Sequential Proton Loss Research Articles

Mechanism of Antiradical Activity of Coumarin-Trihydroxybenzohydrazide Derivatives: A Comprehensive Kinetic DFT Study.

As part of this study, the mechanisms of the antioxidant activity of previously synthesized coumarin-trihydrobenzohydrazine derivatives were investigated: (E)-2,4-dioxo-3-(1-(2-(2″,3″,4″-trihydroxybenzoyl)hydrazineyl)ethylidene)chroman-7-yl acetate (1) and (E)-2,4-dioxo-3-(1-(2-(3″,4″,5″-trihydroxybenzoyl)hydrazineyl)ethylidene)chroman-7-yl acetate (2). The capacity of the compounds to neutralize HO• was assessed by EPR spectroscopy. The standard mechanisms of antioxidant action, Hydrogen Atom Transfer (HAT), Sequential Proton Loss followed by Electron Transfer (SPLET), Single-Electron Transfer followed by Proton Transfer (SET-PT), and Radical Adduct/Coupling Formation (RAF/RCF) were examined using the QM-ORSA methodology. It was estimated that the newly synthesized compounds, under physiological conditions, exhibited antiradical activity via SPLET and RCF mechanisms. Based on the estimated overall rate constants (koverall), it can be concluded that 2 exhibited a greater antiradical capacity. The obtained values indicated a good correlation with the EPR spectroscopy results. Both compounds exhibit approximately 1.5 times more activity in comparison to the precursor compound used in the synthesis (gallic acid).

Mechanism of Antiradical Activity of Newly Synthesized 4,7-Dihydroxycoumarin Derivatives-Experimental and Kinetic DFT Study.

Coumarin derivatives have proven beneficial biological activities, but the mechanism of their radical scavenging potency is not fully understood. In this study, the antiradical capacity of two newly synthesized 4,7-dihydroxycoumarin derivatives: (E)-3-(1-((3-hydroxy-4-methoxyphenyl)amino)-ethylidene)-2,4-dioxochroman-7-yl acetate (A-3OH) and (E)-3-(1-((4-hydroxy-3-methoxyphenyl)amino)ethylidene)-2,4-dioxochroman-7-yl acetate (A-4OH) towards HO• were examined by Electron Paramagnetic Resonance (EPR) Spectroscopy and Density Functional Theory (DFT). The compounds were fully characterized by the elemental microanalysis, IR, and NMR spectroscopies. The effect of pH on the acid–base equilibria is separately discussed and the predominant species at the physiological pH were determined. Several common mechanisms (Hydrogen Atom Transfer (HAT), Single-Electron Transfer followed by Proton Transfer (SET-PT), Sequential Proton Loss followed by Electron Transfer (SPLET), Radical Adduct Formation (RAF), and Intramolecular Hydrogen Atom ion (iHAA)) of radical scavenging were investigated based on thermodynamic and kinetic parameters. EPR results indicated that both compounds significantly reduce the amount of present HO•. The results of the kinetic DFT study demonstrated that both compounds predominantly exhibit antiradical capacity through HAT and SPLET mechanisms. The estimated overall rate constants (koverall) proved that A-4OH shows better antioxidant capacity than A-3OH which is well-correlated with the results obtained by EPR measurement.

Free Radical Scavenging Activity of Dihydrocaffeic Acid: A Quantum Chemical Approach

Based on density functional theory (DFT), to investigate relationships between the antioxidant activity and structure of dihydrocaffeic acid, quantum chemical calculation is used. The optimized structures of the neutral, radical and ionic forms have been carried out by DFT-B3LYP method with the 6-311G(d,p) basis set. Reaction enthalpies related with the hydrogen atom transfer (HAT), single electron transfer proton transfer (SET-PT) and sequential proton loss and electron transfer (SPLET) were calculated in gas and water phase. The HOMO-LUMO energy gap, electron affinity, electronegativity, ionization energy, hardness, chemical potential, global softness and global electrophilicity were calculated by using the same level of theory. Surfaces with a molecular electrostatic potential (MEP) were studied to determine the reactive sites of dihydrocaffeic acid. The difference in energy between the donor and acceptor as well as the stabilization energy was determined through the natural bond orbital (NBO) analysis. The Fukui index (FI) based on electron density was employed to predict reaction sites. Reaction enthalpies are compared with previously published data for phenol and 3,4-dihydroxycinnamic acid.

