Mechanistic insights into the recognition of Fe2+ and solvent-driven selectivity of chalcone-based receptors

Building on recent works [Spectrochim. Acta A: Mol. Biomol. Spectrosc. 287 (2023) 122107; 303 (2023) 123129], this study offers novel insight into the supramolecular recognition of Fe 2+ by receptor R1, wherein the conventional chalcone binding strategy is extended. Density Functional Theory (DFT) is used to differentiate the complexation behavior of chalcone-based receptors (R1, R2, R3), revealing key nucleophilic centres—particularly the carbonyl and phenolic oxygen atoms—as primary coordination sites. Optimized geometries, semi-empirical tight-binding calculations, and molecular dynamics simulations highlight the crucial role of the carbonyl oxygen of R1 and demonstrate that solvent molecules actively participate in metal coordination. This leads to the proposal of a new complexation model for R1, where solvent molecules facilitate stable 1:1 host–guest complex formation. The role of non-covalent interactions (NCIs), including ion–dipole, hydrogen bonding, and van der Waals forces, is also emphasized in governing metal ion (Fe 2+ , Ni 2+ , Cu 2+ ) recognition and selectivity. Quantum mechanical electron density (ED) and reduced density gradient (RDG) analyses visualize and quantify these weak interactions, showing that Fe 2+ forms the most stable complex due to favorable coordination, unlike Ni 2+ and Cu 2+ . These theoretical predictions align with experimental results—such as pH effects, UV–Vis spectroscopy, and NMR titrations—supporting the hypothesis that solvent molecules act as auxiliary ligands. Together, these findings deepen the understanding of chalcone-based receptor design and their metal ion sensing capabilities in mixed solvent environments. • The solvent mixture plays an important role in binding of metal ions by chalcones where keto- and phenolic-groups are distant in the moleculer structure. • The non-covalent interactions dominate over other interactions in the supramolecular recognition. • The applicability of independent gradient model for non-covalent interactions in the metal-chalcone complexation has been explored.