Theoretical Study of Antioxidant and Prooxidant Potency of Protocatechuic Aldehyde.

In this study, the antioxidant and prooxidant potency of protocatechuic aldehyde (PCA) was evaluated using density functional theory (DFT). The potency of direct scavenging of hydroperoxyl (HOO) and lipid peroxyl radicals (modeled by vinyl peroxyl, HC=CHOO) involved in lipid peroxidation was estimated. The repair of oxidative damage in biomolecules (lipids, proteins and nucleic acids) and the prooxidant ability of PCA phenoxyl radicals were considered.

Coumarin -Acylhydrazone Derivatives: Green Synthesis and Antioxidant Potential-Experimental and Theoretical Study.

Coumarin -acylhydrazone derivatives were synthesized in the reaction of 3-acetylcoumarin and different benzohydrazides in the presence of molecular iodine as catalyst and at room temperature. All reactions were rapidly completed, and products were obtained in good to excellent yields. It is important to emphasize that four products were reported for the first time in this study.

A DFT Study on the Kinetics of HOO, CHOO, and O Scavenging by Quercetin and Flavonoid Catecholic Metabolites.

Reaction kinetics have been theoretically examined to ascertain the potency of quercetin () and flavonoid catecholic metabolites - in the inactivation of HOO, CHOO, and O under physiological conditions. In lipidic media, the koverallTST/Eck rate constants for the proton-coupled electron transfer (PCET) mechanism indicate the catecholic moiety of and - as the most important in HOO and CHOO scavenging. 5-(3,4-Dihydroxyphenyl)-γ-valerolactone () and alphitonin () are the most potent scavengers of HOO and CHOO, respectively.

DFT Study of the Direct Radical Scavenging Potency of Two Natural Catecholic Compounds.

To ascertain quercetin's and rooperol's potency of H-atom donation to CHOO and HOO, thermodynamics, kinetics and tunnelling, three forms of chemical reaction control, were theoretically examined. In lipid media, H-atom donation from quercetin's catecholic OH groups via the proton-coupled electron transfer (PCET) mechanism, is more relevant than from C-ring enolic moiety. Amongst rooperol's two catecholic moieties, H-atom donation from A-ring OH groups is favored.

Mactanamide and lariciresinol as radical scavengers and Fe ion chelators - A DFT study.

A DFT based kinetic study of OOH radical scavenging potency of mactanamide (MA) and lariciresinol (LA), two natural polyphenols, indicates their nearly equal potential via the proton coupled electron transfer (PCET) mechanism in lipid media. Contribution of C-H bond breaking to this potency is negligible compared to O-H bond breaking, contrary to recent claims. The predicted potency of both compounds is not sufficient to protect biological molecules from oxidative damage in lipid media.

Radical Scavenging Activity and Pharmacokinetic Properties of Coumarin-Hydroxybenzohydrazide Hybrids.

Free radicals often interact with vital proteins, violating their structure and inhibiting their activity. In previous studies, synthesis, characterisation, and the antioxidative properties of the five different coumarin derivatives have been investigated. In the tests of potential toxicity, all compounds exhibited low toxicity with significant antioxidative potential at the same time.

Theoretical Study of Radical Inactivation, LOX Inhibition, and Iron Chelation: The Role of Ferulic Acid in Skin Protection against UVA Induced Oxidative Stress.

Ferulic acid (FA) is used in skin formulations for protection against the damaging actions of the reactive oxygen species (ROS) produced by UVA radiation. Possible underlying protective mechanisms are not fully elucidated. By considering the kinetics of proton-coupled electron transfer (PCET) and radical-radical coupling (RRC) mechanisms, it appears that direct scavenging could be operative, providing that a high local concentration of FA is present at the place of OH generation.

Inhibitory activity of quercetin, its metabolite, and standard antiviral drugs towards enzymes essential for SARS-CoV-2: the role of acid-base equilibria.

The recently declared global pandemic of a new human coronavirus called SARS-CoV-2, which causes respiratory tract disease COVID-19, has reached worldwide resonance and global efforts are being made to look for possible cures. Sophisticated molecular docking software, as well as available protein sequence and structure information, offer the ability to test the inhibition of two important targets of SARS-CoV-2, furin (FUR) enzyme, and spike glycoprotein, or spike protein (SP), that are key to host cell adhesion and hijacking. The potential inhibitory effect and mechanism of action of acid-base forms of different antiviral drugs, dominant at physiological pH, chloroquine (CQ), hydroxychloroquine (HCQ), and cinanserin (CIN), which have been shown to be effective in the treatment of SARS-CoV-2 virus, is reported with the special emphasis on their relative abundances.

