Photo-oxidation of lipids by singlet oxygen: a theoretical study

The photo-oxidation reactions between lipid model nona-3,6(c,c)-diene and singlet molecular oxygen are investigated using density functional theory and polarized continuum models. Additions to both the 3- and 4-position of the lipid model (corresponding to the 9(13)- and 10(12)-positions of 9,12 lipid dienes such as linoleic acid) are explored. It is concluded that the modes of attack will lead to adduct intermediates which evolve either to dioxetane formation overcoming a significant energy barrier, or to the final LOOH products (hydro-peroxide bonded to either the 3- or 4-position), for which no transition barriers towards H-abstraction could be located. The computed energy surfaces are in close accord with results for the reactions between singlet oxygen and other unsaturated systems, and explain both the observed difference in product distribution in biological samples and, through the high energy barriers to addition of the initial reactants (15–20 kcal/mol), the low reactivity of singlet oxygen in biological membranes.