Determination of Anticancer Zn(II)–Rutin Complex Structures in Solution through Density Functional Theory Calculations of (1)H NMR and UV–VIS Spectra

[Image: see text] Coordination compounds formed by flavonoid ligands are recognized as promising candidates as novel drugs with enhanced antioxidant and anticancer activity. Zn(II)–Rutin complexes have been described in the literature and distinct coordination modes proposed based on (1)H NMR/MS and IR/UV–VIS experimental spectroscopic data: 1:1/1:2 (Zn(II) binding to A-C rings) and 2:1 (Zn(II) binding to A-C-B rings) stoichiometry. Aiming to clarify these experimental findings and provide some physical insights into the process of complex formation in solution, we carried out density functional theory calculations of NMR and UV–VIS spectra for 25 plausible Zn(II)–Rutin molecular structures including solvent effect using the polarizable continuum model approach. The studied complexes in this work have 1:1, 1:2, 2:1, and 3:1 metal–ligand stoichiometry for all relevant Zn(II)–Rutin configurations. The least deviation between theoretical and experimental spectroscopic data was used as an initial criterion to select the probable candidate structures. Our theoretical spectroscopic results strongly indicate that the experimentally suggested modes of coordination (1:2 and 2:1) are likely to exist in solution, supporting the two distinct experimental findings in DMSO and methanol solution, which may be seen as an interesting result. Our predicted 1:2 and 2:1 metal complexes are in agreement with the experimental stoichiometry; however, they differ from the proposed structure. Besides the prediction of the coordination site and molecular structure in solution, an important contribution of this work is the determination of the OH–C5 deprotonation state of rutin due to metal complexation at the experimental conditions (pH = 6.7 and 7.20). We found that, in the two independent synthesis of metal complexes, distinct forms of rutin (OH–C5 and O((−))–C5) are present, which are rather difficult to be assessed experimentally.