Generation of Hydroxyl Radicals during Dismutation of Superoxide by SOD Model Compounds

The reactivities of copper(II) complexes with cimetidine (Cim) and cyclo(histidylhistidyl) (CyHH), both of which are SOD model compounds, toward active oxygen species such as superoxide (O−2) and hydrogen peroxide (H2O2) were investigated by electron spin resonance-spin trapping and thiobarbituric acid methods. At physiological pH values, low concentrations of Cu(II) complexes (0.025 mM) with Cim and CyHH could scavenge O−2, but high concentrations of these compexes (0.25 mM) yielded hydroxyl radicals (.OH) during dismutation of O−2. These Cu(II) complexes could directly react with H2O2 to yield .OH. From these results, it is indicated that .OH formed during the dismutation of O−2 by high concentration of SOD model compounds may be caused by the reaction of H2O2 generated form dismutation of O−2 with Cu(II) complexes. Further, DNA single-stranded breakage was observed during the reactions of H2O2 with these Cu(II) complexes.