ESIPT-Modulated Supramolecular Host–Guest System with Single-Crystal Structural Insights for Selective Multichannel Heavy-Metal Ion Detection and as a Potential AnCE Inhibitor

Abstract A multifunctional supramolecular host–guest system based on an ESIPT-active Schiff base ligand (E)-N′-(5-bromo-2-hydroxybenzylidene)-2-fluorobenzohydrazide monohydrate (FHMB) has been designed and confirmed through single-crystal X-ray diffraction analysis for multichannel heavy-metal ion sensing and explored as a potential angiotensin-converting enzyme (AnCE) inhibitor. FHMB exhibits excitation-dependent dual emission arising from keto–enol tautomerism, enabling sensitive modulation of fluorescence through excited-state intramolecular proton transfer regulation. Complexation with Zn2+, Cd2+, and Pb2+ ions induces distinct turn-on fluorescence responses, characterized by distinct color outputs, allowing for simultaneous and differential detection in aqueous media. In contrast, FHMB exhibits exceptional selectivity toward Zr4+, producing a pronounced ratiometric fluorescence response under different sensing conditions. Binding stoichiometry and thermodynamics were elucidated using Job’s plot, Benesi–Hildebrand, and BindFit analyses, while 1H NMR, SEM–EDX, and elemental mapping confirmed metal-induced coordination and supramolecular reorganization. Practical applicability is validated through solid-state test kits, real-water sample analysis, plant-based Zn2+ imaging, and pharmaceutical zinc tablet detection. Furthermore, molecular docking studies against Drosophila and human AnCE reveal favorable binding interactions, particularly for the FHMB_Cd complex, indicating promising inhibitory potential. Collectively, this work presents a dual-functional supramolecular platform integrating environmental heavy-metal sensing with prospective biochemical modulation, highlighting its relevance for analytical, environmental, and biomedical applications.