Peroxynitrite scavenging by metalloporphyrins and thiolates

The rate constant for the reaction of nitric oxide with superoxide virtually assures that peroxynitrite will be formed to some extent in any cell or tissue where both radicals exist simultaneously. The precise biological targets for peroxynitrite and the nature of the modification of those targets vary dramatically depending on their relative concentrations and the rates and duration of peroxynitrite formation. Thus, peroxynitrite may have physiological functions in addition to pathological ones. Peroxynitrite scavenger compounds may prove to be therapeutic by effectively intercepting higher levels of peroxynitrite and thereby preventing injurious oxidative modifications of cellular components. Thiols and thiolates comprise a class of sacrificial scavengers that react with peroxynitrite anion with rate constants ranging from 2 x 10(3) M(-1) s(-1) to 2 x 10(8) M(-1) s(-1), depending on the microenvironment of the thiol. Several Mn and Fe porphyrins have been shown to react quite rapidly with peroxynitrite (10(6) to 10(7) M(-1) s(-1)) and decompose it in a catalytic manner; Mn porphyrins require exogenous reductants for complete cycling whereas Fe porphyrins do not. Sacrificial thiol/thiolate scavengers effectively quench the total oxidative yield of peroxynitrite, whereas the catalytic porphyrins redirect it and can, under some conditions, enhance total nitration and oxidative yield.