Showing papers on "Hydrogen atom abstraction published in 2016"
TL;DR: This is the first visible-light-induced formation of alkoxyl radicals from N-alkoxyphthalimides, and the Hantzsch ester as the reductant is crucial for the reaction.
Abstract: Reported herein is the first visible-light-induced formation of alkoxyl radicals from N-alkoxyphthalimides, and the Hantzsch ester as the reductant is crucial for the reaction. The selective hydrogen atom abstraction by the alkoxyl radical enables C(sp(3))-H allylation and alkenylation reactions under mild reaction conditions at room temperature. Broad substrate variations, including a structurally complexed steroid, undergo the C(sp(3))-H functionalization reaction effectively with high regio- and chemoselectivity.
216 citations
TL;DR: Uranyl nitrate hexahydrate is described as a convenient, hydrogen atom abstraction catalyst that can mediate fluorinations of certain alkanes upon activation with visible light.
Abstract: The fluorination of unactivated C(sp(3) )-H bonds remains a desirable and challenging transformation for pharmaceutical, agricultural, and materials scientists. Previous methods for this transformation have used bench-stable fluorine atom sources; however, many still rely on the use of UV-active photocatalysts for the requisite high-energy hydrogen atom abstraction event. Uranyl nitrate hexahydrate is described as a convenient, hydrogen atom abstraction catalyst that can mediate fluorinations of certain alkanes upon activation with visible light.
116 citations
TL;DR: In this article, the effects of adding hydrogen and carbon dioxide simultaneously to fuel on soot formation in an axisymmetric laminar coflow ethylene/air diffusion flame at atmospheric pressure were investigated.
114 citations
TL;DR: This study reports the first example of tuning the second coordination sphere of high-valent metal-oxo species by binding a redox-inactive metal ion at the supporting ligand site, thereby modulating their electron-transfer properties as well as their reactivities in oxidation reactions.
Abstract: A mononuclear non-heme manganese(V)–oxo complex, [MnV(O)(TAML)]− (1), was synthesized by activating dioxygen in the presence of olefins with weak allylic C–H bonds and characterized structurally and spectroscopically. In mechanistic studies, the formation rate of 1 was found to depend on the allylic C–H bond dissociation energies (BDEs) of olefins, and a kinetic isotope effect (KIE) value of 16 was obtained in the reactions of cyclohexene and cyclohexene-d10. These results suggest that a hydrogen atom abstraction from the allylic C–H bonds of olefins by a putative MnIV–superoxo species, which is formed by binding O2 by a high-spin (S = 2) [MnIII(TAML)]− complex, is the rate-determining step. A Mn(V)–oxo complex binding Sc3+ ion, [MnV(O)(TAML)]−–(Sc3+) (2), was also synthesized in the reaction of 1 with Sc3+ ion and then characterized using various spectroscopic techniques. The binding site of the Sc3+ ion was proposed to be the TAML ligand, not the Mn–O moiety, probably due to the low basicity of the oxo ...
105 citations
TL;DR: Rate calculations suggest that acid catalysis play a key role in the formation of sulfuric acid in the Earth's stratosphere, Venusian atmosphere, and on heterogeneous surfaces.
Abstract: ConspectusHydrogen atom transfer (HAT) reactions are ubiquitous and play a crucial role in chemistries occurring in the atmosphere, biology, and industry. In the atmosphere, the most common and traditional HAT reaction is that associated with the OH radical abstracting a hydrogen atom from the plethora of organic molecules in the troposphere via R–H + OH → R + H2O. This reaction motif involves a single hydrogen transfer. More recently, in the literature, there is an emerging framework for a new class of HAT reactions that involves double hydrogen transfers. These reactions are broadly classified into four categories: (i) addition, (ii) elimination, (iii) substitution, and (iv) rearrangement. Hydration and dehydration are classic examples of addition and elimination reactions, respectively whereas tautomerization or isomerization belongs to a class of rearrangement reactions. Atmospheric acids and water typically mediate these reactions.Organic and inorganic acids are present in appreciable levels in the a...
