OH Bond Dissociation Enthalpy Research Articles

A comprehensive molecular analysis of cannabidiol: From solid state to antioxidant potential

Cannabis sativa contains approximately 540 natural compounds, including terpenes and flavonoids, and approximately 100 of these compounds are phytocannabinoids, of which the most studied are Δ9-tetrahydrocannabinol and cannabidiol. Due to potential therapeutic properties and psychoactive effects dissociated from cannabis consumption, cannabidiol has received significant attention. This study focuses on molecular modeling and the electronic properties of cannabidiol and cannabidiol-type compounds using chemical reactivity descriptors, aiming to understand the potential antioxidant properties. The radicals formed during free radical scavenging processes were evaluated in thermodynamic and electronic terms through the mechanisms of hydrogen atom transfer and one-electron transfer. The topological parameters showed that the interactions are of the closed-shell type and have a van der Waals character, except where the OH group rotation occurs, resulting in an H bond. Calculations of OH bond dissociation enthalpy and ionization potential showed that CBD-C5 has the best antioxidant potential among cannabidiol-type compounds.

Revisiting the hydrogen atom transfer reactions through a simple and accurate theoretical model: Role of hydrogen bond energy in polyphenolic antioxidants

The importance of hydrogen atom transfer (HAT) reaction has been realized in various fields, ranging from atmospheric chemistry to biological processes. HAT is noteworthy in exploring phenolic antioxidants as these molecules scavenge harmful reactive free radicals through this popular pathway. The determining index of the HAT reaction is the bond dissociation enthalpy (BDE). This article proposes a theoretical model for estimating the OH BDE, a key concept for assessing HAT reactions. The model is shown to have high accuracy, and is computationally cheaper than the conventional methods of computing BDE. It has been tested with 35 polyphenolic systems having antioxidant activity involved through the HAT mechanism. Further, topological parameters within the QTAIM are computed along with the hydrogen bond energies to understand the intramolecular hydrogen bonding in such polyphenolic systems undergoing HAT reactions.

A combined experimental and computational thermodynamic study of fluoronitrophenol isomers

Combustion energies of the 5-fluoro-2-nitrophenol, 4-fluoro-2-nitrophenol, 3-fluoro-4-nitrophenol and 2-fluoro-4-nitrophenol isomers were obtained by means of a rotating-bomb combustion calorimeter. From these determinations, standard molar combustion enthalpies and standard molar formation enthalpies, at T = 298.15 K, in the crystalline state, were derived. The Knudsen mass-loss effusion technique was used to determine the standard molar enthalpies, entropies and Gibbs energies of sublimation, at T = 298.15 K, of the studied compounds. The standard molar enthalpies of sublimation of the four isomers were also measured by Calvet microcalorimetry. The gas-phase standard molar enthalpies of formation were derived from the experimental measurements, at T = 298.15 K, for the fluoronitrophenols studied.Additionally, the standard molar enthalpies of formation were estimated by means of computational methodology at the G3(MP2)//B3LYP level. The estimated values are in very good agreement with experimental data, giving us support to estimate the gas-phase enthalpies of formation of the remaining isomers whose values have not been determined experimentally.A simple group additivity scheme was successfully applied for prediction of molar enthalpies of formation.The computational study was also extended to the determination of OH bond dissociation enthalpies for all the isomers.

On the toxicity of para-substituted phenols and their quinone metabolites: Quantum chemical study

The quantum chemical study of phenols cytotoxicity extended to their metabolites is presented. Based on OH bond dissociation enthalpies (BDE) and octanol-water partition coefficients (LogP) calculated using density functional theory (M06-2X and B3LYP functionals) with 6-311++G(d,p) basis set, their toxicity, in terms of Log(1/C), is described. The characterization of quinoid metabolites is also performed. Observed toxicity of phenols can be correlated with the properties of their ortho-quinone oxidation products/metabolites, i.e. LogP and partial atomic charges at C2 or O2 atoms, too. Found results indicate that ortho-quinones contribute to the overall experimentally determined toxicity of phenols.

