Engineering antioxidant radical scavenging potential: the case of olanzapine in a literature analysis context

Radical scavengers are molecules which can efficiently reduce harmful radicals, such as ROS and RNS, thus mitigating cellular oxidative stress. Among radical scavengers, well-known natural substances are found which are present mainly in fruit and vegetables, whose assumption is typically recommended in a healthy and equilibrated diet. Also, some approved drugs and their metabolites are efficient radical scavengers, thus combining their main therapeutic action with appreciable antioxidant effects. The antioxidant potential results from different elementary chemical processes, among which HAT (Hydrogen Atom Transfer) and RAF (Radical Adduct Formation). Accurate in silico protocols have been validated through which the efficiency of these reactions can be established in terms of both thermodynamic and kinetic feasibility. Anyway, no general prediction can be made by considering merely the chemical structures, except for few cases like polyphenols. A systematic analysis of high level and state of the art computational studies present in literature will be done to attempt drawing structure-scavenging activity relations. In addition, calculations on a specific molecular system (olanzapine) and few metabolites will be carried out in order to better understand the computational procedure leading to the assessment of the antioxidant potential of a molecule starting from elementary radical reactions as well as gaining insight on this well-known molecule which has recently attracted interest also for its antiferroptotic behavior.