Molecular Modelling and Natural Polyphenol Compounds

The mechanism of action as free-radical scavengers and lipid-peroxidation inhibitors is a  H-Atom Transfer (HAT) from the active OH group of the phenolic antioxidant (ArOH) to the free radical (R^•), following:

ArO-H + R^• → ArO^• + R-H

The main mechanism was shown to be the direct HAT, namely CPET (Coupled Proton Electron Transfer). This process is not specific to flavonolignans and other theoretical studies have reached the same conclusions for other series of polyphenols [6-12]. HAT may also proceed in two indirect pathways: ET-PT (Electron Transfer – Proton Transfer) and SPLET (Sequential Proton-Loss-Electron-Transfer).

Depending on the oxidative system reacting with ArOH, the ET-PT mechanism could occur as a secondary or even a major mechanism [5, 13]. The first step of this reaction (i.e. ArO-H + R^• → ArOH^+• + R^-) leads to the formation of the radical cation ArOH^+•, which easily undergoes heterolytic dissociation leading to the same final products than those yielded by HAT (i.e. ArO^• + R-H).

The ArO^• radical may also be formed following a SPLET mechanism [14, 15] where a proton is lost prior to an electron transfer from the subsequent anion to the free radical (i.e. ArO-H → ArO^- + H⁺; ArO^- + R^• → ArO^• + R^-; R^- + H⁺ → RH). This mechanism is strongly enhanced under alkaline conditions, which may favor the first step (i.e., proton loss). Again the same final products as with HAT and ET-PT are formed (i.e. ArO^• + R-H).

Competition between those three mechanisms is strongly influenced by the oxidative system and pH conditions.

A forth mechanism may exist: Adduct formation. In the case of a phenolic compound the radical may add to the aromatic ring. The addition process may be followed by water elimination that depends on the medium, the pH conditions (i.e. proton availability) and the local geometry. It has been observed and heoretically confirmed with ^•OH radicals.