Proton Loss Electron Transfer Mechanism Research Articles

Exploring antioxidative properties of xanthohumol and isoxanthohumol: An integrated experimental and computational approach with isoxanthohumol pKa determination

This study explores the antioxidative activities of xanthohumol (XN) and isoxanthohumol (IXN), prenylated flavonoids from Humulus lupulus (family Cannabaceae), utilizing the oxygen radical absorption capacity (ORAC) and ferric reducing antioxidant power (FRAP) assays along with computational Density Functional Theory methods. Experimentally, XN demonstrated significantly higher antioxidative capacities than IXN. Moreover, we determined IXN pKa values using the UV/Vis spectrophotometric method for the first time, facilitating its accurate computational modeling under physiological conditions. Through a thermodynamic approach, XN was found to efficiently scavenge HOO• and CH3O• radicals via Hydrogen Atom Transfer (HAT) and Radical Adduct Formation (RAF) mechanisms, while CH3OO• scavenging was feasible only through the HAT pathway. IXN exhibited its best antioxidative activity against CH3O• via both HAT and RAF mechanisms and could also scavenge HOO• through RAF. Both Single Electron Transfer (SET) and Sequential Proton Loss-Electron Transfer (SPLET) mechanisms were thermodynamically unfavorable for all radicals and both compounds.

Theoretical Study of Radical Scavenging Antioxidant Activity of Coumarin Derivatives in Licorice Using DFT

Nowdays, much research is focused on exploring antioxidant activity based on natural compounds. Licorice, a traditional natural product rich in antioxidant components, has been widely used in clinical medicine. However, there is a lack of theoretical studies on the active components in licorice. In this context, the antioxidant activity of several common active components of coumarin derivatives in licorice was investigated using a density flooding theory (DFT) approach. The free radical scavenging ability of the compounds was achieved by hydrogen atom transfer (HAT), sequential electron transfer proton transfer (SET-PT) and sequential proton loss electron transfer (SPLET) mechanisms. The effect of solvent on antioxidant activity was also investigated. It was found that in the gas and benzene phases, the compounds studied preferred to undergo the HAT mechanism, while SPLET was favoured in polar solvents. In addition to the above mechanism, the HOMO and LUMO energies of the compounds as well as molecular descriptors and electrostatic potential maps were calculated and applied to predict the antioxidant activity of the compounds. The above studies allow a better understanding of the mechanism of free radical scavenging activity of coumarin derivatives from licorice.

Antioxidant properties of catechin and its 3′O-α-glucoside: Insights from computational chemistry calculations

Density functional theory (DFT) calculations were used to investigate the conformational landscape of catechin and one of its main glucoside derivative (catechin-3′ O- α −glucopyranoside), and to determine the corresponding antioxidant properties. These investigations were carried out in benzene and water using the SMD universal continuum solvation model. Both properties were found to be significantly affected. The structures are characterized in both solvents by strong intramolecular hydrogen bonds (IMHB). In an apolar environment, Hydrogen Atom Transfer (HAT) is by far favored whereas in water the Sequential Proton Loss Electron Transfer (SPLET) mechanism is strongly preferred. In benzene, the catechin fragment has the best antioxidant character (from 27 kJ/mole) whereas in polar surroundings, the glucoside derivative has a slightly better antiradical activity (from 5 kJ/mole). Our results confirm the key role of the 3′-OH and 4′-OH groups of the catechole ring in these properties.

Role of the Solvent and Intramolecular Hydrogen Bonds in the Antioxidative Mechanism of Prenylisoflavone from Leaves of Vatairea guianensis.

