The antioxidant activity of 4‐hydroxycoumarin derivatives and some sulfured analogs

In this work, the relationship between the structure and the radical scavenging activity of seven hydroxycoumarins and their sulfured analogs was investigated for the first time by density functional theory calculation in the gas phase, benzene, and water. Our investigation includes hydrogen atom transfer, single‐electron transfer–proton transfer, and sequential proton loss electron transfer mechanisms. The results revealed that the bond dissociation enthalpy values of sulfured coumarins were lower than those of hydroxylated analogs. The obtained results were in a good agreement with the experimental results. The hydrogen atom transfer mechanism is dominant in both benzene and vacuum. The sequential proton loss electron transfer mechanism represents the most thermodynamically preferred reaction pathway in water. However, single‐electron transfer–proton transfer mechanism is not the most preferred one in all media. Finally, this work contributes to the understanding of the pharmacological activity of the compounds studied. Copyright © 2015 John Wiley & Sons, Ltd.     

Thermodynamic and kinetic analysis of the reaction between biological catecholamines and chlorinated methylperoxy radicals

The antiradical potency of catecholamines (dopamine, epinephrine, norepinephrine, L-DOPA), metabolites of dopamine (homovanillic acid, 3-methoxytyramine and 3,4-dihydroxyphenylacetic acid) and catechol towards substituted methylperoxy radicals is investigated. The thermodynamic parameters, together with the kinetic approach, are used to determine the most probable mechanism of action. The natural bond orbital and quantum theory of atoms in molecules are utilised to explain the highest reactivity of trichloromethylperoxy radical. The preferred mechanism is dependent both on the thermodynamic and kinetic parameters . The number of chlorine atoms on radical, the presence of intra-molecular hydrogen bond and number of hydroxy groups attached to the aromatic ring significantly influence the mechanism. The results suggest that sequential proton loss electron transfer (SPLET) is the most probable for reaction with methylperoxy and hydrogen atom transfer (HAT) for reaction with trichloromethylperoxy radicals, with a gradual transition between SPLET and HAT for other two radicals. Due to the significant deprotonation of molecules containing the carboxyl group, the respective anions are also investigated. The HAT and SPLET mechanisms are highly competitive in reaction with MP radical, while the dominant mechanism towards chlorinated radicals is HAT. The reactions in methanol and benzene are also discussed.     

Theoretical study on the investigation of antioxidant properties of some hydroxyanthraquinones

Anthraquinones are located in an important class of natural compounds having antioxidant properties. Quantum chemical calculations based on the density functional theory were employed to study the relationship between the structure and the antioxidant activity of four hydroxyanthraquinones. The solvation effects on the antioxidant activity were taken into account by using the conductor-like polarisable continuum model with different dielectric constants (ε = 2.25, C₆H₆; ε = 78.39, H₂O). The three antioxidant action mechanisms, hydrogen atom transfer (HAT), single electron transfer-proton transfer and sequential proton loss electron transfer (SPLET) were elucidated. The reaction enthalpies related to the steps in these mechanisms were computed in gas phase and solvents. The calculated results are in line with experimental values. The results showed that HAT was the most favourable mechanism for describing the antioxidant activity of hydroxyanthraquinones in the gas phase and in benzene, whereas in aqueous solution, SPLET represented the most thermodynamically plausible reaction pathway.     

苹果酸结构类似物抗氧化活性的DFT研究

最近从葡萄酒中鉴定并分离出两种苹果酸(MA)结构类似物：2-异丙基苹果酸(2-IPMA)和3-异丙基苹果酸(3-IPMA).使用密度泛函理论(DFT)评估了MA, 2-IPMA和3-IPMA的构象和抗氧化相关热力学性质,结果显示,2-IPMA和3-IPMA的C₂羟基具有较高的自由基清除活性.基于大多数抗氧化剂的单线态比三线态更稳定,预测2-IPMA和3-IPMA将分别在气相条件下通过双氢原子转移(dHAT),顺序双质子损失双电子转移(SdPLdET)和双电子转移质子转移(dET-PT)方式参与自由基清除途径,形成4-甲基-3-氧代戊酸和3-甲基-2-甲酰丁酸.根据低能量消耗优先原则,2-IPMA和3-IPMA优先清除自由基的途径依次为：HAT, ET-PT和SPLET.计算结果证实了当前研究的假设,并表明就反应焓热力学数据而言,两种MA类似物的抗氧化能力有利于HAT途径.     