Theoretical insights on the antioxidant activity of dihydrocaffeic acid

In this work, quantum chemical analysis have been done to study the structure and antioxidant activity (AA) of dihydrocaffeic acid (DHCA) based on the density functional theory (DFT). Structural optimization and thermochemical calculations of the neutral, radical and ionic forms of DHCA have been carried out by DFT-B3LYP/6-311G(d,p) approach. Systematic study of reaction enthalpies related with the hydrogen atom transfer (HAT), single electron transfer proton transfer (SET-PT) and sequential proton loss and electron transfer (SPLET) have also been calculated in gas and water. Global Molecular Descriptors (GMD) and Non-Linear Optical (NLO) properties have been calculated by using the same theory. The interaction between donors and acceptors and stabilization energy have been determined with the help of Natural Bond Orbital (NBO) tool.

Radical scavenging activity of hydroxycinnamic acids in polar and nonpolar solvents: A computational investigation

The aim of this work is to perform a computational study of the radical scavenging activity of a series of common hydroxycinnamic acids (HCAs) in polar and nonpolar solvents in order to rationalize the experimental order obtained in ethanol and to analyze the solvent effect on mechanism and radical scavenging capacity. The thermodynamics of the main mechanisms, namely, hydrogen atom transfer (HAT), sequential proton loss followed by electron transfer (SPLET), and single electron transfer followed by proton transfer (SET-PT) were investigated at the M05-2X/6-31[Formula: see text]G([Formula: see text]) level of theory using the SMD solvation model. This study shows that the SET-PT mechanism is disfavored in all media, whereas HAT is the most thermodynamically favored mechanism in gas phase and SPLET is the preferred reaction pathway in pentyl ethanoate, ethanol and water. The thermodynamically preferred site of antioxidant action and the radical scavenging order are predicted using the BDE[Formula: see text] and (PA[Formula: see text]ETE)[Formula: see text] descriptors corresponding to the HAT and SPLET mechanisms, respectively. The obtained results point out that the mechanism and the radical scavenging potency are influenced by solvent polarity and our predictions are in agreement with the experimental measurements performed in ethanol giving the following descending order: caffeic [Formula: see text] [Formula: see text] [Formula: see text]-coumaric acid. Our results also show that the ortho substitution of caffeic acid by strong electron donating groups leads to a notable increase of their radical scavenging activity and new potent HCA derivatives are designed.

ON THE THERMODYNAMICS OF ANTIOXIDANT ACTION OF NATURALLY OCCURRING HYDROXYDERIVATIVES OF CIS-CINNAMIC ACID

Antioxidant activity represents one of the important features of phenolic acids, such as hydroxyderivatives of cinnamic acid. However, in the case of cis-cinnamic acid derivatives, corresponding thermochemistry data can be still considered scarce. This work is focused on the two most relevant mechanisms of primary antioxidant action in gas-phase, non-polar benzene and in aqueous solution. Reaction enthalpies describing thermodynamics of Hydrogen Atom Transfer (HAT) and Sequential Proton-Loss – Electron Transfer (SPLET) mechanisms were theoretically investigated using (SMD) M06-2X/6-311++G(d,p) method for cis-ortho-coumaric, cis-meta-coumaric, cis-para-coumaric, cis-ferulic, cis-sinapic and cis-caffeic acid and their carboxylate anions. The effect of carboxyl COOH group deprotonation on the thermodynamics of studied mechanisms was assessed for the three environments.

Identification of flavanones from Boesenbergia rotunda as potential antioxidants and monoamine oxidase B inhibitors

Boesenbergia rotunda is a ginger species with great medicinal importance. In this study, two flavanones found in B. rotunda namely pinocembrin and pinostrobin are analyzed for their antioxidant activity and monoamine oxidase inhibition. Frontier molecular orbitals and molecular electrostatic potential were analyzed to understand the electronic properties of these molecules. Quantum chemical descriptors gave an indication that these are potential antioxidant molecules. Mechanism of antioxidant activity was explored using Density Functional Theory (DFT) and was found to be hydrogen atom transfer (HAT) in the gaseous state and in non-polar medium and sequential proton loss and electron transfer (SPLET) in polar medium. Monoamine oxidase B (MAOB) is an important target in the treatment of Parkinson’s disease. Molecular docking studies conducted on these molecules show that they can dock well into the active site monoamine oxidase B. These molecules playing dual role as antioxidants and monoamine oxidase B inhibitors can be considered as good candidates for the treatment of Parkinson’s disease.

