Radical scavenging activity of bromophenol analogs: analysis of kinetics and mechanisms.

Context: This theoretical study explores the antioxidant activity of five bromophenol analogs, with a particular focus on their interaction with different solvent environments of varying polarities. Key findings include the correlation between increased solvent polarity and enhanced antioxidant activity of these analogs, comparable in some instances to ascorbic acid. Notably, compound 5, developed by our research team, demonstrates superior antioxidant activity in both lipid and aqueous solutions, surpassing that of ascorbic acid and other tested analogs.

Strategic design, theoretical insights, synthesis, and unveiling antioxidant potential in a novel ascorbic acid analog.

Context: In this study, we investigated the antioxidant potential of a novel ascorbic acid analog, DsD, assessing its interactions with the methylperoxyl (CH3OO·) radical in aqueous and lipid environments. Our focus was on understanding the acid-base equilibrium and how pH affects DsD's primary reaction mechanisms. Our findings indicate a marked preference for hydrogen atom transfer in lipid media, contrasting with sequential proton loss electron transfer (SPLET) in aqueous solutions.

Role of Imidazole and Chelate Ring Size in Copper Oxidation Catalysts: An Experimental and Theoretical Study.

In this work, the structural, solution, electrochemical, and catalytic properties of the complexes with ligands derived from imidazole and pyridines were studied. A comparative study of five bioinspired copper catalysts with or without coordinated imidazole and with different chelate ring sizes is presented. Catalytic efficiency on the oxidation of 3,5-di-butylcatechol (DTBC) and -aminophenol (OAP) in a MeOH/HO medium was assessed by means of the Michaelis-Menten model.

Functional impact and molecular binding modes of drugs that target the PI3K isoform p110δ.

Targeting the PI3K isoform p110δ against B cell malignancies is at the mainstay of PI3K inhibitor (PI3Ki) development. Therefore, we generated isogenic cell lines, which express wild type or mutant p110δ, for assessing the potency, isoform-selectivity and molecular interactions of various PI3Ki chemotypes. The affinity pocket mutation I777M maintains p110δ activity in the presence of idelalisib, as indicated by intracellular AKT phosphorylation, and rescues cell functions such as p110δ-dependent cell viability.

The Synergy between Glutathione and Phenols-Phenolic Antioxidants Repair Glutathione: Closing the Virtuous Circle-A Theoretical Insight.

Glutathione (GSH) and phenols are well-known antioxidants, and previous research has suggested that their combination can enhance antioxidant activity. In this study, we used Quantum Chemistry and computational kinetics to investigate how this synergy occurs and elucidate the underlying reaction mechanisms. Our results showed that phenolic antioxidants could repair GSH through sequential proton loss electron transfer (SPLET) in aqueous media, with rate constants ranging from 3.

Chemical repair of damaged leucine and tryptophane by thiophenols at close to diffusion-controlled rates: Mechanisms and kinetics.

Thiophenols are chemical species with multiple desirable biological properties, including their primary and secondary antioxidant capacity. In this work, the repairing antioxidant activity of eight different thiophenols has been investigated for damaged leucine and tryptophane. The investigation was carried out employing quantum mechanical and transition state methods to calculate the thermodynamic and kinetic data of the reactions involved, while simulating the biological conditions at physiological pH and aqueous and lipidic medium.

Computationally Designed Sesamol Derivatives Proposed as Potent Antioxidants.

Oxidative stress has been recognized to play an important role in several diseases, such as Parkinson's and Alzheimer's disease, which justifies the beneficial effects of antioxidants in ameliorating the deleterious effects of these health disorders. Sesamol, in particular, has been investigated for the treatment of several conditions because of its antioxidant properties. This article reports a rational computational design of new sesamol derivatives.

The Antioxidant Capability of Higenamine: Insights from Theory.

Density functional theory was employed to highlight the antioxidant working mechanism of higenamine in aqueous and lipid-like environments. Different reaction mechanisms were considered for the reaction of higenamine with the OOH radical. The pH values and the molar fraction at physiological pH were determined in aqueous solution.

