Evolution of Peptidomimetics-Based Chiral Assemblies of β-Sheet, α-Helix, and Double Helix Involving Chalcogen Bonds

Developing chiral assemblies that mimic biological secondary structures, e.g., protein β-sheet, α-helix, and DNA double helix, is a captivating goal in supramolecular chemistry. Here, we create a family of biomimetic chiral assemblies from alanine-based peptidomimetics, wherein the incorporation of <i>N</i>-terminal 2,1,3-benzoselenadiazole groups enables the rarely utilized chalcogen bonding as the adhesive interaction. While the alanine-based acylhydrazine molecule <b>1L</b> was designed as a building unit with an extended conformation, simple derivatization of <b>1L</b> affords folded unilateral <i>N</i>-amidothiourea <b>2L</b> with one β-turn and bilateral <i>N</i>-amidothiourea <b>3L</b> with two β-turns. This derivatization leads to the evolution of molecular assemblies from β-sheet organization (<b>1L</b>) to single helix (α-helix mimic, <b>2L</b>) and ultimately to double helix (<b>3L</b>), illustrating an evolutionary route relating the structures and superstructures. In the case of the double helix formed by <b>3L</b>, an unexpected <i>cis</i>-form that brings the two β-turns into one side was observed, stabilized via the π···π interaction between two <i>N</i>-terminal 2,1,3-benzoselenadiazole groups. This conformation allows double-crossed N-Se···S═C chalcogen bonds to support a DNA-like <i>P</i>-double helix featuring intrastrand noncovalent interactions and interstrand covalent linkages, surviving in both the solid state and in dilute acetonitrile solution phase.