Polyphosphazenes

Polyphosphazenes comprise by far the largest class of inorganic macromolecules. At least 700 different polymers of this type have been synthesized, with a range of physical and chemical properties that rivals that known hitherto only for synthetic organic macromolecules.1 

In addition to linear polyphosphazenes with one type of side group, as shown in 3.1, other molecular architectures have also been assembled. These include polyphosphazenes in which two or more different side groups, R1 and R2, are arrayed along the chain in random, regular, or block distributions (3.2-3.4). Other species exist with short phosphazene branches linked to phosphorus atoms in the main chain (3.5,3.6). Also available are macromolecules in which carbon or sulfur replace some of the phosphorus atoms in 

In the rest of this chapter an attempt will be made to describe how this field developed, how polyphosphazenes are synthesized, how the system provides almost unprecedented opportunities for the design of new macromolecules, and how the molecular structure-property relationships have been developed to produce a wide range of advanced materials. 

Polyphosphazenes are a group of inorganic polymers, having the general molecular stmcture represented by 7. The backbone consists of 

Synthetic approaches to produce polymers with desirable biomedical characteristics for this class of materials have been extensively reviewed (Allcock, 1990 Crommen et al, 1993). Poly[(amino acid ester) phos-phazenes] are knovm to be susceptible toward hydrolytic degradation and hold promise as degradable materials. Recently, Laurencin etal (1987) used a poly(imidazole methylphenoxy) phosphazene to study the release characteristics ofBSA. Protein release was demonstrated using C-labeled BSA in a 20% imidazole-substituted polyphosphazene. Release from this matrix consisted of an initial burst of almost 25% of the protein, followed by release over several hundred hours in which a total of 55% of the protein was released. Polymer degradation for the 20% imidazole-substituted polyphosphazene was also studied and found to be quite slow, with 4% of the polymer degraded in 600 hr. 

The relatively recent explosion of the recombinant DNA field has led to the identification, cloning, expression, and large-scale production of many previously unavailable proteins, including antigens and vaccines. The newest 

Polymers shown to possess immunostimulatory properties in the form of their degraded products are the polyiminocarbonates (Kohn et al, 1986), based on a variation of classical polycarbonates (8). The only stractural 

Further, certain polyiminocarbonate polymers have also shown the potential for delayed release of a small molecule, /7-nitroaniline (pNA) (Pulapura et al, 1990). The release profile of pNA from poly(bisphenol 

Synthesis of polyphosphazenes dates back to 1895 when H. N. Stokes 

Four main ways to synthesize polyphosphazenes have been identified (Zhu and Qiu, 2005)  

Polyphosphazenes have already been investigated for biomedical applications, especially in controlling the release of chemotherapeutic agents (Cho and Allcock, 2007) (and thus in the drug delivery field) and in the temporary replacement of body parts (Deng et al., 2010). For example, following 

6 Polyiamino acids) and pseudo poly(amino acids) 

Alkoxy and aryloxy polyphosphazenes with the general structure OR 

Similar polymorphism and enhanced ordering on heating above T was also observed and is expected for a group of three related phosphazenes. Polyfbis(phen-oxy)phosphazene] (R QHs—, T,j = 423 K) was similarly analyzed with respect to X-ray diffraction and electron microscopy as the trifluoroethoxy compound 73.274) 

Poly[bis(p-methy henoxy)-phosphazene] (RiCHs—CgHj—, about 4 K) was 

The discussion of the behavior of eondis crystals of flexibte linear macromolecules and some of the homolc ous oUgcaners covers a witte range of c aiformational disorder-effects and accompanying motion. For many of the macromolecules in the eondis phase chain-extension afto- erystallization with chain folding is possible [polyethylene, polytetrafluOToethylene, poly(vinylidene fluoride), polydilorotrifluoro-ethylene, some aliphatic nylons and polyphosphazenes]. Stx h extended ehain crystals are exceptionally stable and elose to equlibrium. 

For polyethylene and polytetrafluOToethylene the eondis phase could be traced to the oligomeric homolc ues with s %cial effects due to chain ends (paraffins) and whole molecule rotations (pOTfluoroallcanes). While the plastic crystal phase in cyclo-alkenes (Sect. 3.2) and substituted benzenes (Sect. 5.1.1) is restricted to dynamic disorder of a single conformer about rotation axes normal to the piaMS of the molecules, perfluorobutaM and perfluorohexane have dynamic disordOT restricted to motion about axes parallel to the molecular axis. 

