This review highlights the progress made in recent years in harnessing the peculiar chemistry of the hydroperoxyl, or perhydroxyl, radical (HOO•) during lipid peroxidation, particularly with regard to its interaction with antioxidants. The HOO• radical, the protonated form of superoxide, plays an important role in the propagation and termination of lipid peroxidation in nonaqueous systems. However, differently from alkylperoxyl (ROO•) radicals that have only oxidizing ability, HOO• has a two-faced oxidizing and reducing activity. The HOO• radical can reduce the radical of the antioxidant (phenols and aromatic amines) by H-atom transfer (A• + HOO• ⟶ AH + O2) thus increasing the length of the inhibition period and the effectiveness of the antioxidant. The simultaneous presence of HOO• and ROO• radicals triggers the catalytic antioxidant activity of quinones and nitroxides and explains the antioxidant activity of melanin-like polymers. The HOO• radical can be formed by fragmentation of ROO• radicals deriving from amines, alcohols, substituted alkenes and may be present at low concentrations in many oxidizing systems. Pro-aromatic compounds, like the natural essential oil component γ-terpinene, are the most effective sources of HOO• and behave as co-antioxidants in the presence of nitroxides or quinones. The future developments and applications of HOO• chemistry in the context of the inhibition of autoxidation are also discussed.
Keywords: Superoxide; ferroptosis; lipid peroxidation; nitroxide; polydopamine; γ-terpinene.