Current Status of Polyphosphazene Chemistry - ACS Publications

Chapter 19

Current Status of Polyphosphazene Chemistry Downloaded by UNIV OF MELBOURNE on October 13, 2014 | http://pubs.acs.org Publication Date: January 7, 1988 | doi: 10.1021/bk-1988-0360.ch019

Harry R. Allcock Department of Chemistry, Pennsylvania State University, University Park, PA 16802 Inorganic polymer chemistry is an area of research that links the classical fields of ceramics, metals, and organic polymers, and provides opportunities for the synthesis of new substances that combine the properties of all three. Polyphosphazenes are inorganic macromolecules that illustrate the possibilities available for a wide range of other inorganic systems. In this article, it will be demonstrated that, depending on the synthesis method and molecular structure, it is possible to bias the properties toward those of ceramics, metals, or organic high polymers, and also to develop polymers of biomedical interest.

Polyphosphazenes comprise some of the most i n t e n s i v e l y s t u d i e d i n o r g a n i c macromolecules. They i n c l u d e one o f the o l d e s t known s y n t h e t i c polymers and many of the newest. In m o l e c u l a r s t r u c t u r a l v e r s a t i l i t y , they s u r p a s s a l l o t h e r i n o r g a n i c polymer systems ( w i t h over 300 d i f f e r e n t s p e c i e s now known), and t h e i r uses and d e v e l o p i n g a p p l i c a t i o n s a r e as broad as in many a r e a s o f o r g a n i c polymer chemistry. Moreover, the m o l e c u l a r s t r u c t u r a l , s y n t h e t i c , and p r o p e r t y nuances o f t h e s e polymers i l l u s t r a t e many of the a t t r i b u t e s , problems, and p e c u l i a r i t i e s o f o t h e r i n o r g a n i c m a c r o m o l e c u l a r systems. Thus, t h e y p r o v i d e a "case s t u d y " f o r an u n d e r s t a n d i n g o f what may l i e ahead f o r o t h e r systems now b e i n g probed at the exploratory l e v e l . I n s h o r t , an u n d e r s t a n d i n g of polyphosphazene c h e m i s t r y forms the b a s i s f o r an a p p r e c i a t i o n of a wide v a r i e t y o f r e l a t e d , i n o r g a n i c - b a s e d macromolecular systems and o f the r e l a t i o n s h i p between i n o r g a n i c polymer c h e m i s t r y and the r e l a t e d f i e l d s o f o r g a n i c polymers, c e r a m i c s c i e n c e , and m e t a l s . T h i s r e l a t i o n s h i p is i l l u s t r a t e d in F i g u r e 1. The s c i e n c e o f s o l i d s is the s c i e n c e o f s u p r a m o l e c u l a r systems in which the t h r e e d i m e n s i o n a l s o l i d s t r u c t u r e is h e l d t o g e t h e r by c o v a l e n t bonds

0097-6156/88/0360-0250$06.00/0 © 1988 American Chemical Society

In Inorganic and Organometallic Polymers; Zeldin, M., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1988.

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ALLCOCK

251

Polyphosphazene Chemistry

Downloaded by UNIV OF MELBOURNE on October 13, 2014 | http://pubs.acs.org Publication Date: January 7, 1988 | doi: 10.1021/bk-1988-0360.ch019

Thermally stable, but brittle, heavy and difficult to fabricate

CERAMICS

y

, ' Opportunities for Synthesis of New Materials

METALS Ductile, strong and good electrical conductors, but heavy and prone to oxidation and corrosion

Tough, lightweight, easy to fabricate and corrosion-resistant, but unstable to heat and oxidation

F i g u r e 1. The r e l a t i o n s h i p between t h e t h r e e c l a s s i c a l m a t e r i a l s a r e a s o f c e r a m i c s , p o l y m e r s , and m e t a l s .



