Structure-Antioxidant Activity Relationships in a Series of NO-Donor Phenols

Recently we reported a new class of NO-donor phenols which could be of interest in the treatment of many forms of cardiovascular disease (CD). Their potencies as inhibitors of ferrous salt/ascorbate-induced peroxidation of membrane lipids of rat hepatocytes were assessed as pIC50 through the TBARS assay. In this work we aimed to find quantitative relationships between the antioxidant activity of these compounds and appropriate molecular descriptors. In particular, we determined their log Poct, their reactivity (log Z) in the reaction with 2,2-diphenyl-1-picrylhydrazyl radical (DPPH•) and the theoretical parameter Habs, which describes the enthalpy of homolytic O H bond cleavage. The QSAR equations found through the classical Hansch approach allowed to draw interesting considerations on the possible mechanisms of reaction with radicals in the different environments, while underlining the role of lipophilicity in the antioxidant action.