Inducing chiral order in a synthetic knotted system

The ability of racemic mixtures to spontaneously organize into ordered assemblies with defined chirality, known as chiral self-sorting, has emerged as a central concept in supramolecular chemistry and offers insights into the molecular origins of homochirality observed in biological systems. Although several synthetic systems have exhibited this phenomenon by leveraging reversible noncovalent interactions, exerting precise control over chiral self-sorting in multicomponent assemblies remains a formidable challenge. Here, we report a biomimetic site-specific modification strategy for inducing and regulating chiral organization within a synthetic cinquefoil knotted system. By incorporating a series of amino acid residues, including alanine, serine, phenylalanine, phenylalanine-phenylalanine, and valine-valine dipeptide, into the ligand backbone, we introduce tunable structural features, steric profiles, and noncovalent interaction motifs while preserving the high-yielding and stereoselective formation of the cinquefoil knot. Notably, the dipeptide derivative shifts narcissistic chiral self-sorting from kinetic to thermodynamic control, thereby enabling a transition from an achiral state to high-fidelity self-sorting. Although social chiral self-sorting was not observed, ligand exchange was suppressed only in the dipeptide systems. Simulation analyses revealed distinct energy differences among the systems and identified hydrogen-bonding, CH-π, and π-π interactions unique to the dipeptide helicates, underscoring the decisive role of interstrand weak interactions in establishing chiral order. Analogous to regulatory strategies in biological macromolecules, this localized modification further enables modulation of knot functions, including anion recognition and amplified chiral expression. These findings establish a robust and adaptable platform for understanding and regulating chiral order in multicomponent self-assembly systems and offer a biomimetic blueprint for engineering the functionalities of topologically entangled molecules.