Sequential Proton Loss Electron Transfer Mechanism Research Articles

Predicting the activity of methoxyphenol derivatives antioxidants: II-Importance of the nature of the solvent on the mechanism, a DFT study.

The various mechanisms of primary antioxidant action of a series of 2-Methoxyphenols are investigated in the present work. The electronic properties have just been studied in a joint article, so that we focus here on Hydrogen Atom Transfer (HAT), Single Electron Transfer-Proton Transfer (SET-PT) and Sequential Proton-Loss Electron-Transfer (SPLET) mechanisms. The two computational approaches used in the previous study of the structure and reactivity of these compounds [Computational and Theoretical Chemistry 1229 (2023) 114287] provide identical mechanisms trends in gas phase. In gas media, hydrogen atom transfer (HAT) is more favored. On the contrary, the solvent polarity has a significant effect on the mechanism of the antioxidant activity, since the polarity of the solvent increases the contribution of the SPLET mechanism.

Molecular docking and A DFT study on the antiradical activity of naringenin and hesperetin with nitric oxide, peroxy, and methoxy radicals

AbstractNaturally occurring flavonoids, naringenin (N) and hesperetin (H), were theoretically investigated for their ability to scavenge nitric oxide, peroxy, and methoxy radicals in gas, water, and benzene solvent media. BMK/6‐311+G(d,p) level of theory was used to for determine antiradical activity of the selected compounds and the calculation of reaction enthalpies related to three possible mechanisms of free radical scavenging activity, namely, hydrogen atom transfer (HAT), single electron transfer–proton transfer (SET‐PT), and sequential proton loss electron transfer (SPLET). When the results were examined, it was seen that the SET‐PT mechanism was not an effective antioxidant effect mechanism in any solvent medium. In addition, in the absence of any radicals, HAT in the gas phase, SPLET in the water phase, and HAT and SPLET in the benzene phase are in competition. When the investigated antioxidants were examined in the presence of various radicals in terms of their antiradical scavenging properties, it was observed that the SET‐PT mechanism was not possible in all radicals and all solvent phases due to positive ionization potential (IP) values. In addition, it was determined that the SPLET mechanism pathway was the most likely mechanism pathway with all the radicals examined. In addition, molecular docking calculations of the studied molecules were made to compare the activities against to human peroxiredoxin‐5 (HP5), a protein with antioxidant properties.

Structure-antioxidant activity relationships of dendrocandin analogues determined using density functional theory.

Quantum-chemical calculations based on the density functional theory (DFT) at the B3LYP/6–311 + + G(2d,2p)//B3LYP/6–31G(d,p) level were employed to study the relationship between the antioxidant properties and chemical structures of six dendrocandin (DDCD) analogues in the gas phase and two solvents (methanol and water). The hydrogen atom transfer (HAT), electron-transfer-proton-transfer (ET-PT), and sequential proton-loss-electron-transfer (SPLET) mechanisms are explored. The highest occupied molecular orbital (HOMO), lowest unoccupied molecular orbital (LUMO), reactivity indices (η, μ, ω, ω+, and ω–), and molecular electrostatic potentials (MEPs) were also evaluated. The results suggest that the D ring plays an important role in mediating the antioxidant activity of DDCDs. For all the studied compounds, indicating that HAT was identified as the most favorable mechanism, whereas the SPLET mechanism was the most thermodynamically favorable pathway in polar solvents. The results of our study should aid in the development of new or modified antioxidant compounds.Supplementary InformationThe online version contains supplementary material available at 10.1007/s11224-022-01895-2.

A Computational Study of the Reactions between Dehydrozingerone Derivatives and the Hydroperoxyl Radical in Aqueous and Lipid Media

