Water-Assisted and Protein-Initiated Ring-Opening Polymerization of Proline N-Carboxyanhydride

The production of poly-_L-proline (PLP) via the ring-opening polymerization (ROP) of _L-proline N-carboxyanhydride (ProNCA) is challenging due to a combination of factors, including the stringent requirement of moisture-free conditions, slow monomer conversion, poor control of the molar mass, and premature precipitation of the product in the form of polyproline type I helix. Here, we report water-assisted ROP of ProNCA, which affords well-defined PLP in polyproline II helix in 2-5 minutes. Density functional theory reveals an as-yet-unreported role of water in facilitating proton shift that significantly lowered the energy barrier of the chain propagation. Protein-mediated ROP of ProNCA conveniently affords various protein-PLP conjugates via a grafting-from approach. PLP conjugation not only preserves the biological activities of the native proteins, but also enhances the stability of proteins against extreme conditions. This work provides a simple means and new mechanistic insight to solve a longstanding problem in PLP synthesis and will offer valuable guidance for the development of water-resistant ROP of other NCAs. The facile access of PLP can greatly boost the application potentials of PLP-based functional materials.