Antioxidative potential of ferulic acid phenoxyl radical.

The vast majority of previous studies dealing with antioxidant potency of (poly)phenols does not investigate the fate of phenoxyl radical obtained after single free radical scavenging. We investigated possible pathways of inactivation of ferulic acid phenoxyl radical (FAPR) using DFT method. Direct coupling with a set of 10 physiologically important free radicals, H-atom donation and dimerization were analysed by estimation of Gibbs free energy changes related to these processes.

Effects of conjugation metabolism on radical scavenging and transport properties of quercetin - In silico study.

Quercetin (Q) is a natural polyphenol with high radical scavenging capacity, but low in vivo bioavailability. It is extensively transformed by host phase II metabolism and microbiota. Herein, effects of major in vitro and in vivo conjugation transformations of Q on its radical scavenging capacity and human serum albumin (HSA) binding were studied by using appropriate computational approaches, DFT (U)B3LYP/6-31 + G(d,p) and molecular docking, respectively.

Experimental and theoretical elucidation of structural and antioxidant properties of vanillylmandelic acid and its carboxylate anion.

Vanillylmandelic acid (VMA), an important metabolite of catecholamines that is routinely screened as tumor marker, was investigated by the various spectroscopic techniques (IR, Raman, UV-Vis, antioxidant decolorization assay and NMR). Structures optimized by the employment of five common functionals (M05-2X, M06-2X, B3LYP, CAM-B3LYP, B3LYP-D3) were compared with the crystallographic data. The M05-2X functional reproduced the most reliable experimental bond lengths and angles (correlation coefficient >0.

Theoretical study of the thermodynamics of the mechanisms underlying antiradical activity of cinnamic acid derivatives.

The role of antiradical moieties (catechol, guaiacyl and carboxyl group) and molecular conformation in antioxidative potency of dihydrocaffeic acid (DHCA) and dihydroferulic acid (DHFA) was investigated by density functional theory (DFT) method. The thermodynamic preference of different reaction paths of double (2H/2e) free radical scavenging mechanisms was estimated. Antiradical potency of DHCA and DHFA was compared with that exerted by their unsaturated analogs - caffeic acid (CA) and ferulic acid (FA).

Importance of hydrogen bonding and aromaticity indices in QSAR modeling of the antioxidative capacity of selected (poly)phenolic antioxidants.

The quantitative structure-activity relationship (QSAR) models for predicting antioxidative capacity of 21 structurally similar natural and synthetic phenolic antioxidants was considered. The one-, two- and three-descriptor QSAR models were developed. For this purpose the literature data on the vitamin C equivalent antioxidative capacity (VCEAC) values were used as experimental descriptor of antioxidative capacity.

Free radical scavenging and COX-2 inhibition by simple colon metabolites of polyphenols: A theoretical approach.

Free radical scavenging and inhibitory potency against cyclooxygenase-2 (COX-2) by two abundant colon metabolites of polyphenols, i.e., 3-hydroxyphenylacetic acid (3-HPAA) and 4-hydroxyphenylpropionic acid (4-HPPA) were theoretically studied.

Free radical scavenging potency of quercetin catecholic colonic metabolites: Thermodynamics of 2H/2e processes.

Reaction energetics of the double (2H/2e), i.e., the first 1H/1e (catechol→ phenoxyl radical) and the second 1H/1e (phenoxyl radical→ quinone) free radical scavenging mechanisms of quercetin and its six colonic catecholic metabolites (caffeic acid, hydrocaffeic acid, homoprotocatechuic acid, protocatechuic acid, 4-methylcatechol, and catechol) were computationally studied using density functional theory, with the aim to estimate the antiradical potency of these molecules.

Towards an improved prediction of the free radical scavenging potency of flavonoids: the significance of double PCET mechanisms.

The 1H(+)/1e(-) and 2H(+)/2e(-) proton-coupled electron transfer (PCET) processes of free radical scavenging by flavonoids were theoretically studied for aqueous and lipid environments using the PM6 and PM7 methods. The results reported here indicate that the significant contribution of the second PCET mechanism, resulting in the formation of a quinone/quinone methide, effectively discriminates the active from inactive flavonoids. The predictive potency of descriptors related to the energetics of second PCET mechanisms (the second O-H bond dissociation enthalpy (BDE2) related to hydrogen atom transfer (HAT) mechanism, and the second electron transfer enthalpy (ETE2) related to sequential proton loss electron transfer (SPLET) mechanism) are superior to the currently used indices, which are related to the first 1H(+)/1e(-) processes, and could serve as primary descriptors in development of the QSAR (quantitative structure-activity relationships) of flavonoids.