The effect of phosphate on the nuclease activity of vanadium compounds

• VIVO(acac-R)2 are very efficient DNA cleavers in phosphate buffer.
• The DNA cleaving mechanism is oxidative.
• VIVO(acac)2 may form (VIVO)(VVO)(acac)2(PO4) in biological media.
• (VIVO)(VVO)(acac)2(PO4) increases oxidative stress and DNA cleavage.

The nuclease activity of VO(acac)2 (1, acac = acetylacetone) and its derivatives VO(hd)2 (2, hd = 3,5-heptanedione), VO(Cl-acac)2 (3, Cl-acac = 3-chloro-2,4-pentanedione), VO(Et-acac)2 (4, Et-acac = 3-ethyl-2,4-pentanedione) and VO(Me-acac)2 (5, Me-acac = 3-methyl-2,4-pentanedione), is studied by agarose gel electrophoresis, UV–visible spectroscopy, cyclic and square wave voltammetry and 51V NMR. The mechanism is shown to be oxidative and associated with the formation of reactive oxygen species (ROS). Hydrolytic cleavage of the phosphodiester bond is also promoted by 1, but at much slower rate which cannot compete with the oxidative mechanism. The generation of ROS is much higher in the presence of phosphate buffer when compared with organic buffers and this was attributed to the formation of a mixed-ligand complex containing phosphate, (VIVO)(VVO)(acac)2(HnPO4n-3), presenting a quasi-reversible voltammetric behavior. The formation of this species was further observed by Electrospray Ionization Mass Spectrometry (ESI-MS). Phosphate being an essential species in most biological media, the importance of the formation of mixed-ligand species in other vanadium systems is emphasized.

Oxidovanadium(IV) acetylacetonate and its derivatives were found to have high DNA cleavage activity when in phosphate buffer. The mechanism is oxidative and involves the formation of a mixed-ligand vanadium dimer containing phosphate which presents a very flexible electrochemical behavior.Figure optionsDownload as PowerPoint slide