Some of the most useful polyphosphazenes are fluoroalkoxy derivatives and amorphous copolymers (11.27) that are practicable as flame-retardant, hydrocarbon solvent- and oil-resistant elastomers, which have found aerospace and automotive applications. Polymers such as the amorphous comb polymer poly[bis(methoxyethoxyethoxy)phosphazene] (11.28) weakly coordinate Li ions and are of substantial interest as components of polymeric electrolytes in battery technology. Polyphosphazenes are also of interest as biomedical materials and bioinert, bioactive, membrane-forming and bioerodable materials and hydrogels have been prepared. 

Condensation reactions to polyphosphazenes have been developed that provide an alternative, direct route to ffuoroalkoxyphosphazene polymers and aryl derivatives [eqns (11.31) and (11.32)]. The development of condensation routes to poly(dichlorophosphazene) has also been reported for example, a promising route that operates at 200 °C has been described [eqn (11.33)].  

A synthesis of polydichlorophosphazene that operates at room temperature and allows molecular weight control has been developed starting from the trichlorophosphoranimine Cl3P=NSiMe3 [eqn (11.34)].  

The phosphoranimine monomer is readily prepared in two steps from PCI3 in a one-pot procedure [eqn (11.35)].  

Closely related to polyphosphazenes is the class of polymers known as polyheterophosphazenes, where one or more of the P atoms per repeat unit is substituted by an atom of a heteroelement. The first well-characterised example of such materials involved carbon as the replacement for phosphorus the resulting macromolecules, polycarbophosphazenes, were prepared via ROP, but at a dramatically lower temperature than for (NPCl2)3 [eqn (11.37)]. Subsequently, polymers with three-coordinate sulfur(IV) and four-coordinate sulfur(VI) centres were obtained and these materials were termed poly-thiophosphazenes and polythionylphosphazenes, respectively. The latter polymers [eqn (11.38)] are much more stable than the sulfur(IV) analogues after halogen replacement and several have been explored as matrices for gas sensors as a consequence of their high permeability. 

Reprinted from [a.319] with permission from Elsevier 

Romer in 1924 and their method remains the basis for present-day production on both the laboratory and industrial scales  

Allcock, Phosphorus Nitrogen Compounds, Academic Press, New York, 1972, 498 pp. H. R. Allcock, Chem. Rev. 72, 315-56 (1972) (475 refs.). H. R. Allcock, Chap. 3 in A. H. Cowley (ed.) Rings, Clusters and Polymers of the Main Group Elements, ACS Symposium Series No. 282, Washington, DC, 49-67 (1982). H. R. Allcock in J. E. Mark, R. West and H. R. Allcock, Inorganic Polymers, Prentice Hall, 1991, 304 pp. H. R. Allcock, Chap. 9 in R. Steudel (ed.) The Chemistry of Inorganic Ring Systems, Elsevier, Amsterdam, 145-69 (1992). 

Bonding. All phosphazenes, whether cyclic or chain, contain the formally unsaturated 

4-coordinate P. The experimental facts that have to be interpreted by any acceptable theory of bonding are  

In short, the bonding in phosphazencs is not adequately represented by a sequence of alternating double and single bonds -N=P-N —P- yet it 

N occupy an sp lone-pair in the plane of the ring (or the plane of the local PNP triangle) as in Fig. 12.26a. The situation at P is less clear mainly because of uncertainties concerning the d-orbital energies and the radial extent (size) of these orbitals in the bonding situation (as distinct from the free atom). In so far as symmetry is concerned, the sp lone-pair on each N can be involved in coordinate bonding in the jcy plane 

Reactions. The N atom in c vr7r polyphospha-zenes can act as a weak Br0nsied base (proton acceptor) towards such strong acids a.s HF 

In this Section polymers are discussed having a P-N or P-N-S backbone or polymers in which cyclic phosphazenes form a part of the backbone. Organic 

A number of general reviews on polyphosphazenes have appeared. Specific reviews on polyphosphazenes deal with radiation graft polymerization, anionic polymerization, hydrogel microspheres,controlled biodegradability,coatings, and membrane separation. 