Comparative study on the free radical scavenging mechanism exerted by geraniol and geranylacetone using the combined experimental and theoretical approach

AbstractIn the current study the free radical scavenging mechanism of geraniol and geranylacetone has been investigated experimentally and theoretically. Two fragrant acyclic terpenoids were subjected to the ABTS and DPPH assay. Furthermore, the detailed quantum chemical calculations have been undertaken in order to evaluate the possible pathways underlying the radical scavenging activity of selected compounds in the non‐polar and polar media. The density functional theory (DFT) using the hybrid Becke three‐parameter exchange‐correlation functional (B3LYP) was applied. In general both investigated compounds possessed very weak anti‐radical activity at the applied experimental conditions but geranylacetone was significantly more effective as a ABTS•+ and DPPH• scavenger than geraniol. The comparison of DFT‐predicted reaction enthalpies associated with the hydrogen atom transfer mechanism (HAT), the single electron and proton transfer process (SET‐PT) and the sequential proton loss electron‐transfer (SPLET), revealed that the former mechanism should be favoured in geraniol solvated in both the non‐polar and polar media. On the contrary, an anti‐radical activity of geranylacetone in the non‐polar solvent was ascribed to the hydrogen donation mechanism while in the polar solvent it was assigned to the SPLET. According to the computational results the presence of allylic H‐atom (at the position 1C) close to the –OH group seemed to be essential for the observed anti‐radical activity of geraniol. The scavenging ability of geranylacetone was associated with the presence of both allylic and alkylic hydrogens in the close vicinity of the carbonyl functionality. Copyright © 2015 John Wiley & Sons, Ltd.

Antioxidant activities of cysteine derivatives against lipid oxidation in anhydrous media.

This study investigated antioxidant activities of cysteine derivatives of amino and carboxylic acid moieties against lipid oxidation in anhydrous acetonitrile. Only cysteine derivatives bearing free amino or carboxylate ion were found to exert potent antioxidant activities. Sequential proton loss and electron transfer-like proton shift and subsequent electron transfer (PS-ET) mechanism may facilitate the antioxidant activities of cysteine derivatives against lipid oxidation in anhydrous media.

Hydration Preferences for Mn4Ca Cluster Models of Photosystem II: Location of Potential Substrate–Water Binding Sites

Density functional theory calculations are reported on a set of three model structures of the Mn(4)Ca cluster in the water-oxidizing complex of Photosystem II (PSII), which share the structural formula [CaMn(4)C(9)H(10)N(2)O(16)](q+)·(H(2)O)(n) (q=-1, 0, 1, 2, 3; n=0-7). In these calculations we have explored the preferred hydration sites of the Mn(4)Ca cluster across five overall oxidation states (S(0) to S(4)) and all feasible magnetic-coupling arrangements to identify the most likely substrate-water binding sites. We have also explored charge-compensated structures in which the overall charge on the cluster is maintained at q=0 or +1, which is consistent with the experimental data on sequential proton loss in the real system. The three model structures have skeletal arrangements that are strongly reminiscent, in their relative metal-atom positions, of the 2.9-, 3.7-, and 3.5 Å-resolution crystal structures, respectively, whereas the charge states encompassed in our study correspond to an assignment of (Mn(III))(3)Mn(II) for S(0) and up to (Mn(IV))(3)Mn(III) for S(4). The three models differ principally in terms of the spatial relationship between one Mn (Mn(4)) and a generally robust Mn(3)Ca tetrahedron that contains Mn(1), Mn(2), and Mn(3). Oxidation-state distributions across the four manganese atoms, in most of the explored charge states, are dependent on details of the cluster geometry, on the extent of assumed hydration of the clusters, and in some instances on the imposed magnetic-coupling between adjacent Mn atoms. The strongest water-binding sites are generally those on Mn(4) and Ca. However, one structure type displays a high-affinity binding site between Ca and Mn(3), the S-state-dependent binding-energy pattern of which is most consistent with the substrate water-exchange kinetics observed in functional PSII. This structure type also permits another water molecule to access the cluster in a manner consistent with the substrate-water interaction with the Mn cluster, seen in electron spin-echo envelope modulation (ESEEM) studies of the functional enzyme in the S(0) and S(2) states. It also rationalizes the significant differences in hydrogen-bonding interactions of the substrate water observed in the FTIR measurements of the S(1) and S(2) states. We suggest that these two water-binding sites, which are molecularly close, model the actual substrate-binding sites in the enzyme.