Organobase 1,1,3,3-tetramethyl guanidine catalyzed rapid ring-opening polymerization of α-amino acid N-carboxyanhydrides adaptive to amine, alcohol and carboxyl acid initiators

Abstract

The initiators for ring-opening polymerization (ROP) of α-amino acid N-carboxyanhydrides (NCA) to prepare polypeptides usually require high nucleophilicity. For initiators with lower nucleophilicity, slow initiation and fast propagation lead to poor control over polymerization and polypeptides with uncontrolled dispersities. Herein, the nucleophilicity of different initiators was enhanced by the organobase 1,1,3,3-tetramethylguanidine (TMG), which significantly increased the initiation as well as the propagation rate. For amine, hydroxyl and even carboxyl terminated initiators, TMG catalyzes the rapid polymerization to afford polypeptides with controllable molecular weights and dispersities via the carbamate mechanism. The end groups of polypeptides were confirmed by MALDI-TOF MS. The interaction between initiators/polypeptides and TMG was investigated by ¹H NMR spectroscopy. Block copolypeptides and polypeptide-based hybrid polymers were synthesized using hydroxyl and carboxyl terminated initiators and macroinitiators, respectively. This catalyst simplifies the NCA ROP by significantly expanding the initiator library and extends the potential applications of synthetic polypeptides in various fields.