Dehydrozingerone (the half-analogue of curcumin) is a natural product that is isolated from ginger rhizomes. Recent studies have shown that this compound displays several physiological activities including antioxidant properties, and it can scavenge oxygen-free radicals like hydroxyl, peroxyl and superoxide radicals. In this work, the thermodynamic and kinetic aspects of the antiradical activity of the natural dehydrozingerone DHZ0 (R=H) and the designed derivatives DHZ1 (R=CHO), DHZ2 (R=OMe) and DHZ3 (R=NMe2) towards the hydroperoxyl radical (HOO•) were investigated at the M06-2X/6-311[Formula: see text]G([Formula: see text],[Formula: see text]) level of theory. The calculations have been performed in gas phase, pentyl ethanoate and water solvents using the implicit SMD solvation model. Four potential mechanisms have been investigated, namely, hydrogen atom transfer (HAT), single-electron transfer followed by proton transfer (SET-PT), sequential proton loss electron transfer (SPLET) and radical adduct formation (RAF). The obtained results show that the SET-PT and RAF mechanisms are endergonic processes and are thermodynamically disfavored, whereas the exergonic HAT process is predicted as the most thermodynamically favored mechanism in all media. The SPLET mechanism was excluded due the minor proportions of the anion species at physiological pH. Kinetic calculations show that DHZ3 reacts with HOO• 1860, 1250 and 215 times faster than DHZ0 in gas phase, pentyl ethanoate, and water, respectively. Based on thermodynamic and kinetic calculations, the designed compound DHZ3 is predicted as a good candidate for hydroperoxyl scavenging in both polar and nonpolar media. Drug likeness evaluation of the studied DHZ derivatives shows that the pharmacokinetic parameters satisfy all the Lipinski and Veber rules.

Improving the antioxidant activity of natural antioxidant honokiol by introducing the amino group.

Exploring and synthesizing the compounds with stronger antioxidant activity have always been the goal of researchers. Herein, the substitution effects of the amino (NH2-) group with the excellent electron-donating ability in different positions on the antioxidant activity of Honokiol (Hon) were systematically explored by using the quantum chemistry calculation based on the density functional theory method. The three possible antioxidant mechanisms of Hon and its four NH2-substituted derivatives (Hon1-Hon4), containing the hydrogen atom transfer (HAT), single electron transfer followed by proton transfer (SET-PT), and sequential proton loss electron transfer (SPLET), were explored in depth considering the gas and solvent phases. In addition, the frontier molecular orbital energies, natural bond orbital (NBO) charge population, and global descriptive parameters were used to study their antioxidant activity. The results indicate that compared with the original molecule Hon, the NH2 substituents would have the stronger antioxidant activity. Moreover, the radical scavenging process of Hon and its derivatives has a disposition to the HAT and SPLET mechanisms in the gas and solvent phases, respectively. Meaningfully, owing to the lowest bond dissociation enthalpy and proton affinity values, Hon4 would show the most prominent antioxidant activity by comparison with the other compounds. In conclusion, this work will provide the purposeful reference for designing and synthesizing the antioxidants with more outstanding performance.

The antioxidant potential of retrochalcones isolated from liquorice root: A comparative DFT study

Polyphenolic compounds are known to exhibit potent antioxidant properties owing to the presence of various phenolic groups. The present study reports the antioxidant potentials of six retrochalcones, namely echinatin, and licochalcone A, B, C, D and E, isolated from the root of the Glycyrrhiza species, toward various reactive oxygen and nitrogen species. Different mechanistic pathways, viz. hydrogen atom transfer (HAT), single electron transfer (SET), single electron transfer followed by proton transfer (SET-PT), and sequential proton loss electron transfer (SPLET), have been considered. In addition, two other pathways, i.e. sequential double proton loss electron transfer (SdPLET) and sequential proton loss hydrogen atom transfer (SPLHAT), which are significant for the scavenging of reactive species by the mono-deprotonated forms of retrochalcones, have also been considered. All the calculations were performed using density functional theory at the B3LYP/6–311++G** level in the gas phase and in aqueous solution. The results suggest the predominance of the HAT mechanism in the gas phase, while in aqueous solution, the SPLET mechanism is thermodynamically favored. The possibility of SdPLET increases at higher pH.

