A Comprehensive Study of the Radical Scavenging Activity of Rosmarinic Acid.

Rosmarinic acid (RA) is reported in separate studies to be either an inducer or reliever of oxidative stress, and this contradiction has not been resolved. In this study, we present a comprehensive examination of the radical scavenging activity of RA using density functional theory calculations in comparison with experimental data. In model physiological media, RA exhibited strong HO• radical scavenging activity with overall rate constant values of 2.89 × 1010 and 3.86 × 109 M-1 s-1. RA is anticipated to exhibit excellent scavenging properties for HOO• in an aqueous environment (koverall = 3.18 × 108 M-1 s-1, ≈2446 times of Trolox) following the hydrogen transfer and single electron transfer pathways of the dianion state. The neutral form of the activity is equally noteworthy in a lipid environment (koverall = 3.16 × 104 M-1 s-1) by the formal hydrogen transfer mechanism of the O6(7,15,16)-H bonds. Chelation with RA may prevent Cu(II) from reduction by the ascorbic acid anion (AA-), hence blocking the OIL-1 pathway, suggesting that RA in an aqueous environment also serves as an OIL-1 antioxidant. The computational findings exhibit strong concurrence with the experimental observations, indicating that RA possesses a significant efficacy as a radical scavenger in physiological environments.

Promoting High-Oxidation-State Metal Active Sites in a Hollow Ternary Metal Fluoride Nanoflake Array for Urea Electrolysis.

The adsorption ability of hydrogen, hydroxide, and oxygenic intermediates plays a crucial role in electrochemical water splitting. Electron-deficient metal-active sites can prompt electrocatalytic activity by improving the adsorption ability of intermediates. However, it remains a significant challenge to synthesize highly abundant and stable electron-deficient metal-active site electrocatalysts. Herein, we present a general approach to synthesizing a hollow ternary metal fluoride (FeCoNiF2) nanoflake array as an efficient and robust bifunctional electrocatalyst for the hydrogen evolution reaction (HER) and urea oxidation reaction (UOR). We find that the F anion withdraws electrons from the metal centers, inducing an electron-deficient metal center catalyst. The rationally designed hollow nanoflake array exhibits the overpotential of 30 mV for HER and 130 mV for UOR at a current density of 10 mA cm-2 and superior stability without decay events over 150 h at a large current density of up to 100 mA cm-2. Remarkably, the assembled urea electrolyzer using a bifunctional hollow FeCoNiF2 nanoflake array catalyst requires cell voltages of only 1.352 and 1.703 V to afford current densities of 10 and 100 mA cm-2, respectively, which are 116 mV less compared with that required for overall water splitting.

Exploring the Multitarget Activity of Wedelolactone against Alzheimer's Disease: Insights from In Silico Study.

In this study, Wedelolactone's multitarget activity against Alzheimer's disease was examined using density functional theory and molecular docking techniques. At physiological pH, the pK a and molar fractions have been estimated. The most likely relative rate constants of two radical scavenger mechanisms are formal hydrogen transfer in a lipid environment and single-electron transfer in a water solvent. Compared to Trolox (k overall = 8.96 × 104 M-1 s-1), Wedelolactone (k overall = 4.26 × 109 M-1 s-1) is more efficient in scavenging the HOO• radical in an aqueous environment. The chelation capacity of metals was investigated by examining the complexation of the Cu(II) ion at various coordination positions and calculating the complexation kinetic constants. Furthermore, molecular docking simulations showed that the known forms of Wedelolactone at physiological pH effectively inhibited the AChE and BChE enzymes by comparing their activity to that of tacrine (control). Wedelolactone is a promising drug candidate for Alzheimer's disease therapy in light of these findings.

Insight into the direct conversion of methane to methanol on modified ZIF-204 from the perspective of DFT-based calculations.

