Despite the intensive research on radical scavenging action of flavonoids, a systematic study of the thermochemistry for their mono-deprotonated species in aqueous solution is still missing. In this work, reaction enthalpies related to Sequential Proton-Loss Electron-Transfer (SPLET) mechanism were theoretically investigated for all mono-deprotonated forms of nine flavonoids: apigenin, luteolin, fisetin, kaempferol, quercetin, taxifolin, tricetin, tricin and cyanidin. Differences in reaction enthalpies of the first and the second depmtonation can be lower than 10 kJ mol(-1), when two successive deprotonations occur in different aromatic rings of the molecule. For neutral flavonoids, thermodynamically preferred deprotonation sites are 4'-OH and 7-OH groups. In cyanidin (cation in native form), preferred second deprotonation site is 5-OH group. In the case of the formation of the preferred dianions, reaction enthalpies of the second proton loss are not affected by the structural distinctions between the flavonoids. In aqueous solution, deprotonated flavonoids show higher tendency to enter SPLET mechanism in comparison to Hydrogen Atom Transfer (HAT) or electron transfer.

Very recently, a report on the antioxidant activity of flavonoids has appeared, where authors concluded that Hydrogen Atom Transfer mechanism represents the thermodynamically preferred mechanism in polar media (https://doi.org/10.1016/j.foodres.2018.11.018). Unfortunately, serious errors in the theoretical part of the paper led to incorrect conclusions. For six flavonols (galangin, kaempferol, quercetin, morin, myricetin, and fisetin), reaction enthalpies related to three mechanisms of the primary antioxidant action were computed. Based on the obtained results, the role of intramolecular hydrogen bonds (IHB) in the thermo-dynamics of the antioxidant effect is presented. Calculations and the role of solvation enthalpies of proton and electron in the determination of thermodynamically preferred mechanism is also briefly explained and discussed. The obtained results are in accordance with published works considering the Sequential Proton-Loss Electron-Transfer thermodynamically preferred reaction pathway.

Deprotonated polyphenolics exhibit different free radical scavenging activity than parent molecules. Therefore, this study is focused on the hydrogen atom transfer (HAT) from mono-deprotonated forms (phenoxide anions) of 16 flavonoids in terms of O-H bond dissociation enthalpies, BDE(A), using B3LYP/6-311++G** approach. Solvent (benzene and water) contribution is computed using integral equation formalism polarized continuum model, IEF-PCM. Obtained BDE(A) values are usually lower than BDEs of the parent species. In general, from the thermodynamic point of view, HAT from a phenoxide anion is favored to the electron transfer, i.e. formation of the phenoxy radical. For the studied environments, preferred radical anions are identified. Obtained results can contribute to the explanation of experimentally observed pH dependent antioxidant effect of polyphenolics. (C) 2016 Elsevier B.V. All rights reserved.

For the aromatic OH group in pyridoxine, pyridoxal, pyridoxamine (vitamin B6 components) and their metabolite pyridoxic acid, reaction enthalpies related to various mechanisms of primary antioxidant action, i.e. Hydrogen Atom Transfer (HAT), Single Electron Transfer-Proton Transfer (SET-PT) and Sequential Proton-Loss Electron-Transfer (SPLET) were investigated. B3LYP, M05-2X and M06-2X functionals were employed in this study. Two solvation models were used for the solution-phase calculations in benzene and water: integral equation formalism polarized continuum model, IEF-PCM, as well as newer SMD method. All computational approaches provide identical trends. Comparison of found results with data obtained previously for phenol, alpha-tocopherol and flavonols indicates that vitamin B6 may show weaker antioxidant effect than naturally occurring phenolic antioxidants. (C) 2015 Elsevier B.V. All rights reserved.

In this work, we have calculated bond dissociation enthalpies of selected C-H and O-H bonds in sterols using two semi-empirical quantum chemistry methods AM1 and PM3.

•The attention is focused on 7 naturally occurring sterols and 15 steroid nuclei.•OH and CH bond dissociation enthalpies are studied by DFT/B3LYP approach.•Investigated CH bonds are more labile than OH bonds.•Sterol nucleus is more susceptible to oxidation than side chain.

Flavonoids play important role in the scavenging of free radicals in biological systems. As the phenolic chain-breaking antioxidants they can act via three distinct mechanisms, namely hydrogen atom transfer (HAT), Single Electron Transfer-Proton Transfer (SET-PT) and Sequential Proton-Loss Electron-Transfer (SPLET). Therefore, it is inevitable to study the corresponding reaction enthalpies in solution-phase. For 10 naturally occurring flavonoids: apigenin, luteolin, fisetin, kaempferol, quercetin, epicatechin, taxifolin, tricetin, tricin and cyanidin, O-H bond dissociation enthalpies, ionization potentials, proton dissociation enthalpies, proton affinities and electron transfer enthalpies were investigated using IEF-PCM B3LYP/6-311++G** method in benzene and water in order to: (i) identify the thermodynamically preferred mechanism and OH group in the two solvents and (ii) describe the solvent effect on the homolytic and heterolytic cleavage of OH groups in studied flavonoids. (C) 2014 Elsevier B.V. All rights reserved.