73 citations
TL;DR: The utility of the transformation is demonstrated in the late-stage site-selective functionalization of natural products and pharmaceuticals, allowing rapid derivatization for investigation of structure-activity relationships.
Abstract: We report a simple one-pot protocol that affords functionalization of N-CH3 groups in N-methyl-N,N-dialkylamines with high selectivity over N-CH2R or N-CHR2 groups. The radical cation DABCO+•, prepared in situ by oxidation of DABCO with a triarylaminium salt, effects highly selective and contra-thermodynamic C–H abstraction from N-CH3 groups. The intermediates that result react in situ with organometallic nucleophiles in a single pot, affording novel and highly selective homologation of N-CH3 groups. Chemoselectivity, scalability, and recyclability of reagents are demonstrated, and a mechanistic proposal is corroborated by computational and experimental results. The utility of the transformation is demonstrated in the late-stage site-selective functionalization of natural products and pharmaceuticals, allowing rapid derivatization for investigation of structure–activity relationships.
72 citations
TL;DR: Metal-peroxo intermediates are key species in the catalytic cycles of nonheme metalloenzymes, but their chemical properties and reactivity patterns are still poorly understood.
Abstract: Metal-peroxo intermediates are key species in the catalytic cycles of nonheme metalloenzymes, but their chemical properties and reactivity patterns are still poorly understood. The synthesis and characterization of a manganese(III)-peroxo complex with a pentadentate bispidine ligand system and its reactivity with aldehydes was studied. Manganese(III)-peroxo can react through hydrogen-atom abstraction reactions instead of the commonly proposed nucleophilic addition reaction. Evidence of the mechanism comes from experiments which identify a primary kinetic isotope effect of 5.4 for the deformylation reaction. Computational modeling supports the established mechanism and identifies the origin of the reactivity preference of hydrogen-atom abstraction over nucleophilic addition.
63 citations
TL;DR: In this article, the authors discuss and show how the new mechanisms have been established in terms of the hydrogen bonding changes by reviewing some of the combined experimental and theoretical studies that have recently shed light on the intricate role of both triplet and singlet excited-state hydrogen bondings.
Abstract: The interaction between hydrogen donor and acceptor molecules, known well as hydrogen bonding, forms a ubiquitous network in the natural and synthesis world. The hydrogen bonding role has thus been the subject of intensive work in the past. In this article, we discuss and show how the new mechanisms have been established in terms of the hydrogen bonding changes by reviewing some of the combined experimental and theoretical studies that have recently shed light on the intricate role of both triplet and singlet excited-state hydrogen bondings in photoinduced liquid dynamics and phenomena.
63 citations
TL;DR: The findings show that cobalt(III)-superoxo species are capable of performing hydrogen atom abstraction processes and a stepwise O2-activating process helps to rationalize cobalt-catalyzed aerobic oxidations and sheds light on the possible mechanism of action for Co-bleomycin.
Abstract: Bubbling O2 into a THF solution of CoII(BDPP) (1) at −90 °C generates an O2 adduct, Co(BDPP)(O2) (3). The resonance Raman and EPR investigations reveal that 3 contains a low spin cobalt(III) ion bound to a superoxo ligand. Significantly, at −90 °C, 3 can react with 2,2,6,6-tetramethyl-1-hydroxypiperidine (TEMPOH) to form a structurally characterized cobalt(III)-hydroperoxo complex, CoIII(BDPP)(OOH) (4) and TEMPO•. Our findings show that cobalt(III)-superoxo species are capable of performing hydrogen atom abstraction processes. Such a stepwise O2-activating process helps to rationalize cobalt-catalyzed aerobic oxidations and sheds light on the possible mechanism of action for Co-bleomycin.
62 citations
TL;DR: The stability of N-centered radicals and radical cations of potential relevance in C-H amidation reactions has been quantified using highly accurate theoretical methods in this article, where the stability of neutral N-radicals depends strongly on the type of n-substituent.