Physicochemical, antioxidant properties of carotenoids and its optoelectronic and interaction studies with chlorophyll pigments

The physicochemical and antioxidant properties of seven carotenoids: antheraxanthin, β-carotene, neoxanthin, peridinin, violaxanthin, xanthrophyll and zeaxanthin were studied by theoretical means. Then the Optoelectronic properties and interaction of chlorophyll-carotenoid complexes are analysed by TDDFT and IGMPLOT. Global reactivity descriptors for carotenoids and chlorophyll (Chla, Chlb) are calculated via conceptual density functional theory (CDFT). The higher HOMO–LUMO (HL) gap indicated structural stability of carotenoid, chlorophyll and chlorophyll-carotenoid complexes. The chemical hardness for carotenoids and Chlorophyll is found to be lower in the solvent medium than in the gas phase. Results showed that carotenoids can be used as good reactive nucleophile due to lower µ and ω. As proton affinities (PAs) are much lower than the bond dissociation enthalpies (BDEs), it is anticipated that direct antioxidant activity in these carotenoids is mainly due to the sequential proton loss electron transfer (SPLET) mechanism with dominant solvent effects. Also lower PAs of carotenoid suggest that antioxidant activity by the SPLET mechanism should be a result of a balance between proclivities to transfer protons. Reaction rate constant with Transition-State Theory (TST) were estimated for carotenoid-Chlorophyll complexes in gas phase. Time dependent Density Functional Theory (TDDFT) showed that all the chlorophyll (Chla, Chlb)–carotenoid complexes show absorption wavelength in the visible region. The lower S1–T1 adiabatic energy gap indicated ISC transition from S1 to T1 state.

Antioxidant Activity and Mechanism of Avenanthramides: Double H+/e- Processes and Role of the Catechol, Guaiacyl, and Carboxyl Groups.

Avenanthramides (AVAs), unique phenolic compounds in oats, have attracted increasing interest due to their health benefits. Eight representative AVAs were studied using the density functional theory (DFT) method to elucidate their antioxidant activity and mechanism. Preference of different mechanisms was evaluated based on thermodynamic descriptors involved in double (2H+/2e-) free radical scavenging reactions. It was found that the hydrogen atom transfer (HAT) mechanism is more favorable in the gas and benzene phases, while sequential proton loss electron transfer (SPLET) is preferred in polar media. The results suggest the feasibility of the double HAT and double SPLET mechanisms for 2s and c-series AVAs. The sequential triple proton loss double electron transfer (StPLdET) mechanism represents the dominant pathway in aqueous solution at physiological pH. In addition, the sequential proton loss hydrogen atom transfer (SPLHAT) mechanism provides an alternative pathway to trap free radicals. Results also revealed the important role of the catechol, guaiacyl, and carboxyl moieties.

Antioxidative and α-glucosidase inhibitory constituents of Polyscias guilfoylei: experimental and computational assessments.

Searching for bioactive agents from medicinal plants, eleven constituents were isolated from Polyscias guilfoylei stem for the first time, including a nucleoside uracil (1), two sterols β-sitosterol (2) and daucosterol (3), a saponin androseptoside A (4), two lignans (+)-pinoresinol (5) and (+)-syringaresinol (6), four phenolic acids protocatechuic acid (7), methyl protocatechuate (8), caffeic acid (9), and 5-O-caffeoylquinic acid (10), and a flavonoid quercitrin (11). Metabolites 1, 4, and 6-11 have never been observed in genus Polyscias before. Phenolic compounds 7 and 9 possessed the respective IC50 values of 21.33 and 13.88µg/mL in DPPH (2,2-diphenyl-1-picrylhydrazyl) antioxidative assay, as compared with that of the positive control resveratrol (IC50 = 13.21µg/mL). From density functional theory (DFT) calculated approach, the DPPH free radical scavenging capacity of two compounds 7 and 9 can be explained by the role of OH groups at carbons C-3 and C-4. Antioxidative actions of these two potential agents are followed HAT (H atom transfer) mechanism by OH bond disruption in gas, but SPLET (sequential proton loss electron transfer) mechanism in solvents water and methanol. Compared to 4-OH group, 3-OH group showed better bond disruption enthalpies and better kinetic energies since it reacted with HOO• and DPPH radicals. Sterols 2-3 and flavonoid 11 induced the IC50 values of < 2.0µg/mL better than the positive control acarbose (IC50 = 184.0µg/mL) in α-glucosidase inhibitory assay. Their interactions with human intestinal C- and N-terminal domains of α-glucosidase were explored using molecular docking study. The obtained results proved that compounds 2, 3, and 11 bind relatively stronger with the C-terminal domain than to the N-terminal domain through pivotal residues in the binding site and could be hypothesized as mixed inhibitors.