Thiophenols, Promising Scavengers of Peroxyl Radicals: Mechanisms and kinetics.

The activity of 12 thiophenols as primary antioxidants in aqueous solution has been studied using density functional theory. Twelve different substituted thiophenols were tested as peroxyl radicals scavengers. Single electron transfer (SET) and formal hydrogen transfer (FHT) were investigated.

The other side of the superoxide radical anion: its ability to chemically repair DNA oxidized sites.

The superoxide radical anion can repair oxidative damage. In particular, it was demonstrated that O2˙- can repair oxidized DNA by electron transfer, restoring the original structure of this important molecule. Acid-base equilibria have been considered, and the influence of the pH on the main reaction mechanism has been explored.

Melatonin and its metabolites as chemical agents capable of directly repairing oxidized DNA.

Oxidative stress mediates chemical damage to DNA yielding a wide variety of products. In this work, the potential capability of melatonin and several of its metabolites to repair directly (chemically) oxidative lesions in DNA was explored. It was found that all the investigated molecules are capable of repairing guanine-centered radical cations by electron transfer at very high rates, that is, diffusion-limited.

Chemical Insights into the Antioxidant Mechanisms of Alkylseleno and Alkyltelluro Phenols: Periodic Relatives Behaving Differently.

The possible antioxidant reaction mechanisms of recently synthesized and tested alkylseleno (telluro) phenols have been explored using density functional theory by considering two solvents physiologically relevant, water and pentylethanoate (PE). In addition, the possible pathway for the antioxidant regeneration with ascorbic acid has been investigated. Results show that selenium and tellurium systems follow different chemical behaviors.

The role of acid-base equilibria in formal hydrogen transfer reactions: tryptophan radical repair by uric acid as a paradigmatic case.

The results presented in this work demonstrate the high complexity of chemical reactions involving species with multiple acid-base equilibria. For the case study investigated here, it was necessary to consider two radical species for tryptophan (Trp˙ and Trp˙) and three fractions for uric acid (HUr, HUr and HUr) in order to properly reproduce the experimental results. At pH = 7.

Empirically Fitted Parameters for Calculating pKa Values with Small Deviations from Experiments Using a Simple Computational Strategy.

Two empirically fitted parameters have been derived for 74 levels of theory. They allow fast and reliable pKa calculations using only the Gibbs energy difference between an acid and its conjugated base in aqueous solution (ΔGs(BA)). The parameters were obtained by least-squares fits of ΔGs(BA) vs experimental pKa values for phenols, carboxylic acids, and amines using training sets of 20 molecules for each chemical family.

Assessing the Protective Activity of a Recently Discovered Phenolic Compound against Oxidative Stress Using Computational Chemistry.

The protection exerted by 3,5-dihydroxy-4-methoxybenzyl alcohol (DHMBA), a phenolic compound recently isolated from the Pacific oyster, against oxidative stress (OS) is investigated using the density functional theory. Our results indicate that DHMBA is an outstanding peroxyl radical scavenger, being about 15 times and 4 orders of magnitude better than Trolox for that purpose in lipid and aqueous media, respectively. It was also found to react faster with HOO(•) than other known antioxidants such as resveratrol and ascorbic acid.

Hydrogen Abstraction Reactions from Phenolic Compounds by Peroxyl Radicals: Multireference Character and Density Functional Theory Rate Constants.

An assessment of multireference character in transition states is considered to be an important component in establishing the expected reliability of various electronic structure methods. In the present work, the multireference characters of the transition states and the forming and breaking of bonds for a large set of hydrogen abstraction reactions from phenolic compounds by peroxyl radicals have been analyzed using the T1, M, B1, and GB1 diagnostics. The extent of multireference character depends on the system and on the conditions under which the reaction takes place, and some systematic trends are observed.

