Carbon dioxide stimulates the production of thiyl, sulfinyl, and disulfide radical anion from thiol oxidation by peroxynitrite.

Reaction of peroxynitrite with the biological ubiquitous CO(2) produces about 35% yields of two relatively strong one-electron oxidants, CO(3) and ( small middle dot)NO(2), but the remaining of peroxynitrite is isomerized to the innocuous nitrate. Partial oxidant deactivation may confound interpretation of the effects of HCO3-/CO(2) on the oxidation of targets that react with peroxynitrite by both one- and two-electron mechanisms. Thiols are example of such targets, and previous studies have reported that HCO3-/CO(2) partially inhibits GSH oxidation by peroxynitrite at pH 7.4. To differentiate the effects of HCO3-/CO(2) on two- and one-electron thiol oxidation, we monitored GSH, cysteine, and albumin oxidation by peroxynitrite at pH 5.4 and 7.4 by thiol disappearance, oxygen consumption, fast flow EPR, and EPR spin trapping. Our results demonstrate that HCO3-/CO(2) diverts thiol oxidation by peroxynitrite from two- to one-electron mechanisms particularly at neutral pH. At acid pH values, thiol oxidation to free radicals predominates even in the absence of HCO3-/CO(2). In addition to the previously characterized thiyl radicals (RS.), we also characterized radicals derived from them such as the corresponding sulfinyl (RSO.) and disulfide anion radical (RSSR.-) of both GSH and cysteine. Thiyl, RSO. and RSSR.- are reactive radicals that may contribute to the biodamaging and bioregulatory actions of peroxynitrite.