Ab initio molecular dynamics of free radical-induced oxidation of ergothioneine

Ergothioneine (2-mercaptohistidine trimethylbetaine) is a very stable natural compound largely present in cells and tissues of plants and mammals. The biological role of ET is still incompletely understood but its antioxidant properties are well assessed experimentally. However, no theoretical study had been performed until now to analyze the first steps of the reactions between this natural compound and strong oxidants in order to gain more knowledge on the reaction mechanisms. In this paper, the reaction of ergothioneine with two strong oxidants, hydroxyl radical and peroxinitrite, is modeled in a cluster of forty to fifty water molecules by ab-initio molecular dynamics. The reaction of hydroxyl radical with ergothioneine consists in electron transfer. When hydroxyl radical is initially situated near the sulfur atom, the reaction is not barrier less but passes through a transition state formed by a strong adduct. Otherwise, the charge transfer occurs when the two reactants and a "wire" of water molecules form a loop allowing the charge flow.