THE CORRELATION OF THE OXIDATION POTENTIALS OF STRUCTURALLY RELATED DIBENZO[1,4]DICHALCOGENINES TO THEIR ANTIOXIDANTE CAPACITY IN BIOLOGICAL-SYSTEMS UNDERGOING FREE RADICAL-INDUCED LIPID-PEROXIDATION

A series of structurally related dibenzo[1,4]dichalcogenines possessing similar lipid solubilities but greatly differing oxidation potentials were tested for their ability to inhibit stimulated lipid peroxidation in ADP/Fe2+/ascorbate-treated liver microsomes and in hepatocytes treated with either t-butylhydroperoxide or diquat. In general, there was a close correlation between the half-wave oxidation potential of a particular compound and its antioxidant activity in the microsome and cell systems, with compounds possessing the lowest potential being the most potent antioxidants and vice versa. The Te/O and Te/S and S/O-substituted compounds, with oxidation potentials between 0.65 and 0.87 V, demonstrated most potent activity. Above this potential the antioxidant activity of the structure declined rapidly. The Te/O and Te/S compounds are among the most potent synthetic antioxidants described possessing IC50 values in the microsome system lower than 0.5-mu-M. This study clarifies the critical role of redox potential of an antioxidant site on a particular molecule without the complication of variable lipid solubility and may allow the definition of an optimal potential for antioxidant activity in biological systems.