Evaluation of the Performance of Manganese Phthalocyanines as Superoxide Dismutase Mimics

Abstract

Evaluation of the performance of seven variously substituted manganese(III) phthalocyanine complexes (MnPcs) for the dismutation of superoxide radical (O-2(center dot-)), as superoxide dismutase mimics (SOD mimics), was assessed using cyclic voltammetry, UV visible spectrophotometry and fluorescence. In a first step, the electrochemical analysis of the MnPcs allows showing the fine tuning of the redox potential of the Mn-III/Mn-II couple which is involved in the dismutation process of O-2(center dot-). Thus, the evaluation of the behaviour of the MPcs as SOD mimics were tested toward O-2(center dot-) produced from the xanthine-xanthine oxidase reaction, using cytochrome c and UV visible spectrophometry (McCord-Fridovich assay). All manganese phthalocyanine complexes did not interfere with the xanthine-xanthine oxidase reaction and efficiently dismutated O-2(center dot-) with apparent overall catalytic rate constant values ranging from log k(cat) = 7.81 to 6.62 and improved IC50 (concentration of complex that induces 50% inhibition of the reduction of 10 mu M cytochrome c) values (0.04 to 0.68 mu M) compared to one commercially available Mn porphyrin based SOD mimic (namely manganese (III) tetrakis (1-methyl-4-pyridyl) porphyrin). We used DMSO-treated HL60 cell (human leukemia cells) as a model of O-2(center dot-) production, either extracellular production with Phorbol 12-myristate 13-acetate (PMA) stimulation or intracellular production without PMA stimulation. With these models, analysis of dihydroethidium (DHE) fluorescence for the detection of superoxide production showed that the examined MnPcs act as proficient superoxide dismutase mimics. The obtained results also showed that four of these MPcs are cell permeant.