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.

Reaction of alkylcobalamins with thiols.

Carbon-13 NMR spectroscopy and phosphorus-31 NMR spectroscopy have been used to study the reaction of several alkylcobalamins with 2-mercaptoethanol. At alkaline pH, when the thiol is deprotonated, the alkyl-transfer reactions involve a nucleophilic attack of the thiolate anion on the Co-methylene carbon of the cobalamins, yielding alkyl thioethers and cob(II)alamin. In these nucleophilic displacement reactions cob(I)alamin is presumably formed as an intermediate. The higher alkylcobalamins react more slowly than methylcobalamin. The lower reactivity of ethyl- and propylcobalamin is probably the basis of the inhibition of the corrinoid-dependent methyl-transfer systems by propyl iodide. The transfer of the upper nucleoside ligand of adenosylcobalamin to 2-mercaptoethanol is a very slow process; S-adenosyl-mercaptoethanol and cob(II)alamin are the final products of the reaction. The dealkylation of (carboxymethyl)cobalamin is a much more facile reaction. At alkaline pH S-(carboxymethyl)mercaptoethanol and cob(II)alamin are produced, while at pH values below 8 the carbon-cobalt bond is cleaved reductively to acetate and cob(II)alamin. The reductive cleavage of the carbon-cobalt bond of (carboxymethyl)cobalamin by 2-mercaptoethanol is extremely fast when the cobalamin is in the "base-off" form. Because we have been unable to detect trans coordination of 2-mercaptoethanol, we favor a mechanism that involves a hydride attack on the Co-methylene carbon of (carboxymethyl)cobalamin rather than a trans attack of the thiol on the cobalt atom.