The biological action of cobalt and other metals III. Chelation of cations by dihydrolipoic acid

Abstract

1. 1. Dihydrolipoic acid readily forms chelates with a number of divalent heavy metals; these differ in stability to acid and other properties. 2. 2. The Co 2+-dihydrolipoic acid chelate is oxidized immediately in air with the uptake of 1.5 atoms oxygen per mole chelate. Oxidation is accompanied by an increase in the molecular extinction coefficient from ϵ 480m μ = 5.12·10 3 to ϵ 510m μ = 1.45·10 4 cm 2/mmole. Biologically active derivatives of lipoic acid cannot be recovered from the oxidized complex. 3. 3. Comparative studies with model compounds indicate that both sulphydryl groups of dihydrolipoic acid are involved in the chelation of Co 2+, and presumably certain other cations. 4. 4. Spectrophotometric measurements, chemical analysis and electrometric titration show that in dilute solution dihydrolipoic acid and Co 2+ combine initially in a 2:1 ration, the combination being accompanied by the liberation of one hydrogen ion per mole ligand. 5. 5. Chelates of dihydrolipoic acid with Cu 2+ and Ni 2+ also undergo oxidation at rates which, whilst similar to one another, are greater than that exhibited by dihydrolipoic acid alone, but considerably less than that of the Co 2+ chelate. Oxidation of the Ni 2+ chelate is not accompanied by any change in absorption spectrum. 6. 6. Chelates of dihydrolipoic acid with Zn 2+ and Cd 2+ are stable in air and exhibit no oxygen uptake. These chelates in contrast to those of Co 2+ and Cu 2+, dissociate in acid solution to yield the dithiol and essentially quantitative recovery of biological activity. 7. 7. It is suggested that the senstivity of the Co 2+-dihydrolipoic acid chelate to oxidation may be of significance with regard to the inactivation by Co 2+ of biological systems that are dependent upon the reversible interconversion of lipoic acid and dihydrolipoic acid.