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

Spontaneous resolution leading to conglomerate crystals remains a significant challenge. Here we propose the formation of orthogonal homochiral supramolecular helices in at least two dimensions to allow spontaneous resolution. We suggest the design rationale that the chiral species is made into helical building blocks to allow the helix formation. As a proof-of-concept, acetylalanine was made into a helical short azapeptide, its N-amidothiourea derivative containing a β-turn structure, to which a halogen atom was further introduced at the phenylthiourea aromatic ring. The resultant folded species undergoes both intermolecular hydrogen and halogen bonding across the turn structure to form orthogonal intermolecular hydrogen-bonded and halogen-bonded supramolecular helices in two dimensions, and undergoes chiral resolution upon crystallization. Meanwhile, counterparts containing either an F-substituent with weak halogen bonding or no halogen atom crystallize as racemic compounds., (© 2022 Wiley-VCH GmbH.)