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.

The radical scavenging activity of glycozolidol in physiological environments: a quantum chemical study.

Glycozolidol was isolated from the root of Glycosmis pentaphylla (6-hydroxy-2-methoxy-3-methylcarbazole, GLD). This molecule attracted considerable interest due to its beneficial biological activities that likely stem from its antioxidant activity; yet, the radical scavenging action of GLD has not been investigated thus far. In this study, DFT calculations were used to estimate the radical scavenging activity of GLD against a variety of biologically significant radical species in physiological environments. The findings demonstrated that GLD exerts significant antiradical activity in water at pH = 7.40 and in pentyl ethanoate (as a model of lipidic media) with k overall = 8.23 × 106 and 3.53 × 104 M-1 s-1, respectively. In aqueous solution, the sequential proton-loss electron transfer mechanism made the highest contribution to the activity, whereas in nonpolar solvents the formal hydrogen transfer mechanism dominated the activity. GLD is predicted to have strong antiradical activity against CH3O˙, CH3OO˙, CCl3OO˙, NO2, SO4˙-, DPPH and ABTS+˙ k app ≈ 109 M-1 s-1 and k f ≈ 106 M-1 s-1. The results suggest that GLD is a good radical scavenger in physiological environments.

Theoretical insights into the antiradical activity and copper-catalysed oxidative damage of mexidol in the physiological environment.

Mexidol (MD, 2-ethyl-6-methyl-3-hydroxypyridine) is a registered therapeutic agent for the treatment of anxiety disorders. The chemical structure suggests that MD may also act as an antioxidant. In this study, the hydroperoxyl radical scavenging activity of MD was studied to establish baseline antioxidant activity, followed by an investigation of the effect of MD on the copper-catalysed oxidative damage in biological systems, using computational methods. It was found that MD exhibits moderate radical scavenging activity against HOO• in water and pentyl ethanoate solvents following the single electron transfer and formal hydrogen transfer mechanisms, respectively. MD can chelate Cu(II), forming complexes that are much harder to reduce than free Cu(II): MD chelation completely quenches the Cu(II) reduction by ascorbic acid and suppresses the rate of reduction reaction by O 2 ⋅ - that are the main reductants of Cu(II) in biological environments. Therefore, MD exerts its anti-HO• activity primarily as an OIL-1 inhibitor.

Is Usnic Acid a Promising Radical Scavenger?

Usnic acid (UA) is a natural product found in the lichen genera. Because of the phenolic groups in its structure, UA is suspected to be an antioxidant. Therefore, in this study, the radical scavenging of UA was investigated in physiological environments in silico by using kinetic calculations. It was found that the overall rate constant for the hydroxyl radical scavenging activity was approximately 109 M-1 s-1 in all environments, whereas the HOO• and CH3OO• radical scavenging activities were only significant in the polar environments with k in the range of 103-104 M-1 s-1. The results also revealed that the HO• scavenging activity followed the single electron transfer (SET) and radical adduct formation mechanisms; however, the SET pathway (for the dianion HU2-) played a dominant role in the scavenging of other studied radicals, including CH3O•, CCl3O•, CCl3OO•, NO2, SO4 •-, and N3 •. The activity of UA against these radicals was as high as that of typical phenolic acids such as ferulic acid, p-coumaric acid, caffeic acid, dihydrocaffeic acid, and sinapinic acid (k f ∼ 108 M-1 s-1) in polar solvents. Thus, UA is a promising natural antioxidant in aqueous environments.

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.

A coumarin derivative-Cu2+ complex-based fluorescent chemosensor for detection of biothiols.

Herein, a novel fluorescent sensor has been developed for the detection of biothiols based on theoretical calculations of the stability constant of the complex between a Cu2+ ion and (E)-3-((2-(benzo[d]thiazol-2-yl)hydrazono)methyl)-7-(diethylamino) coumarin (BDC) as a fluorescent ligand. In this study, on the basis of density functional theory method, the Gibbs free energy of ligand-exchange reaction and the solvation model were carried out using thermodynamic cycles. The obtained results are in good agreement with the experimental data. The BDC-Cu2+ complex can be used as a fluorescent sensor for the detection of biothiols in the presence of non-thiol containing amino acids, with a detection limit for cysteine at 0.3 µM. Moreover, theoretical calculations of excited states were used to elucidate variations in the fluorescence properties. The computed results show that the excited doublet states D2 and D1 are dark doublet states, which quench the fluorescence of the complex.

