Understanding the Ring‐Opening Reaction of <i>α</i>‐Amino Acid <i>N</i>‐Carboxyanhydride in an Amine‐Mediated Living Polymerization: A DFT Study

Abstract The primary‐amine‐initiated polymerization of α ‐amino acid N ‐carboxyanhydride (NCA) is a widely‐used and promising way to synthesize polypeptide‐involved materials with various applications. The nucleophilic attack mechanism, also known as normal amine mechanism of ring opening reaction of NCA is investigated in detail by means of the DFT calculation in this work. Three steps, i.e., addition, ring opening and decarboxylation are discussed. The addition of C 5 carbonyl group of NCA by NH 2 group of initiator requires the highest activation energy (≈60 kcal · mol −1 ) and is regarded as the rate‐determining step. These results are compatible with the experimental studies reported previously and provide an inside view of the normal amine mechanism. magnified image