers : The Role of Specific Interactions.

Vol. 70, pp. 119--170. Ward, L M.: Determination of Molecular Orientation by Spectroscopic Techniques. Vol. 66, pp.

81--116. Ward, L M. : The Preparation, Structure and Properties of Ultra-High Modulus Flexible Polymers.

Vol. 70, pp. 1--70. Weidner, R. see Nuyken, 0 . : Vol. 73/74, pp. 145--200. Werber, F. X.: Polymerization of Olefins On Supported Catalysts. Vol. 1, pp. 180--191. Wichterle, 0., Sebenda, J., and Krdli(ek, J.: The Anionic Polymerization of Caprolactam. Vol. 2,

pp. 578--595. Wilkes, G. L. : The Measurement of Molecular Orientation in Polymeric Solids. Vol. 8, pp. 91--136. Wilkes, G. L see Yorkgitis, E. M. Vol. 72, pp. 79--110.

155

Author Index Volumes 1-94

Williams, G. : Molecular Aspects of Multiple Dielectric Relaxation Processes in Solid Polymers. Vol. 33, pp. 59--92. Williams, J. G.: Applications of Linear Fracture Mechanics. Vol. 27, pp. 67--120. W6hrle, D. : Polymere aus Nitrilen. Vol. 10, pp. 35--107. WghHe, D.: Polymer Square Planar Metal Chelates for Science and Industry. Synthesis, Properties and Applications. Vol. 50, pp. 45--134. W6hrle, D. see Kaneko, M.: ¥ol. 84, pp. 141--228. Wolf, B. A. : Zur Thermodynamik der enthalpisch und der entropisch bedingten Entmischung von Polymerl6sungen. Vol. 10, pp. 109--171. Wolf, B. A. see Ballauff, M.: Vol. 84, pp. 1--31. Wong, C. P. : Application of Polymer in Encapsulation of Electronic Parts. Vol. 84, pp. 63--84. Woodward, A. E. and Sauer, J. A. : The Dynamic Mechanical Properties of High Polymers at Low Temperatures. Vol. 1, pp. 114--158. Worsfold, D. J. see Beylen, M. van; Vol. 86, pp. 87--143. Wunderlieh, B.: Crystallization During Polymerization. Vol. 5, pp. 568--619. Wunderlieh, B. and Baur, H. : Heat Capacities of Linear High Polymers. Vol. 7, pp. 151--368. Wunderlich, B. and Grebowicz, J. : Thermotropic Mesophases and Mesophase Transitions of Linear, Flecible Macromolecules. Vor. 60/61, pp. 1--60. Wunderlich, B., M~ller, M., GrebowicG J. and Baur, H. : Conformational Motion and Disorder in Low and High Molecular Mass Crystals. Vol. 87, pp. 1--121. Wrasidlo, W.:Thermal Analysis of Polymers. Vol. 13, pp. 1--99.

Yamashita, Y. : Random and Black Copolymers by Ring-Opening Polymerization. Vol. 28, pp. 1--46. Yamazaki, N. : Electrolytically Initiated Polymerization. Vol. 6, pp. 377--400. Yamazaki, N. and Higashi, F.: New Condensation Polymerizations by Means of Phosphorus Compounds. Vol. 38, pp. 1--25. Yilg6r, I. and McGrath, J. E. : Polysiloxane Containing Copolymers : A Survey of Recent Developments. Vol. 86, pp. 1--86. Yokoyama, Y. and Hall, H. K. : Ring-Opening Polymerization of Atom-Bridged and Bond-Bridged Bicyclic Ethers, Acetals and Orthoesters. Vol. 42, pp. 107--138. Yorkgitis, E. M., Eiss, N. S. Jr., Tran, C., Wilkes, G. L. and McGrath, J. E.: Siloxane-Modified Epoxy Resins. Vol. 72, pp. 79--110. Yoshida, H. and Hayashi, K.: Initiation Process of Radiation-induced Ionic Polymerization as Studied by Electron Spin Resonance. Vol. 6, pp. 401--420. Young, R. N., Quirk, R. P. and Fetters, L. J. : Anionic Polymerizations of Non-Polar Monomers Involving Lithium. Vol. 56, pp. 1--90. Yuki, H. and Hatada, K. : Stereospecific Polymerization of Alpha-Substituted Acrylic Acid Esters. Vol. 31, pp. 1--45.

