In silico design of hydrazone antioxidants and analysis of their free radical-scavenging mechanism by thermodynamic studies

Abstract

Background: Antioxidants are very crucial in maintaining the normal function of body cells, as they scavenge excess free radical in the body. A set of hydrazone antioxidants was designed by in silico screening. The density functional theory (DFT) method was employed to explore the reaction energetics of their free radicalscavenging mechanism. With the aid of the developed quantitative structure-activity relationship (QSAR) model for hydrazone antioxidants, the structure and antioxidant activity of these compounds were predicted. Three potential reaction mechanisms were investigated, namely, hydrogen atom transfer (HAT), single-electron transfer followed by proton transfer (SET-PT) and sequential proton loss electron transfer (SPLET). Bond dissociation enthalpy (BDE), adiabatic ionization potential (AIP), proton dissociation enthalpy (PDE), proton affinity (PA), electron transfer enthalpy (ETE) and Gibbs free energy that characterize the various steps in these mechanisms were calculated in the gas phase. Results: A total of 25 hydrazone antioxidants were designed, in which the molecule MHD 017 gave the best antioxidant activity. Among the tested molecules, MHD 017 at the 10-OH site gave the best results for the various thermodynamic parameters calculated. The reaction Gibbs free energy results also indicate that this is the most favoured site for free radical scavenge. Conclusion: The obtained results show that HAT and SPLET mechanisms are the thermodynamically plausible reaction pathways of free radical scavenge by hydrazone antioxidants. The reactivity of these compounds towards the hydroperoxyl radical (HOO•) was greater than that towards the methyl peroxyl radical (CH 3 OO•) based on the exergonicity of the calculated reaction Gibbs free energy.

Investigation of the Antioxidant and UV Absorption Properties of 2-(2’-hydroxy-5’-methylphenyl)-benzotriazole and Its Ortho-Substituted Derivatives via DFT/TD-DFT

“…Lower O-H BDE values designate lower stability and the ease to which the equivalent O-H bond is broken, giving rise to a higher antioxidant activity [39]. has a better antioxidant potential than phenol.…”

Free radical scavenging mechanism of 1,3,4-oxadiazole derivatives: thermodynamics of O–H and N–H bond cleavage

“…With the aid of the developed QSAR model for 1,3,4-oxadiazole antioxidants, new set of 1,3,4-oxadiazole antioxidants were designed by insertion, deletion and substitution of various substituents on the template molecule [29,30,31,32]. Subsequently, their antioxidant activities were predicted using this QSAR model.…”

“…( 1). BDE represents the standard reaction enthalpy change at a given temperature when a particular chemical bond is broken under standard conditions [32,36]. Lower values of the BDE have been observed to favour lower stability of the O-H bond [37].…”

<em>In Silico</em> design of hydroxylated coumarins and thermodynamic investigation of their free radical scavenging mechanism

“…With the aid of the developed QSAR model for coumarin antioxidants (Alisi et al, 2018), a new set of coumarin antioxidants were designed by ligand based virtual screening. This was achieved by insertion, deletion and substitution of different substitutes on the template molecule as dictated by the results of the coumarin antioxidant model (Melagraki et al, 2009;Asadollahi et al, 2011;Mitra et al, 2011;Alisi et al, 2019). Compound M45 ( Fig.…”