Structure, antioxidative potency and potential scavenging of OH[rad] and OOH[rad] of phenylethyl-3,4-dihydroxyhydrocinnamate in protic and aprotic media: DFT study

DFT methods including B3LYP, B3PW91 and M05–2x associated to 6–31+G(d,p) were used for the structural and antioxidant potency studies of phenylethyl-3,4-dihydroxy-hydrocinnamate (PDH). Solvents were employed according to their protric and aprotic character. So, calculated structures agree with the experimental data. O4H4 is propitious to scavenge radicals whatever the medium except in water where O3H3 and O4H4 are competitive. The explicit solvents of dichloromethane (DCM) and water present a disparity of OH bond dissociation enthalpy and free energy (BDE and BDFE). These parameters are low in continuum except in water. The ionization potentials (IP) and potential affinities (PA) are low in solvents. BDE, IP and PA are each, approximatively constant in mixed solvent treatment in water using n-H2O (n=3,5,8). Elsewhere, H-atom transfer (HAT) mechanism is favoured in vacuum and DCM, whereas sequential proton loss electron transfer (SPLET) is likely in protic solvents. A discord between HAT and SPLET in benzene is observed. The PDH compound is more antioxidant and resistant to oxidation than caffeic acid phenethyl ester (CAPE). The potential of scavenging of OH and OOH whatever the reaction channel shows that they decay rapidly in any media through HAT. PDH is easily deprotonated in the protic solvents and the resulting product is the most antioxidant and the least resistant to oxidation.

Donor-acceptor interactions as descriptors of the free radical scavenging ability of flavans and catechin

Interest in food phenolics has increased in recent years largely due to their antioxidant capacity, free radical scavenging, and potential health benefits. In literature two main reaction mechanisms have been proposed for their role as free radical (FR) scavengers, i.e., the mechanism of a hydrogen atom transfer (HAT) governed by the OH bond dissociation enthalpy (BDE), and the mechanism of single electron transfer (SET) governed by an electron transfer process, the ionization potential (IP) playing an important role.Thirty nonplanar structures were analyzed. The study of (+)-catechin (CTQ) and (4α→6″, 2α→O→1″)-phenylflavans with a R′=H, R=OH; R′=OH, R=H, and R′=OH, R=OH substitution is performed herein. Catechol, phenol, and resorcinol are also included as references. Results obtained with B3LYP hybrid functional with 6-311++G(d,p) and 6-31G(d,p) basis set are analyzed. Two new indicators arising from electron delocalizations are presented herein, thus showing that there is a different set of donor-acceptor interactions to explain FR scavenging mechanisms.

Characterization of π-stacking interactions between aromatic amino acids and quercetagetin

In the present study, the π-stacking interactions between quercetagetin (QUE), which is one of the most representative flavonol compounds with biological and chemical activities, and some aromatic amino acid (AA) residues has been investigated by the quantum mechanical calculations. The trend in the absolute value of stacking interaction energy |ΔE| with respect to AAs is HIS > PHE > TYR > TPR. The results show that the sum of donor-acceptor interaction energy between AAs and QUE (∑E2) and the sum of electron densities ρ calculated at BCPs and CCPs between the rings (∑ρBCPs and ∑ρCCP) can be useful descriptors for prediction of the ΔE values of the complexes. The OH bond dissociation enthalpy (BDE) slightly decreases by the π-stacking interaction, which confirms the positive effect of that interaction on the antioxidant activity of QUE. A reverse trend is observed for BDE when is compared with the |ΔE| values. A reliable relationship is also observed between the Muliken spin density (MSD) distributions of the radical species and the most convenient OH bond dissociations. In addition, reactivity is in good correlation with the antioxidant activity of the complexes.

Deprotonation of flavonoids severely alters the thermodynamics of the hydrogen atom transfer

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 OH 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.