252

INORGANIC AND ORGANOMETALLIC POLYMERS

( c e r a m i c s ) , m e t a l l i c bonds ( m e t a l s ) , i o n i c a t t r a c t i o n s ( s a l t s ) , or a c o m b i n a t i o n of c o v a l e n t and van der Waals f o r c e s ( l i n e a r or branched polymers). In p r a c t i c e , i t is c o n v e n i e n t to c o n s i d e r s o l i d systems in terms of the t h r e e - c o r n e r e d arrangement shown in F i g u r e 1, in » which the h i t h e r t o s e p a r a t e and i n s u l a t e d f i e l d s of o r g a n i c polymers, c e r a m i c s , and m e t a l s form the c o r n e r s t o n e s of t r a d i t i o n a l knowledge and p r a c t i c e f o r m a t e r i a l s r e s e a r c h . A c r u c i a l p o i n t to be emphasized is t h a t f u t u r e developments in the m a t e r i a l s f i e l d w i l l almost c e r t a i n l y occur on the c o n n e c t i n g l i n e s t h a t j o i n these d i s c i p l i n e s or in the c e n t r a l a r e a t h a t l i e s between a l l t h r e e . T h i s is one of the main purposes of i n o r g a n i c polymer r e s e a r c h — t h e s e a r c h f o r new and u s e f u l compounds and m a t e r i a l s t h a t combine the p r o p e r t i e s of polymers w i t h those of c e r a m i c s and/or m e t a l s . Such h y b r i d m o l e c u l e s and s u p r a m o l e c u l a r s o l i d s o f f e r the promise of systems w i t h the f l e x i b i l i t y , s t r e n g t h , toughness, and ease of f a b r i c a t i o n of p o l y m e r s , w i t h the h i g h temperature o x i d a t i v e s t a b i l i t y of c e r a m i c s , and the e l e c t r i c a l or c a t a l y t i c p r o p e r t i e s of metals. Polyphosphazene c h e m i s t r y p r o v i d e s an i l l u s t r a t i o n of what is p o s s i b l e in one r e p r e s e n t a t i v e h y b r i d system. Macromolecules d i f f e r from s m a l l m o l e c u l e s in a number of c r i t i c a l p r o p e r t i e s . F i r s t , the l i n e a r c h a i n s t r u c t u r e c o n f e r s e l a s t i c i t y , toughness, and s t r e n g t h on the s o l i d s t a t e system. This is a consequence of the r e o r i e n t a t i o n a l freedom of the s k e l e t a l bonds and of t h e i r a b i l i t y to absorb impact or undergo e l a s t i c d e f o r m a t i o n by means of c o n f o r m a t i o n a l changes r a t h e r than bond c l e a v a g e . However, the n a t u r e of the s k e l e t a l bonds and the elements i n v o l v e d can have a p o w e r f u l i n f l u e n c e on the t o r s i o n a l b a r r i e r f o r i n d i v i d u a l s k e l e t a l bonds. Second, l i n e a r c h a i n polymers are t h e r m o d y n a m i c a l l y u n s t a b l e at elevated temperatures. E n t r o p i e i n f l u e n c e s f a v o r a breakdown to s m a l l m o l e c u l e s e i t h e r by random f r a g m e n t a t i o n or by depolymerization. The l a t t e r p r o c e s s i n v o l v e s a r e v e r s i o n of the polymer to monomer or s m a l l m o l e c u l e r i n g s . Depolymerization to s m a l l r i n g s is a f e a t u r e common to many i n o r g a n i c polymers a t temperatures above 200-250°C. T h i r d , the i n t r o d u c t i o n of c r o s s l i n k s between c h a i n s c o n f e r s i n s o l u b i l i t y and i n c r e a s e d s o l i d s t a t e r i g i d i t y , o f t e n accompanied by improved t h e r m a l s t a b i l i t y . H i g h degrees of c r o s s l i n k i n g c o n f e r c e r a m i c - t y p e p r o p e r t i e s on the s o l i d , whether the backbone atoms are carbon atoms or i n o r g a n i c s p e c i e s . And f i n a l l y , i r r e s p e c t i v e of the types of elements in the backbone, the p r o p e r t i e s of a l i n e a r polymer w i l l depend on the s i d e groups a t t a c h e d to t h a t backbone. T h i s p r i n c i p l e u n d e r l i e s a l l p o l y o l e f i n and p o l y v i n y l m a c r o m o l e c u l a r s c i e n c e and t e c h n o l o g y . It a p p l i e s e q u a l l y w e l l to i n o r g a n i c polymer systems. An i m p o r t a n t d e v e l o p i n g a r e a t h a t l i e s in the r e g i o n between polymer c h e m i s t r y , c e r a m i c s c i e n c e , and m e t a l s , i n v o l v e s the s e a r c h f o r new e l e c t r i c a l l y - c o n d u c t i n g s o l i d s . L i n e a r polymers may conduct e l e c t r i c i t y by e l e c t r o n i c or i o n i c mechanisms. As w i l l be d i s c u s s e d , polyphosphazenes have been s y n t h e s i z e d t h a t , depending on the s i d e group s t r u c t u r e , conduct by e i t h e r of t h e s e two processes. The h i s t o r i c a l development of polyphosphazene c h e m i s t r y is compared in F i g u r e 2 w i t h those of o t h e r i n o r g a n i c polymer systems. I t s o r i g i n s can be t r a c e d to the l a t e 1 8 0 0 s , (I) a l t h o u g h the f i r s t f


19.

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253

POLY(ORGANOSILOXANES)

POLYPHOSPHAZENES


M

I

POLYSILAZANES

1

I

>

POLYSILANES

I

*

METAL COORDINATION POLYMERS I

POLYSULFUR,

POLYBORATES,

->

POLYPHOSPHATES >

POLYSILICATES (CERAMICS) >

POLY(SULFUR NITRIDE)

1900

1910

1920

1930

1940

1950

1960

1970

1980

1990

F i g u r e 2. Approximate sequence o f development o f d i f f e r e n t a r e a s o f i n o r g a n i c polymer c h e m i s t r y from 1900 t o t h e p r e s e n t . The broken l i n e s r e p r e s e n t a c o n t i n u i n g b u t low l e v e l o f activity. V e r t i c a l b a r s i n d i c a t e a b r u p t b e g i n n i n g s and ends o f transient research e f f o r t s .


