Acceleration of peroxynitrite oxidations by carbon dioxide

Stopped-flow kinetic studies of the isomerization of peroxynitrite to give nitrate have been performed in carbonate-enriched buffers using pH jump and carbonic anhydrase as probes. The data are consistent with the reaction of CO2 and the peroxynitrite anion rapidly forming an unstable nitrosoperoxy-carbonate anion adduct, O=N-OOCO2- (1). The CO2 catalysis of the isomerization of peroxynitrite is not accompanied by the formation of nitrite, hydrogen peroxide, or other hydroperoxidic material like peroxycarbonate. The reaction proceeds via the transient formation of an oxidant or oxidants that is (are) capable of promoting electrophilic nitration reactions. We propose that O=N-OOCO2- rearranges to give a nitrocarbonate anion, O2N-OCO2- (2) which in turn, may serve as the proximal oxidant in biological systems that produce peroxynitrite. At least four different mechanistic classes of reactions that have been ascribed to peroxynitrite can be envisioned to involve 2: (a) hydrolysis to nitrate, (b) one-electron or (c) two-electron oxidations, and (d) electrophilic nitration. Given the fast reaction of peroxynitrite with carbon dioxide and the ubiquitous presence of the latter, the role of CO2 cannot be neglected in complex peroxynitrite reactions in vitro and in vivo.