Atom Transfer Mechanism Research Articles

Cross-Selective Aza-Pinacol Coupling via Atom Transfer Catalysis.

A cross-selective aza-pinacol coupling of aldehydes and imines has been developed to afford valuable β-amino alcohols. This strategy enables chemoselective conversion of aliphatic aldehydes to ketyl radicals, in the presence of more easily reduced imines and other functional groups. Upon carbonyl-specific activation by AcI, a photoinitiated Mn catalyst selectively reduces the resulting α-oxy iodide by an atom transfer mechanism. The ensuing ketyl radical selectively couples to imines, precluding homodimerization by a classical reductive approach. In this first example of reductive, ketyl coupling by atom transfer catalysis, Zn serves as a terminal reductant to facilitate Mn catalyst turnover. This new strategy also enables ketyl radical couplings to alkenes, alkynes, aldehydes, propellanes, and chiral imines.

Catalytic reduction of nitrate by an oxidorhenium (V) complex

The previously published oxidorhenium(V) complex [ReOCl(L1)2] (2), equipped with the bidentate phenol-dimethyloxazoline ligand HL1 (2-(4,4-dimethyl-4,5-dihydro-1,3-oxazol-2-yl)-phenol), shows catalytic activity for the reduction of nitrate to nitrite under mild, ambient and aqueous conditions. The reaction operates under an oxygen atom transfer (OAT) mechanism, using dimethyl sulfide SMe2 (DMS) as oxygen acceptor. Experiments with catalytic amounts of 2 and labelled 15NO3– proved the full reduction of 15NO3– to 15NO2– by 15N NMR spectroscopy.For the second reduction step of nitrite NO2–, we have evidence for a single electron reduction to yield paramagnetic NO, as from one nitrate reduction experiment the paramagnetic cis-dioxidorhenium(VI) complex [Re(O)2(L1)2] (3) could be isolated and characterized by single-crystal X-ray diffraction analysis. Such a single electron reduction of nitrite NO2– would yield NO and complex 3 as the oxidation product.In a stoichiometric experiment of 2, 15NO3– and DMS, nitrous oxide 15N2O could be detected as the only 15N containing product by 15N NMR spectroscopy, proving that further reduction beyond NO is possible with pre-catalyst 2. The rhenium species responsible for the reduction to N2O is currently unknown. Most likely, N2O is formed via an intermediate rhenium nitrosyl complex. Experimental data was gathered by 1H and 15N NMR, IR- and UV–Vis spectroscopy, HR-ESI mass spectrometry, X-ray crystallography, and supported by theoretical computations (DFT).

Energy Read-out as a Probe of Kinetically Hidden Transition States.

The initial energy in a reactive intermediate is derived from the transition state before the intermediate but can affect selectivity after the intermediate. In this way an observable selectivity can report on a prior, kinetically hidden mechanistic step. This new type of mechanistic probe is demonstrated here for the oxidation of 1-methylcyclobutanol by phthaloyl peroxide/Bu4N+Br-, and it supports a hypobromite chain mechanism in place of the previously proposed hydrogen atom transfer mechanism.

Ligand-based design of chalcone analogues and thermodynamic analysis of their mechanism of free radical scavenge.

Overproduction of free radicals in the body may result in oxidative stress, which plays an active role in the development of various health disorders. Consequently, the development of efficient free radical scavengers and evaluation of their antioxidant properties is a research area of interest. In the present research, computational quantum chemical approach based on the density functional theory (DFT) method was employed to elucidate the free radical scavenge of chalcone derivatives via thermodynamic studies. New set of chalcone antioxidants were designed. Their reactivity towards hydroperoxyl (HOO·) and methyl peroxyl (CH3OO·) radicals were investigated through systematic study of their mechanism of free radical scavenge. Various reaction enthalpies and Gibbs free energy that characterize the various steps in these mechanisms were computed in the gas phase and aqueous solution, in order to identify the main channels of reaction. Results in the gas phase indicate that hydrogen atom transfer (HAT) and sequential proton loss electron transfer (SPLET) mechanisms represent the most plausible reaction pathways, while single electron transfer followed by proton transfer (SET-PT) mechanism was thermodynamically unfeasible. However, these mechanisms were thermodynamically favoured in aqueous solution. Also, these chalcone derivatives were observed to be more effective in scavenging HOO· than CH3OO· radicals in both phases. Based on the exergonicity of the obtained results, the molecule MCHM 17 ((E)-1-(3-bromo-5-hydroxyphenyl)-3-(2,5-dihydroxyphenyl)prop-2-en-1-one) at the 5-OH site was found to exhibit the greatest potential to scavenge HOO· and CH3OO· radicals in both phases. This research is a gateway to the efficient exploitation of these compounds in pharmacy and food chemistry.