We have performed Density Functional Theory B3LYP/6-311++G** calculations of reaction enthalpies of antioxidant action mechanisms for nine isoflavones. O-H bond dissociation enthalpies, ionization potentials, proton dissociation enthalpies, proton affinities and electron transfer enthalpies related to Hydrogen Atom Transfer (HAT), Single Electron Transfer-Proton Transfer (SET-PT) and Sequential Proton-Loss Electron-Transfer (SPLET) mechanisms were investigated in gas- and solution-phases. Studies on the radical scavenging ability of isoflavones, contrary to various flavonoids, are still scarce. Thus, understanding of its thermodynamics can be considered beneficial. The selection of isoflavones (daidzein, formononetin, genistein, biochanin A, prunetin, 6-hydroxydaidzein, glycitein, orobol and santal) enables us to evaluate the effects of various structural features, such as the presence of methoxy (4'-OMe, 6-OMe, 7-OMe) and hydroxy (3'-OH, 5-OH, 6-OH) groups, on studied reaction enthalpies. The obtained results show that HAT can be attributed predominantly to the B ring, while SPLET takes place preferentially in the A ring, as was also indicated in experimental works.

Abstract Although the electron transfer is a part of many important processes in biosystems that occur in the solution-phase, there is still no systematic theoretical study of the electron solvation enthalpies. The solvation enthalpies of the electron in different solvents of various polarities: benzene, toluene, acetone, methanol, ethanol, DMSO and water, are investigated. All calculations were performed by B3LYP, BHLYP and PBE approaches with aug-cc-pVDZ, aug-cc-pVTZ and aug-cc-pVQZ basis sets, using the Integral Equation Formalism Polarized Continuum Model (IEF-PCM). The calculations show that the B3LYP and PBE functionals provide similar results. With the exception of benzene, toluene and DMSO, the differences in values for all solvents are lower than 6 kJ mol-1. The BHLYP solvation enthalpies are higher by 20-25 kJ mol-1 than the B3LYP ones.

In this paper, the study of aniline and 42 para- and meta-substituted anilines is presented. Substituted anilines represent model compounds of primary antioxidants from the secondary aromatic amines group. They are also widely used in the various organic syntheses. Anilines and their radicals were studied using DFT/B3LYP, DFT/PBE0 and semi-empirical SCC-DFTB methods in order to assess the substituent effect on the N-H bond dissociation enthalpies (BDEs). Calculated BDEs for para-substituted anilines are in good agreement with available experimental results. Unfortunately, published data for meta-substituted anilines are still scarce. The two DFT methods describe the effect of substituents on BDEs satisfactorily, though Delta BDEs may be overestimated in the case of electron-donating substituents. In the case of para- substituents, dependence of Delta BDE values on Hammett constants is satisfactorily linear. For substituents in meta position, the linearity is worse. SCC-DFTB may provide less reliable substituent effect description. We found very good linearity of Delta BDE vs C-N bond length or its shortening after hydrogen atom abstraction for both, para- and meta-substituted anilines. For N-H BDE, these geometry parameters represent suitable substituent effect descriptors. (C) 2013 Elsevier B.V. All rights reserved.

Theoretical study of 2-phenylpyrrole molecule using various quantum-chemical approaches A systematic theoretical study of 2-phenylpyrrole (PhPy) is presented for its neutral and monocharged states. The calculations were performed using the semiempirical Austin Model 1 (AM1) method, ab initio Møller-Plesset perturbation theory up to the second-order (MP2), density functional theory (DFT) and its tight-binding approximation (DFTB+). The comparison of the obtained equilibrium geometries showed that the C—C bond lengths in the phenylene ring are practically identical for the neutral state. Electric charging leads to significant changes in the geometry with respect to the neutral state. The C—N bonds in PhPy are elongated and the negative charging produces the out-of-plane distortion of N—H bond from the aromatic ring plane. The anionic state of the investigated molecule is connected with a higher perturbation of bond length alternation in both rings in comparison to the cationic state. The vibrationaly broadened absorption spectra, based on the on-the-fly molecular dynamics (MD) simulations, are also presented and compared with experimental spectra. Although the DFTB+ method has the tendency to planarize the investigated molecular structure, the agreement of simulated absorption spectra based on the MD DFTB+ geometries with TD-DFT calculations is acceptable.

