Peroxynitrite (ONOO-) is a major cytotoxic agent that has been implicated in a host of pathophysiological conditions; it is therefore important to develop therapeutic agents to detoxify this potent biological oxidant, and to understand the modes of action of these agents. Water-soluble iron porphyrins, such as 5,10,15,20-tetrakis(N-methyl-4'-pyridyl)porphinatoiron(III) [Fe(III)TMyP] and 5,10,15,20-tetrakis-(2,4,6-trimethyl-3,5-sulfonatophenyl)porphinatoiron(III) [Fe(III)TMPS], have been shown to catalyze the efficient decomposition of ONOO- to NO3- and NO2- under physiological conditions. However, the mechanisms of ONOO- decomposition catalyzed by these water-soluble iron porphyrins have not yet been elucidated. We have shown that there are two different pathways operating in the catalytic decomposition of ONOO- by FeTMPyP. Fe(III)TMyP reacts rapidly with ONOO- to produce oxoFe(IV)TMPyP and NO2 (k ~ 5 x 107 M-1 s-1). The oxoFe(IV) porphyrin, which persisted throughout the catalytic decomposition of ONOO-, was shown to be relatively unreactive toward NO2 and NO2-. This oxoFe(IV) porphyrin was also shown to react with ONOO- (k = 1.8 x 106 M-1 s-1), and it was this oxoFe(IV)-ONOO- reaction pathway that predominated under conditions of excess ONOO- with respect to Fe(III)TMPyP. The competition between the two pathways explains the highly nonlinear relationship observed for k(cat) with respect to ONOO- concentration. Fe(III)-TMPyP is also known to catalyze the dismutation of the ONOO- precursor superoxide (O2-.), and using stopped-flow spectrophotometry, the rate of Fe(III)TMPyP-catalyzed O2-. dismutation has been determined to be 1.9 x 107 M-1 s-1 by direct measurement. A detailed mechanistic understanding of how iron porphyrins function in the catalytic decomposition of both ONOO- and O2-. may prove essential in the exploration of the chemistry and biology of these reactive oxygen species, and in understanding the biological activity of these metalloporphyrins.
All Science Journal Classification (ASJC) codes
- Colloid and Surface Chemistry