Reinvestigation of Acetophenones Oxidation by Performic Acid in Formic Acid.

The Baeyer-Villiger (BV) reaction of acetophenones R-COCH3 (R = phenyl, 4-methylphenyl, 3,4-dimethoxyphenyl) with performic acid (PFA) in formic acid (FA) as the catalyst and solvent was reinvestigated using the MPWB1K functional in conjunction with the 6-311G(d,p) and 6-311++G(d,p) basis sets. For the acid-catalyzed addition step, we used the eight-membered ring transition structure proposed in our previous work. The calculated and experimental results obtained for the BV reaction under the mentioned conditions lead to the conclusion that our mechanism is more reliable than the one reported by Liu and co-workers, in which the acid-catalyzed first step involves a transition state with a six-membered ring structure.

Comprehensive Investigation of the Antioxidant and Pro-oxidant Effects of Phenolic Compounds: A Double-Edged Sword in the Context of Oxidative Stress?

Oxidative stress (OS) is a health-threatening process that is involved, at least partially, in the development of several diseases. Although antioxidants can be used as a chemical defense against OS, they might also exhibit pro-oxidant effects, depending on environmental conditions. In this work, such a dual behavior was investigated for phenolic compounds (PhCs) within the framework of the density functional theory and based on kinetic data. Multiple reaction mechanisms were considered in both cases. The presence of redox metals, the pH, and the possibility that PhCs might be transformed into benzoquinones were identified as key aspects in the antioxidant versus pro-oxidant effects of these compounds. The main virtues of PhCs as antioxidants are their radical trapping activity, their regeneration under physiological conditions, and their behavior as OH-inactivating ligands. The main risks of PhCs as pro-oxidants are predicted to be the role of phenolate ions in the reduction of metal ions, which can promote Fenton-like reactions, and the formation of benzoquinones that might cause protein arylation at cysteine sites. Although the benefits seem to overcome the hazards, to properly design chemical strategies against OS using PhCs, it is highly recommended to carefully explore their duality in this context.

Theoretical Study of the Reactivity and Selectivity of Various Free Radicals with Cysteine Residues.

Radicals in biochemical environments can lead to protein damage. Theoretical studies can help us to understand the observed radical selectivity. In this work, the kinetics and thermodynamics of the hydrogen-transfer (HT) and single-electron transfer (SET) reactions between a cysteine derivative and 17 free radicals of biological significance have been theoretically investigated in aqueous and lipid media. With the exception of the reaction with •OCCl3, all SET reactions in aqueous medium have rate constants in the diffusion-limited regime. The γ site of cysteine was found to be the most reactive for the HT reactions with all the radicals, with rate constants in the diffusion limit for •OH, •OCHCl2, and •OCCl3. The HT reactions from the α and γ positions have very similar ΔG° values and even though the ß position is the least thermodynamically favored, when the HT from ß is exergonic it is a more reactive site than α. The results obtained confirm that the Bell-Evans-Polanyi principle does not apply to the reactions between amino acid residues and free radicals and that reactivity comparisons demand proper kinetic calculations.

Radical-trapping and preventive antioxidant effects of 2-hydroxymelatonin and 4-hydroxymelatonin: Contributions to the melatonin protection against oxidative stress.

BACKGROUND: Melatonin is well known for its antioxidant capacity, which has been attributed to the combined protective effects of the parent molecule and its metabolites. However, the potential role of 2-hydroxymelatonin (2OHM) and 4-hydroxymelatonin (4OHM) in such protection has not been previously investigated. METHODS: The calculations were performed using the Density Functional Theory, with the M05-2X and M05 functionals, the 6-311+G(d,p) basis set and the solvation model based on density (SMD). RESULTS: 4OHM shows excellent antioxidant activity via radical-trapping, reacting with peroxyl radicals faster than Trolox and melatonin. 4OHM can be moderately efficient as a preventing antioxidant by inhibiting Cu(II). This effect would lower the Cu(I) availability, which is the redox state required for the OH to be formed, via Fenton-like reactions. 4OHM turns off the oxidant effects of copper-ascorbate mixtures. The presence of a phenolic group was identified as the key structural feature in the antioxidant activity of 4OHM. On the other hand, 2OHM does not present a phenolic group, despite its formal name. Its keto tautomer was identified as the most abundant one (~100%). This may explain the relative low antioxidant protection of 2OHM. CONCLUSIONS: 4OHM significantly contributes to the overall antioxidant activity exhibited by melatonin, while the effects of 2OHM in this context are predicted to be only minor. This low reactivity might justify the relatively large abundance of 2OHM in biological systems. GENERAL SIGNIFICANCE: Hydroxylated melatonin metabolites, such as 4OHM, may play an important role in the protective effects of melatonin against oxidative stress.

