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 membranes was examined in detail. A comparison of the rates of the lipid peroxidation reaction demonstrated that the electron-donating capacity of the substituted acetylacetonate ligand significantly influences the rate of reaction. 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 1 proceeded without the formation of radicals as shown by EPR spin trap techniques. In contrast, lipid peroxidation initiated with non-chelated bis(cyclopentadienyl)-vanadium(IV) dichloride (6) was associated with the production of radicals under similar experimental conditions. There also was a significant pH effect on the extent of peroxidation initiated with 6 versus the reaction initiated with 1. The mode of action of 1 likely involves the activation of molecular oxygen by the vanadium(IV) center followed by allylic hydrogen atom abstraction from the lipid.
Department of Chemistry, Parker Hughes Institute, St. Paul, MN 55113, USA.
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Kotchevar
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Ghosh
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DuMez
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Uckun
D000332:Aerobiosis; D004563:Electrochemistry; D004578:Electron Spin Resonance Spectroscopy; D006863:Hydrogen-Ion Concentration; D015227:Lipid Peroxidation; D008081:Liposomes / Q000737:chemistry*; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism; D019097:Spin Trapping; D017968:Vanadium Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism
D008081:Liposomes; D009942:Organometallic Compounds; D017968:Vanadium Compounds; D010100:Oxygen