Bond dissociation enthalpies calculated by the PM3 method confirm activity cliffs in radical scavenging of flavonoids

Radical scavenging potency of flavonoids is associated with activity cliffs, i.e., small chemical modifications on flavonoid core can have a significant effect on activity. The presence or absence of the 3′,4′-diOH and/or 3-OH group may serve as an activity switch for radical scavenging. The physicochemical background of such an indicator variable, defined previously (Amić et al. (2003) Croat Chem Acta 76:55–61), is confirmed by computation of bond dissociation enthalpies and selecting the minimal of all values relating to flavonoid OH groups. Bond dissociation enthalpies for hydrogen abstraction from OH groups for 29 flavonoids were calculated by the PM3 method. Minimal bond dissociation enthalpy values were obtained for OH groups attached to C-3, C-3′ and C-4′ positions, and they correspond to the previously introduced indicator variable. Taking into account some driving forces of the radical scavenging mechanism, it is possible to relate structural characteristics of flavonoids to their radical scavenging potency as well as to develop reliable structure-activity models. An erratum to this article can be found at     

The free radical scavenging activity of lespedezacoumestan toward ˙OH radical: A quantum chemical and computational kinetics study

The free radical activity of lespedezacoumestan was investigated toward hydroxyl (˙OH) radical in polar and nonpolar media using density functional theory. Four reaction mechanisms including radical adduct formation, hydrogen atom transfer, sequential single electron‐proton transfer (SET‐PT), and sequential proton loss electron transfer were considered. The rate constants and branching ratio for all possible sites of reaction were calculated and reported for the first time. According to the obtained results, lespedezacoumestan reacts faster with ˙OH radical in aqueous solution than in nonpolar media. Also, lespedezacoumestan is an excellent ˙OH radical scavenger regardless of the environment polarity.     

密度泛函研究细梗胡枝子提取物中新型抗氧化剂的分子结构和活性氧清除机理

采用密度泛函方法研究了从细梗胡枝子中提取的三种新型抗氧化剂的分子结构和活性氧清除机理．研究发现优化后的最优分子构型中都含有分子内氢键,与用二级微扰方法得到的结果一致．根据预测的气相和水相抗氧化剂的键解离能、电离势,以及三种重要活性氧的电子亲和势和氢原子亲和势,详细讨论了三种抗氧化剂的活性氧清除机理并发现其抗氧化活性和实验结果一致.     

The saturated five‐membered heterocyclic molecules as organic hydride donors: a computational study

Several five‐membered heterocyclic molecules were studied theoretically as organic hydride donors. The density functional theory and ab initio methods are employed to study the direct one‐step or multistep sequence suggested for the hydride transfer from the selected molecules: H atom/electron, electron/proton/electron or electron/H atom. Out of the three multistep mechanisms, electron/H atom seems to be a probable pathway in the presence of suitable catalyst/photoreaction that can cause ionization. In the lack of such catalyst/photoreaction, the direct hydride transfer seems to be most probable with the presence of suitable hydride acceptor. A detailed mechanism of the hydride transfer from the five‐membered heterocylic compounds is important in understanding chemical and biological reactions and required for scientifically designing and synthesizing new desired five‐membered heterocyclic compounds as organic hydride donor. Copyright © 2014 John Wiley & Sons, Ltd.     

A quantum chemical study on the OH radical quenching by natural antioxidant fisetin

In this work, the antioxidant ability of fisetin was explored toward hydroxyl (?OH) radical in aqueous and lipid solution using density functional level of theory. Different reaction mechanisms have been studied: hydrogen atom transfer, single electron transfer followed by proton transfer, and radical adduct formation, and sequential proton loss electron transfer. Rate constants for all possible reaction sites have been calculated using conventional transition state theory in conjunction with the Collins‐Kimball theory. Branching ratios for the different channels of reaction are reported for the first time. Results show that the reactivity of fisetin toward hydroxyl (^?OH) radical takes place almost exclusively by radical adduct formation regardless of the polarity of the environment. Also, the single‐electron transfer process seems to be thermodynamically unfavorable in both media.     

Study of scavenging action of zingerone towards the OH radical: formation of vanillin and ferulic acid

The scavenging action of zingerone, a phenolic anti‐oxidant, toward the hydroxyl radical has been studied employing density functional theory. All the relevant potential energy surface extrema were located by optimizing geometries of the reactant complexes, transition states, and product complexes in gas phase. Solvent effect of aqueous media was treated by performing single point energy calculations using the polarizable continuum model. It has been shown how following certain steps of hydrogen abstraction and addition reactions and using a few OH radicals along with zingerone or its degradation products, two other anti‐oxidants, namely vanillin and ferulic acid can be formed. The mechanism of anti‐oxidant action of zingerone through single electron transfer has also been studied. Copyright © 2013 John Wiley & Sons, Ltd.     