This work discusses the electron structure, antioxidative properties, and solvent contribution of two new antioxidant molecules discovered, named S10 and S11, extracted from a medicinal plant called Vatairea guianensis, found in the Amazon rain-forest. To gain a better understanding, a study using density functional theory coupled with the polarizable-continuum model and the standard 6-311++G(d,p) basis set was conducted. The results indicate that S10 has a higher antioxidant potential than S11, confirming the experimental expectations. In the gas phase, the hydrogen atom transfer route dominates the hydrogen scavenging procedure. However, in the water solvents, the antioxidant mechanism prefers the sequential proton loss electron transfer mechanism. Furthermore, the solvent plays a fundamental role in the antioxidant mechanism. The formation of an intramolecular OH···OCH3 hydrogen bond is crucial for accurately describing the hydrogen scavenging phenomenon, better aligning with the experimental data. The results suggest that the two isoflavones investigated are promising for the pharmacologic and food industries.

Antiradical Activity of Lignans from Cleistanthus sumatranus: Theoretical Insights into the Mechanism, Kinetics, and Solvent Effects.

Sumatranus lignans (SL) isolated from Cleistanthus sumatranus have demonstrated bioactivities, e.g., they were shown to exhibit immunosuppressive properties in previous research. Their structure suggests potential antioxidant activity that has not attracted any attention thus far. Consistently, a comprehensive analysis of the antioxidant activity of these compounds is highly desirable with the view of prospective medical applications. In this work, the mechanism and kinetics of the antiradical properties of SL against hydroperoxyl radicals were studied by using calculations based on density functional theory (DFT). In the lipid medium, it was discovered that SL reacted with HOO• through the formal hydrogen transfer mechanism with a rate constant of 101-105 M-1 s-1, whereas in aqueous media, the activity primarily occurred through the sequential proton loss electron transfer mechanism with rate constants of 102-108 M-1 s-1. In both lipidic and aqueous environments, the antiradical activity of compounds 6 and 7 exceeds that of resveratrol, ascorbic acid, and Trolox. These substances are therefore predicted to be good radical scavengers in physiological environments.

Revisiting the scavenging activity of glutathione: Free radicals diversity and reaction mechanisms

Glutathione (GSH) is the most abundant low-molecular-mass thiolated compound in plants and animals, highly relevant in humans since it is one of the principal antioxidant agents capable of scavenging reactive oxygen species (ROS). In addition, it has a function in the immune system and in cell proliferation, and most recently it was discovered that it works against COVID-19. Considering the high flexibility of glutathione, with an atomic configuration and charge state susceptible to minimal changes in its chemical environment, it is of relevance to ascertain what is the scavenging capacity of each of the most probable glutathione species under physiological conditions. In order to find the site and mechanism that contributes the most to the antioxidant activity of GSH, density functional theory (DFT) calculations on multiple species of this molecule were performed in this work. Reactivity indexes, related to hydrogen atom transfer (HAT), single electron transfer-proton transfer (SET-PT), and sequential proton loss electron transfer (SPLET) mechanism were calculated for glutathione. In addition, Gibbs free energies of reaction (ΔG) were obtained for the reactions of GSH with several free radicals to confirm the thermochemical viability of each antioxidant mechanism and to avoid misleading conclusions in terms of considering energetically unfavorable reactions. The results confirm that HAT is the chemical route contributing the most to the antioxidant activity of GSH. However, at least for one radical of interest, SPLET should also be considered.

Synthesis and computational investigation of novel antioxidants prepared by oxidative depolymerization of lignin and aldol condensation of aromatic aldehydes.

Novel antioxidants were synthesized by CuSO4 catalyzed oxidative depolymerization of lignin to form aromatic aldehydes followed by aldol condensation with methyl ethyl ketone (MEK). Aldol condensation was found to greatly improve the antioxidation ability of lignin depolymerized products. Three lignin monomeric aromatic aldehydes, i.e. p-hydroxybenzaldehyde, vanillin, and syringaldehyde were further employed for aldol condensation with MEK, resulting in successful synthesis of new antioxidants, 1-(4-hydroxyphenyl)pent-1-en-3-one (HPPEO), 1-(4-hydroxy-3-methoxyphenyl)pent-1-en-3-one (HMPPEO) and 1-(4-hydroxy-3,5-dimethoxyphenyl)pent-1-en-3-one (HDMPPEO), respectively. Kinetic modeling illustrated that p-hydroxybenzaldehyde had the largest rate to react with MEK, followed by vanillin and then syringaldehyde, which was probably affected by the presence of methoxyl groups. Syringaldehyde derived product (HDMPPEO) displayed the best antioxidation ability. As revealed by density functional theoretical calculation, electron-donating group such as methoxyl group and conjugated side chain could effectively improve the antioxidation ability. Hydrogen atom transfer (HAT) mechanism was prone to occur in non-polar solvents while the sequential proton loss electron transfer (SPLET) mechanism was favored in polar solvents. This work thus can inspire new pathways for valorization of lignin to produce high value-added products.