Zachmann, H. G.: Das Kristallisations- und Schmelzverhalten hochpolymerer Stoffe. Vol. 3, pp. 581 --687. Zaikov, G. E. see Aseeva, R. M. Vol. 70, pp. 171--230. Zakharov, V. A., Bukatov, G. D., and Yermakov, Y. L: On the Mechanism of Olifin Polymerization by Ziegler-Natta Catalysts. Vol. 51, pp. 61--100. Zambelli, A. and Tosi, C.: Stereochemistry of Propylene Polymerization. Vol. 15, pp. 31--60. Zucchini, U. and Cecchin, G.: Control of Molecular-Weight Distribution in Polyolefins Synthesized with Ziegler-Natta Catalytic Systems. Vol. 51, pp. 101-- 154. Zwe(fel, H. see Lohse, F. : Vol. 78, pp. 59--80.

Subject Index

Acid yellow 38, 32 disulfides 69, 93 f Acrylamide gels 48, 50, 55 Adsorption chromatography 52 Azobenzene chromophores 32 if, 45, 47, 51, 55, 60 --, dipole moment 32 -

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Benzocyclobutene (BCB) 17 f Bisbenzocyclobutene (BCB) 17-19 Bis(benzocyclobuteneimide)s 18 Bis(ether anhydride)s 6, 9, 12, 13 Bisl:haleimides (BMI) 16, 19 --, rubber toughened 16

Functional initiators 69, 71f, 73, 78, 80f, 86, 102 Gel dilation, thermal effect 50 Graft copolymer 82

Hydrogen peroxide, initiator 83 f 2-Hydroxytribhenylmethanol, surface wettability 51

Initiator efficiency 69, 74, 75, 88

Laser flash photolysis 39 Lysosomes 121 Cell-adhesive proteins, FN 130 Cellulose microspheres 114 --, amino groups by CNBr activation 115 ', etherification of alkali-cellulose 115 Chromophores 28 Chrysophenine G 29 --, gel 45 Cloud point temperature 65 Contraction effect, photostimulated 44 Critical miscibility temperature, photostimulated change 61 c~-Cyanostilbene 43 -

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Debye equation, light scattering 39 Diamines 2-5 Dianhydrides 6-9 Disulfides 69, 86, 91-95

Electrostatic repulsion, photogenereated charges 36 repulsion 48 Emulsion polymerization 111 -

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Macrophages 107 if, 110 Membrane permeability 55 potential, photoresponsive chromophores 53 f Merocyanine, photoexcited 44 Microsphere attachment, van der Waals interaction 127 -- degradation in cells 131ff size 122 f --, sonication 116 Microspheres, albumin 117 --, biodegradable 116 --, cellulose 114 , , water wettability 124 --, gelatin 117 modified with gelatin 130 --, monodispersed polyacrolein 112 , polystyrene 111 --, PLLA and PGLA 116 --, surface charge 123 , free energies 125 --, -- hydrophobicity 115,123 f, 130 --, zeta potentials 123, 126 -

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158 Miscibility 64 Molecular weight distributions, photoirradiation dependant 62 Monodispersed polyacrolein microspheres 112 -- polystyrene microspheres 111 Mononuclear phagocytes 110 -- system (MPS) 110 Multiblock copolymers 82 f, 86 f, 89, 90, 99, 102 -

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Nondegradable polymer 116

Oligoimides, benzocyclobutene end-capped 19 --, biphenylene-terminated 16 f -- with p-cyclophene groups 19 Opsonins 127 Opsonization 130 Osmotic pressure, photoresponsive polymers 50

Pararosaniline 56 PDLLA 116 P G A 116 PGLA 116 Phagocytes, mononuclear 110 Phagocytosis, biochemistry of 118 f -- of polymer microspheres 107 ff in vitro 118 ff in vivo 135 Phagolysosome 121 Phase separation, polymer mixtures 64 -- temperature 60 transition, photostimulated 58 f PHEMA 45, 47, 55 --, gel membrane 55 pH, photocontrol 57 Photochromic chromophores 29 Photoheating 47 Photoirradiation 27 ff Photoisomerization 29 - - , t r a n s to cis 32 f, 45 Photolysis, laser flash 39 Photoreceptor 28 Photoresist 62 Photoresponsive polymers 27 ff --, conformation change 38 ff Photo-shrinkage 42 f Pinocytosis 119 PLLA 116 PMR-15 14, 15 f -