Abstract: The stability of N-centered radicals and radical cations of potential relevance in C-H amidation reactions has been quantified using highly accurate theoretical methods. Combination with available C-H bond energies for substrate fragments allows for the prediction of reaction enthalpies in 1,5-hydrogen atom transfer (HAT) steps frequently encountered in reactions such as the Hofmann-Loffler-Freytag (HLF) reaction. Protonation of N-radicals is found to be essential in classical HLF reactions for thermochemically feasible HAT steps. The stability of neutral N-radicals depends strongly on the type of N-substituent. Among the electron-withdrawing substituents, the trifluoroacetyl (TFA) group is the least and the toluenesulfonyl (tosyl) group the most stabilizing. This implies that TFA-aminyl radicals have the broadest and tosyl-aminyl radicals the smallest window of synthetic applicability. In how far the intramolecular C-H amidation reactions compete with hydrogen abstraction from common organic solvents can be judged based on a comparison of reaction thermodynamics.
61 citations
TL;DR: A new calibration procedure for quantum Rice-Ramsperger-Kassel (QRRK) unimolecular rate theory within a chemical activation mechanism is employed to calculate the pressure-falloff effect of a radical association with an aromatic ring, and it is shown that the variational effect is important in computing the energy-resolved rate constants.
Abstract: Pressure-dependent reactions are ubiquitous in combustion and atmospheric chemistry. We employ a new calibration procedure for quantum Rice–Ramsperger–Kassel (QRRK) unimolecular rate theory within a chemical activation mechanism to calculate the pressure-falloff effect of a radical association with an aromatic ring. The new theoretical framework is applied to the reaction of H with toluene, which is a prototypical reaction in the combustion chemistry of aromatic hydrocarbons present in most fuels. Both the hydrogen abstraction reactions and the hydrogen addition reactions are calculated. Our system-specific (SS) QRRK approach is adjusted with SS parameters to agree with multistructural canonical variational transition state theory with multidimensional tunneling (MS-CVT/SCT) at the high-pressure limit. The new method avoids the need for the usual empirical estimations of the QRRK parameters, and it eliminates the need for variational transition state theory calculations as a function of energy, although i...
TL;DR: A mild and selective system comprising N-hydroxyphthalimide (NHPI) and Fe(NO3)3·9H2O was developed for the oxidation of benzylic methylenes with an atmospheric pressure of molecular oxygen at 25 °C as mentioned in this paper.
TL;DR: The performance of single-determinant density functional theory was investigated for the kinetics of these reactions by comparing calculated rate constants to experimental data and showed that the M05 functional performs well for the task at hand.
Abstract: An assessment of multireference character in transition states is considered to be an important component in establishing the expected reliability of various electronic structure methods. In the present work, the multireference characters of the transition states and the forming and breaking of bonds for a large set of hydrogen abstraction reactions from phenolic compounds by peroxyl radicals have been analyzed using the T1, M, B1, and GB1 diagnostics. The extent of multireference character depends on the system and on the conditions under which the reaction takes place, and some systematic trends are observed. In particular, the multireference character is found to be reduced by solvation, the size of the phenolic compound, and deprotonation in aqueous solution. However, the deviations of calculated rate constants from experimental ones are not correlated with the extent of multireference character. The performance of single-determinant density functional theory was investigated for the kinetics of these...
TL;DR: In this paper, a combined quantum mechanical/molecular mechanical (QM/MM) calculations and molecular dynamics simulations were used to decipher the mechanism of selective halogenation by SyrB2.
Abstract: The enzyme SyrB2 employs an FeIV–oxo species to achieve selective C–H halogenation of l-threonine. Herein, we use combined quantum mechanical/molecular mechanical (QM/MM) calculations and molecular dynamics (MD) simulations to decipher the mechanism of selective halogenation by SyrB2. Our QM/MM calculations show the presence of three Cl–FeIV–oxo isomers which interconvert, and only the one having its oxo ligand pointing toward the target C–H bond is active during the hydrogen atom abstraction (H-abstraction) process. The fate of the formed Cl–FeIII–OH/R• intermediate is determined by a hydrogen-bonding interaction between the Arg254 residue and the OH ligand of Cl–FeIII–OH. The hydrogen bond not only prevents the OH group from participating in the followup rebound step to form a hydroxylated product but also facilitates the isomerization of the Cl–FeIII–OH/R• intermediate so that the Cl is directed toward the alkyl radical. The role of Arg254 in regulating the selectivity of chlorination is further discus...
