Quercetin and luteolin complexation with first-row transition metals in purely aqueous solutions: stoichiometry and binding site selectivity†

The complexation behaviour of quercetin and luteolin with first-row transition metals (Cr(III), Mn(II), Co(II), Ni(II), and Zn(II)) in aqueous solutions was systematically investigated using potentiometric titrations, UV-Vis and FT-IR spectroscopy, and density functional theory (DFT) calculations. This study aimed to elucidate the stability, stoichiometry, and preferred binding sites of these flavonoid–metal complexes in an entirely aqueous solution at 37 °C as a function of pH under controlled ionic strength. Speciation analysis revealed the formation of 1 : 1, 1 : 2, and 1 : 3 metal-to-ligand complexes, with coordination occurring primarily at the 4,5- or 3,4-binding site, depending on the metal ion and ligand structure. UV-Vis and IR spectral changes confirmed complex formation, while computational modeling provided insights into binding site selectivity and free energy changes associated with coordination. Results highlight the influence of the ligand structure on metal affinity and stability, with quercetin forming more stable complexes than those formed by luteolin owing to the presence of an additional hydroxyl group at position 3. These findings contribute to a deeper understanding of flavonoid–metal interactions, with potential implications for antioxidant activity, metal chelation therapy, and environmental applications.