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

A highly water-soluble, binuclear oxalate-bridged oxidovanadium(IV) was synthesized, characterized, and studied by DFT method. Insulin-mimetic activity in hyperglycemic condition was evaluated in vitro using the 2-NBDG uptake by HepG2 cells. Finally, the chemical species present in aqueous solution and culture medium were investigated by EPR spectroscopy. [Display omitted] •A highly water-soluble, oxalate-bridged binuclear oxidovanadium(IV) complex was synthesized.•Potential insulin-mimetic activity of I was demonstrated in vitro using the 2–NBDG uptake assay.•Spectroscopic and structural studies were performed and DFT accessed the electronic structure. The centrosymmetric oxidovanadium(IV) complex (Et3NH)2[{VO(OH2)(ox)}2(μ–ox)] (I), where ox2− = 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 IC50 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.