Phytosterols, as components of human diet, received much attention because of their cholesterol-lowering and antioxidant properties. We have theoretically studied sterols oxidation in terms of O–H and C–H bond dissociation enthalpies (BDE). In 17 Δ5- and Δ7-sterols, BDEs were obtained for reported sites of oxidation attack. Obtained results indicate that Δ7-sterols are more susceptible to oxidation attack in comparison to Δ5-sterols. In sterol nuclei, the lowest BDE was found for C7–H bond in Δ5-sterols and for C14–H in Δ7-sterols. When Δ5-sterol has a CC double bond in the side chain, the lowest BDEs are usually found for C–H bonds in α-positions to this bond. The homolytic cleavage of hydroxyl O–H bond requires larger energy in comparison to the studied C–H bonds. We have shown that the C–H bonds with lowest BDE values actually correspond to the dominant sites of oxidation attack.

Comprehensive study of three mechanisms of phenolic chain-breaking antioxidant action, i.e. hydrogen atom transfer (HAT), Single Electron Transfer–Proton Transfer (SET–PT) and Sequential Proton-Loss Electron-Transfer (SPLET), for eight naturally occurring flavonoids (polyphenols): apigenin, luteolin, fisetin, kaempferol, quercetin, epicatechin, taxifolin and cyanidin, is presented. Gas-phase OH bond dissociation enthalpies, ionization potentials, proton dissociation enthalpies, proton affinities and electron transfer enthalpies related to these mechanisms were investigated using B3LYP/6-311++G** method. Selection of flavonoids enables to evaluate the effects of various structural features, such as hydroxy groups (3′-OH, 3-OH, 5-OH), C2C3 double bond and C4O keto group, present in the molecules on studied reaction enthalpies. Lowest OH bond dissociation enthalpies (HAT) and proton affinities (SPLET) have been found mostly for 4′-OH groups at ring B. In the second step of SET–PT mechanism, formation of radicals at 4′-OH positions is also thermodynamically favored. However, for five flavonoids, lowest values of electron transfer enthalpies were found in rings A or C.

S—H Bond Dissociation Enthalpies in para- and meta-Substituted Thiophenols: Correlation with Thiophenolic C—S Bond Length For mono-substituted anilines, phenols, and thiophenols it has been found that N—H, O—H and S—H bond dissociation enthalpies (BDE) depend on Hammett constants approximately linearly. For substituents placed in meta position, linearity of found dependences is usually considerably worse in comparison to para-substituted molecules. Therefore, their applicability for prediction of changes in BDE using substituent Hammett constant may be limited. In this work, we have found that the length of thiophenolic C—S bond, R(C—S), or its shortening after hydrogen atom abstraction, ΔR(C—S), represent suitable descriptors of substituent induced changes in S—H BDE. For fifteen studied meta-substituted thiophenols, these geometry descriptors correlate with S—H BDEs considerably better than Hammett constants.

Photoinduced reactions of 9‐oxo‐6,9‐dihydro[1,2,5]selenadiazolo[3,4‐f]quinoline‐8‐carboxylic acid (SeQCA) were investigated in alkaline media (aqueous NaOH solutions) by electron paramagnetic resonance (EPR) spectroscopy, following the in situ formation of paramagnetic species. According to UV–Vis and nuclear magnetic resonance investigations, protonation (pH ≈ 11) and deprotonation (pH ≈ 13) of the imino hydrogen of the 4‐pyridone moiety has to be considered, reflected also in the different EPR spectra observed upon irradiation. Photoinduced generation of radicals was found only for carboxylate substituted SeQCA; other studied selenadiazoloquinolone derivatives, together with those substituted at the C(8) position (R = H, COOCH2CH3, COOCH3, COCH3 or CN), did not generate paramagnetic species during exposure. Consequently, photodecarboxylation was suggested as the decisive step, accompanied by the decomposition of the selenadiazole ring, resulting in the formation of ortho‐hydroxylate anions. EPR parameters elucidated from experimental EPR spectra obtained at pH ≈ 11 and pH ≈ 13 indicate the formation of oxygen‐centered radicals at the decarboxylated 4‐pyridone ring. EPR spin trapping experiments with nitromethane confirmed a very effective photoinduced electron transfer from all the selenadiazoloquinolones investigated. Copyright © 2011 John Wiley & Sons, Ltd.