Mechanistic insight into the free radical scavenging and xanthine oxidase (XO) inhibitor potent of monoacetylphloroglucinols (MAPGs)

Three novel antioxidant candidates based on phenolic polyketide, monoacetylphloroglucinol (MAPG), a natural antibiotic compound produced by plant growth-promoting rhizobacteria (PGPR), Pseudomonas fluorescens F113 have been proposed. Initially, a green and highly efficient route to the synthesis of MAPG and its two analogues from phloroglucinol (PG) has been developed. Afterward, their rational mechanism of antioxidant activity has been investigated based on thermodynamic descriptors involved in the double (/) radical trapping processes. These calculations have been performed using the systematic density functional theory (DFT) method at the B3LYP/Def2-SVP level of theory in the gas phase and aqueous solution. Our findings reveal that the double formal hydrogen atom transfer (df-HAT) mechanism is preferred in the gas phase, while the double sequential proton loss electron transfer (dSPLET) mechanism is preferred in aqueous solution for all MAPGs. The 6–OH group represents the most favorable site for trapping radical species for all MAPGs, which is supported by the pKa values obtained from DFT calculations. The role of acyl substituents on the PG ring has been comprehensively discussed. The presence of acyl substituents has a strong influence on the thermodynamic parameters of the phenolic O–H bond in PG. These results are supported by frontier molecular orbitals (FMOs) analysis, where the addition of acyl substituents increases the chemical reactivity of MAPGs significantly. Based on molecular docking and molecular dynamic simulations (MDs), MAPGs are also predicted to be promising candidates for xanthine oxidase (XO) inhibition. Highlights The antioxidant activity of the three synthesized monoacetylphloroglucinols (MAPGs) has been investigated using the density functional theory (DFT) method. Acyl substituents increase the chemical reactivity and antioxidant activity of MAPGs. Double formal hydrogen atom transfer (df-HAT) is the preferred mechanism in the gas phase. Double sequential proton loss electron transfer (dSPLET) seems to be more favored in aqueous solution. MAPGs are expected to be promising xanthine oxidase (XO) inhibitors.

Antioxidant activity and enzymatic of lichen substances: A study based on cyclic voltammetry and theoretical

The antioxidant activity of nine lichen substances, including methylatrarate (1), methyl haematommate (2), lobaric acid (3), fumarprotocetraric acid (4), sphaerophorin (5), subsphaeric acid (6), diffractaic acid (7), barbatolic acid (8) and salazinic acid (9) has been determined through cyclic voltammetry. The compounds 1–4 presented slopes close to the Nernst constant of 0.059 V, indicating a 2H+/2e− relation between protons and electrons, as long as the compounds 5, 6, 7, 8, and 9 present slopes between 0.037 V and 0.032 V, indicating a 1H+/2e− relation between protons and electrons. These results show a high free radical scavenging activity by means of the release of H+, suggesting an important antioxidant capacity of these molecules. Theoretical calculations of hydrogen bond dissociation enthalpies (BDE), proton affinities (PA), and Proton Transfer (PT) mechanisms, at M06-2x/6-311+G(d,p) level complement the experimental results. Computations support that the best antioxidant activity is obtained for the molecules (3, 4, 5, 6, 7 and 8), that have a carboxylic acid group close to a phenolic hydroxyl group, through hydrogen atomic transfer (HAT) and sequential proton loss electron transfer (SPLET) mechanisms. Additional computations were performed for modelling binding affinity of the lichen substances with CYPs enzymes, mainly CYP1A2, CYP51, and CYP2C9*2 isoforms, showing strong affinity for all the compounds described in this study.