TL;DR: Density-functional calculations of the full reaction coordinate demonstrate the importance of the end-on coordination of superoxide to Cu for HAA along the triplet spin surface and the large inner-sphere reorganization energy at the ET site is used as a control mechanism to arrest premature ET and dictate the correct timing of ET.
Abstract: Peptidylglycine α-hydroxylating monooxygenase (PHM) and dopamine β-monooxygenase (DβM) are copper-dependent enzymes that are vital for neurotransmitter regulation and hormone biosynthesis. These enzymes feature a unique active site consisting of two spatially separated (by 11 A in PHM) and magnetically noncoupled copper centers that enables 1e– activation of O2 for hydrogen atom abstraction (HAA) of substrate C–H bonds and subsequent hydroxylation. Although the structures of the resting enzymes are known, details of the hydroxylation mechanism and timing of long-range electron transfer (ET) are not clear. This study presents density-functional calculations of the full reaction coordinate, which demonstrate: (i) the importance of the end-on coordination of superoxide to Cu for HAA along the triplet spin surface; (ii) substrate radical rebound to a CuII hydroperoxide favors the proximal, nonprotonated oxygen; and (iii) long-range ET can only occur at a late step with a large driving force, which serves to inhibit deleterious Fenton chemistry. The large inner-sphere reorganization energy at the ET site is used as a control mechanism to arrest premature ET and dictate the correct timing of ET.
TL;DR: This work broadens the landscape of nonheme iron enzymes and makes a connection to Fenton chemistry, with implications on new potential biocatalysts that may harness hydroxyl radicals for C-H bond functionalizations.
Abstract: The iron(IV)–oxo (ferryl) intermediate has been amply established as the principal oxidant in nonheme enzymes and the key player in C–H bond activations and functionalizations. In contrast to this status, our present QM/MM calculations of the mechanism of fosfomycin biosynthesis (a broad range antibiotic) by the nonheme HppE enzyme rule out the iron(IV)–oxo as the reactive species in the hydrogen abstraction (H-abstraction) step of the pro-R hydrogen from the (S)-2-hydroxypropylphosphonic substrate. Moreover, the study reveals that the ferryl species is bypassed in HppE, while the actual oxidant is an HO• radical hydrogen-bonded to a ferric-hydroxo complex, resulting via the homolytic dissociation of the hydrogen peroxide complex, Fe(II)–H2O2. The computed energy barrier of this pathway is 12.0 kcal/mol, in fair agreement with the experimental datum of 9.8 kcal/mol. An alternative mechanism involves the iron-complexed hydroxyl radical (FeIII–(HO•)) that is obtained by protonation of the iron(IV)–oxo group...
TL;DR: Molecular dynamics simulations of the reaction of dimethyldioxirane (DMDO) with isobutane find the time gap between C-H bond-breaking and C-O bond formation ranges from 30 to 150 fs, close to the <200 fs lifetime of radical pairs from DMDO hydroxylation of trans-1-phenyl-2-ethylcyclopropane measured by Newcomb.
Abstract: We report molecular dynamics simulations of the reaction of dimethyldioxirane (DMDO) with isobutane. The reaction involves hydrogen atom abstraction in the transition state, and trajectories branch to the oxygen rebound pathway, which gives tert-butanol and acetone, or a separated radical pair. In the gas phase, only 10% of the reactive trajectories undergo the oxygen rebound pathway, but this increases to 90% in simulations in an implicit acetone solvent (SMD) because the oxygen rebound becomes barrierless in solution. Short-lived diradical species were observed in the oxygen rebound trajectories. The time gap between C–H bond-breaking and C–O bond formation ranges from 30 to 150 fs, close to the <200 fs lifetime of radical pairs from DMDO hydroxylation of trans-1-phenyl-2-ethylcyclopropane measured by Newcomb.