Direct oxidation of methane over oxo-doped ZIF-204, a bio-mimetic metal-organic framework, is investigated under first-principles calculations based on density functional theory. In the pristine ZIF-204, the tetrahedral methane molecule anchors to an open monocopper site via the so-called η2 configuration with a physisorption energy of 0.24 eV. This weak binding arises from an electrostatic interaction between the negative charge of carbon in the methane molecule and the positive Cu2+ cation in the framework. In the modified ZIF-204, the doped oxo species is stabilized at the axial position of a CuN4-base square pyramid at a distance of 2.06 Å. The dative covalent bond between Cu and oxo is responsible for the formation energy of 1.06 eV. With the presence of the oxo group, the presenting of electrons in the O_pz orbital accounts for the adsorption of methane via hydrogen bonding with an adsorption energy of 0.30 eV. The methane oxidation can occur via either a concerted direct oxo insertion mechanism or a hydrogen-atom abstraction radical rebound mechanism. Calculations on transition-state barriers show that reactions via the concerted direct oxo insertion mechanism can happen without energy barriers. Concerning the hydrogen-atom abstraction radical rebound mechanism, the C-H bond dissociation of the CH4 molecule is barrierless, but the C-O bond recombination to form the CH3OH molecule occurs through a low barrier of 0.16 eV. These predictions suggest the modified ZIF-204 is a promising catalyst for methane oxidization.

Insights into antiradical mechanism and pro-oxidant enzyme inhibitor activity of walterolactone A/B 6-O-gallate-ß-d-pyranoglucoside originating from Euonymus laxiflorus Champ. using in silico study.

The ability of a new compound, Wal, (walterolactone A/B 6-O-gallate-ß-d-pyranoglucoside) originating from Euonymus laxiflorus Champ. as a hydroperoxyl radical scavenger and pro-oxidant enzyme inhibitor was studied in silico. Different mechanisms, reaction locations, and chemical species of Wal in aqueous solution were taken into consideration. Formal hydrogen transfer from the OH group has been discovered as the chemical process that contributes most to the antioxidant properties of Wal in nonpolar and aqueous solutions. The overall rate coefficients for polar and non-polar environments are expected to have values of 7.85 × 106 M-1 s-1 and 4.84 × 105 M-1 s-1, respectively. According to the results of the investigation, Wal has greater scavenging activity against the HOO˙ radical than the reference antioxidant Trolox at physiological pH (7.4). In addition, docking results indicate that Wal's antioxidant properties involve the inhibition of the activity of enzyme families (CP450, MP, NO, and XO) that are responsible for ROS production.

Coupling Amorphous Ni Hydroxide Nanoparticles with Single-Atom Rh on Cu Nanowire Arrays for Highly Efficient Alkaline Seawater Electrolysis.

Exploring efficient catalysts for alkaline seawater electrolysis is highly desired yet challenging. Herein, coupling single-atom rhodium with amorphous nickel hydroxide nanoparticles on copper nanowire arrays is designed as a new active catalyst for the highly efficient alkaline seawater electrolysis. We found that an amorphous Ni(OH)2 nanoparticle is an effective catalyst to accelerate the water dissociation step. In contrast, the single-atom rhodium is an active site for adsorbed hydrogen recombination to generate H2. The NiRh-Cu NA/CF catalyst shows superior electrocatalytic activity toward HER, surpassing a benchmark Pt@C. In detail, the NiRh-Cu NA/CF catalyst exhibits HER overpotentials as low as 12 and 21 mV with a current density of 10 mA cm-2 in fresh water and seawater, respectively. At high current density, the NiRh-Cu NA/CF catalyst also exhibits an outstanding performance, where 300 mA cm-2 can be obtained at an overpotential of 155 mV and shows a slight fluctuation in the current density over 30 h.

The hydroperoxyl and superoxide anion radical scavenging activity of anthocyanidins in physiological environments: Theoretical insights into mechanisms and kinetics.

The HOO• and O2•- scavenging activities of 12 natural anthocyanidins were investigated in physiological environments by using DFT calculations. The results suggest high HOO• scavenging activity in aqueous medium with overall rate constants in the range of koverall = 1.58 × 108 - 7.59 × 109 M-1 s-1, whereas in lipid medium only weak activity is predicted. O2•- scavenging is also fast in water with kapp = âˆ¼109 M-1 s-1. Like in the case of many other antioxidants that contain acidic moieties, the anion states (H3A- and H2A2-) and the single electron transfer mechanism play a dominant role in the HOO• scavenging activity of anthocyanidins in water at pH = 7.4. Analysis of the mechanism suggests that the O2•- and HOO• radical scavenging can occur as a regeneration cycle that might increase the protective efficiency of anthocyanidins against oxidative stress.

