Theoretical Calculations of Carbon−Oxygen Bond Dissociation Enthalpies of Peroxyl Radicals Formed in the Autoxidation of Lipids

Theoretical calculations were carried out to provide a framework for understanding the free radical oxidation of unsaturated lipids. The carbonbondhydrogen bond dissociation enthalpies (BDEs) of organic model compounds and oxidizable lipids (RbondH) and the carbonbondoxygen bond dissociation enthalpies of peroxyl radical intermediates (RbondOO*) have been calculated. The carbonbondhydrogen BDEs correlate with the rate constant for propagation of free radical autoxidation, and the carbonbondoxygen BDEs of peroxyl radicals correlate with rate constants for beta-fragmentation of these intermediates. Oxygen addition to intermediate carbon radicals apparently occurs preferentially at centers having the highest spin density. The calculated spin distribution therefore provides guidance about the partitioning of oxygen to delocalized carbon radicals. Where the CbondH BDEs are a function of the extent of conjugation in the parent lipid and the stability of the carbon radical derived therefrom, CbondOO* BDEs are also affected by hyperconjugation. This gives way to different rates of beta-fragmentation of peroxyl radicals formed from oxygen addition at different sites along the same delocalized radical. We have also studied by both theory and experiment the propensity for benzylic radicals to undergo oxygen addition at their ortho and para carbons which, combined, possess an equivalent unpaired electron spin density as the benzylic position itself. We find that the intermediate peroxyl radicals in these cases have negative CbondOO* BDEs and, thus, have rate constants for beta-fragmentation that exceed the diffusion-controlled limit for the reaction of a carbon-centered radical with oxygen.