Superoxide (O2.-) and peroxynitrite (ONOO-) have been implicated in many pathophysiological conditions. To develop novel catalysts that have both ONOO- decomposition and O2.- dismutase activity, and to understand the mechanisms of these processes, we have explored the reactivity of 5,10,15,20-tetrakis- (N-methyl-4'-pyridyl)porphinatomanganese(III) [Mn(III)TMPyP] toward ONOO- and 02.-. The reaction of Mn(III)TMPyP with ONOO- to generate an oxomanganese(IV) porphyrin species [(oxoMn(IV)] is fast, but Mn(III)TMPyP is not catalytic for ONOO- decomposition because of the slow reduction of oxoMn(IV) back to the Mn(III) oxidation state. However, biological antioxidants such as ascorbate, glutathione, and Trolox rapidly turn over the catalytic cycle by reducing oxoMn(IV). Thus, Mn(III)TMPyP becomes an efficient peroxynitrite reductase when coupled with ascorbate, glutathione, and Trolox (k(c) ~2 x 106 M-1 s-1), though the direct reactions of ONOO- with these biological antioxidants are slow (88 M-1 s-1, 5.8 x 102 M-1 s-1 and 33 M-1 s-1, respectively). Mn(III)TMPyP is known to catalyze the dismutation of O2.-, and using stopped-flow spectrophotometry, the rate of Mn(III)TMPyP-catalyzed dismutation has been measured directly (k(c) = 1.1 x 107 M-1 s-1). Further, O2.-, like the biological antioxidants, rapidly reduces oxoMn(IV) to the Mn(III) oxidation state (k ~108 M-1 s-1), transforming Mn(III)TMPyP into a O2.--coupled ONOO- reductase. Under conditions of oxidative stress and reduced antioxidant levels, Mn(III)TMPyP may deplete O2.- primarily as a function of its ONOO- reductase activity, and not through its O2.- dismutase activity.
|Original language||English (US)|
|Number of pages||9|
|Journal||Journal of the American Chemical Society|
|State||Published - Jan 1 1998|
All Science Journal Classification (ASJC) codes
- Colloid and Surface Chemistry