Radical scavenging capacity, UV activity, and molecular docking studies of 2ʹ, 5ʹ, 3, 4-Tetrahydroxychalcone: An insight into the photoprotection

A theoretical evaluation of radical scavenging activity and UV absorbing ability of chalcone named 2ʹ, 5ʹ, 3, 4-Tetrahydroxychalcone has been performed in the gas phase and aqueous media. The DFT-B3LYP/6–311+G (d, p) level of theory was utilized for geometry optimization and the calculation of reaction enthalpies, while the CAM-B3LYP/6–311+G (d, p) level of theory was employed for TDDFT analysis. Three potential working mechanisms of radical scavenging activity, hydrogen atom transfer mechanisms (HAT), stepwise electron transfer proton transfer (SET-PT), and sequential proton loss electron transfer mechanisms (SPLET) were investigated within the gas phase and aqueous phase. The results obtained demonstrate that the HAT will be the probable mechanism in the gas phase whereas SPLET will be in the water medium. Using the same level of theory, explicit surface analysis of the title compound was performed. The compound wave function analysis and molecular docking investigations were also performed in the optimized structure. The theoretical UV spectra were recorded in both the solvents and the compound's electronic absorption spectrum was analyzed using the TD-DFT method. The distribution of hole and electrons in the peaks of maximal oscillator strength corresponds to local excitation within the molecule. The Quantum Theory of Atoms in Molecule (QTAIM) was used to compute the strength of intramolecular hydrogen bonds and non-covalent interactions. The global reactivity parameters and electrostatic potential (ESP) were also included to define the reactivity of the whole molecule. The spin density distribution analysis was come upon to be complementary to the radical scavenging activity. Besides the radical scavenging activity of the compound, it can also be used as a potential UVA filter.

Effect-Directed Profiling of Strawberry Varieties and Breeding Materials via Planar Chromatography and Chemometrics.

Strawberries are an important fruit in the European diet because of their unique taste and high content of essential nutrients and bioactive compounds. The anthocyanins are known to be colorful phenolics in strawberries. In 17 samples of six strawberry cultivars produced in Serbia, i.e., the common varieties Alba, Asia, and Clery as well as promising breeding materials (11.29.11, 11.34.6, and 11.39.3), the anthocyanin profile as well as antimicrobial and antioxidative activity profiles were determined. All investigated extracts showed antioxidative and antibacterial activities against Gram-negative Aliivibrio fischeri. The responses were quite similar in number and intensity. The HPTLC-DPPH• scavenging assay and HPTLC-Aliivibrio fischeri bioassay coupled with high-resolution mass spectrometry identified pelargonidin-3-O-glucoside (Pg-3-glc) as the main anthocyanin and prominent antioxidative and antimicrobial compound in strawberries. The density functional theory calculations at the M06-2X/6-31+G(d,p) level showed that Pg-3-glc quenches free radicals via sequential proton loss electron transfer mechanism in water and in pentyl ethanoate, where the 5-OH group is the most reactive site for proton and hydrogen atom transfer. The results were confirmed via spectrophotometry. The highest total phenolic content was found in Clery and 11.39.3, while statistically significant differences between the genotypes regarding the antioxidant activity were not confirmed. Although very similar in the anthocyanin, antioxidative, and antimicrobial profile patterns, the strawberry genotypes were successfully classified using principal component analysis.