Antioxidant Properties of Kanakugiol Revealed Through the Hydrogen Atom Transfer, Electron Transfer and M2+ (M2+ = Cu(II) or Co(II) Ion) Coordination Ability Mechanisms. A DFT Study In Vacuo and in Solution

DFT studies on the conformational and antioxidant properties of kanakugiol were performed to investigate factors that contribute to its conformational preferences and to elucidate its antioxidant properties and mechanisms. The antioxidant activity has been considered through the ability of kanakugiol to scavenge free radical species and through its ability to chelate metal ions. The antiradical activity was performed using the B3LYP and the B3P86 and by using both the 6-31+G(d,p) and the 6-311+G(d,p) basis sets. The gas-phase interaction of kanakugiol with Cu (II) and Co (II) ions were studied by means of G96LYP/6-311+G(3df,2p)//G96LYP/6-31G(d) calculations. The results show that the preferred neutral conformers are stabilised by the presence of intramolecular hydrogen bonds (IHBs) and the orientation of both the OCH3 groups and the prop-2-en-1-one chain. The neutral and cationic radical species are stabilised by both IHBs and the spin density delocalisation of the unpaired electron. A comparison of the OH bond dissociation enthalpy and the ionisation potential values across media suggests that each parameter has the lowest value in acetonitrile and highest value in vacuo, which indicates that kanakugiol may have an optimal tendency to scavenge radical species in polar aprotic media. Among the metal ion complexes, the preferred geometry is dependent on the media; in vacuo the preferred complex is one in which the metal ion is dentated to the π system of the aromatic ring while in water solution, the preferred complex is one in which the metal ion is dentated between O atoms. An estimation of metal ion affinity in aqueous solution shows a remarkable decrease with respect to the results in vacuo. The charge on metal ions decreases on interaction with kanakugiol, suggesting that both metal ions are reduced while kanakugiol is oxidised. An analysis of the spin density distribution and the electron delocalisation index elucidates the difference in the type of bonding between the Co(II) and Cu(II) complexes.

Antioxidant properties of xanthones extracted from the pericarp of Garcinia mangostana (Mangosteen): A theoretical study

A theoretical study on antioxidant properties of fourteen xanthones extracted from the pericarp of G. Mangostana has been performed. Three main reaction mechanisms are investigated: hydrogen atom transfer (HAT), single electron transfer–proton transfer (SETPT) and sequential proton loss electron transfer (SPLET). The OH bond dissociation enthalpy (BDE), ionization energy (IE), proton affinity (PA) and electron transfer energy (ETE) parameters were computed in gas phase and water. The results show that HAT would be the most favorable mechanism for explaining antioxidant activity of xanthones in gas phase, whereas the SPLET mechanism is thermodynamically favored in water.

DFT studies on antioxidant mechanisms, electronic properties, spectroscopic (FT-IR and UV) and NBO analysis of C-glycosyl flavone, an isoorientin

The relationship between structure and electronic properties of isoorientin, a C-glycoside flavone is investigated to relate its radical scavenging activity using molecular descriptors. To elucidate the antioxidant activity of polyphenolics, three mechanisms namely hydrogen atom transfer (HAT), single electron transfer–proton transfer (SET–PT) and sequential proton-loss electron-transfer (SPLET) are employed. In gas-phase, OH bond dissociation enthalpies (BDE), ionization potential (IP), proton dissociation enthalpies (PDE), proton affinity (PA) and electron transfer enthalpy (ETE) are computed and correlated relevant to antioxidant potency of the title compound employing DFT/6-311G(d,p) protocol. The theoretically simulated FT-IR and the UV–visible absorption spectra have been compared with the experimental data. Based on the absorbed UV spectra and TD-DFT calculations, assignment of the absorption bands are carried out. In addition, formation of intramolecular hydrogen bond and most possible interaction sites are explained by using natural bond orbital (NBO) analysis.

Reaction enthalpies of O[sbnd]H bonds splitting-off in flavonoids: The role of non-polar and polar solvent

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, OH 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.

