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.
Kotchevar
A T
AT
Department of Chemistry, Parker Hughes Institute, St. Paul, MN 55113, USA.
Ghosh
P
P
DuMez
D D
DD
Uckun
F M
FM
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