The rate of homolysis of adducts of peroxynitrite to the C=O double bond

Nucleophilic addition of the peroxynitrite anion, ONOO^-, to the two prototypical carbonyl compounds, acetaldehyde and acetone, was investigated in the pH interval 7.4-14. The process is initiated by fast equilibration between the reactants and the corresponding tetrahedral adduct anion, the equilibrium being strongly shifted to the reactant side. The adduct anion also undergoes fast protonation by water and added buffers. Consequently, the rate of the bimolecular reaction between ONOO^- and the carbonyl is strongly dependent on the pH and on the concentration of the buffer. The pK_a of the carbonyl-ONOO adduct was estimated to be 11.8 and 12.3 for acetone and acetaldehyde, respectively. It is shown that both the anionic and the neutral adducts suffer fast homolysis along the weak O-O bond to yield free alkoxyl and nitrogen dioxide radicals. The yield of free radicals was determined to be about 15% with both carbonyl compounds at low and high pH, while the remainder collapses to molecular products in the solvent cage. The rate constants for the homolysis of the adducts vary from ca. 3 x 10⁵ to ca. 5 x 10⁶ s^-1, suggesting that they cannot act as oxidants in biological systems. This small variation around a mean value of about 10⁶ s^-1 suggests that the O-O bond in the adduct is rather insensitive to its protonation state and to the nature of its carbonyl precursor. An overall reaction scheme was proposed, and all the corresponding rate constants were evaluated. Finally, thermokinetic considerations were employed to argue that the formation of dioxirane as an intermediate in the reaction of ONOO^- with acetone is an unlikely process.