Theoretical investigation on the bond dissociation enthalpies of phenolic compounds extracted from Artocarpus altilis using ONIOM(ROB3LYP/6-311++G(2df,2p):PM6) method

Theoretical calculations have been performed to predict the antioxidant property of phenolic compounds extracted from Artocarpus altilis. The OH bond dissociation enthalpy (BDE), ionization energy (IE), and proton dissociation enthalpy (PDE) of the phenolic compounds have been computed. The ONIOM(ROB3LYP/6-311++G(2df,2p):PM6) method is able to provide reliable evaluation for the BDE(OH) in phenolic compounds. An important property of antioxidants is determined via the BDE(OH) of those compounds extracted from A. altilis. Based on the BDE(OH), compound 12 is considered as a potential antioxidant with the estimated BDE value of 77.3kcal/mol in the gas phase.

Theoretical study of the substituent effects on O–H BDE of trans-resveratrol derivatives in water and benzene: NBO analysis of intramolecular hydrogen bonds

The effect of solvents and intramolecular hydrogen bonds on the three O–H bond dissociation enthalpies (BDEs) of non-substituted and substituted trans-resveratrols has been studied in water and benzene using DFT/B3LYP method. The formation of strong intramolecular hydrogen bonds in several radicals results in low BDEs. The solvent alters the intramolecular hydrogen bonds stabilization energies. In electron-withdrawing groups where the substituent causes high polarity of the parents and especially radicals, the effect of the solvent is stronger. When the substitution has a poor effect on the resveratrol molecule, the solvent has weak influence on formed radical stability, too. Besides intramolecular hydrogen bonds, the position, as well as electron-donating or electron-withdrawing character of a substituent in both, polar or nonpolar solvents, is able to affect OH BDEs substantially.

Investigation of oxidation attack sites in sterols: Thermodynamics of hydrogen atom transfer

B3LYP study of 7 naturally occurring sterols was carried out in terms of OH and CH bond dissociation enthalpies (BDE) to identify thermodynamically favored oxidation attack site. In all compounds, OH BDEs are significantly higher than CH BDEs. Found results showed that sterol nuclei are more susceptible to the oxidation than side chains. Lowest BDE values were found for the C14H bond in the majority of molecules with C14 atom in the α-position to a CC double bond. C5C6C7C8 alternating double bonds cause further drop in C14H BDE. Because the nuclei are responsible for the reported oxidation instability of sterols, 15 various steroid nuclei were also investigated.

A Computational Study of RXHn X–H Bond Dissociation Enthalpies

Bond dissociation enthalpies can exhibit dramatic variations resulting from substituent effects. These variations result from changes in electronic structure that accompany bond dissociation. We have studied bond dissociation enthalpies (BDEs) at the W1BD level of theory for a series of RX-H compounds where X = CH2, NH, O, PH, and S. The substituents, R, included H, H3C, H2N, HO, F, H2P, HS, and Cl. The experimentally available BDEs were reproduced in a very satisfactory fashion. Most of the substituent effects could be related to a conjugative interaction in the two-center three-electron systems in the radicals formed by H abstraction. Comparisons of isoelectronic species demonstrate the important roles that variations in electronegativity and hybridization can play in determining BDEs. The OH and SH BDEs were linearly related, and the same was found with N-H and P-H BDEs. The relative effects of H2P and HS as substituents, in contrast to H2N and HO, could be related to the need to promote a 3s electron to 3p before H2P can participate in π-bonding. We must also include electronegativity differences to account for the observed transfer of a sulfur lone pair to an oxygen but the absence of the reverse process.

Theoretical study of the substituent effect on the hydrogen atom transfer mechanism of the irigenin derivatives antioxidant action

In this paper, 21 substituents with various electron donating and electron withdrawing characters were placed in available positions of irigenin in order to study their effect on the O – H bond dissociation enthalpy (BDE) via DFT/B3LYP method. Results indicated the substituents in X3 and X4 positions have exerted stronger influence upon BDE values of irigenin derivatives when compared with same substituents in X1 and X2 positions. The results show that intramolecular hydrogen bond effects are able to considerably stabilize the parents and radicals. The natural bond orbital (NBO) analysis results also confirmed the intramolecular hydrogen bond stabilization. The formation of strong intramolecular hydrogen bonds in several radicals results in low BDEs. The 3- OH BDE values for substituents in X2 position have linear dependencies with Hammett constants (Fig. 2 and Eq. (2)). Found dependencies are suitably linear, that can be important for the synthesis of novel antioxidants based on irigenin.