A decomposition mechanism for Mn2(DSBDC) metal-organic frameworks in the presence of water molecules.

In this work, we investigate the effects of water on the structural stability of Mn2(DSBDC) metal-organic framework (MOF) using DFT-based calculations. It has been found that the adsorption of multiple water molecules forming a hydrogen bond network around the Mn centers plays an important role in the decomposition process. Different effects contribute to the destabilization of the MOF: water molecules that directly coordinate to the open sites displayed by a part of the Mn centers can induce a significant shift in the charge distribution as indicated by the analysis of charge density differences and the Bader charges. This adsorption process leads to a slight elongation of the metal-linker bonds. The direct interaction with the Mn center is the most stable adsorption mode for water in Mn2(DSBDC). Once these adsorption sites at the Mn centers are fully occupied, additional water molecules start to bind via hydrogen bonds to the already present water molecules or, more importantly, to the linker molecules. This, in return, leads to a significant weakening of the Mn-linker bonds, thus allowing water insertion into the Mn-linker bonds with a barrier of only 0.16 eV, which is believed to initiate the decomposition of the Mn2(DSBDC) framework. Based on a kinetic Monte Carlo model, it can be shown that high temperatures can prevent the adsorption of water molecules around the Mn sites and thus slow down the MOF decomposition.

Radical Scavenging Activity of Natural Anthraquinones: a Theoretical Insight.

Anthraquinones (ANQs) isolated from Paederia plants are known to have antidiarrheal, antitussive, anthelmintic, analgesic, anti-inflammatory, antihyperlipidemic, antihyperglycaemic, and antimicrobial activities. The antioxidant properties were also noted but not confirmed thus far. In this study, the superoxide and hydroperoxide radical scavenging activities of six ANQs were evaluated using a computational approach. The results suggest that the ANQs exhibit low HOO• antiradical activity in all environments, including the gas phase (k < 102 M-1 s-1). In contrast, the ANQs might exert excellent O2 •- radical scavenging activity, particularly in aqueous solution. The rate constants of the superoxide anion scavenging in water (at pH = 7.4) range from 3.42 × 106 to 3.70 × 108 M-1 s-1. Compared with typical antioxidants such as ascorbic acid and quercetin, the superoxide anion scavenging activity of ANQs is significantly higher. Thus, the ANQs are promising O2 •- radical scavengers in polar media.

The radical scavenging activity of abietane diterpenoids: Theoretical insights.

Salvia species are frequently used in traditional medicine and are a source of diterpenoid antioxidants. In this study, the hydroperoxide radical scavenging activity of seven known abietane diterpenoids (ADs), isolated from Salvia barrelieri, are investigated using a quantum chemical approach. The ADs are 7-oxoroyleanone-12-methyl ether (1), 7a-acetoxyroyleanone-12-methyl ether (2), royleanone (3), horminone (4), 7-acetylhorminone (5), cryptojaponol (6), and inuroyleanol (7). It was found that formal hydrogen transfer is the main mechanism of the antiradical activity of these ADs in nonpolar environments, whereas the single electron transfer mechanism of anion states is favored in aqueous environment. The antioxidant activity of compounds 1-5 involves H-abstraction at the C7(15)-H bonds whereas for the compounds 6 and 7 the H abstraction takes place at the O12-H bond. The HOO• scavenging activity of compounds 1-5 is minor in all of the studied media, however 6 and 7 exhibit excellent antiradical activity in aqueous solution. Remarkably, the HOO• scavenging activity of compound 7 is substantially higher than that of Trolox, the reference antioxidant: the calculated rate constant was 122.3 times higher in polar and 6.1 times higher in nonpolar environments, respectively. Consistently 7 is a promising radical scavenger in physiological environments.

Is natural fraxin an overlooked radical scavenger?

