The Synthesis And Properties Of Glycosylated Polyphosphazenes Via Click Chemistry

Glycosylated polyphosphazenes have drawn considerable attention in the past decades along with the development of glycobiology. However, how to combine the specific biological function of carbohydrate compound and the tunable polyphosphazene efficiently to obtain biomimetic glycosylated polyphosphazene remains a great challenge in fields of polymer chemistry, biomedical science and material science. In this work, azide-alkyne and thiol-alkyne click chemistry were used to synthesize glycosylated polyphosphazene controllably and effectively. The related experiments and results are summarized as follows:Glycosylated polyphosphazenes were achieved by nucleophilic substitution of poly(dichlorophosphazene) with propargylamine and subsequent azide-alkyne click reaction of poly[di(propargylamine)phosphazene](PDPAP) with2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl azide (N3-GlcAc4). Effects of N3-GlcAc4amount and reaction time on the structure of resulting polymer were carefully studied. The synthetic process was clearly monitored by FT-IR,1H NMR and elemental analysis. The result showed that the relative proportion of the carbohydrate groups could be easily controlled over a broad range by varying the amount of N3-GlcAc4and the reaction time.Furthermore, to avoid the toxicity of copper catalysis residuals, a metal-free approach to synthesize glycosylated polyphosphazenes via the photo-initiated thiol-yne click reaction was introduced in this work. Since each alkyne group is capable of consecutive reaction with two thiol groups in thiol-yne reaction and this reaction is a two-step process, high steric hindrance of2,3,4,6-tetra-O-acetyl-1-thio-β-D-glucopyranose (SH-GlcAc4) played a key role in the overall reaction process. Our research demonstrated that approximately55%of the alkyne groups participated in the thiol-yne click reaction and about8%of the alkyne groups were converted to alkene groups at the end of the reaction. In order to minimize the influences of steric effect, alkane groups were introduced in the side groups of polyphosphazenes by applying alkyne/alkane mixture substitution. Results showed that when the mixed-substituent polyphosphazene contained37%of alkyne groups in the side group, each alkyne group could react with two thiol groups completely and almost no alkyne/alkene group remained after the thiol-yne click reaction.Amphiphilic polyphosphazenes with different contents of carbohydrate group in the side chain were synthesized. Self-assembly behavior of amphiphilic polyphosphazene was systematically studied using dynamic light scattering, fluorescence spectroscopy and transmission electron microscopy. Moreover, dynamic light scattering, ultraviolet spectrophotometer and fluroescence microscopy were used to study the interaction between polyphosphazene micelles and lectins. The results demonstrated that the micelles could recognize concanavalin A (Con A) efficiently.