Hydrogen Transfer Mechanism Research Articles

On the Mechanism of Hydrogen Transfer in the HSCH(O) ⇌ (S)CHOH and HSNO ⇌ SNOH Reactions

The 1,3-intramolecular hydrogen transfer in the HSCH(O) <--> (S)CHOH and HSNO <--> SNOH reactions is studied through density functional theory calculations. The reaction force together with structural and electronic properties is monitored along the reaction path to characterize the mechanism of hydrogen transfer. It is found that in both reactions the hydrogen transfer is activated by the structural rearrangement of the backbone atoms that allow the electrostatic interactions to promote the hydrogen transfer in a stepwise mechanism.

The Mechanism of Aluminum-Catalyzed Meerwein−Schmidt−Ponndorf−Verley Reduction of Carbonyls to Alcohols

The mechanistic details of the Meerwein-Schmidt-Ponndorf-Verley (MSPV) reduction of ketones to the corresponding alcohols were investigated both experimentally and computationally. Density functional theory (DFT) was used to assess the energetics of several proposed pathways (direct hydrogen transfer, hydridic, and radical). Our results demonstrate that a direct hydrogen transfer mechanism involving a concerted six-membered ring transition state is the most favorable pathway for all calculated systems starting from a small model system and concluding with the experimentally investigated BINOLate/Al/(i)PrOH/MePhC=O system. Experimental values for the activation parameters of acetophenone reduction using the BINOLate/Al/(i)PrOH system (DeltaG# = 21.8 kcal/mol, DeltaH# = 18.5 kcal/mol, DeltaS# = -11.7 au) were determined on the basis of kinetic investigation of the reaction and are in good agreement with the computational findings for this system. Calculated and experimental kinetic isotope effects support the concerted mechanism.

Mechanism of homogeneously and heterogeneously catalysed Meerwein-Ponndorf-Verley-Oppenauer reactions for the racemisation of secondary alcohols.

The mechanism of hydrogen transfer from alcohols to ketones, catalysed by lanthanide(III) isopropoxides or zeolite Beta has been studied. For the lanthanide catalysed reactions, (S)-1-phenyl-(1-(2)H(1))ethanol and acetophenone were used as case studies to determine the reaction pathway for the hydrogen transfer. Upon complete racemisation all deuterium was present at the 1-position, indicating that the reaction exclusively takes place via a carbon-to-carbon hydrogen transfer. Zeolite Beta with different Si/Al ratios was applied in the racemisation of (S)-1-phenylethanol. In this case the racemisation does not proceed via an oxidation/reduction pathway but via elimination of the hydroxy group and its re-addition. This mechanism, however, is not characteristic for all racemisation reactions with zeolite Beta. When 4-tert-butyl cyclohexanone is reduced with this catalyst, a classical MPV reaction takes place exclusively. This demonstrates that zeolite Beta has a substrate dependent reaction pathway.

Coenzyme Binding in F 420-Dependent Secondary Alcohol Dehydrogenase, a Member of the Bacterial Luciferase Family

F 420-dependent secondary alcohol dehydrogenase (Adf) from methanogenic archaea is a member of the growing bacterial luciferase family which are all TIM barrel enzymes, most of which with an unusual nonprolyl cis peptide bond. We report here on the crystal structure of Adf from Methanoculleus thermophilicus at 1.8 Å resolution in complex with a F 420-acetone adduct. The knowledge of the F 420 binding mode in Adf provides the molecular basis for modeling F 420 and FMN into the other enzymes of the family. A nonprolyl cis peptide bond was identified as an essential part of a bulge that serves as backstop at the Re-face of F 420 to keep it in a bent conformation. The acetone moiety of the F 420-acetone adduct is positioned at the Si-face of F 420 deeply buried inside the protein. Isopropanol can be reliably modeled and a hydrogen transfer mechanism postulated. His39 and Glu108 can be identified as key players for binding of the acetone or isopropanol oxygens and for catalysis.

Mechanism of hydrogen transfer to imines from a hydroxycyclopentadienyl ruthenium hydride. Support for a stepwise mechanism

The negligible double kinetic deuterium isotope effect (k(HH)/k(DD)= 1.05) in the reaction where [2,3,4,5-Ph4(eta5-C4COH)Ru(CO)2H (2) transfers a hydride and a proton to N-phenyl-[1-(4-methoxyphenyl)ethylidene]amine (4) indicates that no bond to hydrogen is broken or formed in the rate-determining step.

Mechanism of homogeneous Ir(III) catalyzed regioselective arylation of olefins.

The mechanism of hydroarylation of olefins by a homogeneous Ph-Ir(acac)(2)(L) catalyst is elucidated by first principles quantum mechanical methods (DFT), with particular emphasis on activation of the catalyst, catalytic cycle, and interpretation of experimental observations. On the basis of this mechanism, we suggest new catalysts expected to have improved activity. Initiation of the catalyst from the inert trans-form into the active cis-form occurs through a dissociative pathway with a calculated DeltaH(0 K)() = 35.1 kcal/mol and DeltaG(298 K)() = 26.1 kcal/mol. The catalytic cycle features two key steps, 1,2-olefin insertion and C-H activation via a novel mechanism, oxidative hydrogen migration. The olefin insertion is found to be rate determining, with a calculated DeltaH(0 K)() = 27.0 kcal/mol and DeltaG(298 K)() = 29.3 kcal/mol. The activation energy increases with increased electron density on the coordinating olefin, as well as increased electron-donating character in the ligand system. The regioselectivity is shown to depend on the electronic and steric characteristics of the olefin, with steric bulk and electron withdrawing character favoring linear product formation. Activation of the C-H bond occurs in a concerted fashion through a novel transition structure best described as an oxidative hydrogen migration. The character of the transition structure is seven coordinate Ir(V), with a full bond formed between the migrating hydrogen and iridium. Several experimental observations are investigated and explained: (a) The nature of L influences the rate of the reaction through a ground-state effect. (b) The lack of beta-hydride products is due to kinetic factors, although beta-hydride elimination is calculated to be facile, all further reactions are kinetically inaccessible. (c) Inhibition by excess olefin is caused by competitive binding of olefin and aryl starting materials during the catalytic cycle in a statistical fashion. On the basis of this insertion-oxidative hydrogen transfer mechanism we suggest that electron-withdrawing substituents on the acac ligands, such as trifluoromethyl groups, are good modifications for catalysts with higher activity.

