The Chemistry of Peroxynitrite: Implications for Biological Activity

In biological systems, nitric oxide (NO) combines rapidly with superoxide (O₂ ^-) to form peroxynitrite ion (ONOO^-), a substance that has been implicated as a culprit in many diseases. Peroxynitrite ion is essentially stable, but its protonated form (ONOOH, pK_a = 6.5 to 6.8) decomposes rapidly via homolysis of the O-O bond to form about 28% free NO₂ and OH radicals. At physiological pH and in the presence of large amounts of bicarbonate, ONOO^- reacts with CO₂ to produce about 33% NO₂ and carbonate ion radicals (CO₃ ^-) in the bulk of the solution. The quantitative role of OH / CO₃ ^- and NO₂ radicals during the decomposition of peroxynitrite (ONOOH/ONOO^-) under physiological conditions is described in detail. Specifically, the effect of the peroxynitrite dosage rate on the yield and distribution of the final products is demonstrated. By way of an example, the detailed mechanism of nitration of tyrosine, a vital aromatic amino acid, is delineated, showing the difference in the nitration yield between the addition of authentic peroxynitrite and its continuous generation by NO and O₂ ^- radicals.