An oxalate-bridged oxidovanadium(iv) binuclear complex that improves the in vitro cell uptake of a fluorescent glucose analog

Gabriel B. Baptistella, Graciele C. M. Manica, Susan W. de Souza, Francielli S. Santana, Lucas G. Fachini, David L. Hughes, Eduardo L. de Sá, Geraldo Picheth, Jaísa F. Soares, Fabiane G. M. Rego, Giovana G. Nunes

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    Abstract

    The centrosymmetric oxidovanadium(IV) complex (Et 3NH) 2[{VO(OH 2)(ox)} 2(μ–ox)] (I), where ox 2− = oxalate, was synthesized and characterized by X-ray diffraction (single-crystal and powder, PXRD), thermogravimetric (TGA), magnetic susceptibility (at room temperature) and spectroscopic analyses (infrared, Raman and electron paramagnetic resonance, EPR, spectroscopies). In the solid state, each vanadium center is coordinated by the oxygen atoms of a bis-bidentate oxalate bridging ligand, a terminal oxalate, an oxo group and one water molecule. The electronic structure of the binuclear complex was investigated by density functional theory (DFT) calculations, both in vacuum and in a simulated aqueous environment, employing the ωB97XD functional and the def2TZVP basis set. The cytotoxicity of I was evaluated in vitro in the human hepatocellular carcinoma cell line HepG2, giving an IC 50 value of 15.67 µmol L −1 after incubation for 24 h. The EPR analysis of I in aqueous solution suggested the maintenance of the binuclear structure, while in the hyperglycemic medium DMEM the complex suffers dissociation to give a mononuclear oxidovanadium(IV) species. HepG2 cell treatment with 0.10 and 0.50 µmol L −1 of I in DMEM increased 2-NBDG (2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-D-glucose) uptake significantly (up to 91% as compared to HepG2 in hyperglycemic condition, 59%). These results indicate a promising activity of I to be investigated further in additional antidiabetic studies.

    Original languageEnglish
    Article number115071
    JournalPolyhedron
    Volume198
    Early online date30 Jan 2021
    DOIs
    Publication statusPublished - 1 Apr 2021

    Keywords

    • 2-NBDG uptake
    • Crystal structure analysis
    • HepG2 cells
    • Oxalate
    • Oxidovanadium(IV)

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