Hydroxyl Radical is the Active Species in Photochemical DNA Strand Scission by Bis(peroxo)vanadium(V) Phenanthroline

Abstract

Bis(peroxo)vanadium(V) complexes are widely investigated as anticancer agents. They exert their antitumor and cyctotoxic effects through inhibition of tyrosine phosphatases and DNA cleavage, respectively. The latter process remains poorly understood. The mechanism of DNA cleavage by NH(4)[(phen)V(O)(eta(2)-O(2))(2)] (phen = 1,10-phenanthroline) was investigated. Kinetic studies on DNA cleavage revealed that the complex is a single-strand nicking agent with no specificity. EPR experiments using 2,2,6,6-tetramethyl-4-piperidone (TMP) and 5,5'-dimethyl-1-pyrroline-N-oxide (DMPO) as spin-traps for singlet oxygen and hydroxyl radical, respectively, implicated hydroxyl radical production upon photodecomposition of bis(peroxo)vanadium(V). This was corroborated by benzoate inhibition of DNA strand scission and stoichiometric oxidation of 2-propanol to acetone upon irradiation of bis(peroxo)vanadium(V) phenanthroline. High-resolution polyacrylamide gel analysis of the vanadium cleavage reaction and [Fe(II)EDTA](2)(-)/H(2)O(2) resulted in comigration of "ladder" pattern bands, which superimposed when both reactions were run on the same lane. These findings identify hydroxyl radical produced from the photooxidation of the peroxo ligand on vanadium as the active species in DNA cleavage.

The kinetics and mechanism of oxidation of isopropanol with the hydrogen peroxide-vanadate ion-pyrazine-2-carboxylic acid system

“…As with the oxidation of alkanes in acetonitrile catalyzed by vanadate ions, the oxidation of isopropanol in isopropanol as a solvent occurs at a much lower rate in the absence of pyrazinecarboxylic acid (see works on the oxidation of alcohols catalyzed by vanadium derivatives [20][21][22][23][24][25][26]). …”

Studies on DNA cleavage and antimicrobial screening of transition metal complexes of 4-aminoantipyrine derivatives of N2O2 type

“…Among the different therapeutic strategies to eradicate cancer cells through DNA damage, the view of using small water soluble transition metal complexes, capable of oxidative or hydrolytic DNA cleavage as anticancer drugs is a challenging issue in bioinorganic chemistry [24,25]. Many transition metal complexes with vanadium [26], iron [27], copper [28,29], cobalt [30], lanthanides [31,32] and also actinides [33] have been reported as efficient DNA cleavage agents with or without sequence specificity, moreover the ligand or the metal in these complexes can be varied in an easily controlled manner to facilitate the individual applications [34].…”

Unique Ligand‐Based Oxidative DNA Cleavage by Zinc(II) Complexes of Hpyramol and Hpyrimol

“…[4,5] Among the different therapeutic strategies to eradicate cancer cells through DNA damage, the view of using small water-soluble transition-metal complexes, capable of oxidative or hydrolytic DNA cleavage as anti-cancer drugs, is a challenging topic in bioinorganic chemistry. [6,7] Many transition-metal complexes with V, [8] Fe, [9] Cu, [10,11] Co, [12] lanthanides, [13,14] and also actinides [15] have been reported as efficient DNA cleaving agents with or without sequence specificity. Of these metals, zinc is the second most abundant transition-metal ion present in the human body, [16,17] and is in the active sites of several enzymes such as superoxide dismutase, proteins containing zinc finger motifs and zinc hydrolases, in particular, owing to its Lewis acid character.…”