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

The demand and pursuit of chemical entities with UV filtration and antioxidant properties for enhanced photoprotection have been driven in recent times by acute exposure of humans to solar ultraviolet radiations. The structural, electronic, antioxidant and UV absorption properties of drometrizole (PBT) and designed ortho-substituted derivatives are reported via DFT and TD-DFT in the gas and aqueous phases. DFT and TD-DFT computations were performed at the M062x-D3Zero/6-311++G(d,p)//B97-3c and PBE0-D3(BJ)/def2-TZVP levels of theory respectively. Reaction enthalpies related to hydrogen atom transfer (HAT), single-electron transfer followed by proton transfer (SET-PT), and sequential proton loss electron transfer (SPLET) mechanisms were computed and compared with those of phenol. Results show that the presence of -NH2 substituent reduces the O-H bond dissociation enthalpy and ionization potential, while that of -CN increases the proton affinity. The HAT and SPLET mechanisms are the most plausible in the gas and aqueous phases respectively. The molecule with the -NH2 substituent (PBT1) was identified to be the compound with the highest antioxidant activity. The UV spectra of the studied compounds are characterized by two bands in the 280 - 400 nm regions. Results from this study provide a better comprehension antioxidant mechanism of drometrizole and present a new perspective for the design of electron-donor antioxidant molecules with enhanced antioxidant-photoprotective efficiencies for applications in commercial sunscreens.

Synthesis, antioxidant activity, and density functional theory study of some novel 4-[(benzo[d]thiazol-2-ylimino)methyl]phenol derivatives: a comparative approach for the explanation of their radical scavenging activities.

Background and purpose:Radicals produced by Fenton and Haber-Weiss reactions play detrimental roles in our body. Some oxidized proteins as toxic configurations are identified in amyloid-β deposits. These deposits mostly occur in conditions, such as Alzheimer’s disease. Here, we report the synthesis, evaluation of the antioxidant activity, and implementation of density functional theory (DFT) calculations of some4- [(benzo[d]thiazol-2-ylimino) methyl]phenol derivatives. The aim of this study was to provide a comparative theoretical-experimental approach to explain the antioxidant activities of the compounds.Experimental approach:Compounds were synthesized by the reaction between para hydroxybenzaldehyde and aminobenzothiazole derivatives. The scavenging activity of the compounds was evaluated. Various electronic and energetic descriptors such as high occupied molecular orbital and low unoccupied molecular orbital energy gaps, bonding dissociation enthalpy of OH bond, ionization potential, electron affinity, hardness, softness, and spin density of the radical and neutral species were calculated. DFT calculations with B3LYP hybrid functional and 6-311++ G** basis set in the polarizable continuum model were utilized to obtain these descriptors.Findings/Results:Ascorbic acid showed the best DPPH scavenging activity. However, 4d and 4c showed promising antioxidant activity. The values of EHOMO for 4c and 4d were closer to zero, thus, they showed the best scavenging activities. The computational results were in accordance with the experimental ones. The energetic descriptors indicated that the sequential proton loss-electron transfer mechanism is preferred over other mechanisms.Conclusion and implication:Antioxidant activity of 4-[(Benzo[d]thiazol-2-ylimino) methyl]phenol derivatives confirmed by experimental and theoretical documents proves them as novel antioxidants against amyloid-β based disease.

How the functional group substitution and solvent effects affect the antioxidant activity of (+)-catechin?

Based on the density functional theory method, the antioxidant activity of (+)-Catechin (CAT) and its two derivatives, substituted by the electron-donating group -N(CH3)2 (CAT-DA) and electron-withdrawing group -CF3 (CAT-TF), were explored in gas and solvent phases. The parameters related to three antioxidant mechanisms: hydrogen atom transfer (HAT), single electron transfer followed by proton transfer (SET-PT) and sequential proton loss electron transfer (SPLET), were calculated. Results indicate the antioxidant reaction of these three compounds tends to the HAT mechanism in gas phase with the lowest BDE values of 75.2 kcal/mol, 74.4 kcal/mol and 78.6 kcal/mol for CAT, CAT-DA and CAT-TF, respectively, and prefers to the SPLET mechanism in the studied solvents. Furthermore, the increased solvent polarity can promote the expression of SET-PT mechanism, but inhibit the SPLET mechanism. Strikingly, CAT-DA shows the largest the highest occupied molecular orbital energies (−5.317 eV and − 5.570 eV in gas and ethanol phase) and the lowest vertical ionization potentials (6.817 eV and 5.270 eV in gas and water phase) among the three compounds, suggesting that this compound would exhibit the strongest electron-donating ability. The above results mean that introducing the -N(CH3)2 group into the structure of CAT would effectively improve its antioxidant activity, which provides a theoretical reference for the synthesis of more efficient antioxidants.