Theoretical investigation on the antioxidative activity of anthocyanidins: A DFT/B3LYP study

Anthocyanidins are an important class of plant pigment, in the present work the antioxidative properties of anthocyanidins have been explored by density functional theory calculations, three main antioxidative mechanisms, which include H atom transfer (HAT), single electron transfer (SET) and sequential proton loss electron transfer (SPLET), have been investigated at B3LYP/6-311G(d,p) level of theory. The O–H bond dissociation enthalpies (BDEs), ionization potentials (IPs), electron affinities (EAs), proton affinities (PAs) and electron transfer enthalpies (ETEs) are investigated in gas phase and aqueous solution. Results show 3-OH and 4′-OH posses lower BDE as compared to other OH groups, the substituents in B-ring influence 4′-OH BDE, but exhibit negligible influence on other OH BDEs. Among all investigated anthocyanidins, pelargonidin has the highest IP and EA in gas phase, substituent in ortho position of 4′-OH leads to remarkable decrease in IP and EA. OH substituent in B-ring almost show no influence on PAs and ETEs of 3-, 5-, and 7-phenolate anions, but OCH3 substituent influence them significantly. For PAs and ETEs of 4′-phenolate anion, two types of substituents both exhibit remarkable influence. Base on the simplest anthocyanidins, pelargonidin, molecular simplification has been performed to explore the necessary pharmacophores responsible for the antioxidative activity of anthocyanidins.

Quantum chemical and experimental study of 1,2,4-trihydroxy-para-menthane

The conformational analysis of the para-menthane (PM) and 1,2,4-trihydroxy-para-menthane (TPM) is performed using the quantum chemical density functional theory (DFT) and ab initio Møller-Plesset perturbation theory up to the second order (MP2). In TPM, three hydroxyl groups generate eight stereoisomers comparing to the four para-menthane stereoisomers. From the thermodynamics point of view, the most preferred conformations show the chair-shaped configuration of the cyclohexane ring. The obtained energy barriers for the isopropyl group rotation in the chair-shaped stereoisomers are between 35 and 45kJmol−1. The crystal structure as well as the solvated TPM stereoisomer isolated from the Tea tree oil, Melaleuca alternifolia (Maiden & Betche) Cheel, were investigated experimentally. Isolated stereoisomer corresponds to the most energetically preferred conformation and the calculated structural data agree very well with the results from the X-ray and nuclear magnetic resonance measurements. Finally, the influence of the conformation and the presence of the intramolecular hydrogen bonds on the homolytic OH bond dissociation enthalpies and proton affinities were also discussed with respect to the simple alcohols (methanol, iso-propanol, iso-pentanol, tert-butanol, cyclohexanol) and phenol.

Improvement of antioxidative activity of resveratrol by elongating conjugated chain: A DFT theoretical study

Elongation of the conjugated chain of resveratrol has been proved to be an effective strategy to further improve its antioxidative capacity and radical scavenging ability. In this work, quantum chemical calculations based on density functional theory have been employed at B3LYP/6-311G(d,p) level of theory to study the influence of the conjugated chain length on equilibrium geometries and properties of relevant species. Our results show elongation of conjugated chain significantly decreases 4′-OH bond dissociation enthalpy (BDE), ionization potential (IP) and proton affinities (PAs) of phenolate ions in gas phase. In aqueous solution 4′-OH BDE, IP are lower as compared to that in gas phase, for PAs of phenolate ions almost no change is induced, but significant decrease in electron transfer enthalpy (ETE) is presented. These indicate that longer conjugated chain is favorable for the radical scavenging capacity and antioxidative activity. In addition, stable s-cis conformers of long chain reservatrol analogs are found to be more favorable for production of phenoxyl radicals and cation radicals as compared to trans conformers, with concomitant enhancement of the antioxidative activity.