Hydroxyl Radical Scavenging of Indole-3-Carbinol: A Mechanistic and Kinetic Study.

Indole-3-carbinol (I3C) is the product of the enzymatic hydrolysis of glucobrassicin in the human body. I3C exhibits diverse bioactivities. It is used as a supplement to enhance the efficiency of some cancer therapies and is available as an over-the-counter dietary supplement described as a potential antioxidant, among other health benefits. Thus, it is important to develop an in-depth understanding of its antioxidant activity. In this study, the hydroxyl radical scavenging of I3C has been investigated in silico under physiologically relevant conditions (aqueous and lipid-mimetic pentyl ethanoate environment) using thermochemical and kinetic calculations. For benchmarking purposes, the results were compared to known experimental data. The overall reaction rate constant of the HO• radical scavenging of I3C in water was found to be 2.30 × 1010 M-1 s-1 and over two times lower in lipid-mimetic pentyl ethanoate solvent at 7.74 × 109 M-1 s-1. The results also highlighted that the HO• radical scavenging follows almost exclusively the radical adduct formation mechanism (>94%) in a lipid mimetic medium, whereas this mechanism contributes about 60% in aqueous environments. I3C is considered a dopamine-like antioxidant, its main function being prevention of oxidative degradation of lipids; our study supports this view.

Antioxidant Activities of Monosubstituted Indolinonic Hydroxylamines: A Thermodynamic and Kinetic Study.

Indolinonic hydroxylamine (IH) is known as a potential artificial antioxidant in apolar environments. Here, a library of 108 monosubstituted derivatives was screened in silico to identify a lead compound for increased antioxidant activity, following a strategy of shortlisting based on thermochemical and kinetic properties. It was found that the presence of substituents at the 2, 4, and 7 positions increased, while substituents in other positions decreased the BDE(O-H) values, in good correlation to the electron-donating ability of substituents. Among the studied compounds, the N and 5 amine-substituted derivatives have the lowest BDE(O-H) values (62.4-64.0 kcal mol-1). The presence of the strong electron-withdrawing substituents can decrease the proton affinities of the derivatives, whereas the decrease of ionization energies correlates to the electron-donating ability of the substituents. It was also found that the formal hydrogen transfer (FHT) mechanism is the favored pathway for the HOO· radical scavenging. Kinetic calculations showed that the rate constant of the reaction between N-NHMe-IH compound and HOO· radical following the FHT mechanism (k = 3.00 × 107 M-1 s-1) is about 8223 and 5253 times higher than those of Trolox and ascorbic acid, respectively, in the pentyl ethanoate solvent. Thus, N-NHMe-IH is expected to be the most powerful antioxidant reported to date in lipid environments.

Is Indolinonic Hydroxylamine a Promising Artificial Antioxidant?

Indolinonic hydroxylamine (IH) is a new-generation artificial antioxidant that, due to its ability to fractionate into apolar environments, is considered for prevention against lipid peroxidation. For this reason, it is important to understand, and compare, its activity in polar and nonpolar environments. In this study, the antioxidant activity of IH has been evaluated against HO• and HOO• radicals in water and, for a lipid-mimetic environment, pentyl ethanoate solvent, using kinetic calculations. It was found that the overall reaction rate constant of the HO• radical scavenging is more than 7 times higher in aqueous (8.98 × 109 M-1 s-1) than in apolar (1.22 × 109 M-1 s-1) media. However, HOO• scavenging was 35 times faster in apolar media (1.00 × 105 M-1 s-1 vs 2.80 × 103 M-1 s-1). In a lipid environment, the HAT mechanism was favored for the antioxidant activity for both radical species, whereas in aqueous solution the SET mechanism defined the HO• scavenging, while HAT described the HOO• scavenging. IH was shown to be one of the most active antioxidants in lipid environment, an essential characteristic for the protection of biological systems.

Author Correction: Density functional theory study of the role of benzylic hydrogen atoms in the antioxidant properties of lignans.

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