Free Radicals Induced Oxidative Stress at a Molecular Level: The Current Status, Challenges and Perspectives of Computational Chemistry Based Protocols

Abstract

Oxidative stress is frequently caused by an excess of free radicals and has been associated with a wide variety of health disor-ders. Therefore, finding strategies for scavenging free radicals has be-come an active area of research. This review summarizes, from a physicochemical perspective, relevant strategies to fight oxidative stress via antioxidants, including prevention, deactivation of oxidants, and repair of damaged targets. Different reaction mechanisms in-volved in the chemical protection exerted by antioxidants are dis-cussed, as well as their relative importance depending on several aspects. Some of them are the polarity of the environment, the pH of aqueous phase, and the chemical nature of the reacting radicals. Data that can currently be obtained from computational, quantum, chemis-try, protocols are detailed and their reliability is analyzed. Viable crite-ria to identify optimal antioxidants using such protocols are provided. Current challenges and future directions in this area of research are discussed. A large set of antioxidants are compared and their trends in activity, based on kinetic data, is provided.

Melatonin and its metabolites as chemical agents capable of directly repairing oxidized DNA

“…As the values in Table show, the dominant species at physiological p H are the neutral molecules. However, it has been previously demonstrated that anions can play important roles in reactions mediated by electron transfer, even when they are in a small proportion . That might be the case for NAS, AFMK, 6OHM, and 4OHM, and thus, their anions were also included in the investigation.…”

“…However, it has been previously demonstrated that anions can play important roles in reactions mediated by electron transfer, even when they are in a S C H E M E 2 Structures of melatonin and its metabolites F I G U R E 1 Structure of the three-unit double-stranded DNA (3uDNA) model small proportion. 133,135,136 That might be the case for NAS, AFMK, 6OHM, and 4OHM, and thus, their anions were also included in the investigation. On the other hand, the pKa values for melatonin, c3OHM, and AMK are too high for the anionic species to be chemically relevant.…”

“…More detailed information on this protocol can be found elsewhere. 122,133 In addition to the structural fragments shown in Scheme 1, a three-unit double-stranded DNA oligomer (3uDNA) was also used in the investigation. In this particular case, the calculations were carried out with the ONIOM method using a two-layer approach (Figure 1).…”

Antioxidant Potential of Five Compounds Extract From the Marine Fungus Aspergillus Flocculosus by DFT Method: Hat and Set Mechanism.

“…The geometries and vibrational frequencies were investigated at the M05-2X/6-31+G(d) model chemistries in the gas phase. The HAT and SET mechanisms, which are the most widely accepted antioxidant actions, were evaluated [6,7]. Three intrinsic properties including BDE, adiabatic IE and EA which characterize for the above mechanisms were calculated in the gas phase as follows [8,9].…”

Study of the mechanisms of antioxidative action of different antioxidants

“…In these reactions a newly formed radical, which is more stable and less reactive than the previous one, is generated. There are several mechanisms of the antioxidant actions of free radicals: hydrogen atom transfer (HAT), proton coupled electron Transfer (PCET), single electron transfer followed by proton transfer (SET-PT), sequential proton loss electron transfer (SPLET), radical adduct formation (RAF), and sequential proton loss hydrogen atom transfer (SPLHAT) (Klein et al 2007;Litwinienko and Ingold 2007;Galano 2015;Galano et al 2016;Mazzone et al 2016). …”