Ruthenium-Catalyzed Dehydrogenation Through an Intermolecular Hydrogen Atom Transfer Mechanism.

The direct dehydrogenation of alkanes is among the most efficient ways to access valuable alkene products. Although several catalysts have been designed to promote this transformation, they have unfortunately found limited applications in fine chemical synthesis. Here, we report a conceptually novel strategy for the catalytic, intermolecular dehydrogenation of alkanes using a ruthenium catalyst. The combination of a redox‐active ligand and a sterically hindered aryl radical intermediate has unleashed this novel strategy. Importantly, mechanistic investigations have been performed to provide a conceptual framework for the further development of this new catalytic dehydrogenation system.

Theoretical insights into the direct radical scavenging activities of 8-hydroxyquinoline: Mechanistic, thermodynamic and kinetic studies

A Density Functional Theory study of the mechanisms, thermodynamics and kinetics of some antiradical reactions of 8-hydroxyquinoline (8HQ) against •OH is reported. The radical adduct formation (RAF), hydrogen atom transfer (HAT) and single electron transfer (SET) mechanisms are investigated. The results indicate that 8HQ is an efficient RAF-dependent direct •OH radical deactivator, in accordance with recent experimental findings that 8HQ is a potent scavenger of reactive oxygen species (ROS). The ortho and para carbons to the hydroxyl group in 8HQ, not including the bridgehead carbon, are identified as highly favorable RAF sites in polar and nonpolar solvents. Interestingly, RAF via the para carbon is thermodynamically feasible, fast (with apparent rate constants 2.867 × 108 and 1.012 × 107M-1s-1 in water and benzene, respectively), and contributes over 70% of 8HQ’s antioxidant capacity. Our results support the viewpoint that direct ROS scavenging plays a key role in 8HQ’s anti-neurodegenerative activities.

DFT / TDDFT insights into excited state intra-molecular hydrogen atom transfer mechanism in Liqcoumarin: an EFP1 study.

The theoretical calculations were carried out on Liqcoumarin (LC) and its water complex LC+(H20)4-[LCH] at the ground (S0) / first excited states (S1) by employing density functional theory (DFT) / state specific time-dependent density functional theory (SS-TDDFT). In LC and LCH, there is an intra-molecular hydrogen bond between hydroxyl group and acetyl group along with four inter-molecular hydrogen bonds in the hydrated molecule. The computational studies of molecular structural parameters, electrostatic potential, NBO analysis, molecular orbital's, and UV-Vis spectra of both molecules under polar solvents were explored by B3LYP / 6-31G (d,p) / PCM / EFP1 method. The intra-molecular hydrogen atom transpires between hydroxyl to acetyl group in both pure andhydrated molecules confirm the ICT process, and it affirms through potential energy surface (PES) scans.

Novel phenolic compounds by DFT: Electronic effects on antioxidant activity of 4‐vinylphenol derivatives