Food Antioxidants: Chemical Insights at the Molecular Level.

In this review, we briefly summarize the reliability of the density functional theory (DFT)-based methods to accurately predict the main antioxidant properties and the reaction mechanisms involved in the free radical-scavenging reactions of chemical compounds present in food. The analyzed properties are the bond dissociation energies, in particular those involving OH bonds, electron transfer enthalpies, adiabatic ionization potentials, and proton affinities. The reaction mechanisms are hydrogen-atom transfer, proton-coupled electron transfer, radical adduct formation, single electron transfer, sequential electron proton transfer, proton-loss electron transfer, and proton-loss hydrogen-atom transfer. Furthermore, the chelating ability of these compounds and its role in decreasing or inhibiting the oxidative stress induced by Fe(III) and Cu(II) are considered. Comparisons between theoretical and experimental data confirm that modern theoretical tools are not only able to explain controversial experimental facts but also to predict chemical behavior.

Lipoic acid and dihydrolipoic acid. A comprehensive theoretical study of their antioxidant activity supported by available experimental kinetic data.

The free radical scavenging activity of lipoic acid (LA) and dihydrolipoic acid (DHLA) has been studied in nonpolar and aqueous solutions, using the density functional theory and several oxygen centered radicals. It was found that lipoic acid is capable of scavenging only very reactive radicals, while the dehydrogenated form is an excellent scavenger via a hydrogen transfer mechanism. The environment plays an important role in the free radical scavenging activity of DHLA because in water it is deprotonated, and this enhances its activity. In particular, the reaction rate constant of DHLA in water with an HOO(•) radical is close to the diffusion limit. This has been explained on the basis of the strong H-bonding interactions found in the transition state, which involve the carboxylate moiety, and it might have implications for other biological systems in which this group is present.

A theoretical and experimental evaluation of imidazolium-based ionic liquids for atmospheric mercury capture.

In this work, the capacity of three different imidazolium-based ionic liquids (ILs) for atmospheric mercury capture has been evaluated. Theoretical calculations using monomer and dimer models of ILs showed that [BMIM]⁺[SCN]⁻ and [BMIM]⁺[Cl]⁻ ionic liquids capture gaseous Hg°, while [BMIM]⁺[PF6]⁻ shows no ability for this purpose. These findings are supported by experimental data obtained using particle induced X-ray emission (PIXE) trace element analysis. Experimental and theoretical infrared data of the ILs were obtained before and after exposure to Hg. In all cases, no displacement of the bands was observed, indicating that the interaction does not significantly affect the force constants of substrate bonds. This suggests that van der Waals forces are the main forces responsible for mercury capture. Since the anion-absorbate is the driving force of the interaction, the largest charge-volume ratio of [Cl]⁻ could explain the higher affinity for mercury sequestration of the [BMIM]⁺[Cl]⁻ salt.

Acid-catalyzed nucleophilic additions to carbonyl groups: is the accepted mechanism the rule or an exception?

The transesterification reaction, and in particular the methanolysis of ethyl acetate with sulfuric acid as catalyst, is used as a model reaction to study the acid-catalyzed nucleophilic addition to a carbonyl group. Continuum solvation methods (SMD and IEF-PCM) and the MPWB1K functional are used. The reaction mechanism is studied in methanol and in acetonitrile as solvents. Our results indicate that the acid-catalyzed addition mechanism is stepwise, and the transition state (TS) is a contact ion-pair. The counteranion of the acid catalyst remains in the reaction site playing an important role in the TS of this reaction. Changes in the reaction kinetics and the ionic/nonionic nature of the TS with the ionizing ability of the solvent and the strength of the acid catalyst are explored. Additional calculations at the CBS-Q3 level of theory reinforce the conclusions of this paper. The results obtained allow the generalization of important ideas regarding the mechanism of the nucleophilic addition to carbonyl groups.

Antioxidant activity of trans-resveratrol toward hydroxyl and hydroperoxyl radicals: a quantum chemical and computational kinetics study.