Theoretical evaluation of the antioxidant activity of some stilbenes using the Density Functional Theory

In this paper, the antiradical potential of trans-2,4,3′,5′-tetrahydroxystilbene (T-OXY), trans-2,3′,4-trihydroxystilbene (T-RES), cis-2,4,1′,3′-tetrahydroxystilbene (C-OXY) and cis-2,1′,4-trihydroxystilbene (C-RES) is investigated by BDE (E0) and ETS-NOCV calculations, in water, benzene, DMSO, and ethanol. The study of solubility by the COSMO-RS model demonstrates that the compounds are very soluble in DMSO. The hydrogen atom transfer (HAT), sequential proton loss electron transfer (SPLET), and single electron transfer followed by proton transfer (SET-PT) mechanisms are explored as possible oxidation paths of these compounds using the DFT calculations at B3LYP/6-311++G(2d,2p) level of theory in DMSO. For all the studied compounds, the HAT was found to be the thermodynamically dominant mechanism, indicating that the investigated compounds can be classified according to their antiradical activity in the following sequence order T-OXY˃T-RES˃C-OXY˃C-RES. The evaluation of ΔHBDE reaction enthalpies, ΔHIP, and ΔHPA linked to the three mechanisms with certain radicals (HO·, HOO·, CH3O· and CH3OO·, NO·, and NO2·) are determined. The results indicate the HAT and SPLET mechanisms are competitive in inhibiting those species. QTAIM calculations reveal the existence of critical points in the two conformers. The Diels-Alder intramolecular cyclization of (C-OXY) leads to two new tautomers: trans-cycle-OXY (T-CYCLE-OXY) and cis-cycle-OXY (C-CYCLE-OXY) with a significant improvement in the antioxidant activity. In conclusion, T-OXY and T-CYCLE-OXY are identified as the best antioxidant candidates among those tested.

Antioxidant action of deprotonated flavonoids: Thermodynamics of sequential proton-loss electron-transfer

Despite the intensive research on radical scavenging action of flavonoids, a systematic study of the thermochemistry for their mono-deprotonated species in aqueous solution is still missing. In this work, reaction enthalpies related to Sequential Proton-Loss Electron-Transfer (SPLET) mechanism were theoretically investigated for all mono-deprotonated forms of nine flavonoids: apigenin, luteolin, fisetin, kaempferol, quercetin, taxifolin, tricetin, tricin and cyanidin. Differences in reaction enthalpies of the first and the second deprotonation can be lower than 10 kJ mol−1, when two successive deprotonations occur in different aromatic rings of the molecule. For neutral flavonoids, thermodynamically preferred deprotonation sites are 4′-OH and 7-OH groups. In cyanidin (cation in native form), preferred second deprotonation site is 5-OH group. In the case of the formation of the preferred dianions, reaction enthalpies of the second proton loss are not affected by the structural distinctions between the flavonoids. In aqueous solution, deprotonated flavonoids show higher tendency to enter SPLET mechanism in comparison to Hydrogen Atom Transfer (HAT) or electron transfer.

