Mapping the reaction of peroxynitrite with CO2:: Energetics, reactive species, and biological implications

The reaction of peroxynitrite with CO2 produces the free radicals CO3·- and ·NO2 in ca. 30% yield. Peroxynitrite reacts faster with CO2 than with most biological molecules; this reaction generates the radicals CO3·- and ·NO2 that are the species that are responsible for the oxidations and nitrations of many biological species that take place when both peroxynitrite and CO2 are present. The reactive species ONOOCO2- and O2NOCO2- are very short-lived and decompose before they can react with biological molecules. A molecule must react with peroxynitrite with a pseudo-first-order rate constant substantially larger than 46 s-1 in order to be an effective scavenger of peroxynitrite and compete with the reaction with CO2 (14). This threshold is very high and most scavengers may reach toxic levels before this condition can be met. However, targeting the free radicals CO3·- and ·NO2 may offer a viable approach to block the deleterious effects of peroxynitrite. The biological reactions of ·NO2 (69), and in particular the reactions CO3 (27), had received relatively little attention until recently (2, 15, 40, 70, 71). The reaction of peroxynitrite with CO2 is unique in the sense that it simultaneously produces the free radicals CO3·- and ·NO2. However, the biological implications of these radicals may be more general and widespread than originally thought. Remarkably, in biological systems, ·NO2 can also be produced from nitrite (72), independently of nitric oxide synthase, and CO3·- may be produced in association with the hydroxyl radical (73). Considerable amount of research is still needed to fully assess the biological impact of the reactions of these free radicals.