A computational study of phosphazene oligomers has shown a profound influence of intramolecular interactions on the backbone conformation. A NP bonding model in terms of an ionic cr-bond and a n-bond induced by negative hyperconjugation has been proposed.Molecular dynamics simulations have been carried out for and [NP(OC6H4Me-4)2]n Calculations for 

R = Bu or Hex give (NPMeR)x[NPR(CH2SiMc3)]y. Replacing MeaSiCl by ferrocenecarboxylaldehyde in the presence of NH4CI (proton donor) results in the formation of (NPMeR)x[NPR(CH2CH(OH)(CpFeCp))]y. 

Heating Me3SiNPCH2C(Me)=C(Me)CH20Ph (36) during 14 days at 190 °C yields a novel type polymer with formula [NPCH2C(Me)=C(Me)CH2]n (37). 

The phosphonitrile chloride [poly(dichlorophosphazene)] series is obtained by heating phosphorus pentachloride and ammonium chloride in solvents such as chlorobenzene and tetrachloroethane  

Hexachlorocyclotriphosphazene, (NPCl2)3, and octachlorocyclotetra-phosphazene, (NPCl2)4, form high-molecular-weight polymers at 250°C  

The polymerization equilibrium with the organic derivatives of the cyclic oligomers is so unfavorable that no polymerization occurs under thermal polymerization conditions. For this reason, polyphosphazenes with 

The linear poly(fluoroalkoxyphosphazenes) are used commercially as elastomers for arctic conditions. Cross-linked network products of the cyclic oligomers are suitable for surface coatings or reinforced resins for the temperature range 250-550°C. 

4 Hydrolytically Sensitive Fiber-Forming Bioiesmbable Polymers 

Although polymers with the —P=N— backbone were produced as long ago as the 1890s by ring-scission polymerization of (NPCljls, moisture hydrolyzes the polymer to a brittle material. 

In the 1960s and 1970s, H. R. Allcock used the dichloro-polymer as a precursor for various derivatives and there are now hundreds of stable polyphosphazenes known [16,17], 

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Properties. One of the characteristic properties of the polyphosphazene backbone is high chain dexibility which allows mobility of the chains even at quite low temperatures. Glass-transition temperatures down to —105° C are known with some alkoxy substituents. Symmetrically substituted alkoxy and aryloxy polymers often exhibit melting transitions if the substituents allow packing of the chains, but mixed-substituent polymers are amorphous. Thus the mixed substitution pattern is deUberately used for the synthesis of various phosphazene elastomers. On the other hand, as with many other flexible-chain polymers, glass-transition temperatures above 100°C can be obtained with bulky substituents on the phosphazene backbone. 

Phosphazene polymers are inherently good electrical insulators unless side-group stmctures allow ionic conduction in the presence of salts. This insulating property forms the basis for appHcations as wire and cable jackets and coatings. Polyphosphazenes also exhibit excellent visible and uv radiation transparency when chromophoric substituents are absent. 

Biomedical Applications. In the area of biomedical polymers and materials, two types of appHcations have been envisioned and explored. The first is the use of polyphosphazenes as bioinert materials for implantation in the body either as housing for medical devices or as stmctural materials for heart valves, artificial blood vessels, and catheters. A number of fluoroalkoxy-, aryloxy-, and arylamino-substituted polyphosphazenes have been tested by actual implantation ia rats and found to generate Httle tissue response (18). 

Eig. 1. Schematic bioactive polyphosphazenes. (a) General stmcture, where X = hydrophilic /hydrophobic group that hydrolyzes with concurrent polymer breakdown, Y = difunctional group for attaching bioactive agent to polymer, and T = bioactive agent, (b) Actual example where X = —OC H, Y = and... 

REPLACEThus alkyl- and aryl-substituted polyphosphazenes and their immediate precursors are also quite amenable to synthetic modifications, with the potential for the synthesis of a wide variety of materials being quite evident. 

Applications. Polymers with small alkyl substituents, particularly (13), are ideal candidates for elastomer formulation because of quite low temperature flexibiUty, hydrolytic and chemical stabiUty, and high temperature stabiUty. The abiUty to readily incorporate other substituents (ia addition to methyl), particularly vinyl groups, should provide for conventional cure sites. In light of the biocompatibiUty of polysdoxanes and P—O- and P—N-substituted polyphosphazenes, poly(alkyl/arylphosphazenes) are also likely to be biocompatible polymers. Therefore, biomedical appHcations can also be envisaged for (3). A third potential appHcation is ia the area of soHd-state batteries. The first steps toward ionic conductivity have been observed with polymers (13) and (15) using lithium and silver salts (78). 

