Effect of N-alkylation in N-carboxyanhydride (NCA) ring-opening polymerization kinetics

Polypeptoids are an emerging class of biomimetic polymers prepared by ring-opening polymerization (ROP) of N-alkylated-N-carboxyanhydride (NNCA) monomers. The N-alkylation provides a unique structural isomerism with peptides but its influence on NNCA reactivity is not yet fully understood. In this report, we provide a comprehensive study using 12 monomers to better rationalize the contribution of the steric hindrance and electronic effects of the N-alkyl group toward the synthesis of NNCA and their reactivity in polymerization reactions. We found that varying the alkyl group does not significantly influence the formation of NNCAs prepared by the Leuchs method. In marked contrast, depending on the alkyl group, the efficiency of the NNCA polymerization initiated by allylamine showed that electron-donating groups enhanced the ROP kinetic rates through a significant inductive effect and could counterbalance the negative influence of bulky groups during the propagation steps.

Automated summary

This report provides a comprehensive study on the contribution of the N-alkyl group to the synthesis of NNCA and its reactivity in polymerization reactions. We found that electron-donating groups can enhance the kinetic rates of polymerization reactions.