Mechanism of Peroxynitrite Oxidation of Aliphatic CH Bonds in Saturated and Unsaturated Hydrocarbons. A Theoretical Model for the CH Oxidation of Lipids

The oxidation of aliphatic CH bonds in methane, propane, isobutane, propene, and 1,4-pentadiene with peroxynitrous acid and peroxynitrite anion has been studied computationally with the B3LYP, MP2, and QCISD(T) levels of theory. The CCD, CISD, and CCSD(T) methods were also used for the parent systems, methane−ONOOH and methane−ONOO-. Three pathways were considered: path a, direct oxygen insertion into a C−H bond (two-electron oxidation); path b, H atom abstraction leading to alkyl radicals (one-electron oxidation); and path c, O−O bond homolysis of ONOOH (initial oxidation by hydroxyl radicals). Transition structures were located for path a which correspond to a concerted electrophilic oxygen insertion into the CH leading to the corresponding alcohols. At the QCISD(T)/6-31+G*//B3LYP/6-31+G* level, the activation barriers for the path a oxidation of methane, propane, isobutane, propene, and 1,4-pentadiene with ONOOH are 30.8, 18.1, 17.0, 21.1, and 17.8 kcal mol-1 and with ONOO- they are 35.8, 29.4, 26.3, 25.0, and 14.0 kcal mol-1, respectively. The direct abstraction of the hydrogen atom from the hydrocarbons by these oxidants (path b) yielding alkyl radicals is thermodynamically much less favorable than the two-electron oxidation even for 1,4-pentadiene (model for lipids). The calculated lower limit for the free energy of activation for the two-electron CH oxidation of 1,4-pentadiene with ONOOH (ΔG≠298 = 20.5 kcal mol-1) is higher than the free energy of homolysis of the O−O bond (path c) in ONOOH (ΔG298 = 12.2−17.4 kcal mol-1, theoretical and experimental estimates). This supports the hypothesis that the reactive species in hydrocarbon oxidations by peroxynitrous acid, and in lipid peroxidation induced by peroxynitrous acid in the presence of air, is the discrete hydroxyl radical formed in the homolysis of this acid.