A second class of important electrolytes for rechargeable lithium batteries are soHd electrolytes. Of particular importance is the class known as soHd polymer electrolytes (SPEs). SPEs are polymers capable of forming complexes with lithium salts to yield ionic conductivity. The best known of the SPEs are the lithium salt complexes of poly(ethylene oxide) [25322-68-3] (PEO), —(CH2CH20) —, and poly(propylene oxide) [25322-69-4] (PPO) (11—13). Whereas a number of experimental battery systems have been constmcted using PEO and PPO electrolytes, these systems have not exhibited suitable conductivities at or near room temperature. Advances in the 1980s included a new class of SPE based on polyphosphazene complexes suggesting that room temperature SPE batteries may be achievable (14,15). 

A random copolymer can be formed by postpolymetization reaction with a mixture of reagents, eg, in the case of polyphosphazenes (eq. 37) (45,46). 

Routes to prepare substituted polymer directly were pioneered with the polymerization of /V-trimethy1si1y1phosphoranamines to form low to moderate molecular weight polyphosphazenes (6) where R is alkyl or aryl (8). 

Hexachlorocyclotriphosphazene (cycHc trimer) is a respiratory irritant. Nausea has also been noted on exposure (10). Intravenous and intraperitoneal toxicity measurements were made on mice. The highest nonlethal dose (LDq) was measured as 20 mg/kg (11). Linear chloropolymer is also beUeved to be toxic (10). Upon organic substitution, the high molecular weight linear polymers have been shown to be inert. Rat implants of eight different polyphosphazene homopolymers indicated low levels of tissue toxicity (12). EZ has been found to be reasonably compatible with blood (13), and has lower hpid absorption than fiuorosihcone. 

SPh determination of silicon and phosphorus in form of Si-Mo and P-Mo heteropolyacids are used successfully for series determination of these heteroelements in OEC and polymers (polysiloxanes, polyphosphazenes, etc.). 

Whilst exhibiting the excellent low-temperature flexibility (with a Tg of about -80°C) and very good heat resistance (up to 200°C) typical of a silicone rubber, the fluorosilicones also exhibit good aliphatic oil resistance and excellent aging resistance. However, for some applications they have recently encountered a challenge from the polyphosphazenes (see Section 13.10). 

Figure 12.25 Melting points of various series of e>Wr -polyphosphazenes (NPX2) showing the higher values for even.

Applications. Many applications have been proposed for polyphosphazenes, particularly the non-cyclic polymers of high molecular weight, but those with the most desirable properties are extremely expensive and costs will have to drop considerably before they gain widespread use (cf. silicones, p. 365). The cheapest compounds are the chloro series... 

Figure 12.30 Potential uses of polyphosphazenes (a) A thin film of a poly(aminophosphazene) sueh materials are of interest for biomedical applications, (b) Fibres of poly[bis(trifluoroethoxy)phosphazene] these fibres are water-repellant, resistant to hydrolysis or strong sunlight, and do not burn, (c) Cotton cloth treated with a poly(fluoroalkoxyphosphazene) showing the water repellaney eonferred by the phosphazene. (d) Polyphosphazene elastomers are now being manufaetured for use in fuel lines, gaskets, O-rings, shock absorbers, and carburettor eomponents they are impervious to oils and fuels, do not bum, and remain flexible at very low temperatures. Photographs by eourtesy of H. R. Allcock (Pennsylvania State University) and the Firestone Tire and Rubber Company.

The physical properties of polyphosphazene depend on the nature and the number of substitutes. However, the flexibility of the P-N backbone is the property in common. Because of the weakness of the rotation energy around the N-P bond (3.38 and 21.8 kJ/mol, respectively for... 

Potin P and Jaeger RD. Polyphosphazenes Synthesis, structures, properties, applications. Eur Polym J, 1991, 415, 341-348. 

Allcock HR, Crane CA, Morrissey CT, Nelson JM, Reeves SD, Honeyman CH, and Manners I. Living cationic polymerization of phosphoranimines as an ambient temperature route to polyphosphazenes with controlled molecular weights. Macromolecules, 1996, 29, 7740-7747. 

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