Wet synthesis approach afforded four new heteroleptic mononuclear neutral diamagnetic oxidovanadium(V) complexes, comprising salicylaldehyde-based 2-furoic acid hydrazones and a flavonol coligand of the general composition [VO(fla)(L-ONO)]. The complexes were comprehensively characterized, including chemical analysis, conductometry, infrared, electronic, and mass spectroscopy, as well as 1D 1H and proton-decoupled 13C(1H) NMR spectroscopy, alongside extensive 2D 1H1H COSY, 1H13C HMQC, and 1H13C HMBC NMR analyses. Additionally, the quantum chemical properties of the complexes were studied using Gaussian at the B3LYP, HF, and M062X levels on the 6-31++g(d,p) basis sets. The interaction of these hydrolytically inert vanadium complexes and the BSA was investigated through spectrofluorimetric titration, synchronous fluorimetry, and FRET analysis in a temperature-dependent manner, providing valuable thermodynamic insights into van der Waals interactions and hydrogen bonding. Molecular docking was conducted to gain further understanding of the specific binding sites of the complexes to BSA. Complex 2, featuring a 5-chloro-substituted salicylaldehyde component of the hydrazone, was extensively examined for its biological activity in vivo. The effects of complex administration on biochemical and hematological parameters were evaluated in both healthy and diabetic Wistar rats, revealing antihyperglycemic activity at millimolar concentration. Furthermore, histopathological analysis and bioaccumulation studies of the complex in the brain, kidneys, and livers of healthy and diabetic rats revealed the potential for further development of vanadium(V) hydrazone complexes as antidiabetic and insulin-mimetic agents.

Solution synthesis afforded five novel neutral heteroleptic octahedral paramagnetic mononuclear oxidovanadium(IV) complexes of general composition [VO(bpy)L], where L is a dianionic tridentate ONO-donor hydrazone ligand derived from 2-furoic acid hydrazide and salicylaldehyde and its 5-substituted derivatives. Characterization was carried out by elemental analysis, mass spectrometry, infrared, electron, NMR, and EPR spectroscopy, cyclic voltammetry and conductometry. The molecular and crystal structure of the complex with 5-chloro-salicylaldehyde 2-furoic acid hydrazone (2) was determined. The quantum chemical properties of the vanadium complexes were studied at B3LYP and M062X levels with the lanl2dz basis set using Gaussian. Additionally, Swiss-ADME analysis was performed and complex (4), featuring a 5-nitro substituent on the hydrazone ligand, was selected for further investigation. The effects of the in vivo application of the complex on selected biochemical parameters in healthy and diabetic Wistar rats were investigated. Strong antidiabetic effect associated with moderate hypoalbuminemia was observed. Furthermore, the interaction of complexes with BSA was studied by spectrofluorimetry. A significant conformational change of BSA in the presence of vanadium complexes was found. Synchronous fluorescence spectra revealed significant changes in the tyrosine microenvironment of BSA. The FRET analysis was also used and the non-radiative process of energy transfer is elucidated. Thermodynamic data suggest van der Waals forces and hydrogen bonding as predominant binding modes of complexes to BSA.