In this work, we have carried out a systematic study of the antioxidant activity of trans-resveratrol toward hydroxyl ((•)OH) and hydroperoxyl ((•)OOH) radicals in aqueous simulated media using density functional quantum chemistry and computational kinetics methods. All possible mechanisms have been considered: hydrogen atom transfer (HAT), proton-coupled electron transfer (PCET), sequential electron proton transfer (SEPT), and radical adduct formation (RAF). Rate constants have been calculated using conventional transition state theory in conjunction with the Collins-Kimball theory. Branching ratios for the different paths contributing to the overall reaction, at 298 K, are reported. For the global reactivity of trans-resveratrol toward (•)OH radicals, in water at physiological pH, the main mechanism of reaction is proposed to be the sequential electron proton transfer (SEPT). However, we show that trans-resveratrol always reacts with (•)OH radicals at a rate that is diffusion-controlled, independent of the reaction pathway. This explains why trans-resveratrol is an excellent but very unselective (•)OH radical scavenger that provides antioxidant protection to the cell. Reaction between trans-resveratrol and the hydroperoxyl radical occurs only by phenolic hydrogen abstraction. The total rate coefficient is predicted to be 1.42 × 10(5) M(-1) s(-1), which is much smaller than the ones for reactions of trans-resveratrol with (•)OH radicals, but still important. Since the (•)OOH half-life time is several orders larger than the one of the (•)OH radical, it should contribute significantly to trans-resveratrol oxidation in aqueous biological media. Thus, trans-resveratrol may act as an efficient (•)OOH, and also presumably (•)OOR, radical scavenger.

Molecular description of indigo oxidation mechanisms initiated by OH and OOH radicals.

In this work, we report a quantum chemistry mechanistic study of the hydroxyl (•OH) and hydroperoxyl (•OOH) radicals initiated oxidation of indigo, within the density functional theory framework. All possible hydrogen abstraction and radical addition reaction pathways have been considered. We find that the reaction between a free indigo molecule and an •OH radical occurs mainly through two competing mechanisms: H-abstraction from an NH site and •OH addition to the central C═C double bond. Although the latter is favored, both channels occur, the indigo chromophore group structure is modified, and thus the color is changed. This mechanism adequately accounts for the loss of chromophore in urban air, including indoor air such as in museums and in urban areas. Regarding the reactivity of indigo toward •OOH radicals, only •OOH-addition to the central double bond is thermodynamically feasible. The corresponding transition state free energy value is about 10 kcal/mol larger than the one for the •OH initiated oxidation. Therefore, even considering that the •OOH concentration is considerably larger than the one of •OH, this reaction is not expected to contribute significantly to indigo oxidation under atmospheric conditions.

Role of allyl group in the hydroxyl and peroxyl radical scavenging activity of S-allylcysteine.

S-Allylcysteine (SAC) is the most abundant compound in aged garlic extracts, and its antioxidant properties have been demonstrated. It is known that SAC is able to scavenge different reactive species including hydroxyl radical (•OH), although its potential ability to scavenge peroxyl radical (ROO•) has not been explored. In this work the ability of SAC to scavenge ROO• was evaluated, as well as the role of the allyl group (-S-CH(2)-CH═CH(2)) in its free radical scavenging activity. Two derived compounds of SAC were prepared: S-benzylcysteine (SBC) and S-propylcysteine (SPC). Their abilities to scavenge •OH and ROO• were measured. A computational analysis was performed to elucidate the mechanism by which these compounds scavenge •OH and ROO•. SAC was able to scavenge •OH and ROO•, in a concentration-dependent way. Such activity was significantly ameliorated when the allyl group was replaced by benzyl or propyl groups. It was shown for the first time that SAC is able to scavenge ROO•.

ROS initiated oxidation of dopamine under oxidative stress conditions in aqueous and lipidic environments.

Dopamine is known to be an efficient antioxidant and to protect neurocytes from oxidative stress by scavenging free radicals. In this work, we have carried out a systematic quantum chemistry and computational kinetics study on the reactivity of dopamine toward hydroxyl (•OH) and hydroperoxyl (•OOH) free radicals in aqueous and lipidic simulated biological environments, within the density functional theory framework. Rate constants and branching ratios for the different paths contributing to the overall reaction, at 298 K, are reported. For the reactivity of dopamine toward hydroxyl radicals, in water at physiological pH, the main mechanism of the reaction is proposed to be the sequential electron proton transfer (SEPT), whereas in the lipidic environment, hydrogen atom transfer (HAT) and radical adduct formation (RAF) pathways contribute almost equally to the total reaction rate. In both environments, dopamine reacts with hydroxyl radicals at a rate that is diffusion-controlled. Reaction with the hydroperoxyl radical is much slower and occurs only by abstraction of any of the phenolic hydrogens. The overall rate coefficients are predicted to be 2.23 × 10(5) and 8.16 × 10(5) M(-1) s(-1), in aqueous and lipidic environment, respectively, which makes dopamine a very good •OOH, and presumably •OOR, radical scavenger.

