Key steps and intermediates in the catalytic mechanism for the reduction of peroxides by the antioxidant ebselen

Hydrogen peroxide and lipid hydroperoxides are formed during aerobic metabolism and contribute to oxidative stress, a major factor in many diseases and degenerative conditions. Although the selenoenzyme glutathione peroxidase (GPx) affords antioxidant protection in vivo by catalytically reducing harmful peroxides with glutathione, certain conditions benefit from the administration of small-molecule GPx mimetics for additional protection. To date, ebselen has been the most widely studied such compound, but its catalytic mechanism is complex and highly variable with conditions. Progress in elucidating the mechanistic details of its antioxidant activity is described in this review.