The applicability of the semiempirical Self-Consistent Charge Density-Functional Based Tight Binding approach (SCC-DFTB) is tested and compared with the reference ab initio Møller–Plesset perturbation theory up to the second-order (MP2) and density functional theory (DFT). In this context, the calculations of 2-phenylthiophene and 2,2′-bithiophene molecules are presented with respect to the optimal geometries and torsional potentials. The vibrational broadenings of absorption spectra based on the combined on-the-fly molecular dynamics (MD) simulations were analyzed for the studied model molecules as well as for selected representative oligomeres or star-shaped molecules built from the thiophene and phenyl units. Our calculations showed that the SCC-DFTB method has the tendency to planarize the mutual distortion between the thiophene–thiophene or thiophene–phenyl units and to overestimate the energy barriers for perpendicular structures with respect to the benchmark MP2 and DFT results. The semiempirical TD-B3LYP//MD(SCC-DFTB) or ZINDO//MD(SCC-DFTB) simulations at a temperature of 300K produce narrower absorption spectroscopic bands comparing to the reference TD-B3LYP//MD(B3LYP) results. The temperature increase to 600K ensures the higher population of distorted MD(SCC-DFTB) geometries and consequently a more realistic shape of the absorption bands with respect to the internal vibrational and rotational modes.

The redox behavior of the series of 7-substituted 6-oxo-6,9-dihydro[1,2,5]selenadiazolo[3,4-h]quinolines and 8-substituted 9-oxo-6,9-dihydro[1,2,5]selenadiazolo[3,4-f]quinolines with R(7), R(8) = H, COOC(2)H(5), COOCH(3), COOH, COCH(3), and CN has been studied by in situ EPR and EPR/UV-vis spectroelectrochemistry in dimethylsulfoxide. All selenadiazoloquinolones undergo a one-electron reduction process to form the corresponding radical anions. Their stability strongly depends on substitution at the nitrogen atom of the 4-pyridone ring. The primary generated radical anions from N-ethyl-substituted quinolones are stable, whereas for the quinolones with imino hydrogen, the initial radical anions rapidly dimerize to produce unusually stable sigma-dimer (σ-dimer) dianions. These are reversibly oxidized to the initial compounds at potentials considerably less negative than the original reduction process in the back voltammetric scan. The dimer dianion can be further reduced to the stable paramagnetic dimer radical trianion in the region of the second reversible reduction step. The proposed complex reaction mechanism was confirmed by in situ EPR/UV-vis cyclovoltammetric experiments. The site of the dimerization in the σ-dimer and the mapping of the unpaired spin density both for radical anions and σ-dimer radical trianions with unusual unpaired spin distribution have been assigned by means of density functional theory calculations.

Newly synthesized derivatives of 6‐oxo‐6,9‐dihydro[1,2,5]selenadiazolo[3,4‐ h ]quinoline variously substituted at position 7 (R = H, COOH, COCH 3 , CN, COOC 2 H 5 and COOCH 3 ) are established in strongly alkaline aqueous solutions (0.1 M NaOH; pH ∼ 13) as N(9)‐deprotonated structures, but in less alkaline solutions (0.001 M NaOH; pH ∼ 11) the N(9)‐protonated oxo tautomeric forms dominate. Upon their anodic oxidation in alkaline solutions, the selenadiazole ring is replaced, forming instead the paramagnetic species analogous to the ortho semiquinone radical anions as monitored by in situ EPR spectroscopy. The quantum chemical calculations for two representative selenadiazoloquinolones (R = H and COOH) and their anodic oxidation products presented are in agreement with experiments. Copyright © 2011 John Wiley & Sons, Ltd.

In this article, we have studied para- and meta-substituted thiophenols in order to study the effect of various electron-donating and electron-withdrawing groups in the gas-phase and in the four solvents on the enthalpies of homolytic and heterolytic S–H bond cleavage. Reaction enthalpies related to hydrogen atom transfer (HAT), single electron transfer–proton transfer (SET–PT) mechanism and sequential proton loss electron transfer (SPLET) mechanisms were studied using B3LYP/6-311++G** method. Solvent contribution to the enthalpies was computed employing integral equation formalism IEF-PCM method. Obtained results were confronted with available experimental data. Besides, reaction enthalpies and substituent effects were compared with previously published data for phenols with identical group ofsubstituents. In studied environments, thermodynamically favored reaction pathway was determined.

A systematic comparative theoretical and spectroscopic study has been performed on a series of four recently prepared ethyl 4-oxoquinoline-3-carboxylate derivatives possessing a variety of biological activities. The most probable oxo- and hydroxy-tautomeric neutral molecular forms were identified using density functional theory (DFT). Vertical optical transitions were calculated for global minima using time-dependent version of DFT. Calculated spectra were compared with the experimental electronic spectra of quinolones measured in various aprotic solvents (toluene, acetonitrile, dimethylsulfoxide). Finally, the structures and spin density distributions of radical anions obtained upon photoinduced reduction of two nitro-substituted derivatives in titania suspension were deduced from the comparison of calculated isotropic hyperfine coupling constants with experimental data determined from EPR spectra.