Polypeptoids with tunable cloud point temperatures synthesized from N-substituted glycine N-thiocarboxyanhydrides

Abstract

N-substituted glycine N-thiocarboxyanhydrides (NTAs) are alternative monomers for preparing polypeptoids. With an easy synthetic approach and stability during purification and storage, they have much more potential for mass production than the corresponding N-carboxyanhydrides (NCAs). Thermoresponsive copolypeptoids are synthesized by copolymerization of sarcosine NTA (Sar-NTA) with N-butylglycine NTA (NBG-NTA) initiated by benzylamine in THF at 60 °C. Polypeptoids with a degree of polymerization over 150 are obtained for the first time through primary amine-initiated NTA polymerizations. The molecular weights (MWs) and compositions of poly(sarcosine-r-N-butylglycine)s [P(Sar-r-NBG)s] are controlled by the feed molar ratios of [Sar]/[NBG]/[benzylamine]. The thermal behaviors of the copolypeptoids are investigated. Reactivity ratios of Sar-NTA and NBG-NTA are determined as 1.70(7) and 0.63(7), indicating a random distribution of the two monomers in the polypeptoid products. The structure and precise amino chain end of P(Sar-r-NBG) are confirmed by MALDI-ToF mass analysis. P(Sar-r-NBG)s have lower critical solution temperatures (LCST) and exhibit reversible phase transitions in aqueous solution. Their cloud point temperatures (T_cps) are tunable between 27 and 71 °C by adjusting the sarcosine molar fraction in copolymers. In addition, T_cp transitions depend on the MWs and the concentrations of the polypeptoids, as well as salt additives, to a certain degree. A biocompatibility study on P(Sar-r-NBG) reveals a controlled cytotoxicity related to the composition of polypeptoids. Easily accessible from NTA polymerizations, polypeptoids are therefore novel degradable materials with LCST for biomedical applications.