Antioxidant activities of dihydrolipoic acid and its structural homologues.

The relationships between structure and antioxidant activity of dihydrolipoic acid (DHLA) were studied using homologues of DHLA: bisonor-DHLA (a derivative which lacks two carbons in the hydrophobic tail), tetranor-DHLA (which lacks four carbons) and a methyl ester derivative. It was observed that: i) DHLA homologues with shorter hydrocarbon tails (i.e., bisnor- and tetranor-DHLA) had greater ability to quench superoxide radicals (O2-); ii) no differences among homologues with different chain lengths were found for peroxyl radical (ROO.) scavenging in aqueous solution, and iii) DHLA was the best membrane antioxidant in terms of ROO. scavenging and lipid peroxidation inhibition. Differences among the DHLA homologues in their antioxidant properties in polar and apolar environments generally agreed with differences in their partition coefficients. The methyl ester was the least effective antioxidant both in aqueous phase and in membranes. Tetranor-DHLA was found not only to be less effective in preventing ROO.-induced lipid peroxidation, but also to induce lipid peroxidation in the presence of residual iron. Thus, the complexity of biological systems seems to complicate generalizations on the correlation of molecular structure with antioxidant activity of DHLA.