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

Yongli Ji, Caoyu Yang, Yutong Ye, Yin Zhang (), Tingting Zhao, Shuyue Kong, Hongli Chen, Pai Liu, Zelong Zhao, Yilong Li, Jing Li, Ruixiao Ma, Zhiyong Ban, Kuo Yuan, Zhiyong Tang, Yi Liu (), Meiting Zhao () and Jun Guo ()
Additional contact information
Yongli Ji: Tiangong University
Caoyu Yang: National Center for Nanoscience and Technology
Yutong Ye: Tiangong University
Yin Zhang: University of North Texas
Tingting Zhao: Tiangong University
Shuyue Kong: Tiangong University
Hongli Chen: Tiangong University
Pai Liu: Tiangong University
Zelong Zhao: Tiangong University
Yilong Li: Tiangong University
Jing Li: Tiangong University
Ruixiao Ma: Tiangong University
Zhiyong Ban: Tiangong University
Kuo Yuan: Tianjin University of Technology
Zhiyong Tang: National Center for Nanoscience and Technology
Yi Liu: Tiangong University
Meiting Zhao: Tianjin University
Jun Guo: Tiangong University

Nature Communications, 2025, vol. 16, issue 1, 1-15

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.

Date: 2025
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DOI: 10.1038/s41467-025-63459-2

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