The pH dependence of lipid peroxidation using water-soluble azo initiators

We report here the pH dependence of the rate of lipid peroxidation of methyl linoleate/Triton mixed micelles using a series of water-soluble azo initiators. The cationic initiators 2,2'-azobis(2-amidinopropane) (ABAP) and 2,2'-azobis[2-(2-imidazolin-2-yl)propane] (ABIP) exhibit similar behavior, in which increased pH results in dramatically enhanced rates of peroxidation. Rate data for ABAP and ABIP were fitted to a single proton equilibrium, which yielded apparent kinetic pKa values for the rate of approximately 7 and 6, respectively. The azo initiator 4,4'-azobis(4-cyanopentanoic acid) (ABCPA), which yields a negatively charged radical upon thermolysis at neutral pH, was also studied. In contrast to the effects observed with ABAP and ABIP, peroxidation rates with ABCPA exhibit an inverse pH dependence, in which the rates of peroxidation increase with decreasing pH, with an apparent pKa of approximately 5. By comparison, methyl linoleate oxidation rates with 2,2'-azobis (2-cyanopropane) (ABCP) display minimal changes over the pH range 5 to 7.5. Two alternatives can be advanced to account for this behavior, including either a buffer effect which is specific to the cationic initiators or an altered amidinium pKa (approximately 6 to 7) in either the initial carbon-centered radical or the subsequent peroxyl radical generated upon thermolysis of ABAP or ABIP. In the latter case, the kinetic pH dependence could thus reflect an enhanced competence of neutral radicals over charged radicals to partition into the micelles and initiate peroxidation.