Hydrogen abstraction from H‐donor substrates by the 6‐CF3‐benzotriazol‐N‐oxyl radical (TFNO)

The aminoxyl radical 6‐trifluoromethyl‐benzotriazol‐N‐oxyl (TFNO) has been generated from the parent hydroxylamine 6‐CF₃‐1‐hydroxy‐benzotriazole (TFBT) by one‐electron oxidation with a Ce^IV salt and characterized by spectrophotometry and cyclic voltammetry (CV). Rate constants of H‐abstraction (k_H) by TFNO from a number of H‐donor benzylic substrates have been determined spectrophotometrically in MeCN solution at 25 °C. A radical H‐atom transfer (HAT) route of oxidation is substantiated for TFNO by several pieces of evidence. The kinetic data also testify the relevance of stereoelectronic effects upon the HAT reactivity of TFNO. Copyright © 2010 John Wiley & Sons, Ltd.     

A mechanistic dichotomy in concerted versus stepwise pathways in hydride and hydrogen transfer reactions of NADH analogues

A mechanistic dichotomy of one‐step versus stepwise pathways in hydride and hydrogen transfer reactions of NADH analogues is discussed including the relation between two pathways: a continuous change versus a discontinuous change of the mechanism. Examples of stepwise electron–proton–electron transfer through a charge transfer (CT) complex in hydride transfer from NADH analogues to hydride acceptors are presented including the detection and the reactivity of the intermediate, that is, radical cations of NADH analogues. The relation between stepwise versus one‐step mechanisms of hydride and hydrogen transfer reaction of NADH analogues is also clarified by showing examples of the change of the mechanism including the borderline. Copyright © 2008 John Wiley & Sons, Ltd.     

DNA strand breaks induced by concerted interaction of H radicals and low-energy electrons

We propose a mechanism of DNA single strand breaks induced by low-energy electrons. Density functional theory calculations have been performed on a neutral, hydrogenated, and/or negatively charged nucleotide of cytosine in the gas phase to identify barriers for the phosphate-sugar O–C bond cleavage. Attachment of the first excess electron induces intermolecular proton transfer to cytosine. The resulting neutral radical of hydrogenated cytosine binds another excess electron, and the excess charge is localized primarily on the C6 atom. A barrier encountered for proton transfer from the C2’ atom of the adjacent sugar unit to the C6 atom of cytosine is 3.6 and 5.0 kcal/mol, based on the MPW1K and B3LYP electronic energies corrected for zero-point vibrations, respectively. The proton transfer is followed by a barrier-free sugar-phosphate C–O bond cleavage. The proton transfer is impossible for the neutral nucleotide, as there is no local minimum for the product. In the case of anionic and hydrogenated nucleotides the same barrier determined at the B3LYP level is as large as 29.3 and 22.4 kcal/mol respectively. This illustrates that the consecutive hydrogenation and electron attachment make the nucleotide of cytosine susceptible to a strand break. The rate of the C–O bond cleavage in the anion of hydrogenated nucleotide of cytosine is estimated to be ca. 10¹⁰  s^-1. The proposed mechanism proceeds through bound anionic states, not through metastable states with finite lifetimes and discrete energy positions with respect to the neutral target. The results suggest that at least for DNA without hydration even very low-energy electrons may cleave the DNA backbone.     

The enthalpies of dissociation of the N?O bonds in two quinoxaline derivatives

The present work reports the first experimental thermochemical study of mono‐N‐oxides derived from quinoxaline, namely, 3‐methoxycarbonyl‐2‐methyl‐quinoxaline N‐oxide and 3‐ethoxycarbonyl‐2‐methyl‐quinoxaline N‐oxide. The values of the enthalpies of formation, in the condensed state, and of the enthalpies of sublimation, derived from static bomb calorimetry and Calvet microcalorimetry measurements, respectively, are combined to derive the standard molar enthalpies of formation in the gaseous phase for these two compounds. From the latter values, the first and second N? O bond dissociation enthalpies for the corresponding di‐N‐oxides have been obtained. The gas‐phase experimental results are also compared with calculated data obtained with a density functional theory approach. Copyright © 2008 John Wiley & Sons, Ltd.     

