Simultaneous formation of helical and sheet-like assemblies from short azapeptides enables spontaneous resolution

Abstract

As determined by the homochirality of amino acid building units, protein secondary structures α-helix and β-sheet are single-handed chiral superstructures extending in one and quasi-two dimensions, respectively. Synthetic molecular assemblies that mimic the structural homochirality of proteins would provide insights into the origin of biological homochirality and inform the development of chiral separation techniques. Here we fabricated a homochiral 3D assembly consisting of 1D helical and 2D sheet-like assemblies that feature molecular packings resembling α-helix and β-sheet, respectively. This was achieved by using an alanine derivative, a β-turn structured short azapeptide from p-iodobenzoylalanine-based N-amido-N′-phenylthiourea. While N–H⋯SC/OC hydrogen bonds between the β-turn scaffolds afford a 2D pleated sheet-like structure, the head-to-tail C–I⋯π halogen bonds, together with the N–H⋯OC hydrogen bonds, support a 1D helical-like assembly, serving as linkers to connect the 2D sheet-like structures into a 3D superstructure. The two biomimetic assembly modes share the N–H⋯OC hydrogen bonds and can allow 3D homochiral elongation, driving spontaneous resolution of the short azapeptides to generate conglomerate crystals.