AbstractConsidering the biological importance of phenolic compounds and their antioxidant activities, we have reached for 10 novel 2,6‐diX‐4‐vinylphenol derivatives (X = NMe2, NH2, OMe, Me, H, Br, Cl, F, CN, and CF3, 1NMe2‐10CF3), at the B3LYP/6‐311++G** level of theory. To evaluate their antioxidant efficiency, the OH bond dissociation energy (BDE) and vertical ionization potential (IPV) are investigated for all structures in gas, water, and benzene phases, using conductor‐like polarized continuum model (CPCM) via B3LYP, LC‐ωPBE, M05‐2X, and M06‐2X functionals. The results indicate that in going from electron‐withdrawing groups (EWGs) to electron‐donating groups (EDGs), the BDE and IPV values decrease which may suggest the increasing efficiency of antioxidants via hydrogen atom transfer (HAT) and single electron transfer (SET) mechanisms, respectively. The calculated rate constants (krxn) for reactions between 1NMe2‐10CF3 with ·OOH and·OH radicals indicate that 1NMe2 shows the highest one. The nucleus‐independent chemical shift (NICS) index, energies of highest occupied and lowest unoccupied molecular orbitals (EHOMO and ELUMO, respectively), and natural bond orbital (NBO) analysis provide relevant results to understand the nature of antioxidant activity and stability of their corresponding radicals. The lowest BDE and IPV values are observed in gas and water phases, respectively. Structure 1NMe2 turns out as the most efficient antioxidant for showing the lowest values of BDE and IPV and highest values of NICS, EHOMO, second‐order perturbation energy (E2) and natural charge. Spin densities and electrostatic potential (ESP) maps appear consistent with the obtained results. The overall order of antioxidant efficiency in gas, water, and benzene phases is 1NMe2 > 2NH2 >3OMe > 4Me > 5H > 6Br > 7Cl > 8F > 9CN > 10CF3.

Revealing the mechanism of the water autoprotolysis on the basis of Marcus theory and TD-DFT methodology

The rate constants for the autoprotolysis (kA) and corresponding ions recombination (kR) reaction of water and related protic liquids are computed considering both processes as reversible, sequential two-step reactions according to a breaking mechanism, which is supported both experimentally and computationally. The first step, according to the Marcus Theory (MT), consists of an horizontal single electron transfer (SET) occurring in the most stable water dimer, the reaction initial state (IS), to produce the transition state (TS). The second step is a hydrogen atom transfer (HAT), taking place consecutively at the said TS, leading to the reaction final state (FS) after relaxation. The optimized structure of the endergonic FS was calculated by means of the Time Dependent Density Functional Theory (TD-DFT). The determination of the free energy of activation for the autoprotolysis and for the corresponding ions recombination (∆GA≠ and ∆GR≠, respectively) was carried out following the outer-sphere adiabatic MT. The generality of both the proposed mechanism and used computational method is supported by the accurate calculation (MAPE ca. 13%) of the autoprotolysis constants (pKA) of water and five protic liquids (small alcohols and ammonia), covering a range of ca. 15 pKA units. Alternative feasible water mechanisms such as the Single Proton Transfer (SPT) mechanism, based on the non-concerted proton transfer between two water molecules, and the Concerted SET and Hydrogen Atom Transfer (CSETHAT) mechanism were also considered. Nonetheless, all these alternative mechanisms were discarded due to their computed slower autoprotolysis kinetics.

Antioxidant and Anticancer Properties of Functionalized Ferrocene with Hydroxycinnamate Derivatives-An Integrated Experimental and Theoretical Study.

Two ferrocenyl derivatives, Fc-CA and Fc-FA, were synthesized by a condensation reaction between the amino ferrocene and hydroxycinnamic acids, that is, caffeic acid (CA) and ferulic acid (FA). The structures and purity of all compounds were characterized by 1H- and 13C NMR spectroscopies, Mass spectrometry (MS), and elemental analysis. The antioxidant properties of Fc-CA and Fc-FA and of its ligand were studied for free radical scavenging activity toward DPPH•, superoxide anion (O2•-), NO•, and ABTS•+ by UV-vis and electron spin resonance spectroscopies. The cytotoxicity of Fc-CA and Fc-FA against MCF-7 and MDA-MB-231 breast cancer cells and MRC-5 human lung fibroblasts cell was higher than that of cisplatin. The geometry and electronic structures of all compounds were then simulated using density functional theory at M05-2X/6-311+G(d,p) level of theory. Thermodynamics of the free radical quenching reactions by common mechanisms reveal the higher antioxidant properties of the Fc-CA and Fc-FA in comparison to their ligands. An in-depth study of the free radical scavenging activity against HOO• and HO• radicals was performed for two of the most favorable and competitive mechanisms, the hydrogen transfer (either hydrogen atom transfer or proton-coupled electron transfer mechanisms) and the radical adduct formation. The in silico studies indicated that ferrocenyl derivatives exhibited prominent binding affinity to protein models in comparison to CA and FA. Their dock scores were notable at ligand binding sites of ERα, Erβ, and JAK2 proteins. Dock pose analysis also shed light into the possible mechanism of action for the studied compounds.