Electron Spin Resonance of Alkali Metal Contact Ion Pairs of 2,6-di-tert-Butylbenzoquinone in Non Polar Solvent

The question whether excited triplet states of quinones react with a number of substrates such as alcohols, phenols, and amines, via electron transfer mechanism has attracted much attention in recent years. The existence of some triplet exciplex was postulated by Kobashi et al¹ in their study of hydrogen atom abstraction by p-chloranil using laser flash spectrocopic detection. In some recent e.s.r. and CIDEP studies^2,3, however, there is no compelling evidence that the photoreduction of quinones and benzophenones undergoes an initial electron transfer mechanism. It should be noted that most of the e.s.r. studies of quinone radical anions had been carried out in polar solvents. In flash photolysis studies some evidence has indeed been obtained^1,4 in which the efficiency of hydrogen abstraction by excited triplet quinones increases with solvent polarity and therefore it is possible that the initial primary process involves electron transfer followed immediately by proton transfer. On the other hand, we     

A theoretical study of antioxidant activity of some Schiff bases derived from biologically important phenolic aldehydes and phenylenediamines

Because of their numerous biological as well as industrial importance, the study of Schiff bases is an emerging field for the researchers, in recent time. In this study, we have designed some Schiff bases derived from biologically important precursors. The antioxidant activities of the designed compounds are thoroughly studied theoretically using density functional theory taking various parameters like bond dissociation enthalpy, ionization enthalpy, proton dissociation enthalpy, and electron transfer enthalpy followed by the study of effects of solvent, spin density, and molecular orbital on antioxidant activity of the compounds. The comparison of antioxidant activity of the compounds with that of phenol and their parent aldehydes reveals the superior antioxidant activity of the designed compounds. This study contributes towards the information of an important bridge between bioorganic and computational chemistry.     

三硝基甲烷键离解能和生成焓的理论计算

采用密度泛函(DFT)四种交换/相关函数(B3LYP、B3P86、B3PW91和PBE0)结合不同的基函数,求得了三硝基甲烷C-NO2键的离解能(BDE),并且通过合理选择参考物硝基甲烷,设计等键等电子对反应,计算了气相三硝基甲烷分子的生成焓(HOF).与实验数据进行比较,PBE0/6-31g*计算出的BDE值最好,误差为-2.1 kcal mol-1;PBE0密度泛函结合带极化函数的6-31g基组得到的HOF值与实验值吻合的最好(误差在0.1 kcal mol-1以内).     

Does gold cluster promote or scavenge radicals? A controversy at DFT

Anticancer character of gold cluster has been indicated through its free radical scavenging properties. This is in contrast to its free radical promoting ability suggested by other workers. Here, we address this controversy by probing the stabilizing effects of Au₃ cluster on RO^? vs its impacts on RO–H bond dissociation enthalpy, at B3LYP/ LACVP+* level (R═H, methyl, ethyl, n‐propyl, i‐propyl, n‐butyl, t‐butyl, and phenyl). In the presence of Au₃ cluster, bond dissociation enthalpy of O–H bond and the spin density at the RO^? oxygen are reduced dramatically. These are clear evidences for both the Au₃ facilitation of the RO–H bond breakage and its scavenging of RO^? radical. Since O–Au anchoring bond is responsible for the interaction of Au₃ cluster and ROH (or RO^?), its nature was interpreted by means of the quantum theory of atoms in molecules and the natural bond orbital. The results indicate that O–Au bond is stronger and has more covalent character in RO^?–Au₃ than in ROH–Au₃. The interaction of Au₃ cluster with RO^? is 1.5 to 3 times more than that with ROH. As a result, gold cluster scavenging property appears more prominent than its free radical initiation activity.     

Dissociation of H_2 on Mg-coated B_(12)C_6N_6

The dissociation of H_2 molecule is the first step for chemical storage of hydrogen, and the energy barrier of the dissociation is the key factor to determine the kinetics of the regeneration of the storage material. In this paper, we investigate the hydrogen adsorption and dissociation on Mg-coated B_(12)C_6N_6. The B_(12)C_6N_6 is an electron deficient fullerene, and Mg atoms can be strongly bound to this cage by donating their valance electrons to the virtual 2p orbitals of carbon in the cluster. The preferred binding sites for Mg atoms are the B_2C_2 tetragonal rings. The positive charge quantity on the Mg atom is 1.50 when a single Mg atom is coated on a B_2C_2 ring. The stable dissociation products are determined and the dissociation processes are traced. Strong orbital interaction between the hydrogen and the cluster occurs in the process of dissociation, and H_2 molecule can be easily dissociated. We present four dissociation paths, and the lowest energy barrier is only 0.11 eV, which means that the dissociation can take place at ambient temperature.