Hydroxyl radical is the active species in photochemical DNA strand scission by bis(peroxo)vanadium(V) phenanthroline.
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.
Sam
Mui
M
Department of Chemistry and Biochemistry, University of California, Los Angeles, California 90095, USA.
Hwang
Jung H
JH
Chanfreau
Guillaume
G
Abu-Omar
Mahdi M
MM
D001483:Base Sequence; D004247:DNA / Q000737:chemistry* / Q000528:radiation effects; D017665:Hydroxyl Radical / Q000737:chemistry*; D009942:Organometallic Compounds / Q000737:chemistry*; D010084:Oxidation-Reduction; D010618:Phenanthrolines / Q000737:chemistry*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014639:Vanadium / Q000737:chemistry*
D009942:Organometallic Compounds; D010618:Phenanthrolines; D014639:Vanadium; D017665:Hydroxyl Radical; D004247:DNA