TL;DR: This study demonstrates a promising strategy in expanding radical SAM chemistry, providing an effective way to access nucleoside-containing compounds by using radical SAM-dependent reactions by using a substrate analogue containing an olefin moiety.
Abstract: Radical S-adenosyl-l-methionine (SAM) enzymes utilize a [4Fe-4S] cluster to bind SAM and reductively cleave its carbon-sulfur bond to produce a highly reactive 5'-deoxyadenosyl (dAdo) radical. In almost all cases, the dAdo radical abstracts a hydrogen atom from the substrates or from enzymes, thereby initiating a highly diverse array of reactions. Herein, we report a change of the dAdo radical-based chemistry from hydrogen abstraction to radical addition in the reaction of the radical SAM enzyme NosL. This change was achieved by using a substrate analogue containing an olefin moiety. We also showed that two SAM analogues containing different nucleoside functionalities initiate the radical-based reactions with high efficiencies. The radical adduct with the olefin produced in the reaction was found to undergo two divergent reactions, and the mechanistic insights into this process were investigated in detail. Our study demonstrates a promising strategy in expanding radical SAM chemistry, providing an effective way to access nucleoside-containing compounds by using radical SAM-dependent reactions.
TL;DR: Reactive properties of Loratadine are theoretically investigated using both density functional theory (DFT) calculations and molecular dynamics simulations and covalent and noncovalent interactions between LOR and •OH have also been investigated.
Abstract: Antihistamines are frequently used pharmaceuticals that treat the symptoms of allergic reactions. Loratadine (LOR) is an active component of the second generation of selective antihistaminic pharmaceutical usually known as Claritin. Frequent usage of this type of pharmaceuticals imposes the need for understanding their fundamental reactive properties. In this study we have theoretically investigated reactive properties of LOR using both density functional theory (DFT) calculations and molecular dynamics (MD) simulations. DFT study is used for collecting information related to the molecule stability, structure, frontier molecular orbitals, quantum molecular descriptors, charge distribution, molecular electrostatic potential surfaces, charge polarization, and local reactivity properties according to average local ionization energy surfaces. Based on these results, N24 atom of pyridine ring and oxygen atom O1 were identified with nucleophilic nature. In order to collect the information necessary for the proposition of degradation compounds we also calculated bond dissociation energies (BDE) for hydrogen abstraction and single acyclic bonds as well. According to BDE, the oxidation is likely to occur in the piperidine and cycloheptane rings. MD simulations were used in order to understand the interactions with water through radial distribution functions (RDF). Based on RDFs the most important interactions with solvent are determined for carbon atom C5, chlorine atom Cl15, and oxygen atom O1. Collected results based on DFT calculations and MD simulations provided information important for suggestion of possible degradation compounds. Covalent and noncovalent interactions between LOR and •OH have also been investigated.
TL;DR: Computational evidence shows that a combination of aromatization, steric and stereoelectronic effects assists the fragmentation to alkoxy radicals in radical cascades using traceless directing groups.
Abstract: Direct evidence for the formation of alkoxy radicals is reported in radical cascades using traceless directing groups. Despite the possibility of hydrogen abstraction in the fragmenting step, followed by loss of R-OH, β-scission is preferred for the formation of alkoxy radicals. For the first time, the C-O radical was intermolecularly trapped using a silyl enol ether. Various C–X fragmenting groups were explored as possible traceless directing groups for the preparation of extended polyaromatics. Computational evidence shows that a combination of aromatization, steric and stereoelectronic effects assists the fragmentation to alkoxy radicals. Additionally, a new through-space interaction was discovered between O and Sn in the fragmentation as a specific transition state stabilizing effect.
TL;DR: In this paper, the reaction pathways in coal self-heating were investigated, and the key factors for the development of coal self heating were identified, although their detailed reaction pathways were still unclear.
Abstract: Hydroxyl groups are one of the key factors for the development of coal self-heating, although their detailed reaction pathways are still unclear. This study investigated the reaction pathways in co...
TL;DR: The present reaction rates for these reactions have been used in a toluene combustion mechanism, and their effects on some combustion properties are demonstrated.