254


s t a b l e p o l y ( o r g a n o p h o s p h a z e n e s ) were not mid-1960 s.

synthesized u n t i l

the

f

Synthesis

of Polyphosphazenes


Three approaches have been developed f o r the s y n t h e s i s of p o l y phosphazenes. These a r e : (1) The macromolecular s u b s t i t u t i o n r o u t e ; (2) The c y c l i c t r i m e r or t e t r a m e r s u b s t i t u t i o n / p o l y m e r i z a t i o n r o u t e , and (3) D i r e c t s y n t h e s i s from o r g a n o s i l y l p h o s p h a z e n e monomers. T h i s l a s t method is d e s c r i b e d in d e t a i l in another Chapter and w i l l not be c o n s i d e r e d f u r t h e r in t h i s review. M a c r o m o l e c u l a r S u b s t i t u t i o n Route. The c u r r e n t surge in p o l y phosphazene r e s e a r c h is m a i n l y a r e s u l t of the development in the mid I 9 6 0 s (2-4) of a s u b s t i t u t i v e r o u t e to the s y n t h e s i s of organo phosphazene h i g h polymers. B e f o r e t h a t time, o n l y a s p o r a d i c i n t e r e s t in the s u b j e c t e x i s t e d because the known polymers, c r o s s linked poly(dihalophosphazenes), (1,5) were i n s o l u b l e and h y d r o l y t i c a l l y unstable. The s u b s t i t u t i v e method of s y n t h e s i s is i l l u s t r a t e d in Scheme I . Thermal p o l y m e r i z a t i o n of h e x a c h l o r o c y c l o t r i p h o s p h a z e n e ( I ) y i e l d s an u n c r o s s l i n k e d , o r g a n i c s o l v e n t - s o l u b l e h i g h polymer ( I I ) ( 2 - 4 ) . This r e a c t i o n must be c o n t r o l l e d c a r e f u l l y to a v o i d the f o r m a t i o n of the c r o s s l i n k e d , i n s o l u b l e polymer known as " i n o r g a n i c r u b b e r " ( 1 ) . The c y c l i c t r i m e r ( I ) , o b t a i n e d from phosphorus p e n t a c h l o r i d e and ammonium c h l o r i d e , is a v a i l a b l e c o m m e r c i a l l y and is now used on a l a r g e s c a l e in the p o l y m e r i z a t i o n r e a c t i o n . U n c r o s s l i n k e d poly(dichlorophosphazene) ( I I ) is a h i g h l y r e a c t i v e m a c r o m o l e c u l a r intermediate. The c h l o r i n e atoms can be r e p l a c e d by a wide v a r i e t y of o r g a n i c or o r g a n o m e t a l l i c s i d e g r o u p s . Replacement of the c h l o r i n e atoms c o n v e r t s the h y d r o l y t i c a l l y - s e n s i t i v e i n t e r m e d i a t e t o one of many w a t e r - s t a b l e p o l y m e r i c d e r i v a t i v e s , u s u a l l y w i t h o u t c l e a v a g e of the backbone bonds. T h i s r e a c t i o n is the b a s i s of n e a r l y a l l the polyphosphazene c h e m i s t r y and t e c h n o l o g y developed d u r i n g the l a s t 20 y e a r s . The i m p o r t a n t consequence of t h i s r e a c t i o n pathway is t h a t m o l e c u l a r d i v e r s i t y can be a c h i e v e d by m a c r o m o l e c u l a r s u b s t i t u t i o n r a t h e r than by the more c o n v e n t i o n a l method of p o l y m e r i z a t i o n or c o p o l y m e r i z a t i o n of d i f f e r e n t monomers. I t a l l o w s polymers w i t h d i f f e r e n t s i d e groups or c o m b i n a t i o n s of s i d e groups to be p r e p a r e d w i t h an i d e n t i c a l backbone and m o l e c u l a r weight d i s t r i b u t i o n . Thus, d i r e c t comparisons can be made of the e f f e c t s of d i f f e r e n t s i d e groups on p h y s i c a l properties. I t a l s o a l l o w s g r o s s or s u b t l e p r o p e r t y changes to be d e s i g n e d i n t o a macromolecule, a f e a t u r e t h a t a s s i s t s both l a b o r a t o r y s t u d i e s and t e c h n o l o g i c a l i n n o v a t i o n s . Because of these advantages, the s u b s t i t u t i o n r o u t e has been a major reason f o r both the r e c e n t e x p a n s i o n of r e s e a r c h in polyphosphazenes and the use of these polymers in advanced t e c h n o l o g y . Four examples of the e f f e c t s of changes in s i d e group s t r u c t u r e a r e i l l u s t r a t e d in the polymers d e p i c t e d as I I and V I - V I I I . This method of s y n t h e s i s can be used as a p r e l u d e to the g e n e r a t i o n of a w i d e r s t r u c t u r a l v a r i e t y i f o r g a n i c r e a c t i o n c h e m i s t r y is c a r r i e d out on the o r g a n i c s i d e g r o u p s . F o r example, the glucosylphosphazene polymer shown as X has been p r e p a r e d by the c h e m i s t r y shown in Scheme II. 1



19. ALLCOCK


Scheme 1.


