Non-conventional antioxidant systems to counteract ferroptosis based on the chemistry of the hydroperoxyl radical

Oxidation by oxygen mediated by free radicals is a pervasive process that plays a fundamental role in various aspects of human life. The process of oxidation, which is relevant to humans, mostly has a negative impact on practical value, like food decay, lubricating and edible oils degradation, skin pigmentation disorders, ferroptosis triggering, etc. Studying the antioxidant behavior of essential oils (EOs) on quantitative grounds with our kinetic approach and focusing on their main phenolic components allowed quantification and full rationalization of the antioxidant activity of many essential oils, offering solid grounds for their further investigation and application in food science. Different flavonoids and corresponding chalcones were chosen to be investigated by our kinetic approaches and computational approaches to provide insights into the kinetics of biochemical interactions, which would allow their rational use as multi-mode natural antioxidants in food science. Catechol derivatives were selected with a previously unrecognized antioxidant mechanism to show that their oxidation products (quinones) and intermediates (the semiquinone radicals) could be regenerated by H-atom transfer from the HOO• radical, at variance with the well-established role of such radicals as alternative chain-carriers in the autoxidation of some organic substrates and as the main cause of oxidative stress in biological systems. A series of endo-functionalized molecular receptors based on a calix[4]pyrrole scaffold, which exhibit H-atom transfer reactivity towards free radicals (e.g., ROO•), were also studied as novel unconventional supramolecular antioxidants. The chemical structure and shape of the molecular receptors were shown to affect the affinity towards free radicals, which mimicked enzyme modulation in biological systems. Finally, two novel selenylated phenolic derivatives were investigated in biomimetic model systems, where they exhibited outstanding antioxidant activity, promising relevant potential to prevent or treat oxidative stress-related disorders.