A S-Sn Lewis Pair-Mediated Ring-Opening Polymerization of α-Amino Acid N-Carboxyanhydrides: Fast Kinetics, High Molecular Weight, and Facile Bioconjugation

The rapid and controlled generation of poly peptides with ultrahigh molecular weight (MW) and well defined chain end functionality has been a great challenge. To tackle this problem, we report here an initiation system based on a S-Sn Lewis pair, trimethylstannyl phenyl sulfide (PhS-SnMe3), for the ring-opening polymerization (ROP) of alpha-amino acid N-carboxyanhydrides (NCAs). This initiator displays a strong solvent effect, and can yield polypeptides with high MW (>1.0 x 10(5) g.mol(-1)) and low polydispersity index within a few hours. The MWs of the obtained polypeptides are strongly dependent on the THE/DMF ratio. The polymerization follows a typical first-order kinetic character with respect to the monomer concentration in mixed THE and DMF. Moreover, a highly reactive phenyl thioester is in situ generated at the C-terminus of the polypeptides, which is readily accessible for native chemical ligation affording high MW and site-specific protein polypeptide conjugates. Together, this initiator sheds light on regulating the ROP of NCAs via appropriate Lewis pair and solvent selection, and is particularly useful in preparing ultrahigh MW polypeptides within a short period of time.