Fisetin and Robinetin antiradical activity under solvent effect: density functional theory study

The structural and antioxidant activity of two flavonols, namely, Fisetin and Robinetin, have been investigated employing the density functional theory (DFT) using B3LYP functional and 6-311++G (d, p) basis set. The calculations were performed in the gas phase and under the solvent effect of water, dimethylsulfoxide (DMSO), methanol, and benzene. The Hydrogen-Atom Transfer (HAT), single Electron Transfer Followed by Proton Transfer (SET-PT), and sequential Proton Loss Electron Transfer (SPLET) mechanisms were investigated to rationalize the radical scavenging capacities and to identify the favored antioxidant mechanism. Hence, the bond dissociation enthalpies (BDE) ionization potential (IP), IE, proton dissociation enthalpy (PDE), proton affinity (PA), and electron Transfer enthalpy (ETE) related to each mechanism were reported and discussed in function of the solvent effect. For both flavonols, the results showed that 4'-OH hydroxyl is the preferred active site following the trend 4'-OH > 3'-OH > 3-OH > (5'-OH) > 7-OH. Besides, the HAT mechanism is energetically the most favored pathway. The energetically favored solvents follow the trends water > DMSO > benzene > methanol and benzene > DMSO > methanol > water, for Fisetin and Robinetin, respectively.

Computational study of synthetic and natural polymer additives — Antioxidant potential of BHA, TBHQ, BHT, and curcumin

The antioxidant potential of commonly used synthetic and natural antioxidant additives, including butylated hydroxytoluene (BHT), butylated hydroxyanisole (BHA), tert‑butylhydroquinone (TBHQ), and natural additive, curcumin have been studied and compared by calculating the bond dissociation enthalpy (BDE), ionization potential (IP), proton dissociation enthalpy (PDE), proton affinity (PA), and electron transfer enthalpy (ETE) values for each potential hydrogen donor site. The results indicate that, in each additive an OH group has the highest antioxidant potential (lowest BDE value). The studied molecules can be ranked based on their antioxidant potential as follows: BHT > BHA ≈ TBHQ > curcumin A > curcumin D. By comparing with commonly used polymers, in each studied species, there is at least one X-H bond which has a lower BDE value than in the corresponding polymeric material. Thus, all studied additives are potentially applicable to protect polymeric materials. BHT is the best radical scavenger additive in case of the hydrogen atom transfer (HAT), and the sequential proton loss electron transfer (SPLET) mechanisms to donate a H atom, but in single electron transfer proton transfer (SETPT) curcumin could also be suitable.

Multiple free radical scavenging reactions of flavonoids

The multiple free radical scavenging reactions of flavonoids have been studied considering the gas, benzene, and water phases by applying density functional theory (DFT). Intramolecular hydrogen-bonds are found in all the most stable geometries of flavonoids and can reduce the antioxidant activity of hydroxyl groups, acting as hydrogen-bond donors (5−OH, 3−OH and 3’−OH), while enhancing the antioxidant activity of hydroxyl groups, acting as hydrogen-bond acceptors (4’−OH). In the gas and benzene phases, all of the flavonoids first prefer performing continuous di-hydrogen atom transfer (HAT) reaction from the B ring OH groups to trap two free radicals with the formation of stable quinones for ampelopsin, taxifolin, dihydro orobol and eriodictyol and benzodioxole for hesperetin. They would trap the third free radical via the HAT in the gas phase. In the benzene phase, ampelopsin also favours to apply HAT to trap the third free radical, and the other flavonoids would use the sequential proton loss electron transfer (SPLET) mechanism. In the water phase, the investigated flavonoids would first perform consecutive proton loss (PL) reactions from all of the OH groups with the formation of polyanions. The multiple PL reactions begin from the 7−OH group. The second PL reaction prefers performing in the OH groups on the B benzene ring due to the better delocalization of the negative charge via conjugation over the entire skeleton. The polyanions of the investigated flavonoids scavenge three free radicals via three consecutive ET reactions.

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.

Ligand-based design of chalcone analogues and thermodynamic analysis of their mechanism of free radical scavenge.

