Computer-designed melatonin derivatives: potent peroxyl radical scavengers with no pro-oxidant behavior

The antioxidant activity of five melatonin derivatives, recently designed, was investigated using the density functional theory. Different mechanisms and reaction sites were considered, as well as the polarity of the environment and the pH in aqueous solution. These melatonin analogs are predicted to be, in both media, more potent peroxyl radical scavengers than Trolox, ascorbic acid, resveratrol and melatonin itself. The possibility that the open-shell species, yielded by the reactions between free radicals and the investigated compounds, represent a hazard to the integrity of biomolecules were also explored. The obtained results indicate that they should be innocuous to lipids, proteins, and DNA, i.e., their pro-oxidant effects are expected to be negligible. The gathered data indicate that while melatonin itself is not a good peroxyl radical scavenger, functionalizing its molecular framework may produce derivatives that excellent for that purpose.