Evaluation of structural properties and antioxidant capacity of Proxison: A DFT investigation

Proxison is a new synthetic flavonoid-based molecule with promising capability in protection of neural cells against oxidative stress. All structural analysis such as point group, energy, polarity, HOMO and LUMO energies, HOMO-LUMO energies gap (Eg), ionization potential (I), electron affinity (A), chemical potential (μ), global hardness (η), global electrophilicity (ω), density of states (DOS) plot, molecular electrostatic potential (MEP) profile, natural bond orbital (NBO), IR, 1H NMR, 13C NMR, UV–Vis spectra as well as antioxidant capacity of Proxison molecule have been calculated using B3LYP/6-311++G (d,p) level of theory and evluated with details. The antioxidant property of Proxison can be explained by hydrogen atom transfer and transition metals chelating mechanisms.

An asymmetric performance between mangiferin and isomangiferin as antioxidants

Abstract The electronic performance between mangiferin and isomangiferin as antioxidants was achieved using electron and hydrogen atom transfer mechanisms at DFT/B3LYP/6-31+G(d,p) level. According to theoretical properties of these molecules a structural and electronic symmetry among 3-hydroxyl of xanthone, 2’-hydroxyl of sugar, and ether moiety of sugar were stablished. The sugar moiety changes on 2 and 4 positions showed that isomangiferin is more potent than mangiferin by electron transfer and mangiferin by hydrogen transfer. Hydrogen bonds between sugar and resorcinol rings can be involved to their electronic behavior and favored conformations of low energies. Sugar moiety in both compounds is responsible for the antioxidant capacity increase in xanthone ring.

Anti-oxidation properties of 2-substituted furan derivatives: A mechanistic study

2-(p-phenyl substituted styryl)-furans were synthesized and studied the excited state and anti oxidation properties using absorption, fluorescence, density functional theory and DPPH radical scavenging assay. 2-(p-hydroxy phenyl styryl)-furan (6) exhibits good antioxidant properties with IC50 ~ 40 μM as compared to the amine, chloro, cyano methoxy and nitro substituted styryl compounds (1–5, 7–8) (IC50 > 150 μM). It is shown that furans 1–3 with strong electron withdrawing nitro, cyano and chloro substituent do not show antioxidant properties. The O–H bond dissociation energy (BDE) of p-hydroxy substituted furan compound is comparable to the BDE of vitamin E. The antioxidant activity of furan compound is further reduced with increasing the dipolar nature of the molecule. From the thermodynamic parameters and antioxidant properties, it is shown that there is a correlation of antioxidant properties with the ground state dipole moment, X–H bond dissociation energy (X: O; N) and proton affinity (PA). In presence of the furan compound, the quenching of DPPH radical is occurred predominantly through hydrogen atom transfer mechanism.

Comparison of Vitamin C and Its Derivative Antioxidant Activity: Evaluated by Using Density Functional Theory.

Vitamin C (VC) is an essential antioxidant, but its application is limited because of its unstable chemical properties. Hence, a variety of VC derivatives have emerged in practical antioxidant applications. To explore the relationship between the antioxidant properties and the chemical structures of vitamin C and its derivatives, density functional theory (DFT) was used in this work to calculate the reaction enthalpies of the mechanisms related to radical scavenging activity. The structures were optimized at the B3LYP-D3(BJ)/6-31G* level of theory. Single point calculations (SPE) were performed at the PWPB95-D3 (BJ)/def2-QZVPP level. To estimate the solvent effect on antioxidant properties, the SMD (solvation model based on density) method was used. The results showed that in the process of optimizing the chemical structure of vitamin C, the antioxidant capacity of its derivatives decreased slightly in aqueous solvents. In the calculation process, it is also found that in the choice of antioxidant mechanism, these compounds are more inclined to the hydrogen atom transfer (HAT) mechanism, and from the chemical structure point of view, the double bond of the lactone ring is essential for its free radical scavenging activity. In general, it is necessary to continue to optimize the structure of VC to obtain derivatives with better oxidation resistance and more practical value.