Fraxin (FX) (7-hydroxy-6-methoxycoumarin 8-glucoside) is a typical natural product of the coumarin family. This compound was shown to protect endothelial cells from oxidative stress; however, the nature of its antioxidant properties is still ambiguous. In this study, we report on a systematic evaluation of the radical scavenging activity of FX using a two-tier protocol based on thermodynamic and kinetic calculations. The results show that FX has moderate activity in the aqueous physiological environment against a range of radicals including HO˙, CCl3O˙, CCl3OO˙, NO2, , and HOO˙. The latter was examined in detail due to the prevalence of HOO˙ as a source of oxidative stress in biological systems. HOO˙ scavenging activity was promising in the gas phase but low in physiological environments with k overall = 1.57 × 106, 3.13 × 102 and 2.68 × 103 M-1 s-1 in the gas phase, pentyl ethanoate and water solvents, respectively. The formal hydrogen transfer mechanism at the O7-H bond dominates the hydroperoxyl radical scavenging of FX in the nonpolar media, whereas, in the polar environment, the activity is exerted by the single electron transfer mechanism of the anion state. This activity falls behind typical antioxidants such as Trolox, ascorbic acid, and trans-resveratrol under the studied conditions. Thus FX may have multiple health benefits, but it is not an outstanding natural antioxidant.

Substituent Effects on the N-H Bond Dissociation Enthalpies, Ionization Energies, Acidities, and Radical Scavenging Behavior of 3,7-Disubstituted Phenoxazines and 3,7-Disubstituted Phenothiazines.

The substituent effects on the N-H bond dissociation enthalpies (BDE), ionization energies (IE), acidities (proton affinity, PA), and radical scavenging behavior of 3,7-disubstituted phenoxazines (PhozNHs) and 3,7-disubstituted phenothiazines (PhtzNHs) were determined using density functional theory, with the M05-2X functional in conjunction with the 6-311++G(d,p) basis set. These thermochemical parameters calculated in both gas phase and benzene solution with respect to the changes in several different substituents including halogen, electron-withdrawing, and electron-donating groups at both 3 and 7 positions in both PhozNHs and PhtzNHs systems were analyzed in terms of the inherent relationships between them with some quantitative substituent effect parameters. The kinetic rate constants of hydrogen-atom exchange reactions between PhozNH and PhtzNH derivatives with the HOO• radical were also calculated, and the effects of the substituents on the kinetic behaviors of these reactions were thereby quantitatively evaluated.

Pivotal Role of Heteroatoms in Improving the Corrosion Inhibition Ability of Thiourea Derivatives.

1,3-Diphenyl-2-thiourea (DPTU) and 1-phenyl-3-(2-pyridyl)-2-thiourea (PPTU) were selected as the researched subject for investigating the effect of heteroatoms on the low carbon steel corrosion inhibition ability. Results from the potentiodynamic polarization measurements (PPM) indicate that the addition of a nitrogen atom in the benzene ring increases the corrosion inhibition efficiency of PPTU (97.2%), being higher than that of DPTU (93.1%) at the same condition of 2.0 × 10-4 M at 30 °C. The Nyquist diagrams show that increasing the concentrations of both DPTU and PPTU will enhance the charge-transfer resistance and reduce the double-layer capacitance. The obtained data based on PPM and electrochemical impedance spectroscopy methods are in accordance to the analysis based on the scanning electrochemical microscopy images. Besides, results from quantum chemical calculations prove that the heteroatoms in the inhibitor molecules are the adsorption centers, and the benzene rings increase the electrostatic interaction between the inhibitor molecules and the steel surface. Results from Monte Carlo and molecular dynamics simulation have clarified the adsorption mechanism of DPTU and PPTU on the steel surface. Adsorption energies confirm that PPTU displays the higher inhibition ability as compared with DPTU.

From the perspectives of DFT calculations, thermodynamic modeling, and kinetic Monte Carlo simulations: the interaction between hydrogen and Sc2C monolayers.

In this study, we have examined the adsorption properties of hydrogen on pristine Sc2C monolayers by DFT calculations. Based on these calculations, we have proposed a thermodynamic model to estimate the hydrogen storage capability within the typical ranges for the operating temperature and pressure. Our thermodynamic modeling has shown that the maximum uptake of usable hydrogen could reach up to 7.2 wt% under cryogenic conditions. When calculating the usable hydrogen uptake, we have taken into consideration that, under realistic operating conditions, not all hydrogen adsorbed on pristine Sc2C can be desorbed from the surface, as some surface-adsorbate interactions are too strong. On the other hand, the interaction between the usable hydrogen and Sc2C appears to be too weak to reach the targets for the year 2025 set by the US Department of Energy (5.5 wt% at operating temperatures between 233 K and 358 K and delivery pressures of up to 12 bar). According to the modeling results, one needs to decrease the temperature to 120 K to reach 5.5 wt% hydrogen uptake at 12 bar. The results obtained with the thermodynamic model have been confirmed with a kinetic Monte Carlo simulation, which has also been used to estimate the time scale of the hydrogen adsorption and desorption processes. In addition, we have also evaluated the changes in the electronic structure of the Sc2C monolayer upon adsorbing hydrogen. As the band gap of Sc2C changes significantly upon adsorbing H2, Sc2C may have more potential as a hydrogen detector instead of as a hydrogen storage material.

