Fast and controlled Ring-Opening Polymerization of N-carboxyanhydrides via a cooperative bifunctional amino acid

The Ring-Opening Polymerization (ROP) of amino acid N-Carboxyanhydrides (NCAs) offers a straightforward method for preparing polypeptide-like polymers that display characteristics of their natural counterparts, e.g. secondary structure, and enables rapid in vitro screenings. Although recent publications have progressed in achieving water tolerance, a universally user-friendly solu-tion has yet to be achieved. In this communication, we provide a new polymerization set-up that uses an amino acid salt as an initiator. The bifunctional initiator is key for a fast and controlled polymerization, as the carboxylate opens the NCA in the initiation step, and the acyl group is fur-ther transferred to the nitrogen atom in the amine functionality via a concerted low-barrier mecha-nism. Then, it undergoes accelerated chain propagation via the newly generated carbamate rest in the N-acylated chain, as revealed by theoretical calculations at the DFT level and experimental observations. The fast polymerization kinetics enables the polymerization process to be carried out even in the presence of water. In addition, different amino acids can be used as initiators. The concerted O→N acyl shift and the fast and controlled kinetics shed light on cooperative initiating phenomena.