Probing structural properties and antioxidant activity mechanisms for eleocarpanthraquinone

In this work, we present a computational investigation on the structure and energetics of eleocarpanthraquinone, a newly isolated polyphenolic anthrone-antraquinone. Properties such as bond lengths, angles, atomic charges, bond dissociation enthalpies (BDEs), and ionization potential (IP) were determined through the use of density functional theory (DFT). The B3LYP and M06-2X exchange-correlation functionals were employed along with the 6-31+G(d,p), 6-31+ +G(d,p), and 6-311+G(d,p) basis sets for performing computations in the gas-phase, water, methanol, and ethanol. The conformation presenting all the hydroxyl groups undergoing hydrogen-bond interactions with neighboring oxygen atoms (conformation 5) was assigned as the most stable structure while its counterpart presenting no hydrogen-bond interaction was found to be 36.45 kcal/mol less stable than conformation 5 in the potential energy surface probed at the B3LYP/6-311+G(d,p) level of theory in the gas-phase, for instance. More importantly, the lowest O-H bond dissociation enthalpy was determined to be 93.80 kcal/mol at the B3LYP/6-311+G(d,p) level of theory in water against the 146.58 kcal/mol regarding the IP computed at the same approach, suggesting the hydrogen atom transfer mechanism as being preferred over the single electron transfer mechanism in regards to the antioxidant potential for the case of eleocarpanthraquinone; the same conclusion was drawn from the outcomes of all the other approaches used.

The Effect of Sacred Lotus (Nelumbo nucifera) and Its Mixtures on Phenolic Profiles, Antioxidant Activities, and Inhibitions of the Key Enzymes Relevant to Alzheimer's Disease.

Sacred lotus (Nelumbo nucifera) has long been used as a food source and ingredient for traditional herbal remedies. Plant parts contain neuroprotective agents that interact with specific targets to inhibit Alzheimer’s disease (AD). Organic solvents including methanol, ethyl acetate, hexane, and n-butanol, are widely employed for extraction of sacred lotus but impact food safety. Seed embryo, flower stalk, stamen, old leaf, petal, and leaf stalk of sacred lotus were extracted using hot water (aqueous extraction). The extractions were analyzed for their bioactive constituents, antioxidant and anti-AD properties as key enzyme inhibitory activities toward acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and β-secretase 1 (BACE-1). Results showed that the sacred lotus stamen exhibited significant amounts of phenolics, including phenolic acids and flavonoids, that contributed to high antioxidant activity via both single electron transfer (SET) and hydrogen atom transfer (HAT) mechanisms, with anti-AChE, anti-BChE, and anti-BACE-1 activities. To enhance utilization of other sacred lotus parts, a combination of stamen, old leaf and petal as the three sacred lotus plant components with the highest phenolic contents, antioxidant activities, and enzyme inhibitory properties was analyzed. Antagonist interaction was observed, possibly from flavonoids–flavonoids interaction. Further in-depth elucidation of this issue is required. Findings demonstrated that an aqueous extract of the stamen has potential for application as a functional food to mitigate the onset of Alzheimer’s disease.

Novel silylphenol antioxidants by density functional theory

AbstractWe have scrutinized five novel silylphenol antioxidants, including 2‐silylphenol (1), 4‐silylphenol (2), 2,6‐disilylphenol (3), 2,4‐disilylphenol (4), and 2,4,6‐trisilylphenol (5), at M06/6–311++G** level of theory. To evaluate the antioxidant efficiency, the electronic effects on O─H bond dissociation energy (BDE) and vertical ionization potential (IPv) of 1–5 are investigated, which are mainly governed by electronic effects. The conductor‐like polarized continuum model (CPCM) is applied to measure the antioxidant capacity in the solution phase. The results show that antioxidants with the lowest BDE and IPv values can efficiently act via hydrogen atom transfer (HAT) and single electron transfer (SET) mechanisms, respectively. The stability of resulting radicals is measured by nucleus independent chemical shift (NICS) index, natural bond orbital (NBO) analysis, and nucleophilicity (N) index. The BDE shows lower values in the gas phase with respect to water, while water exhibits lower IPv values than gas. Structure 5 turns out as the most efficient antioxidant. The overall order of antioxidant efficiency in both gas and water phases is 5 > 2 > 3 > 4 > 1.