Functionalization and antioxidant activity of polyaniline-fullerene hybrid nanomaterials: a theoretical investigation.

Functionalized fullerene is one of the most advantageous nanotechnologies to develop novel materials for potential biomedical applications. In this study, we applied the ONIOM-GD3 approach to explore the nucleophilic addition reaction mechanism between polyaniline (emeraldine and leucoemeraldine forms) and fullerene. Potential energy surfaces were also analyzed to predict the predominantly formed products of the functionalized reaction. The themoparameters, such as bond dissociation enthalpy (BDE), ionization energy (IE), and electron affinity (EA), characterized by two mechanisms HAT and SET, were used to evaluate the antioxidant activities of the selected compounds. Moreover, the calculated HOMO, LUMO, and DOS results indicate that the electronic structures of polyaniline-fullerene were significantly affected by the presence of fullerene. The computational results show that C60-L1 seems to be the best antioxidant following the SET mechanism.

The antioxidant activity of natural diterpenes: theoretical insights.

Diterpenes that were isolated from Crossopetalum gaumeri (Loes.) Lundell (Celastraceae) plants are reported to exhibit a range of biological activities, in particular as radical scavengers. Thus further insight into the antioxidant activity of diterpenes in physiological environments is much needed but not studied yet. In this study, the antioxidant activity of nine natural diterpenes was evaluated using kinetic and thermodynamic calculations. It was found that the sequential proton loss electron transfer (SPLET) mechanism is favored in polar environments, whereas formal hydrogen transfer (FHT) is the main pathway for the radical scavenging of these diterpenes in the gas phase as well as in lipid media. The rate constants for the HOO˙ radical scavenging of these compounds in the gas phase, polar and nonpolar solvents are in the range of 2.29 × 10-2 to 4.58 × 107, 9.74 × 10-3 to 1.67 × 108 and 3.54 × 10-5 to 1.31 × 105 M-1 s-1, respectively. 7-Deoxynimbidiol (6), exhibits the highest HOO˙ radical scavenging with k overall = 1.69 × 108 M-1 s-1 and 9.10 × 104 M-1 s-1 in water and pentyl ethanoate solvents, respectively, that is about 1300 times higher than that of Trolox in polar environments. It is thus a promising natural antioxidant in physiological environments.

Hydrogen adsorption mechanism of MOF-74 metal-organic frameworks: an insight from first principles calculations.

The microscopic mechanism of the H2 adsorption of two Mg-MOF-74 isoreticular frameworks, one with a benzenedicarboxylate (BDC) linker and the other with a dihydroxyfumarate (DHF) linker, were studied on the basis of density functional theory (DFT) method. Possible adsorption sites on the internal surface of the two MOFs were detected using ab initio molecular dynamics (AIMD) annealing simulations. The simulations were able to reproduce all adsorption sites which have been experimentally observed for the BDC-based M-MOF-74 frameworks with M = Ni and Zn. In descending order of binding strengths, they are the adsorption sites primarily induced by the open metal sites P1, the oxygen atoms of the oxido groups P2 and the aromatic rings P3. The H2-framework binding strengths were properly evaluated by taking into account the vibrational zero-point energy (ZPE) contribution. An additional type of adsorption sites induced by the oxygen atoms of the carboxyl groups P4 is predicted for the Mg-MOF-74 framework. Two types of adsorption sites primarily induced by the open metal sites P1 and oxygen atoms of the carboxyl groups P2 were predicted for the DHF-based Mg-MOF-74 framework. Detailed analysis of the electron density showed that the electrostatic interaction of the H2 molecule with the charge distribution of the local framework environment within a radius of ∼3.5 Šis a key factor to define adsorption positions and binding strength. The absence of the P4 sites in the BDC-based Zn-MOF-74 framework is caused by the lower charge density at the oxygen atoms induced by less electro-positive metal. The substitution of the nonaromatic DHF linker for the aromatic BDC linker reduces the binding strength at the metal induced adsorption sites by 1.45 kJ mol-1 due to the absence of the aromatic ring.

