The investigation of thermosensitive properties of phosphazene derivatives bearing amino acid ester groups

Abstract

In this study, a series of phosphazene derivatives having amino acid esters were synthesized from the reactions of amino acid esters with cyclophosphazenes. Hexachlorocyclotriphosphazene, (N3P3Cl6) and octachlorocyclotetraphosphazene (N4P4Cl8) have been reacted with carboxylic amino acid esters; glycine ethyl ester hydrochloride, glycine methyl ester hydrochloride, β-alanine ethyl ester hydrochloride, β-alanine methyl ester hydrochloride and methyl 6-aminohexanoate hydrochloride to obtain cyclophosphazene compounds containing amino acid esters as side groups. All obtained compounds (1–9) were characterized using spectroscopic methods and elemental analysis. The molecular structures of compounds 2, 5 and 6 were also characterized by X-ray crystallographic studies. Hydrolytic degradations of compounds (1–9) were observed by 31P NMR spectroscopy under acidic condition (pH = 1–3) and at body temperature (35–38 °C). Concentration-dependent lower critical solution temperatures (LCST) of compounds were examined to determine their thermosensitive behaviors in aqueous solution. It is found that all compounds degraded to harmless products such as amino acid, phosphates, ammonium salts. LCSTs of compounds 1, 2 and 6 were found to be around body temperature that is important for biomedical applications.