Mechanism and kinetics of the water-assisted formic acid + OH reaction under tropospheric conditions.

In this work, we have revisited the mechanism of the formic acid + OH radical reaction assisted by a single water molecule. Density functional methods are employed in conjunction with large basis sets to explore the potential energy surface of this radical-molecule reaction. Computational kinetics calculations in a pseudo-second-order mechanism have been performed, taking into account average atmospheric water concentrations and temperatures. We have used this method recently to study the single water molecule assisted H-abstraction by OH radicals (Iuga, C.; Alvarez-Idaboy, J. R.; Reyes, L.; Vivier-Bunge, A. J. Phys. Chem. Lett. 2010, 1, 3112; Iuga, C.; Alvarez-Idaboy, J. R.; Vivier-Bunge, A. Chem. Phys. Lett. 2010, 501, 11; Iuga, C.; Alvarez-Idaboy, J. R.; Vivier-Bunge, A. Theor. Chem. Acc. 2011, 129, 209), and we showed that the initial water complexation step is essential in the rate constant calculation. In the formic acid reaction with OH radicals, we find that the water-acid complex concentration is small but relevant under atmospheric conditions, and it could in principle be large enough to produce a measurable increase in the overall rate constant. However, the water-assisted process occurs according to a formyl hydrogen abstraction, rather than abstraction of carboxylic hydrogen as in the water-free case. As a result, the overall reaction rate constant is considerably smaller. Products are different in the water-free and water-assisted processes.

Mechanism and kinetics studies on the antioxidant activity of sinapinic acid.

The OOH radical scavenging activity of sinapinic acid (HSA) has been studied in aqueous and lipid solutions, using the Density Functional Theory. HSA is predicted to react about 32.6 times faster in aqueous solution than in lipid media. The overall rate coefficients are predicted to be 5.39 × 10(5) and 1.66 × 10(4) M(-1) s(-1), respectively. Branching ratios for the different channels of reaction are also reported for the first time, as well as the UV-Vis spectra of the main products of reaction. It was found that the reactivity of sinapinic acid towards OOH radicals takes place almost exclusively by H atom transfer from its phenolic moiety. However it was found to react via SET, at diffusion-limit controlled rate constants, with ˙OH, ˙OCCl(3) and ˙OOCCl(3) radicals. It was found that the polarity of the environment and the deprotonation of HSA in aqueous solution, both increase the reactivity of this compound towards peroxyl radicals.

Computational and experimental study of the interactions between ionic liquids and volatile organic compounds.

Computational chemistry calculations were performed to investigate the interactions of ionic liquids with different classes of volatile organic compounds (VOCs), including alcohols, aldehydes, ketones, alkanes, alkenes, alkynes and aromatic compounds. At least one VOC was studied to represent each class. Initially, 1-butyl-3-methylimindazolium chloride (abbreviated as C(4)mimCl) was used as the test ionic liquid compound. Calculated interaction lengths between atoms in the ionic liquid and the VOC tested as well as thermodynamic data suggest that C(4)mimCl preferentially interacts with alcohols as compared to other classes of volatile organic compounds. The interactions of methanol with different kinds of ionic liquids, specifically 1-butyl-3-methylimidazolium bromine (C(4)mimBr) and 1-butyl-3-methylimidazolium tetrafluoroborate (C(4)mimBF(4)) were also studied. In comparing C(4)mimCl, C(4)mimBr, and C(4)mimBF(4), the computational results suggest that C(4)mimCl is more likely to interact with methanol. Laboratory experiments were performed to provide further evidence for the interaction between C(4)mimCl and different classes of VOCs. Fourier transform infrared spectroscopy was used to probe the ionic liquid surface before and after exposure to the VOCs that were tested. New spectral features were detected after exposure of C(4)mimCl to various alcohols. The new features are characteristic of the alcohols tested. No new IR features were detected after exposure of the C(4)mimCl to the aldehyde, ketone, alkane, alkene, alkyne or aromatic compounds studied. In addition, after exposing the C(4)mimCl to a multi-component mixture of various classes of compounds (including an alcohol), the only new peaks that were detected were characteristic of the alcohol that was tested. These experimental results demonstrated that C(4)mimCl is selective to alcohols, even in complex mixtures. The findings in this work provide information for future gas-phase alcohol sensor design.

Quantum chemistry and TST study of the mechanisms and branching ratios for the reactions of OH with unsaturated aldehydes.