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Subject index Polyacrylamide gels 48, 50, 55 Polyalkylcyanoacrylate nanoparticles 116 Polyamide, azobenzene groups 33, 58 Poly(dimethylsiloxane) 33 Poly(D,L-lactic acid) (PDLLA) 116 Polyetherimides 9, 13, 19 --, by nitro-displacement 3, 9 f --, Ultem 6, 9, 19, 22 Poly(glycolic acid) (PGA) 116 Poly(2-hydroxyethyl methacrylate) (PHEMA), azobenzene groups 47, 55 --, gel 45 -- membrane 55 Polyimide foams 19 f --, Kapton 2, 12 --, Kerimid s e e Bismaleimides 16 --, LARK-TPI 2, 13 --, p-cyclophene groups 19 --, phenyl-substituted 10, 11 --, photo-imagable 20 --, Thermid 13, 14 --, Upilex 6, 10, 21 with acetylene groups 13 f, 17-19 with benzocyclobutene (BCB) groups 17-19 with benzhydrol groups 11 with improved processability 9-11 with norbornenedicarboxylimide groups 14, 15 with phenylene sulfide units 13 Polyimides l f f --, alkyl-substituted 20 --, azobeuzene groups 39 --, biphenylene end-capped 17 by amide-imide exchange reaction 10 -- by Diels-Alder cycloaddition 18 by ether-phenol exchange reaction 10 --, coefficient of linear thermal expansion (CLTE) of 21 --, color 21, 22 --, composites 13 f --, crystalline 11-13 --, crystallinity 11-13 Polyisoimides 14 Poly(L-lactic acid) (PLLA) 116 Poly(L-glutamic acid) membrane 56 --, helix 57 Polymer blends, miscibility 64 -- microspheres, phagocytosis 107 ff mixtures, phase separation 64 Poly(methacrylic acid) 29, 32 -- membrane, spirobenzopyran groups 54 --, photo-effect of swelling 46 --, spirobenzopyran groups 38, 57 Poly(methyl methacrylate), spirobenzopyran groups 37 -

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159

Subject Index Poly(methyl vinyl ether)/polystyrene blends 64 Poly(n-butyl methacrylate), photoirradiated 52 Poly(N-isopropylacrylamide), azobenzene groups 60 Polypeptides, azobenzene groups 38 Polyquinoline, stilbene groups 36 Polystyrene, azobenzene groups 60, 63 --, spirobenzopyran groups, photoresist 62 microspheres, monodispersed 111 Polyureas, azobenzene groups 36 Poly(vinyl chloride) membrane 54 f -

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Seed (two-step) polymerization 111 Single-step polymerization 111 Size/shape changes, photostimulated 42 Soap-free emulsion polymerization 111 Sol-gel phase transition 62 f Solvent evaporation method, preparation of cellulose microspheres 114 Spirobenzopyran, azobenzene groups 37 --, membranes 54 --, merocyanine, photochem, isomerization 44 --, photochromic 53 Stilbene groups, polyquinoline 36 --, photoisomerization 64 Surface wettability, photocontrolled 51f

Telechelic oligomers 69 if, 74, 90, 96, 99 f products, rhodium catalysis 100 f Telomerization redox catalyst 98, 99 -- telechelic oligomers 69, 72 f, 91f, 97-102 --, telogens 69, 91, 94, 96-102 --, telomer 97 Termination, disproportionation 72, 74, 79 --, macroradicals 74 --, monomer 73 f --, recombination 72-74 Tetraalkylthiuram disulfides 86 f Tetraphenyl ethanes 69, 89 f Theta solvents, polystyrene/azobenzene groups 60 Thioureas, initiators 94 Thiuram disulfides 69, 86 f, 94 Transfer constants 85, 86, 88, 90-95, 97, 102 Triphenylmethane leucocyanide 48 f --, acrylamide gel 55 leucoderivatives 36, 48, 56 -- leucohydroxide 48 f --, wettability change 51 Turbidity change, photostimulated 60 Two-step or seed polymerization 111 -

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Unfolding process, photostimulated 41 Xanthogens 69, 87 f, 94-97