Abstract: Hydrogen abstraction from toluene by OH, H, O, CH3, and HO2 radicals are important reactions in oxidation process of toluene Geometries and corresponding harmonic frequencies of the reactants, transition states as well as products involved in these reactions are determined at the B3LYP/6-31G(2df,p) level To achieve highly accurate thermochemical data for these stationary points on the potential energy surfaces, the Gaussian-4(G4) composite method was employed Torsional motions are treated either as free rotors or hindered rotors in calculating partion functions to determine thermodynamic properties The obtained standard enthalpies of formation for reactants and some prodcuts are shown to be in excellent agreement with experimental data with the largest error of 05 kcal mol–1 The conventional transition state theory (TST) with tunneling effects was adopted to determine rate constants of these hydrogen abstraction reactions based on results from quantum chemistry calculations To faciliate its applica
TL;DR: It is demonstrated that the 5'-deoxyadenosyl radical is considerably more versatile in its chemistry than previously anticipated: hydrogen atom abstraction from Nα-cyclopropyltryptophan occurs at Cα rather than the amino group with NosL Y90A and replacing the substrate amine with a ketone or an alkene changes the chemistry from hydrogen atoms abstraction to double bond addition.
Abstract: Tryptophan lyase (NosL) is a radical S-adenosyl-l-methionine (SAM) enzyme that catalyzes the formation of 3-methyl-2-indolic acid from l-tryptophan. In this paper, we demonstrate that the 5′-deoxyadenosyl radical is considerably more versatile in its chemistry than previously anticipated: hydrogen atom abstraction from Nα-cyclopropyltryptophan occurs at Cα rather than the amino group with NosL Y90A and replacing the substrate amine with a ketone or an alkene changes the chemistry from hydrogen atom abstraction to double bond addition. In addition, the 5′-deoxyadenosyl radical can add to the [4Fe−4S] cluster and dithionite can be used to trap radicals at the active site.
TL;DR: This work reports on the formation of a variety of organotin hydrides with tin in the oxidation states Sn(II) , Sn(I) -Sn(III) and Sn(III), all accessed by the controlled removal of hydrogen from the tetravalent Ar'Sn(IV) trihydride (Ar'=2,6-dimesitylphenyl, mesityl= 2,4, 6-trimethylphenyl).
Abstract: Hydrogen can be selectively removed from organotin trihydrides to generate the corresponding organohydrostannylene intermediates. Depending on the size of the substituent and the mode of generation, the intermediates undergo further reactions. Herein, we report on the formation of a variety of organotin hydrides with tin in the oxidation states Sn(II) , Sn(I) -Sn(III) and Sn(III) -Sn(III) , all accessed by the controlled removal of hydrogen from the tetravalent Ar'Sn(IV) trihydride (Ar'=2,6-dimesitylphenyl, mesityl=2,4,6-trimethylphenyl).
TL;DR: The kinetics of hydrogen abstraction by five radicals from a biodiesel surrogate, methyl propanoate, is theoretically investigated, and the predicted rate coefficients for MP + OH agree remarkably well with experimental data over a wide temperature range.
Abstract: The kinetics of hydrogen abstraction by five radicals (H, CH3, O(3P), OH, and HO2) from a biodiesel surrogate, methyl propanoate (MP), is theoretically investigated. We employ high-level ab initio quantum chemistry methods, coupled-cluster singles and doubles with perturbative triples correction (CCSD(T)) and multi-reference singles and doubles configuration interaction (MRSDCI) with the Davidson-Silver (DS) correction, and obtain chemically accurate reaction energetics. Overall, MRSDCI + DS predicts comparable energetics to CCSD(T) for MP + H/CH3/O/OH. The rate constants are computed using transition state theory (TST-Rice–Ramsperger–Kassel–Marcus theory) in conjunction with the separable-hindered-rotor approximation, variable reaction coordinate TST, and the multi-structure all-structure (MS-AS) approach. A simplified method, semi-multi-structure, is also employed for MP + OH/HO2, and the rate coefficients with this less expensive method are in good agreement with the results obtained with the MS-AS method. The fitted modified Arrhenius expressions are provided over a temperature range of 250 to 2000 K. The predicted rate coefficients for MP + OH agree remarkably well with experimental data over a wide temperature range. Branching ratio analysis of all the studied reactions shows that abstractions of the secondary H atoms within MP are expected to dominate the consumption of fuel at low temperatures, and the contributions of abstractions from the two methyl groups increase with temperature for all abstracting radicals.
