Synthesis, crystal structures and urease inhibitory activity of oxidovanadium(V) complexes with aroylhydrazone and acetohydroxamate ligands

Abstract

Two new mononuclear oxidovanadium(V) complexes, [VOL1(AHA)] (1) and [VOL2(AHA)] (2), where L1 and L2 are the dianionic aroylhydrazone ligands derived from 3-chlorobenzohydrazide and pyridine-2-carbohydrazide, respectively, and AHA is acetohydroxamate, have been synthesized and structurally characterized. The complexes were obtained in good yields through a convenient one-pot reaction of vanadyl acetylacetonate, the corresponding aroylhydrazide and acetohydroxamic acid (AHA), in which the aroylhydrazone ligands were generated in situ by condensation of the hydrazides with acetylacetone released from the vanadium precursor. Single crystal X-ray diffraction analysis revealed that 1 and 2 are closely related neutral mononuclear oxidovanadium(V) species. In both complexes, the V(V) center adopts a distorted octahedral NO5 coordination environment, being coordinated by a tridentate ONO aroylhydrazone ligand, a bidentate acetohydroxamate ligand and a terminal oxido group. The strong trans influence of the V=O group results in pronounced axial bond elongation, while the chelate bite angles contribute to the distortion from an ideal octahedral geometry. The complexes were further evaluated for their urease inhibitory activities. Complex 1 exhibited excellent inhibition, with an IC50 value of 0.3 ± 0.2 μmol L–1, whereas 2 showed substantially weaker activity (IC50 > 100 μmol L–1). Molecular docking analysis indicated that 1 fits favorably into the active-site pocket of urease, with hydrophobic contacts involving Met366, Ala365, Val320 and Met317, supporting its strong inhibitory activity. These results demonstrate that incorporation of aroylhydrazone and acetohydroxamate donors into a single oxidovanadium(V) coordination sphere represents a promising strategy for developing potent metal-based urease inhibitors.