255

256


0CH CFH

CI

o

I

f

P -

I

I

OCH CF

Cl

2

3

VI

II

(Microcrystalline, filmand fiber-forming polymer: stable to water, hydro phobic)

(Elastomer: sensitive to water) Downloaded by UNIV OF MELBOURNE on October 13, 2014 | http://pubs.acs.org Publication Date: January 7, 1988 | doi: 10.1021/bk-1988-0360.ch019

Ν = Ρ -

NHCH3'

OCH CF 2

3

I Ν = Ρ -

Ν = Ρ -

I

I

0CH (CF2)CF H 2

NHCH3

2

VIII

VII

(Water-soluble and waterstable)

(Elastomer: stable to water, hydrophobic)

RONa

CH 0H t

1

CI

ONo

°-T"

CF,C00H

-N-P—

-

II

NoCI

4îs -H-I OR

IX

Scheme 2.


19.

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257


D e p r o t e c t i o n of X, and subsequent o x i d a t i o n , r e d u c t i o n , and a c e t y l a t i o n r e a c t i o n s can, w i t h c a r e , be c a r r i e d out w i t h o u t d e c o m p o s i t i o n o f the i n o r g a n i c backbone. R e a c t i o n s o f t h i s type a r e of p a r t i c u l a r i n t e r e s t f o r t h e s y n t h e s i s o f b i o a c t i v e o r biocompatible polyphosphazenes. I t s h o u l d be noted t h a t most of t h e s u b s t i t u t i o n - b a s e d s y n t h e s i s work w i t h p o l y ( o r g a n o p h o s p h a z e n e s ) has been preceded by e x p l o r a t o r y s t u d i e s a t the s m a l l m o l e c u l e , model compound l e v e l , o f t e n w i t h t h e use of c y c l i c t r i m e r I as a model f o r polymer I I ( 6 ) . C y c l i c T r i m e r S u b s t i t u t i o n / P o l y m e r i z a t i o n Route. I t is o f t e n e a s i e r t o r e p l a c e c h l o r i n e atoms in phosphazenes by o r g a n i c s i d e groups a t the c y c l i c t r i m e r o r t e t r a m e r l e v e l than a t the h i g h polymer l e v e l . T h i s is p a r t i c u l a r l y t r u e when o r g a n o m e t a l l i c r e a g e n t s a r e employed as h a l o g e n replacement n u c l e o p h i l e s . Thus, an a l t e r n a t i v e r o u t e t o p o l y ( o r g a n o p h o s p h a z e n e s ) i n v o l v e s the s y n t h e s i s o f o r g a n o - s u b s t i t u t e d c y c l i c t r i m e r i c o r t e t r a m e r i c phosphazenes, f o l l o w e d by p o l y m e r i z a t i o n o f these t o t h e analogous h i g h polymer (Scheme I I I ) . So f a r , i t has proved d i f f i c u l t t o p o l y m e r i z e c y c l i c o l i g o m e r s t h a t bear o r g a n i c s i d e groups o n l y , but some s p e c i e s t h a t bear b o t h halogeno and o r g a n i c s i d e groups can be induced t o p o l y m e r i z e . S e v e r a l c y c l i c t r i m e r s t h a t f a l l i n t o t h i s c a t e g o r y a r e shown in e q u a t i o n s 1-3. The r i n g s t r a i n i n h e r e n t in s p e c i e s XV i n c r e a s e s i t s propensity for polymerization. A s u b s t a n t i a l number o f organoh a l o g e n o c y c l o p h o s p h a z e n e s have now been p o l y m e r i z e d ( 7 - 1 7 ) . After p o l y m e r i z a t i o n , t h e h a l o g e n atoms can be r e p l a c e d by treatment w i t h a l k o x i d e s , a r y l o x i d e s , p r i m a r y o r s e c o n d a r y amines, o r o r g a n o m e t a l l i c reagents. Different

Classes

of P o l y ( o r g a n o p h o s p h a z e n e s )

W i t h t h i s s y n t h e t i c and m o l e c u l a r s t r u c t u r a l d i v e r s i t y , polyphosphazene c h e m i s t r y has d e v e l o p e d i n t o a f i e l d t h a t r i v a l s many a r e a s o f o r g a n i c polymer c h e m i s t r y w i t h r e s p e c t t o t h e t a i l o r e d s y n t h e s i s o f polymers f o r s p e c i f i c e x p e r i m e n t a l o r t e c h n o l o g i c a l uses. Indeed, h y b r i d systems a r e a l s o a v a i l a b l e in which o r g a n i c polymers bear phosphazene u n i t s as s i d e g r o u p s . T h i s is d i s c u s s e d in another Chapter. An u n d e r s t a n d i n g o f modern polyphosphazene c h e m i s t r y can be o b t a i n e d by c o n s i d e r i n g t h e f o l l o w i n g a s p e c t s o f the f i e l d . ( 1 ) Phosphazene polymers w i t h s i d e group systems t h a t a l l o w the h i g h i n h e r e n t f l e x i b i l i t y of t h e backbone t o become m a n i f e s t . Such polymers a r e r u b b e r y e l a s t o m e r s (18-20) s e v e r a l o f which have been d e v e l o p e d in government and i n d u s t r y as h i g h t e c h n o l o g y m a t e r i a l s . Other examples a r e o f i n t e r e s t as s o l i d i o n i c c o n d u c t i o n media ( 2 1 ) . (2) Polyphosphazenes w i t h b i o c o m p a t i b l e o r b i o l o g i c a l l y a c t i v e g r o u p s — i n c l u d i n g s e v e r a l examples t h a t a r e w a t e r - s o l u b l e , b i o d e g r a d a b l e , o r a r e b i o a c t i v e as s o l i d s . (3) Membrane m a t e r i a l s . ( 4 ) Polyphosphazenes w i t h t r a n s i t i o n m e t a l s in the s i d e g r o u p s , s e v e r a l of which have i n t e r e s t i n g c a t a l y t i c o r e l e c t r o a c t i v e p r o p e r t i e s . ( 5 ) Polymers w i t h r i g i d , s t a c k a b l e s i d e groups t h a t can impart e i t h e r s e m i c o n d u c t i v i t y or l i q u i d c r y s t a l l i n e c h a r a c t e r . The e l a s t o m e r c h e m i s t r y and t e c h n o l o g y a r e d i s c u s s e d in a n o t h e r C h a p t e r . A s p e c t s 2-5 a r e i l l u s t r a t e d by the examples g i v e n in t h e following sections.



