Oxidovanadium(v) complexes of aroylhydrazones incorporating heterocycles: synthesis, characterization and study of DNA binding, photo-induced DNA cleavage and cytotoxic activities

Abstract

Four neutral oxidovanadium(V) complexes VO₂L¹ (1), VO₂L² (2), VOL³(OEt) (3) and VOL⁴(OEt)EtOH (4) [where HL¹ = 2-thiophenoylhydrazone of 2-acetylpyridine, HL² = 2-amino benzoylhydrazone of 2-benzoyl pyridine, H₂L³ = isonicotinoylhydrazone of 2-hydroxy acetophenone, H₂L⁴ = 2-furoylhydrazone of 2-hydroxy-1-napthaldehyde] with a hydrazone scaffold containing either furan, thiophene and pyridine residues have been synthesised. All complexes were thoroughly characterized by various spectroscopic (IR, UV-Vis, NMR and ESI-MS) and single crystal X-ray diffraction techniques. Crystallography establishes five-coordinate geometries, distorted toward square pyramidal for each of 1 and 2, based on a tridentate-O,N,N coordinating anion and two oxido-O atoms. The dianion in 3 is tetradentate, coordinating one V atom as for 1 and 2, and bridging another via the pyridyl-N atom, and the N₂O₄ octahedral coordination geometry is completed by oxido- and ethanolate-O atoms. The result of the V–N bridging is a helical coordination polymer. An NO₅ octahedral geometry is found in 4 defined by a tridentate-O,N,O anion, as well as oxido-, ethanolate- and ethanol-O atoms. Biological studies reveal that 1–4 have DNA binding propensity and show these to interact with CT-DNA through the minor groove binding mode, with binding constants ranging from 10³ to 10⁵ M⁻¹. All complexes show good photo-induced cleavage of pUC19 supercoiled plasmid DNA with 3 showing the highest photo-induced DNA cleavage activity of ∼65%. Additionally, 1–4 are cytotoxic against the human cervical cancer cell line (HeLa) with IC₅₀ values ranging from 10 to 20 μM.