Free-radical scavenging by tryptophan and its metabolites through electron transfer based processes.

Free-radical scavenging by tryptophan and eight of its metabolites through electron transfer was investigated in aqueous solution at physiological pH, using density functional theory and the Marcus theory. A test set of 30 free radicals was employed. Thermochemical and kinetic data on the corresponding reactions are provided here for the first time.

Kinetics of radical-molecule reactions in aqueous solution: a benchmark study of the performance of density functional methods.

The performance of 18 density functional approximations has been tested for a very challenging task, the calculations of rate constants for radical-molecule reactions in aqueous solution. Despite of the many difficulties involved in such an enterprise, six of them provide high quality results, and are recommended to that purpose. They are LC-ωPBE, M06-2X, BMK, B2PLYP, M05-2X, and MN12SX, in that order.

Theoretical study on the peroxyl radicals scavenging activity of esculetin and its regeneration in aqueous solution.

The study of the ˙OOH, ˙OOCH3 and ˙OOCHCH2 radicals scavenging processes by esculetin (ES) was carried out in aqueous and lipid media, using the density functional theory. Three reaction mechanisms were considered: single electron transfer (SET), hydrogen transfer (HT) and radical adduct formation (RAF). Rate constants and branching ratios for the different paths are reported.

A computational methodology for accurate predictions of rate constants in solution: application to the assessment of primary antioxidant activity.

The accurate prediction of rate constants for chemical reactions in solution, using computational methods, is a challenging task. In this work, a computational protocol designed to be a reliable tool in the study of radical-molecule reactions in solution is presented. It is referred to as quantum mechanics-based test for overall free radical scavenging activity (QM-ORSA) because it is mainly intended to provide a universal and quantitative way of evaluating the free radical scavenging activity of chemical compounds.

Antioxidant activity of propyl gallate in aqueous and lipid media: a theoretical study.

In this work, we have carried out a quantum chemistry and computational kinetics study on the reactivity of propyl gallate towards ˙OOH, ˙OOCH3 and ˙OOCHCH2 radicals, in aqueous and lipid media. We have considered three reaction mechanisms: hydrogen transfer (HT), radical adduct formation (RAF) and single electron transfer (SET). Rate constants and relative branching ratios for the different paths contributing to the overall reaction, at 298.

On the chemical repair of DNA radicals by glutathione: hydrogen vs electron transfer.

The chemical repair of radical-damaged DNA by glutathione in aqueous solution has been studied using density functional theory. Two main mechanisms were investigated: the single electron transfer (SET) and the hydrogen transfer (HT). Glutathione was found to repair radical damaged DNA by HT from the thiol group with rate constants that are close to the diffusion-limited regime, which means that the process is fast enough for repairing the damage before replication and therefore for preventing permanent DNA damage.

On the evolution of one-electron-oxidized deoxyguanosine in damaged DNA under physiological conditions: a DFT and ONIOM study on proton transfer and equilibrium.

Different deprotonation paths of the radical cation formed by one-electron oxidation of 2'-deoxyguanosine (2dG) sites in DNA have been studied using Density Functional Theory (M05-2X/6-31+G(d,p)) and ONIOM methodology (M05-2X/6-31+G(d,p):PM6) in conjunction with the SMD model to include the solvent effects. Models of increased complexity have been used ranging from the isolated nucleoside to a three unit double-stranded oligomer including the sugar units, the base pairing with cytidine, and the phosphate linkage. The reported results correspond to aqueous solution, at room temperature, and pH = 7.

Influence of the environment on the protective effects of guaiacol derivatives against oxidative stress: mechanisms, kinetics, and relative antioxidant activity.

The peroxyl radical scavenging activity of five guaiacol derivatives (GD) has been studied in nonpolar and aqueous solutions, using the density functional theory. The studied GD are guaiacol, vanillin, vanillic alcohol, vanillic acid, and eugenol. It was found that the environment plays an important role in the peroxyl scavenging activity of these compounds.