Overproduction of free radicals in the body may result in oxidative stress, which plays an active role in the development of various health disorders. Consequently, the development of efficient free radical scavengers and evaluation of their antioxidant properties is a research area of interest. In the present research, computational quantum chemical approach based on the density functional theory (DFT) method was employed to elucidate the free radical scavenge of chalcone derivatives via thermodynamic studies. New set of chalcone antioxidants were designed. Their reactivity towards hydroperoxyl (HOO·) and methyl peroxyl (CH3OO·) radicals were investigated through systematic study of their mechanism of free radical scavenge. Various reaction enthalpies and Gibbs free energy that characterize the various steps in these mechanisms were computed in the gas phase and aqueous solution, in order to identify the main channels of reaction. Results in the gas phase indicate that hydrogen atom transfer (HAT) and sequential proton loss electron transfer (SPLET) mechanisms represent the most plausible reaction pathways, while single electron transfer followed by proton transfer (SET-PT) mechanism was thermodynamically unfeasible. However, these mechanisms were thermodynamically favoured in aqueous solution. Also, these chalcone derivatives were observed to be more effective in scavenging HOO· than CH3OO· radicals in both phases. Based on the exergonicity of the obtained results, the molecule MCHM 17 ((E)-1-(3-bromo-5-hydroxyphenyl)-3-(2,5-dihydroxyphenyl)prop-2-en-1-one) at the 5-OH site was found to exhibit the greatest potential to scavenge HOO· and CH3OO· radicals in both phases. This research is a gateway to the efficient exploitation of these compounds in pharmacy and food chemistry.

Cholinium-Based Ionic Liquids from Hydroxycinnamic Acids as New Promising Bioactive Agents: A Combined Experimental and Theoretical Investigation

Cholinium-based ionic liquids (Cho-ILs) are very attractive compounds for medicinal and pharmaceutical applications as bioavailability enhancers in drug formulations and active components in pharmaceutical ingredients. In this study, we synthesized six Cho-ILs from hydroxycinnamic acids (HCA) ([Cho][HCA] ILs), a group of bioactive compounds with poor water solubility. [Cho][HCA] ILs and their parent acids were evaluated for solubility, thermal stability, and antioxidant activity. Furthermore, [Cho][HCA] ILs were screened for their cytotoxicity. To rationalize the experimental antioxidant activities, density functional theory (DFT) calculations were performed. The theoretical approach allowed for identification of the most likely radical scavenging mechanisms involving HCAs and the corresponding ionic forms under the studied experimental conditions and to rationalize the observed activity differences between salts and acids. Overall, our results revealed a higher solubility and free-radical scavenging activity for [Cho][HCA] ILs than corresponding HCAs, a relatively high thermal stability (melting temperature > 100 °C) and negligible cytotoxicity activity. Furthermore, DFT calculations showed that both the hydrogen atom transfer and the sequential proton loss electron transfer mechanisms are likely to occur in aqueous and ethanolic solutions. The picture emerging from our results supports the increasingly expressed idea that [Cho][HCA]ILs are promising candidates for applications in pharmaceutical formulation.

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.

In Silico Evaluation of the Radical Scavenging Mechanism of Mactanamide.

Mactanamide (MA) is a diketopiperazine isolated from marine fungi of the genus Aspergillus. This compound is known as a natural antioxidant from experimental studies, yet this activity has not been successfully modeled thus far. In this work, the hydroperoxyl radical scavenging activity of MA was evaluated in the gas phase and physiological environments by thermodynamic and kinetic calculations. The results revealed that the HOO• radical scavenging of MA in the lipid media follows the formal hydrogen transfer mechanism via hydrogen abstraction at the O11–H bond. In the aqueous solution, however, the antioxidant activity follows the sequential proton loss electron transfer mechanism. The rate constant of the HOO• scavenging of MA in the polar environment is about 1045 times (koverall = 2.23 × 106 M–1 s–1) higher than that in the lipid medium (koverall = 2.20 × 103 M–1 s–1). In polar media, the HOO• radical scavenging activity of MA is therefore 18 times higher than that of Trolox, the reference compound when assessing antioxidant activity. The results presented here align well with the experimental data, validating the mechanistic pathways and thus providing useful insights into the antioxidant activity of MA.