Tyrosine-bearing polyphosphazenes

Tyrosine-functionalized polyphosphazenes were synthesized, and their hydrolytic stability, pH-sensitive behavior, and hydrogel-forming capabilities were investigated. The physical and chemical properties of the polymers varied with the type of linkage between the tyrosine unit and phosphazene backbone. Poly[(ethyl glycinat-N-yl)(ethyl tyrosinat-N-yl)phophazenes] (linkage via the amino group of tyrosine) were found to be hydrolytically erodible. The rate of hydrolysis was dependent on the ratio of the two side groups, the slowest rate being associated with the highest concentration of tyrosine. The hydrolysis products were identified as phosphates, tyrosine, glycine, ammonia, and ethanol derived from the ester group. The hydrolytically stable phenolic-linked tyrosine derivatives were prepared from N-t-BOC-L-tyrosine methyl ester and alkoxy-based cosubstituents. Polyphosphazenes with both propoxy and phenolic-linked tyrosine side groups showed a pH-sensitive solubility behavior, which was dependent on the ratio and nature of the two side groups. The polymer was soluble in aqueous media below pH 3 and above pH 4. From pH 3-4, the polymer was insoluble. Replacement of propoxy by trifluoroethoxy units yielded a polymer that was insoluble in aqueous media at all pH values. Replacement of propoxy by methoxyethoxyethoxy groups gave a polymer that was soluble at all pH values. Exposure of both the propoxy and methoxyethoxyethoxy polymers to calcium ions in aqueous media caused gel formation due to ionic cross-linking through the carboxylate groups.