Role of C‒H bond in the antioxidant activities of rooperol and its derivatives: A DFT study

Rooperol and its derivatives, derived from the Hypoxis rooperi plant, are polyphenolic and norlignan compounds with excellent antioxidant activities. The reaction enthalpies for the free-radical scavenging by rooperol and its six derivatives were studied using density functional theory. We found that the C−H groups played a significant role in the antioxidant activities in non-polar phases. In the gas and benzene phases, rooperol and its derivatives preferentially underwent the free-radical scavenging process via the 3‒CH group by following the hydrogen atom transfer (HAT) mechanism. In polar phases, the sequential proton loss electron transfer (SPLET) was the most preferred mechanism, and the phenolic O‒H groups played a significant role. Additionally, we found that when the hydrogen atom in the OH group was replaced by a glucose moiety, the antioxidant activity of the adjacent OH group was reduced. ROP, DHROP-I, DHROP-II, ROP-4″-G and ROP-4′G have catechol moiety, they may proceed double step-wise mechanisms to trap free radicals. In the gas and benzene phases, the preferable mechanism is dHAT. In water phase, it is SPLHAT.

Kinetics and mechanism of reactive radical mediated fluconazole degradation by the UV/chlorine process: Experimental and theoretical studies

The emerging organic contaminants can be effectively removed in the UV/chlorine process by produced hydroxyl radical (HO) and chlorine-derived radicals (Cl, ClO, etc.). However, the degradation mechanism and pathways of reactive radical reaction with contaminants are still unclear. Here we investigated the reactive radical mediated reaction kinetics and mechanism of fluconazole in UV/chlorine process using theoretical calculations and experimental studies. The results showed that fluconazole could be degraded effectively by UV/chlorine treatment than by UV photolysis and chlorination alone. The Cl and HO were found to play a major role in degradation of fluconazole by hydrogen atom transfer and radical adduct formation mechanisms, respectively. The single-electron transfer pathway of Cl, HO and ClO seems to be impossible due to the high free energy barriers of 21.87 kcal mol−1, 35.12 kcal mol−1 and 46.05 kcal mol−1, respectively. Six transformation products were identified by high resolution mass spectrometry and they were formed via fluconazole de-fluorination, hydroxylation, cleavage and cyclization with the triazole ring. The water quality parameters such as pH and coexisting components (DOM, HCO3−/CO32−) could influence the removal of fluconazole in UV/chlorine process by impacting the generation of reactive radicals. The toxicity of fluconazole to aquatic organisms can be decreased by UV/chlorine process, and only trace amounts of chloroform were detected.

Phenol Oxidation by a Nickel(III)-Fluoride Complex: Exploring the Influence of the Proton Accepting Ligand in PCET Oxidation.

In order to gain insight into the influence of the H+ -accepting terminal ligand in high-valent oxidant mediated proton coupled electron transfer (PCET) reactions, the reactivity of a high valent nickel-fluoride complex [NiIII (F)(L)] (2, L=N,N'-(2,6-dimethylphenyl)-2,6-pyridinecarboxamidate) with substituted phenols was explored. Analysis of kinetic data from these reactions (Evans-Polanyi, Hammett, and Marcus plots, and KIE measurements) and the formed products show that 2 reacted with electron rich phenols through a hydrogen atom transfer (HAT, or concerted PCET) mechanism and with electron poor phenols through a stepwise proton transfer/electron transfer (PT/ET) reaction mechanism. The analogous complexes [NiIII (Z)(L)] (Z=Cl, OCO2 H, O2 CCH3 , ONO2 ) reacted with all phenols through a HAT mechanism. We explore the reason for a change in mechanism with the highly basic fluoride ligand in 2. Complex 2 was also found to react one to two orders of magnitude faster than the corresponding analogous [NiIII (Z)(L)] complexes. This was ascribed to a high bond dissociation free energy value associated with H-F (135 kcal mol-1 ), which is postulated to be the product formed from PCET oxidation by 2 and is believed to be the driving force for the reaction. Our findings show that high-valent metal-fluoride complexes represent a class of highly reactive PCET oxidants.