Effects of ring size and polar functional groups on the glutathione peroxidase-like antioxidant activity of water-soluble cyclic selenides.

To elucidate the effects of ring structure and a substituent on the glutathione peroxidase- (GPx-) like antioxidant activities of aliphatic selenides, series of water-soluble cyclic selenides with variable ring size and polar functional groups were synthesized, and their antioxidant activities were evaluated by NADPH-coupled assay using H2O2 and glutathione (GSH) in water and also by NMR spectroscopy using H2O2 and dithiothreitol (DTT(red)) in methanol. Strong correlations were found among the GPx-like activity in water, the second-order rate constants for the oxidation of the selenides, and the HOMO energy levels calculated in water. The results support the conclusion that the oxidation process is the rate-determining step of the catalytic cycle.