Scheme 3.


19.

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Biocompatible


259

o r B i o a c t i v e Polyphosphazenes


T h i s s u b j e c t can be c o n s i d e r e d in terms o f f i v e d i f f e r e n t types o f molecules or m a t e r i a l s : (a) b i o l o g i c a l l y i n e r t , w a t e r - i n s o l u b l e polymers; (b) w a t e r - i n s o l u b l e polymers t h a t bear b i o l o g i c a l l y a c t i v e s u r f a c e groups; ( c ) w a t e r - s w e l l a b l e p o l y m e r i c g e l s , o r a m p h i p h i l i c polymers t h a t f u n c t i o n as membranes; (d) w a t e r - i n s o l u b l e but b i o e r o d a b l e polymers t h a t erode in aqueous media w i t h c o n c u r r e n t r e l e a s e o f a l i n k e d o r e n t r a p p e d b i o a c t i v e m o l e c u l e ; and ( e ) w a t e r - s o l u b l e polymers t h a t bear b i o a c t i v e agents as s i d e g r o u p s . (a) B i o l o g i c a l l y - I n e r t , W a t e r - I n s o l u b l e Polymers. Polymers o f t h i s type a r e o f b i o m e d i c a l i n t e r e s t as m a t e r i a l s f o r the c o n s t r u c t i o n o f a r t i f i c i a l h e a r t v a l v e s , b l o o d v e s s e l s , s o f t t i s s u e p r o s t h e s e s , or as c o a t i n g s f o r d e v i c e s such as pacemakers. A number of d i f f e r e n t polyphosphazenes a r e b e i n g c o n s i d e r e d f o r such u s e s , but s p e c i a l a t t e n t i o n has been f o c u s e d on two c l a s s e s — t h o s e t h a t bear f l u o r o a l k o x y s i d e groups, and those w i t h a r y l o x y s i d e u n i t s ( 2 2 ) . Both types a r e h y d r o p h o b i c m a t e r i a l s t h a t , depending on t h e s i d e group arrangements, can e x i s t as e l a s t o m e r s o r as m i c r o c r y s t a l l i n e f i b e r - o r f i l m - f o r m i n g m a t e r i a l s . P r e l i m i n a r y s t u d i e s have suggested t h a t these two c l a s s e s of polyphosphazenes a r e i n e r t and b i o c o m p a t i b l e in subcutaneous t i s s u e i m p l a n t a t i o n e x p e r i m e n t s . (b) W a t e r - I n s o l u b l e Polymers t h a t Bear B i o l o g i c a l l y - A c t i v e S u r f a c e Groups. Three examples w i l l be g i v e n o f polyphosphazenes t h a t have these c h a r a c t e r i s t i c s . F i r s t , t h e a n t i c o a g u l e n t h e p a r i n has been attached to the surface of a poly(aryloxyphosphazene) v i a a q u a t e r n i z e d a r y l o x y s i d e group system ( 2 3 ) . Second, dopamine has been l i n k e d c o v a l e n t l y t o a p o l y ( a r y l o x y phosphazene) v i a a d i a z o - c o u p l i n g t e c h n i q u e ( 2 4 ) . Experiments showed t h a t r a t p i t u i t a r y c e l l s in c u l t u r e responded t o t h e s u r f a c e - b o u n d dopamine in a s i m i l a r manner t o t h a t found when t h e dopamine was f r e e in s o l u t i o n . T h i r d , a poly[bis(phenoxy)phosphazene] has been c o a t e d on porous alumina p a r t i c l e s , s u r f a c e n i t r a t e d , reduced t o t h e a m i n o - d e r i v a t i v e , and then c o u p l e d t o the enzyme g l u c o s e - 6 - p h o s p h a t e dehydrogenase o r t r y p s i n by means o f g l u t a r i c d i a l d e h y d e . The i m m o b i l i z e d enzymes were more s t a b l e than t h e i r c o u n t e r p a r t s in s o l u t i o n , and they c o u l d be used in c o n t i n u o u s f l o w enzyme r e a c t o r equipment ( 2 5 ) . ( c ) W a t e r - S w e l l a b l e P o l y m e r i c G e l s o r A m p h i p h i l i c Polymers t h a t F u n c t i o n as Membranes. Two polyphosphazene systems have been s t u d i e d in d e t a i l ( 2 6 ) — m i x e d s u b s t i t u e n t polymers t h a t bear both methylamino and t r i f l u o r o e t h o x y groups ( X V I ) , w i t h the polymer c h a i n s l i g h t l y c r o s s l i n k e d v i a t h e methylamino u n i t s by g a m m a - i r r a d i a t i o n , and p o l y [ b i s ( m e t h o x y e t h o x y e t h o x y ) p h o s p h a z e n e (XVII), again l i g h t l y c r o s s l i n k e d by gamma r a y s . The l a t t e r polymer is w a t e r - s o l u b l e in the u n c r o s s l i n k e d s t a t e ( 2 7 ) . I t a l s o f u n c t i o n s as a s o l i d e l e c t r o l y t e medium f o r s a l t s such as l i t h i u m t r i f l a t e ( 2 1 ) . (d) W a t e r - I n s o l u b l e but B i o e r o d a b l e Polymers t h a t Erode in Aqueous Media w i t h C o n c u r r e n t R e l e a s e o f a L i n k e d o r Entrapped B i o a c t i v e Molecule. The f i r s t examples o f polyphosphazenes t h a t f u n c t i o n in t h i s way were s p e c i e s t h a t c o n t a i n e d e t h y l g l y c i n a t e o r o t h e r amino