A thermodynamic and kinetic study of the antioxidant activity of natural hydroanthraquinones.

Novel hydroanthraquinones isolated from marine algal-derived endophytic fungus Talaromyces islandicus EN-501 exhibited promising antioxidant properties in preliminary studies, raising the prospect of adapting these compounds for therapeutic use in diseases caused by oxidative stress. For medicinal applications it is beneficial to develop a full understanding of the antioxidant activity of these compounds. In this study, the hydroperoxide radical scavenging activity of five natural hydroanthraquinones was evaluated by kinetic and thermodynamic calculations. The results showed that the radical scavenging of these hydroanthraquinones in the gas phase and in lipid solvents was defined by the formal hydrogen transfer mechanism, that for the polar environments was decided by the sequential proton loss electron transfer pathway. The hydroanthraquinones exhibited good hydroperoxide scavenging activity in both polar and non-polar media. The overall rate constant values for the radical scavenging reaction were in the range of 3.42 × 101 to 2.60 × 105 M-1 s-1 and 3.80 × 106 to 5.87 × 107 M-1 s-1 in pentyl ethanoate and water solvents, respectively. Thus the activity of 8-hydroxyconiothyrinone B (1) is about 2.6 and 444.6 times higher than that of Trolox in the studied solvents, identifying 8-hydroxyconiothyrinone B as a promising antioxidant.

Theoretical Study for Exploring the Diglycoside Substituent Effect on the Antioxidative Capability of Isorhamnetin Extracted from Anoectochilus roxburghii.

Radical-scavenging activity of isorhamnetin (1) and its diglycosides, named isorhamnetin-3,5'-O-ß-D-diglucoside (2) and isorhamnetin-3,7-O-ß-D-diglucoside (3) extracted from Anoectochilus roxburghii, has been studied through three main antioxidant pathways: hydrogen atom transfer (HAT), single electron transfer followed by proton transfer, and sequential proton loss electron transfer (SPLET). All thermodynamic parameters related to these radical-scavenging mechanisms were computed at the B3LYP/6-311G(d,p) level of theory both in the gas phase and in solution. The results suggest that HAT is the predominant mechanism in the gas phase, while SPLET is supported in an aqueous environment. In addition, the stability of radicals has also been explored by electron spin density and intramolecular hydrogen bonding. The potential energy profiles and kinetic calculations for the reactions between the selected compounds and the CH3OO• radical were calculated at 298.15 K. Among all investigated, compound 2 has the highest antioxidant activity with the lowest Gibbs free energy (-4.05 kcal/mol) and the highest hydrogen atom transfer rate constant (3.61 × 105 M-1 s-1). Substitution of the OH and OMe groups by two glucoses at the 3 and 5' sites of isorhamnetin has a significant impact on its antioxidant activity.

Antioxidant Motifs in Flavonoids: O-H versus C-H Bond Dissociation.

Flavonoids provide potential health benefits due to their antioxidant properties. The antioxidant activity of natural flavonoids is primarily exerted by phenolic hydroxyl groups; however, C-H bonds also contribute to these properties. In this study, the contributions of phenolic groups and C-H bonds to the antioxidant properties of 13 flavonoids were investigated by using the (RO)B3LYP/6-311++G(2df,2p)//B3LYP/6-311G(d,p) model chemistry in the gas phase and water and ethanol solvents. It was found that the C-H bonds have lower bond dissociation energies than O-H bonds in the 4-carbonyl and/or 3-hydroxyl group containing flavonoids and hence define antioxidant activity. The HOO· radical scavenging of the selected flavonoids is also investigated in detail through the potential energy surface, natural bond orbitals, and kinetic calculations. It was found that the favored radical scavenging mechanism of the flavonoids is hydrogen atom transfer, with the gas phase rate constants in the range of 7.23 × 103-2.07 × 109 L·mol-1·s-1. The results suggest that the flavonoids, isomelacacidin, isoteracacidin, melacacidin, and teracacidin, have antioxidant properties as high as typical phenolic compounds such as quercetin, trans-resveratrol, trolox, and ascorbic acid.