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Here, atomically precise heterometallic nanoclusters undergo organic acid\u2013induced coordination twisting and core symmetry breaking, dynamically modulating their coordination environment for enantiomeric resolution. Chiral amino acids stabilize cluster chirality, yielding enantiopure clusters matching the amino acid configuration. These clusters exhibit strong chiroptical responses, including circular dichroism (CD) and circularly polarized luminescence (CPL), enabling reliable quantification of enantiomeric excess (ee) across 20 chiral acids. Significantly, the system can be rationally regenerated and reused, enabling multiple cycles of consistent, quantitative chiral sensing. Mechanistic studies reveal that recognition arises from electrostatic preconcentration, followed by coordination and hydrogen bonding, which lock substrate configurations and transfer chiral information. Furthermore, threonine\u2010modified chiral heterometallic clusters also enable enantioselective coordination\u2010driven drug sensing, exemplified by ibuprofen recognition via ligand exchange, as unambiguously confirmed by single\u2010crystal X\u2010ray analysis. This work establishes a versatile coordination\u2010driven platform for high\u2010throughput, real\u2010time, and quantitative enantioselective sensing, highlighting the potential of atomically precise clusters for chiral recognition and drug analysis.<\/jats:p>","DOI":"10.1002\/adma.202522830","type":"journal-article","created":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T16:54:22Z","timestamp":1773939262000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Organic Acid\u2010Induced Twisting in Heterometallic Clusters Enables Multimodal Chiroptical Sensing and Enantioselective Drug Recognition"],"prefix":"10.1002","volume":"38","author":[{"given":"Jia\u2010Yin","family":"Wang","sequence":"first","affiliation":[{"name":"Tianjian Laboratory of Advanced Biomedical Sciences Henan Key Laboratory of Crystalline Molecular Functional Materials College of Chemistry Zhengzhou University  Zhengzhou 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