Induction of aerobic peroxidation of liposomal membranes by bis(cyclopentadienyl)-vanadium(IV) (acetylacetonate) complexes

The ability of bis(cyclopentadienyl)-vanadium(IV) (acetylacetonate) (1) to initiate oxygen-dependent lipid peroxidation in zwitterionic liposomal memb ranes was examined in detail. A comparison of the rates of the lipid peroxi dation reaction demonstrated that the electron-donating capacity of the sub stituted acetylacetonate ligand significantly influences the rate of reacti on. An increase in the rate of lipid peroxidation correlated to a decrease in the V-IV/V-V redox potential. Notably, lipid peroxidation initiated with I proceeded without the formation of radicals as shown by EPR spin trap te chniques. In contrast. lipid peroxidation initiated with non-chelated bis(c yclopentadienyl)-vanadium(IV) dichloride (6) was associated with the produc tion of radicals under similar experimental conditions. There also was a si gnificant pH effect on the extent of peroxidation initiated with 6 versus t he reaction initiated with 1. The mode of action of 1 likely involves the a ctivation of molecular oxygen by the vanadium(IV) center followed by allyli c hydrogen atom abstraction from the lipid. (C) 2001 Elsevier Science B.V. All rights reserved.