Carboxylate, polyphosphazenes

As already reported in Table 6, the solubility of phosphazene polymers is strongly influenced by the nature of the substituent groups attached at the phosphorus atoms along the -P=N- skeleton. Water-solubility, for instance, can be induced in polyphosphazenes by using strongly polar substituents (e.g. methylamine [84], glucosyl [495], glyceryl [496], polyoxyethylene mono-methylether [273] or sulfonic acid [497,498] derivatives), or may be promoted by acids or bases when basic (amino substituents like ethylamine [499]) or acid (e.g. aryloxy carboxylate [499] or aryloxy hydroxylate [295]) substituents are exploited. 

A substantial number of bioactive molecules, such as polypeptides, N-acetyl-DL-penicillamine, p-(dipropylsulfamoyl)benzoic acid, and nicotinic acid, contain a carboxylic acid function, and this provides a site for linkage to a polyphosphazene chain. A number of prototype polymers have been synthesized in which pendent amino groups provide coupling sites for the carboxylic acid (34). The amide linkages so formed are potentially bioerodible, but the use of a hydrolytic sensitizing cosubstituent would be expected to accelerate the process. 

Finally, a new water-soluble polyphosphazene was recently synthesized that has the structure shown in 36 (46). This polymer has two attributes as a biomedical macromolecule. First, the pendent carboxylic acid groups are potential sites for condensation reactions with amines, alcohols, phenols, or other carboxylic acid units to generate amide, ester, or anhydride links to polypeptides or bioactive small molecules. Second, polymer forms ionic crosslinks when brought into contact with di- or trivalent cations such as Ca or Ai3+. The crosslinking process converts the water-soluble polymer to a hydrogel, a process that can be reversed when the system... 

In addition to providing fully alkyl/aryl-substituted polyphosphazenes, the versatility of the process in Figure 2 has allowed the preparation of various functionalized polymers and copolymers. Thus the monomer (10) can be derivatized via deprotonation—substitution, when aP-methyl (or P—CH2—) group is present, to provide new phosphoranimines some of which, in turn, serve as precursors to new polymers (64). In the same vein, polymers containing a P—CH3 group, for example, poly(methylphenylphosphazene), can also be derivatized by deprotonation—substitution reactions without chain scission. This has produced a number of functionalized polymers (64,71—73), including water-soluble carboxylate salts (11), as well as graft copolymers with styrene (74) and with dimethyl siloxane (12) (75). 

The principal polyphosphazenes that have been used in hydrogels are those with linear or branched ethyleneoxy side chains, aryloxy groups with carboxylic acid substituents, or mixed-substituent polymers that bear hydrophilic methylamino side groups plus a hydrophobic cosubstituent such as phenoxy or trifluoroethoxy. Cross-linking is usually accomplished by gamma-ray irradiation or, in the case of the carboxylic acid functional species, by treatment with a di- or tri-valent cation. Here, we will consider another example based on MEEP (3.79), a polymer that is well suited to the clean method of radiation cross-linking. 

The main class of bioerodible polyphosphazenes that have been developed so far are polymers with amino acid ester side groups. They are prepared by the reaction of poly(dichlorophosphazene) with the ethyl or propyl esters of amino acids such as glycine, alanine, phenylalanine, and so on (reaction (57)).196 The ethyl or propyl ester of the amino acid must be used as the nucleophile in this reaction for two reasons. First, a free carboxylic acid unit would provide a second nucleophilic site that could lead to... 

Two series of new polyphosphazenes were prepared by derivatization of preformed poly(methylphenylphosphazene), [Me(Ph)PN]p. This Involved Initial deprotonatlon of part of the methyl substituents with n-BuLi followed by treatment of the intermediate anion with carbon dioxide or with fluorinated aldehydes or ketones. With appropriate workup procedures, either carboxylic acid, ester, carboxylate salt, or fluorinated alcohol derivatives were obtained. These reactions and the characterization of the products are discussed In this paper. Related derivatization reactions are also discussed. 

Molecules, bearing a carboxylic group, can be attached to a polyphosphazene chain through linkage to a spacer group. For this, p-(aminomethyl)phenoxy was used by Allcock et al (1982) to substitute bioactive molecules such as N-acetyd-DL-penicillamine, p-(dipropylsulfamoyl)benzoic acid and 2,4-dichlorophenoxyacetic acid. 

A significant amoimt of research was devoted to post-functionahzation of aryloxy- or methyl-substituted polyphosphazenes. In the first case, electrophihc aromatic substitution reactions were used to obtain sulfonated (113-116), car-boxylated (117) nitrated (aminated) (118,119) and phosphonated (120,121) products (Fig. 7a). Alternatively, methyl substituents were deprotonated with n-BuLi and subsequently treated with a desired nucleophile (Fig. 7b). Using this method, polyphosphazenes bearing carboxylic (122), alcohol (123,124), ester (125), and other (63,126) groups became available. Numerous studies have been devoted... 

Separation of Tritiated Water. Aromatic polyphosphazene membranes were investigated in the separation of tritiated water from normal water, because of their excellent radiological, thermal, and chemical stabihty (170,171). For these experiments carboxylated poly(diaryloxy)phospohazenes were used. A tritium depletion as high as 33% was reported. 

Polyphosphazenes with simple alkyl and aryl substituents directly attached to the backbone by P-C linkages can be prepared by the condensation polymerization of N-silylphosphoranimine precursors. These simple polymers can then be converted to a variety of functionalized polyphosphazenes by derivatization reactions. In this paper, the synthesis and characterization of some derivatives of poly(methylphenyl-phosphazene), [Me(Ph)P=N]and the copolymer, [Me(Ph)P=N]j [Me2P=N)y, are discussed. These polymers include grafted copolymers, water soluble carboxylated polymers, and polymers with silyl, vinyl, alcohol, ester, ferrocene, phosphine, thiophene, and/or fluoroalkyl groups. 

In order to further control the properties of the polyphosphazenes, we are now investigating the materials obtained by derivatizing the copolymer [Me(Ph)PN][Me2PN]y, 2, where x = y Tg = ca. 0°C). The decreased solubility of this polymer in THF relative to the homopolymer 1 necessitates longer reaction times for deprotonation. Both the silylated (eq 4) and carboxylated (eq 5) derivatives have very different solubilities relative to the homopolymer derivatives. For example, the silyl derivatives are partially soluble in hexane (24) and both the 50% substituted acid and the lithium salt of the 25% substituted acid are... 

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