Synthesis and Characterization of Methionine- and Cysteine-Substituted Phosphazenes

The preparation of phosphazenes that possess reversible cross-linking groups to control mechanical stability and hydrolysis has been accomplished using cysteine and methionine amino acid side groups. Small molecule models and linear polymeric phosphazenes that contain methionine ethyl ester and cysteine ethyl disulfide ethyl ester side groups were synthesized. Protection of the free thiol groups was carried out to circumvent unwanted cross-linking of the phosphazenes through the cysteine ethyl ester N- and S-termini. Cyclic trimeric cysteine ethyl disulfide ethyl ester model compounds were deprotected by S-S bond cleavage using beta-mercaptoethanol, dithiothreitol (DTT), and zinc in aqueous hydrochloric acid. For the high polymeric derivatives, the extent of S-S bond cleavage varied depending on the deprotection method used. With the exception of the Zn/HCl method, the resultant deprotected polymers were soluble in common organic solvents and underwent minimal chain cleavage during the reaction sequence. The protected or deprotected high polymers arc candidates for reversible cross-linking in drug delivery systems and for cross-link stabilization of tissue engineering scaffolds.