INTERACTION OF VANADIUMIV COMPLEXES WITH DNA

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Interaction of vanadium compounds with DNA

Publication . Butenko, Nataliya; Cavaco, Isabel Maria Palma Antunes

The DNA cleavage activity of several vanadium complexes (VC) was studied. The focus was on vanadium acetylacetonate, VIVO(acac)2, 1, and several β-diketonate oxidovanadium(IV/V) derivatives: VIVO(hd)2 (2, hd = 3,5-heptanedione), VIVO(Cl-acac) 2, (3, Cl-acac = 3-chloro-2,4-pentanedione), VIVO(Et-acac)2 (4, Et-acac = 3-ethyl- 2,4- pentanedione) and VIVO(Me-acac)2 (5, Me-acac = 3-methyl-2,4-pentanedione), VV2O4(acac)2 (6), VVO2(acac)(phen) (7, phen = 1,10-phenanthroline) and VVO(OH)(OMe)(acac) (8). The nuclease activity of 28 additional vanadium, copper and nickel complexes was also analysed and compared. The experimental techniques involved digestion of plasmid DNA (pDNA) followed by agarose gel electrophoreses to evaluate nuclease efficiency. pDNA was prepared and purified to assure the absence of interference from EDTA (ethylenediaminetetraacetic acid) and Tris present in commercial pDNA. The stability of complexes in aqueous solutions was studied by UV/vis spectroscopy and electroanalytical techniques, cyclic (CV) and square wave voltammetry (SWV). The nature of DNA cleavage mechanisms was assayed using fluorescent probes and 1H and 51V NMR spectroscopy. VIVO(acac)2 was found to be efficient in cleaving pDNA. The extent of this pDNA cleavage is dependent on buffer media. In organic buffers (Tris, HEPES MOPS) no significant changes are observed, whereas in phosphate medium the nuclease activity is remarkable. The activity of the different complexes follows the order 3>1≥2>>4~5. The V(V) derivatives, 6-8, do not show any significant activity, except in the presence of an oxidant activating agent. CV results show that 1-3 have a quasi-reversible electrochemical behaviour, while of 4 and 5 have an irreversible one, similar to 6. The DNA cleavage by these complexes takes place through an oxidative mechanism. Complex 1 also cleaves DNA hydrolytically, however the reaction is too slow to compete with the radical mechanism. In conclusion, phosphate buffer potentiates the DNA cleavage by VIVO(acac)2 derivatives through a species which presents a quasi-reversible redox behaviour and facilitates the formation of ROS, probably a mixed V(IV)-V(V)-acac-phosphate complex.

2013Doctoral thesis

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