The effect of solvent polarity on the antioxidant potential of echinatin, a retrochalcone, towards various ROS: a DFT thermodynamic study

The antioxidant properties of echinatin (Ech), isolated from liquorice, have recently been reported. It is well known that the free radical species can be deactivated by phenolic antioxidants via different mechanistic pathways. In this work, the scavenging of eighteen different reactive oxygen species (ROS) has been considered, focussing on three main working mechanisms, namely hydrogen atom transfer (HAT), single electron transfer followed by proton transfer (SET-PT) and sequential proton loss electron transfer (SPLET). The investigations have been performed in different dielectric media, viz. gas phase, benzene, methanol and aqueous solution, using density functional theory (DFT) calculations at the M05-2X/6-311++G** level. Various molecular descriptors have been elucidated for Ech as well as the ROS and compared with the reference antioxidant molecule, trolox. In addition, the redox potentials and the equilibrium constants have been calculated to discuss the feasibility of the overall scavenging process. The results demonstrate that the 4-OH group is the first site for H-atom donation, followed by 4’-OH. Further, it has been found that HAT would be the most favourable mechanism in the gas phase. The SPLET mechanism is thermodynamically favoured in polar media like water and methanol, while in the case of non-polar solvents like benzene, the two mechanisms are observed to be competitive.

Molecular design of curcumin analogues with potent antioxidant properties and thermodynamic evaluation of their mechanism of free radical scavenge

BackgroundFree radical attack of cellular structures in the human system is the major cause of various forms of degenerative diseases. Consequently, recent research has been focused on the development of new antioxidants with more efficient free radical scavenging potentials. Ligand-based virtual screening was employed in the rational design of potent antioxidant derivatives of curcumin by the density functional theory method. Various antioxidant descriptors that characterize the three major mechanisms of free radical scavenge, namely, hydrogen atom transfer (HAT), single electron transfer followed by proton transfer (SET-PT), and sequential proton loss electron transfer (SPLET), were calculated. Also, the spin density distribution on the generated radicals and the frontier orbital distribution and energy of the studied compounds were evaluated in order to gain further insight on the reaction mechanism. The reaction Gibbs free energy for scavenging the two important peroxyl radicals (HOO· and CH3OO·) was calculated in order to evaluate the preferred mechanism of free radical scavenge by these compounds.ResultsThe investigated compounds were able to scavenge HOO· and CH3OO· radicals by HAT and SPLET mechanisms in the gas phase and aqueous solution, based on the computed results of reaction enthalpies and Gibbs free energy. The SET-PT mechanism for these compounds was observed to be thermodynamically unfeasible in the gas phase. However, the thermodynamic feasibility of free radical scavenge by SET-PT mechanism was observed in aqueous solution. Among the investigated compounds, MCC 009 (1E,4E)-1-(3-(aminomethyl)-4-hydroxyphenyl)-5-(4-hydroxy-3-((hydroxy (methyl)amino)methyl)phenyl)penta-1,4-dien-3-one at the 19-OH position possessed the highest capacity to scavenge both HOO· and CH3OO· radicals by HAT, SET-PT, and SPLET mechanisms. The reaction Gibbs free energy of scavenging HOO· radical by this molecule in the gas phase and aqueous solution is ∆rGBDEgas = − 58.18, {Delta _r{G}_{BDE}}_{H_2O}=-73.77 , ∆rGAIPgas = 611.48, {Delta _r{G}_{AIP}}_{H_2O}=-74305.49 , ∆rGPDEgas = − 669.66, {Delta _r{G}_{PDE}}_{H_2O}=74231.72 , ∆rGPAgas = − 271.40, {Delta _r{G}_{PA}}_{H_2O}=-73.09 ,∆rGETEgas = 213.22, and {Delta _r{G}_{ETE}}_{H_2O}=-0.69 .ConclusionNew set of curcumin derivatives with potent free radical scavenging properties was successfully designed, and their mechanism of free radical scavenging evaluated by thermodynamic studies. This research is a gateway to the exploitation of the considered curcumin derivatives in food chemistry and pharmacy.

Quinolone and isoquinolone alkaloids: the structural-electronic effects and the antioxidant mechanisms

Quinolone and isoquinolone alkaloids, which were found in the plant kingdom, are now potential antioxidants. In this case study, a quantum calculated procedure utilizing the density functional theory (DFT)-B3LYP method coupled with basis set 6–311++G(d,p) was used to investigate free-radical quenching activity of alkaloidal quinolone viridicatol (1) and alkaloidal isoquinolone 5-hydroxy-8-methoxy-4-phenylisoquinolin-1(2H)-one (2). On the basis of thermodynamic perspective and from the findings, the powerful antioxidative potential of these two title compounds in the liquids water, methanol, and especially DMSO was mostly driven by the proton affinity (PA), consistent with the SPLET (sequential proton loss electron transfer) mechanism. The environmental effect has also been investigated, and the antioxidative action caused by O–H bond disruption is easier than that of N–H bond in both the gaseous phase and liquids. In the gaseous phase, the combinations of two studied compounds and •OOH/DPPH radicals are kinetic evidence, including two intermediates and one transition state. From thermodynamic and kinetic viewpoints, compound 2 can be seen as a therapeutically useful agent in antioxidative treatment because of the role of a 5-hydroxy group.