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a c i d e s t e r s i d e groups ( 2 8 ) . H y d r o l y s i s r e s u l t s in a breakdown o f the polymer t o amino a c i d , e t h a n o l , and phosphate, a l l o f which can be m e t a b o l i z e d , and ammonia which can be e x c r e t e d . Subsequent a p p l i c a t i o n o f t h i s c h e m i s t r y has c o n f i r m e d the b i o c o m p a t i b i l i t y of the system and has l e d t o t h e development of a c o n t r o l l e d drug r e l e a s e system ( 2 9 ) . A d i f f e r e n t approach r e p o r t e d r e c e n t l y (30) i n v o l v e s t h e s y n t h e s i s and e v a l u a t i o n o f polyphosphazenes t h a t c o n t a i n b o t h a r y l o x y and i m i d a z o l y l s i d e g r o u p s . H y d r o l y t i c removal o f t h e i m i d a z o l y l u n i t s takes p l a c e w i t h a c o n c u r r e n t e r o s i o n o f the s o l i d polymer in a manner t h a t is a p p r o p r i a t e f o r the c o n t r o l l e d r e l e a s e o f e n t r a p p e d drug m o l e c u l e s . ( e ) W a t e r - S o l u b l e Polymers t h a t Bear B i o a c t i v e S i d e Groups. P o l y phosphazenes t h a t bear methylamino ( 3 1 ) , g l u c o s y l , o r a l k y l e t h e r (27) s i d e groups a r e s o l u b l e in water. P o l y [ b i s ( m e t h y l a m i n o ) phosphazene] was used in e a r l y work as a c o o r d i n a t i o n c a r r i e r f o r p l a t i n u m a n t i t u m o r drugs ( 3 2 ) . The c h e m i s t r y now e x i s t s f o r the l i n k a g e o f a wide range o f b i o a c t i v e a g e n t s , such as l o c a l a n e s t h e t i c s ( 3 3 ) , s t e r o i d s ( 3 4 ) , a n t i b a c t e r i a l agents ( 3 5 ) , o r p r o t e i n s t o polyphosphazenes which, in c o n j u n c t i o n w i t h the w a t e r - s o l u b i l i z i n g groups, o f f e r s a promise f o r a v a r i e t y o f pharmacological a p p l i c a t i o n s . Polyphosphazenes

