Disassembly of chiral hydrogen-bonded frameworks into single-unit organometallic helices for enantioselective amyloid inhibition

Abstract

Abstract Chiral nanostructures hold transformative potential across diverse fields, yet their assembly construction remains hindered by the high entropic barrier of dissymmetric building units. Inspired by biological structural dynamics, we construct two chiral copper-based hydrogen-bonded frameworks [D(L)-Cu-crystals] via hydrogen-bonded assembly using chiral metal-organic helical as the building unit. Single-crystal X-ray diffraction elucidates hierarchical chirality evolution from asymmetric coordinations to helical chains and framework packing. Furthermore, disassembling D(L)-Cu-crystals yields corresponding single-unit chiral metal-organic helices [D(L)-Cu-SMOHs], fully exposed active sites and well-preserved helical architectures. Notably, D(L)-Cu-SMOHs inhibit amyloid fibrillization effectively with pronounced chirality discrimination, driven by entropy-favored hydrophobic interaction. Molecular docking reveals that D-Cu-SMOH exhibits enhanced binding to critical amyloidogenic regions relative to the L-enantiomer. This work establishes a dynamic and reversible assembly-disassembly approach applicable for constructions of chiral nanomaterials. Moreover, it provides insights into understanding enantioselective amyloid inhibition, extending applications in asymmetric catalysis, enantioselective separation and chiroptical devices.