Combined experimental and theoretical studies of the structure-antiradical activity relationship of heterocyclic hydrazone compounds

The present paper describes combined experimental and theoretical studies of twelve heterocyclic compounds bearing hydrazone functional group (1–12). Experimentally, the free radical scavenging activity of all the compounds have been investigated using DPPH, ABTS, and DMSO alkaline assays. The obtained results showed that these compounds are potent antiradical agents. The best results have been obtained with the imidazole derivatives 5 and 12, which showed higher antiradical activity than the BHT standard in DPPH and ABTS assays. Theoretical calculations, by means of DFT/B3LYP approach, were carried out in order to explain the experimental results. Some structural characteristics such as molecular descriptors, highest occupied molecular orbital, and molecular electrostatic potential mapping have been computed. The mechanisms, HAT (hydrogen atom transfer), SETPT (sequential electron transfer proton transfer), and SPLET (sequential proton loss electron transfer) have been studied and discussed. In addition, the reactions toward HO•, MeO•, HOO•, and MeOO• radicals have been investigated. As results, the radical scavenger properties of the studied compounds were confirmed. The HAT was found to be the thermodynamically dominant mechanism in the gas-phase for all the studied compounds, whereas the SPLET mechanism is the thermodynamically favorable pathway in ethanol. A good correlation with DPPH and ABTS assays was found between experimental and theoretical results.

Thermochemical behavior of sorghum procyanidin trimers with C4–C8 and C4–C6 interflavan bonds in the reaction with superoxide anion radical and H2O2-forming NADH-oxidase flavoenzyme

The thermochemical behavior of four sorghum procyanidin trimers (SPT) with C4−C8 and C4−C6 interflavan bonds, in the reaction with O2− via the concerted double proton-transfer electron-transfer (CDPTET) and sequential proton-loss electron-transfer (SPLET) mechanisms, as well as with a H2O2-forming NADH-oxidase flavoenzyme, were analyzed by computational methods. Our results revealed that both CDPTET and SPLET mechanisms could be viable to develop in an aqueous medium. However, the free energies and rate constants of reaction showed that SPLET could be more favored. The SPT2 with interflavan bonds C4–C8 and C4–C6 in its most stable and predominant conformation (Compact-Extended), reached apparent rate constants of 1.07 × 106 (CDPTET) and 9.8 × 106 (SPLET) to scavenge the O2− in aqueous media. Likewise, SPT2 could prevent binding of NAD(P)H to the NADH-oxidase flavoenzyme, suggesting the greatest potential of this procyanidin to prevent the production and activity of the O2− in aqueous media.

Theoretical insights into the antioxidant activity of moracin T

Moracin T is a natural product isolated from Morus mesozygia (Moraceae), which acts as potent antioxidant agent. In this study, density functional theory-based computational methods have been performed to evaluate systematically the radical scavenging behaviour of this compound. Structural characteristics such as frontier molecular orbitals and molecular electrostatic potential mapping have been investigated. Thermodynamic parameters related to the three main antiradical mechanisms, hydrogen atom transfer (HAT), sequential electron transfer proton transfer (SETPT), and sequential proton loss electron transfer (SPLET) have been studied. In addition, two variants of SPLET mechanism namely sequential proton loss hydrogen atom transfer (SPLHAT) and double sequential proton loss electron transfer (D-SPLET) have been investigated. The reaction of moracin T with hydroperoxyl radical (HOO•), as representative reactive oxygen species, was also studied. The obtained results are of great significance in better understanding the chemical mechanism of the radical-scavenging action and open new perspectives for the design of new potent antioxidant agents.