w i t h T r a n s i t i o n M e t a l s in the S i d e Groups

T h i s a s p e c t o f polyphosphazene c h e m i s t r y has r e c e n t l y been reviewed elsewhere (36) and o n l y a b r i e f account w i l l be g i v e n h e r e . M e t a l l o p h o s p h a z e n e s a r e a new type o f macromolecule d e s i g n e d t o b r i d g e t h e gap between polymers and m e t a l s . A l t h o u g h s t i l l a t an e x p l o r a t o r y s t a g e of l a b o r a t o r y development, they may p r o v i d e a c c e s s t o e l e c t r o n i c a l l y - c o n d u c t i n g polymers, m a g n e t i c a l l y - a c t i v e polymers, m a c r o m o l e c u l a r c a t a l y s t s , e l e c t r o d e m e d i a t o r systems, o r polymers c r o s s l i n k e d by m e t a l atoms. T r a n s i t i o n m e t a l s have been l i n k e d t o c y c l o - and p o l y phosphazenes by f o u r d i f f e r e n t methods. F i r s t , and most o b v i o u s , t h e l i n k a g e makes use o f the c o o r d i n a t i n g power of t h e backbone n i t r o g e n atoms. The p l a t i n u m d i c h l o r i d e adduct ( r e f e r r e d t o e a r l i e r ) f a l l s into this category. Second, as a l o g i c a l development o f t h e f i r s t approach, p o l y phosphazenes have been s y n t h e s i z e d t h a t bear phosphine u n i t s connected t o a r y l o x y s i d e groups ( 3 7 ) . The phosphine u n i t s b i n d o r g a n o m e t a l l i c compounds, such as those o f i r o n , c o b a l t , osmium, o r ruthenium (38). In s e v e r a l cases, the c a t a l y t i c a c t i v i t y of the m e t a l is r e t a i n e d in the m a c r o m o l e c u l a r system ( 3 9 ) . A s i m i l a r b i n d i n g o f t r a n s i t i o n m e t a l s has been a c c o m p l i s h e d t h r o u g h n i d o c a r b o r a n y l u n i t s l i n k e d t o a polyphosphazene c h a i n ( 4 0 ) . T h i r d , m e t a l l o c e n e u n i t s , such as f e r r o c e n e o r r u t h e n o c e n e , have been l i n k e d t o phosphazene c y c l i c t r i m e r s o r t e t r a m e r s and t h e s e were p o l y m e r i z e d and s u b s t i t u t e d t o g i v e polymers o f t h e type mentioned p r e v i o u s l y ( 4 1 ) . Polyphosphazenes w i t h f e r r o c e n y l groups c a n be doped w i t h i o d i n e t o form weak s e m i c o n d u c t o r s . Polymer c h a i n s t h a t bear both r u t h e n o c e n y l and f e r r o c e n y l s i d e groups a r e p r o s p e c t i v e e l e c t r o d e m e d i a t o r systems. F i n a l l y , a t t h e c y c l i c t r i m e r and t e t r a m e r l e v e l s , compounds o f


262


types XVIII and XIX have been s y n t h e s i z e d , and m e t a l - s u b s t i t u t e d high polymers have a l s o been p r e p a r e d . The development of o r g a n o m e t a l l i c r e a c t i o n c h e m i s t r y a t the s m a l l m o l e c u l e l e v e l , as e x e m p l i f i e d by compounds X V I I I and XIX is an i l l u s t r a t i o n of the key r o l e p l a y e d by s m a l l m o l e c u l e model compound work in the development of h i g h p o l y m e r i c phosphazene c h e m i s t r y .


Polyphosphazenes w i t h R i g i d , S t a c k a b l e

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Groups

The c o n n e c t i o n between polymer c h e m i s t r y and c e r a m i c s c i e n c e is found in the ways in which l i n e a r macromolecules can be c o n v e r t e d i n t o g i a n t " u l t r a s t r u c t u r e " systems, in which t h e whole s o l i d m a t e r i a l comprises one g i a n t m o l e c u l e . T h i s t r a n s f o r m a t i o n c a n be a c c o m p l i s h e d in two w a y s — f i r s t by the f o r m a t i o n of c o v a l e n t , i o n i c , or c o o r d i n a t e c r o s s l i n k s between polymer c h a i n s , and second, by t h e i n t r o d u c t i o n of c r y s t a l l i n e o r d e r . I n t h e second approach, s t r o n g van d e r Waals f o r c e s w i t h i n t h e c r y s t a l l i n e domains c o n f e r r i g i d i t y and s t r e n g t h n o t u n l i k e t h a t found when c o v a l e n t c r o s s l i n k s a r e present. A d i f f e r e n c e between m i c r o c r y s t a l l i t e - b a s e d u l t r a s t r u c t u r e and c o v a l e n t l y - c r o s s l i n k e d systems is t h a t m i c r o c r y s t a l l i t e s melt at s p e c i f i c t e m p e r a t u r e s , a l l o w i n g the polymer t o be f a b r i c a t e d by h e a t i n g a t modest t e m p e r a t u r e s . Subsequent c o o l i n g of the system below the c r y s t a l l i z a t i o n temperature a l l o w s the p h y s i c a l p r o p e r t y advantages of the s o l i d s t a t e t o become m a n i f e s t . Liquid c r y s t a l l i n i t y is a l s o p o s s i b l e i f some o r d e r is r e t a i n e d in t h e molten s t a t e . C r y s t a l l i n e o r d e r n o t o n l y adds m e c h a n i c a l s t r e n g t h , i t a l s o p r o v i d e s o p p o r t u n i t i e s f o r t h e appearance of o t h e r p r o p e r t i e s t h a t depend on s o l i d s t a t e o r d e r — s u c h as e l e c t r o n i c c o n d u c t i v i t y . F o r these r e a s o n s , s e v e r a l e x p l o r a t o r y s t u d i e s have been made o f t h e f e a s i b i l i t y of attachment of c r y s t a l l i z a b l e s i d e groups t o p o l y phosphazenes. Three examples a r e g i v e n below. TCNQ-Polyphosphazene Systems. T e t r a c y a n o q u i n o d i m e t h a n e (XX) s a l t s c r y s t a l l i z e in t h e form of s t a c k e d a r r a y s t h a t a l l o w e l e c t r i c a l semiconductivity (42). A l t h o u g h t h i s phenomenon has been s t u d i e d in many l a b o r a t o r i e s , i t has not been p o s s i b l e t o f a b r i c a t e c o n d u c t i v e f i l m s o r w i r e s from these s u b s t a n c e s because of the b r i t t l e n e s s t h a t is c h a r a c t e r i s t i c o f o r g a n i c s i n g l e c r y s t a l s . However, i t seemed p o s s i b l e t h a t , i f the f l e x i b i l i t y and ease of f a b r i c a t i o n o f many polyphosphazenes c o u l d be combined w i t h t h e e l e c t r i c a l p r o p e r t i e s o f TCNQ, c o n d u c t i n g polymers might be a c c e s s i b l e . In r e c e n t s t u d i e s , i t has been found t h a t TCNQ u n i t s can be a t t a c h e d t o q u a t e r n i z e d polyphosphazene m o l e c u l e s , ( 4 3 ) . The q u a t e r n i z a t i o n s i t e s a r e e i t h e r backbone n i t r o g e n atoms or amino o r phosphino u n i t s on t h e s i d e c h a i n s . A l t h o u g h t h e l o a d i n g o f TCNQ was not h i g h , t h e p o l y m e r i c system p o s s e s s e d s u f f i c i e n t e l e c t r i c a l s e m i c o n d u c t i v i t y t o suggest t h a t the TCNQ u n i t s were f o r m i n g s t a c k e d arrays w i t h i n the s o l i d matrix. This suggested that other s i d e groups might behave in a s i m i l a r manner. Polyphosphazene-Phthalocyanine S t r u c t u r e s . Thus, a r e l a t e d s t u d y was c a r r i e d o u t w i t h copper p h t h a l o c y a n i n e u n i t s l i n k e d c o v a l e n t l y t o a poly(aryloxyphosphazene) (44). Non-polymeric copper p h t h a l o c y a n i n e forms o r d e r e d s t a c k e d s t r u c t u r e s in t h e c r y s t a l l i n e s t a t e . When