A theoretical study is presented on the mechanism of OH reactions with three unsaturated aldehydes, relevant to atmospheric chemistry. Using acrolein as test molecule, several methods were tested in conjunction with the 6-311 ++ G(d,p) basis set. Based on the results from this study, the MPWB1K and M05-2X functionals were selected for the further study of acrolein, methacrolein and crotonaldehyde. All possible reaction channels have been modeled. Calculated overall rate coefficients at M05-2X/6-311 ++ G(d,p) are in excellent agreement with experimental data, supporting the proposed mechanisms. The previously proposed global mechanisms were confirmed, and specific mechanisms were identified. The causes of the mechanism for crotonaldehyde being different from the one of acrolein and methacrolein were clarified. The agreement between experiment and calculations validates the use of the chosen DFT methods for kinetic calculations, especially for large systems and cases in which spin contamination is an important issue.

Guanosine + OH radical reaction in aqueous solution: a reinterpretation of the UV-vis data based on thermodynamic and kinetic calculations.

Thermodynamic and kinetic calculations have been used to reinterpret the UV-vis data related to the OH radical oxidation of guanosine. The main channel of reaction (70-75%) is proposed to be the formation of a guanosine radical cation followed by deprotonation. It accounts for both the absorbance decay at approximately 620 nm and the build-up at approximately 300 nm. A secondary channel yielding the G8OH adduct was found to contribute to the overall reaction by 12% at least.

The Baeyer-Villiger reaction: solvent effects on reaction mechanisms.

This study focuses on the Baeyer-Villiger reaction of propanone and performic acid, with formic acid as catalyst. Continuum solvation methods (EIF-PCM and CPCM) and two density functionals (B3LYP and MPWB1K) are used to study solvent effects on two types of reaction mechanisms: concerted non-ionic and stepwise ionic. The ionic mechanism is the one found in most organic chemistry textbooks; it begins with the protonation of the ketone by the acid catalyst, even though this reaction normally takes place in non-polar solvents such as dichloromethane. Our calculations show that the concerted non-ionic pathway, which is the least energetic in non-polar solvents such as dichloromethane, becomes more energetic the more polar the solvent. After investigating a variety of non-ionic and ionic pathways in water, it is found that the addition step seems to be ionic but the migration step, which is rate-determining, is uncatalyzed, non-ionic and fully concerted. These results confirm the experimental findings in solvents of low to medium polarity that the rate constant of the reaction decreases as the solvent polarity increases. Moreover, we find that contrary to what is commonly accepted, in the addition and migration ionic steps the deprotonation of the ionic species occurs in a concerted manner with the other chemical events taking place.

Theoretical explanation of nonexponential OH decay in reactions with benzene and toluene under pseudo-first-order conditions.

OH radical reactions with benzene and toluene have been studied in the 200-600 K temperature range via the CBS-QB3 quantum chemistry method and conventional transition-state theory. Our study takes into account all possible hydrogen abstraction and OH-addition channels, including ipso addition. Reaction rates have been obtained under pseudo-first-order conditions, with aromatic concentrations in large excess compared to OH concentrations, which is the case in the reported experiments as well as in the atmosphere. The reported results are in excellent agreement with the experimental data and reproduce the discontinuity in the Arrhenius plots in the 300 K < T < 400 K temperature range. They support the suggestion that the observed nonexponential OH decay is caused by the existence of competing addition and abstraction channels and by the decomposition of thermalized OH-aromatic adducts back to reactants. We also find that the low-temperature onset of the nonexponential decay depends on the concentration of the aromatic compounds and that the lower the concentration, the lower the temperature onset. Under atmospheric conditions, nonexponential decay was found to occur in the 275-325 K range, which corresponds to temperatures of importance in tropospheric chemistry. Branching ratios for the different reaction channels are reported. We find that for T > or = 400 K the reaction occurs exclusively by H abstraction. At 298 K, ipso addition contributes 13.0% to the overall OH + toluene reaction, while the major products correspond to ortho addition, which represents 43% of all possible channels.

Branching Ratios of Aliphatic Amines + OH Gas-Phase Reactions: A Variational Transition-State Theory Study.

A theoretical study on the mechanism of the OH + aliphatic amines reactions is presented. Geometry optimization and frequencies calculations have been performed at the BHandHLYP/6-311++G(2d,2p) level of theory for all stationary points. Energy values have been improved by single-point calculations at the above geometries using CCSD(T) and the same basis set. All the possible hydrogen abstraction channels have been modeled, involving the rupture of C-H and N-H bonds. It was found that as the temperature decreases the contributions of the channels involving NH sites to the overall reaction also decrease, suggesting that for upper layers in the troposphere these channels become less important. Their percentage contributions to the overall reaction, at 298 K, were found to be about 20%, 2%, and 48% for methylamine, ethlylamine, and dimethylamine, respectively.