Hexamethyldisilazane-Mediated Controlled Polymerization of α-Amino AcidN-Carboxyanhydrides

• DOI: 10.1021/ja074961q
• Publication Date: 2007-10-27T06:27:03Z
• Authors: Hua Lu; Jianjun Cheng
• Keywords: Models, Chemical; Polymers; Organosilicon Compounds; Amino Acids; Peptides; 01 natural sciences; Anhydrides; Biotechnology; 0104 chemical sciences

Ring-opening polymerizations of α-amino acid N-carboxyanhydrides (NCAs) initiated with amines typically form polypeptides with uncontrolled molecular weights and broad molecular weight distributions. However, we found that hexamethyldisilazane (HMDS)-mediated controlled NCA polymerizations gave polypeptides with predictable molecular weights and narrow molecular weight distributions. Using MS, NMR, and FT-IR, we demonstrated that the initiation step involved the cleavage of the N−Si bond of HMDS and the formation of a trimethylsilyl carbamate (TMS-CBM) terminal group. Polypeptide chains were propagated through the migration of TMS of the TMS-CBM end group to the incoming monomer and formed a new TMS-CBM terminal group. This organosilicon reagent mediated NCA polymerization offers a metal-free strategy for the convenient synthesis of homo- or block polypeptides with predictable molecular weights and narrow molecular weight distributions.