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t r e a t e d w i t h i o d i n e o r o t h e r dopants, t h e s e a r e t r a n s f o r m e d i n t o e l e c t r i c a l semiconductors (45-46). I n t h e phosphazene p o l y m e r i c system, some p h t h a l o c y a n i n e group s t a c k i n g a l s o appears t o o c c u r , even though t h e p h t h a l o c y a n i n e c o n c e n t r a t i o n is low. Doping w i t h i o d i n e g e n e r a t e d weak e l e c t r i c a l s e m i c o n d u c t i v i t y . L i q u i d C r y s t a l l i n e Polymers. The t h i r d example is t h e r e c e n t s y n t h e s i s in our l a b o r a t o r y o f a l i q u i d c r y s t a l l i n e polyphosphazene (47). The s t r u c t u r e o f t h i s macromolecule is shown in XXI. T h i s p a l e y e l l o w polymer shows t y p i c a l m i c r o c r y s t a l l i n e p r o p e r t i e s a t temperatures below 118°C. H e a t i n g above 118°C l e a d s t o t h e f o r m a t i o n of a mesophase, in which some m o l e c u l a r o r d e r is r e t a i n e d . The mesophase m e l t s above 127°C t o g i v e an i s o t r o p i c m e l t . T h i s is a s t r i k i n g i l l u s t r a t i o n o f the way in which a h i g h l y f l e x i b l e polymer c h a i n , c o u p l e d t o r i g i d u n i t s v i a f l e x i b l e s p a c e r groups, a l l o w s l i q u i d c r y s t a l l i n e s t a c k i n g of the aromatic azide u n i t s to occur. I t appears from r e c e n t p a r a l l e l work t h a t t h e same phenomenon e x i s t s even when a non-mesogenic c o s u b s t i t u e n t group is p r e s e n t ( 4 8 ) . H i s t o r i c a l Perspective The development o f s y n t h e t i c r o u t e s t o new polyphosphazene s t r u c t u r e s began in the mid I960's ( 2 - 4 ) . The i n i t i a l e x p l o r a t o r y development of t h i s f i e l d has now been f o l l o w e d by a r a p i d e x p a n s i o n o f s y n t h e s i s r e s e a r c h , c h a r a c t e r i z a t i o n , and a p p l i c a t i o n s - o r i e n t e d work. The i n f o r m a t i o n shown in F i g u r e 3 i l l u s t r a t e s the sequence o f development of s y n t h e t i c pathways t o polyphosphazenes. I t seems c l e a r t h a t t h i s f i e l d has grown i n t o a major a r e a o f polymer c h e m i s t r y and t h a t polyphosphazenes, as w e l l as o t h e r i n o r g a n i c macromolecules, w i l l be used i n c r e a s i n g l y in p r a c t i c a l a p p l i c a t i o n s where t h e i r unique p r o p e r t i e s a l l o w t h e s o l u t i o n o f d i f f i c u l t e n g i n e e r i n g and b i o m e d i c a l problems. Acknowledgment s Our work has been s u p p o r t e d m a i n l y by t h e Army R e s e a r c h O f f i c e , A i r F o r c e O f f i c e o f S c i e n t i f i c Research, O f f i c e o f N a v a l R e s e a r c h , and the P u b l i c H e a l t h S e r v i c e t h r o u g h t h e N a t i o n a l H e a r t , Lung, and Blood Institute. Literature 1. 2. 3. 4. 5. 6. 7. 8.

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RECEIVED September 30, 1987


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