Carboxylic Acid-Catalyzed Controlled Ring-Opening Polymerization of Sarcosine N-Carboxyanhydride: Fast Kinetics, Ultra-High Molecular Weight, and Mechanistic Insights

The rapid and controlled synthesis of high molecular weight (MW) polysarcosine (pSar), a potential polyethylene glycol (PEG) alternative, via the ring-opening polymerization (ROP) of N-carboxyanhydride (NCA) is rare and challenging. Here, we report carboxylic acid-catalyzed well-controlled ROP of Sar-NCA, which accelerates the polymerization rate up to 50 times, and enables the robust synthesis of pSar with unprecedented high molecular weight (MW) up to 586 kDa (DP ~ 8200) and exceptionally narrow dispersity (Ð) below 1.02. Density functional theory (DFT) calculations combined with mechanistic experiments identify the carbamic acid as dormant species before generating the secondary amine for chain propagation, and elucidate the role of carboxylic acid as a bifunctional catalyst that significantly facilitates proton transfer processes and avoids charge separation. High MW pSar demonstrates improved thermal and mechanical properties over low MW pSar. This work provides a simple yet highly efficient approach to ultra-high MW pSar and generates new fundamental understandings useful not only for the ROP of Sar-NCA but also other NCAs.