Precision Synthesis of Polysarcosine via Controlled Ring-Opening Polymerization of N -Carboxyanhydride: Fast Kinetics, Ultrahigh Molecular Weight, and Mechanistic Insights.

The rapid and controlled synthesis of high-molecular-weight (HMW) 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 the well-controlled ROP of sarcosine NCA (Sar-NCA) that is catalyzed by various carboxylic acids, which accelerate the polymerization rate up to 50 times, and enables the robust synthesis of pSar with an unprecedented ultrahigh molecular weight (UHMW) up to 586 kDa (DP ∼ 8200) and exceptionally narrow dispersity ( D̵ ) below 1.05. Mechanistic experiments and density functional theory calculations together elucidate the role of carboxylic acid as a bifunctional catalyst that significantly facilitates proton transfer processes and avoids charge separation and suggest the ring opening of NCA, rather than decarboxylation, as the rate-determining step. UHMW pSar demonstrates improved thermal and mechanical properties over the low-molecular-weight counterparts. This work provides a simple yet highly efficient approach to UHMW pSar and generates a new fundamental understanding useful not only for the ROP of Sar-NCA but also for other NCAs.