DFT Study on Amine-Mediated Ring-Opening Mechanism of α-Amino Acid N-Carboxyanhydride and N-Substituted Glycine N-Carboxyanhydride: Secondary Amine versus Primary Amine.

Is decarboxylation the rate-determining step of amine-mediated ring-opening polymerizations (ROPs) of α-amino acid N-carboxyanhydride (NCA) and N-substituted glycine N-carboxyanhydride (NNCA)? Can a secondary amine initiate living a ROP of NCA to produce primary amine as an active chain end? We investigate the normal amine mechanism (NAM) of polymerizations of l-alanine-NCA (Ala-NCA) and sarcosine-NCA (Sar-NCA) principally by means of density functional theory (DFT) computation. Detailed Gibbs free energy profiles of elemental reactions in NAM of Ala-NCA and Sar-NCA ROPs have been successfully obtained. In addition, the reaction pathways are checked by DFT, Møller-Plesset perturbation theory, and coupled cluster theory. The rate-determining steps in all ROPs of NCA and NNCA initiated by either secondary or primary amine are amine addition on a 5-carbonyl group rather than decarboxylation. The energy barrier in the case of a secondary amine is lower than that of a primary amine with quite a small difference, which confirms that the secondary amine can initiate the ROPs of NCA and NNCA as fast as, if not faster than, a primary amine does, which supports the experimental results. All the results obtained from various calculation methods show that the reactivity ratios (r) of Ala-NCA and Sar-NCA as well as the product of r1 × r2 are close to 1, indicating a random copolymerization of the two different kinds of NCAs.