TL;DR: Using molecular dynamics simulations, it is predicted that the inclusion of nonadiabatic electronic excitations influences the dynamics of preadsorbed hydrogen abstraction from the W(110) surface by hydrogen scattering.
Abstract: Using molecular dynamics simulations, we predict that the inclusion of nonadiabatic electronic excitations influences the dynamics of preadsorbed hydrogen abstraction from the W(110) surface by hydrogen scattering. The hot-atom recombination, which involves hyperthermal diffusion of the impinging atom on the surface, is significantly affected by the dissipation of energy mediated by electron–hole pair excitations at low coverage and low incidence energy. This issue is of importance as this abstraction mechanism is thought to largely contribute to molecular hydrogen formation from metal surfaces.
TL;DR: In this paper, the thermal chemistry of formic acid on clean and oxygen-predosed Cu(110) single-crystal surfaces was studied under ultrahigh-vacuum (UHV) conditions by temperature programmed desorption (TPD) and X-ray photoelectron spectroscopy (XPS).
TL;DR: A different binding mode from the one accepted for 15- LOX-2 exclusive 15-HPETE production in front of the double (although highly 15-) 12/15 regiospecificity of 15-LOX-1 is proposed, which provides a molecular basis for specific inhibitor design.
Abstract: Lipoxygenases (LOXs) are a family of enzymes involved in the biosynthesis of several lipid mediators. In the case of human 15-LOX, the 15-LOX-1 and 15-LOX-2 isoforms show slightly different reaction regiospecificity and substrate specificity, indicating that substrate binding and recognition may be different, a fact that could be related to their different biological role. Here, we have used long molecular dynamics simulations, QM(DFT)/MM potential energy and free energy calculations (using the newly developed DHAM method), to investigate the binding mode of the arachidonic acid (AA) substrate into 15-LOX-2 and the rate-limiting hydrogen-abstraction reaction 15-LOX-2 catalyzes. Our results strongly indicate that hydrogen abstraction from C13 in 15-LOX-2 is only consistent with the “tail-first” orientation of AA, with its carboxylate group interacting with Arg429, and that only the pro-S H13 hydrogen will be abstracted (being the pro-R H13 and H10 too far from the acceptor oxygen atom). At the B3LYP/6-31G(...
TL;DR: A truncated model of the FeMo cofactor is used to explore a new mechanism for the conversion of N2 to NH3 by the nitrogenase enzyme, and reducing the barrier for this step justifies the "extra expense" of H2 production.
Abstract: A truncated model of the FeMo cofactor is used to explore a new mechanism for the conversion of N2 to NH3 by the nitrogenase enzyme. After four initial protonation/reduction steps, the H4CFe8S9 cluster has two hydrogen atoms attached to sulfur, one hydrogen bridging two iron centers and one hydrogen bonded to carbon. The loss of the CH and FeHFe hydrogens as molecular hydrogen activates the cluster to addition of N2 to the carbon center. This unique step takes place at a nearly planar four-coordinate carbon center and leads to an intermediate with a significantly weakened N-N bond. A hydrogen attached to a sulfur atom is then transferred to the distal nitrogen atom. Additional prontonation/reduction steps are modeled by adding a hydrogen atom to sulfur and locating the transition states for transfer to nitrogen. The first NH3 is lost in a thermal neutral step, while the second step is endothermic. The loss of H2 activates the complex by reducing the barrier for N2 addition by 3.5 kcal/mol. Since this is the most difficult step in the mechanism, reducing the barrier for this step justifies the "extra expense" of H2 production.
TL;DR: In this paper, a new method for the synthesis of 1,3-disubstituted benzimidazole derivatives was developed using aza-Michael addition and tested on isolated hepatocytes for their toxicity and antioxidant activity.