Controlled Synthesis of Crystalline and Helical N-Alkyl Poly(l-alanine)

The synthesis of N-substituted polypeptides is challenging due to steric hindrance. Here, N-alkyl poly(l-alanine)s, with controlled molecular weights (Mns) and narrow distributions, were efficiently synthesized by primary amine-initiated and acetic acid-catalyzed ring-opening polymerizations of N-alkyl-(l)-alanine N-carboxyanhydrides [NAlkyl-(l)-Ala-NCAs] in toluene of low polarity and low proton-accepting ability. The N-alkyl poly(l-alanine)s, with chiral centers at backbones and different alkyl substituents at side chains, showed a relatively extended helical structure similar to that of the PPII-helix of poly(l-proline). The elongation of the alkyl side chains and the increase in temperatures had negligible effects on the helix structure, as revealed by the circular dichroism measurements. The differential scanning calorimetry and X-ray diffraction measurements showed that the polymers were crystalline. Besides, the NAlkyl-(l)-Ala-NCAs were capable of copolymerizing with other monomers, producing structurally diverse copolymers. The efficient synthesis of N-alkyl poly(l-alanine)s, combined with the structural tunability, hydrophobicity, crystallinity, protein-like skeleton, enzymatic stability, and stable helix, makes the polymers attractive structural units in self-assembly and the biomedical field.