Synthesis and Thermoresponsive Properties of N -Alkylated Polyamides: Polycondensation of Amino Acid Dimers as a Synthetic Platform for Backbone-Expanded Polypeptoids

Studies on polypeptoids have mainly focused on poly(α-peptoid)s, whereas backbone-expanded polypeptoids, such as poly(γ-peptoid)s and poly(δ-peptoid)s, remain largely unexplored because of the lack of suitable polymerization methods. Herein, we established a general synthetic method for N-alkylated polyamide-x by polycondensation of amino acid dimers and synthesized three novel backbone-expanded polypeptoids bearing simple alkyl side chains: N-Me-PA-5, N-Et-PA-4, and N-nPr-PA-3. Among these polymers with the same repeat-unit formula, C6H11NO, those corresponding to poly(γ-peptoid)s and poly(δ-peptoid)s exhibited LCST-type thermoresponsiveness in water, whereas the polymer corresponding to poly(β-peptoid) was insoluble. These results suggest that aqueous behavior can vary with the allocation of carbon atoms between the main-chain spacer and the N-alkyl side chain. This synthetic method expands the structural diversity of polypeptoids and allows backbone-expanded polypeptoids to serve as a structural bridge between N-alkylated nylon-p,q and poly(α-peptoid)s, enabling their aqueous behavior to be compared in terms of amide-bond arrangement and spacing.