Mechanism of the Chain Termination of the Allylnickel(II)-Catalyzed Polymerization of 1,3-Butadiene. A Density Functional Investigation for the Cationic [NiII(RC3H4)(cis-C4H6)L]+ Active Catalyst

Alternative mechanisms of chain termination of the allylnickel(II)-catalyzed polymerization of 1,3-dienes have been investigated by employing a gradient-corrected DFT method: namely, (I) the hydrogen transfer mechanism and (II) the hydrogen elimination mechanism. Several conceivable pathways for each of these mechanisms have been scrutinized for the well-characterized trans-1,4 regulating cationic allylnickel(II) [NiII(η3-RC3H4)(cis-C4H6)L]+ active catalyst. The transfer of a hydrogen atom from the C4(butenyl) carbon of the growing polymer chain to the coordinated monomer, which starts with the butadiene π-complex, is suggested to be the favorable mechanism of chain termination. This process is found to preferably proceed in a concerted fashion outside of the immediate proximity of the nickel atom. On the other hand, the hydrogen elimination occurring from the monomer insertion product by hydrogen abstraction from the polymer chain (C4(butenyl) carbon) yielding initially an diene hydride species, is seen to be kinetically disfavored. Accordingly, hydrogen elimination represents a less likely channel for chain termination. The monomer π-complex is the crucial species of the entire polymerization reaction course, as it serves as the precursor for the critical monomer insertion and allylic anti−syn elementary steps of the chain propagation cycle, as well as for the favorable hydrogen transfer chain termination channel. The present study provides, for the first time, a theoretically well-founded insight into the mechanism of molecular weight regulation for the allylnickel(II)-catalyzed polymerization of 1,3-dienes.

Iridium(I) versus Ruthenium(II). A Computational Study of the Transition Metal Catalyzed Transfer Hydrogenation of Ketones

We present a density functional theory based computational study comparing simplified models for the ruthenium(II)- and iridium(I)-catalyzed transfer hydrogenation of ketones. For the ruthenium compound our results confirm earlier findings that the hydrogenation involves a ruthenium hydride and occurs via a concerted hydrogen transfer mechanism with no direct ruthenium−ketone binding along the reaction path. In contrast, for the iridium compound our calculations suggest that the reaction proceeds via direct hydrogen transfer between simultaneously coordinated ketone and alcohol. We find that for both metal complexes the formation of a very stable metal−alkoxide complex plays an important role. For the ruthenium-catalyzed reaction it constitutes a resting state that does not take an active part in the transfer hydrogenation, while for the iridium-catalyzed reaction it is an important intermediate along the reaction path.

Mechanism and energetics of intramolecular hydrogen transfer in amide and peptide radicals and cation-radicals.

Intramolecular hydrogen transfer in five model amide and peptide radicals and cation-radicals was investigated by combined B3LYP-MP2 calculations. Hypervalent ammonium radicals produced by electron capture in protonated peptides undergo competitive elimination of ammonia, H-atom loss, and H-atom migration to neighboring amide carbonyls. The calculated transition state energies for H-atom migration are slightly but uniformly lower than those for H-atom loss. Transition state theory calculations with inclusion of quantum tunneling effects predict k(H migration)/k(H loss) branching ratios that increase with the ring size of the cyclic transition state for the migration. Intramolecular hydrogen-atom migration in amide and peptide radicals can be described by the proton-coupled electron transfer mechanism. The migrating hydrogen atom shows a negligible spin density and substantial positive charge that are typical of a proton migration. Electron transfer occurs through a pi-orbital system and proceeds in the same (clockwise) or opposite (counterclockwise) direction as the proton motion, depending on the electronic properties of the chain connecting the ammonium group and the amide bond.

Natural abundance hydrogen isotope affiliation between the reactants and the products in glucose fermentation with yeast.

In glucose fermentation, the hydrogen source of products such as ethanol and glycerol is the medium and the sugar. The site-specific natural isotope ratios of the products, (D/H)(i), and that of the medium and sugar, (D/H)(k), may be related by a matrix, A, of redistribution coefficients, a(ik), that characterizes the specific genealogies of the hydrogen atoms. (D/H)(i) = [A](D/H)(k), where (D/H)(i) and (D/H)(k) are the column vectors of the isotope ratios of sites i and k that can be measured by (2)H NMR. The complete redistribution matrix was determined in a set of isotope labeling experiments. Thus, we obtained a mathematical model representing the hydrogen isotope affiliation during alcoholic fermentation. It not only provides information about the biochemical reaction mechanism but also can be used to estimate the isotopic data of the products, based on those of the substrate and the medium. The results prove, in a quantitative way, that the metabolites contain isotopic information about the precursor in a biotransformation and can be used to identify its origin. The method established for the study of the hydrogen-transfer mechanism can be applied to other chemical and biochemical reactions.

Application of 2H NMR to the study of natural site-specific hydrogen isotope transfer among substrate, medium, and glycerol in glucose fermentation with yeast

2H NMR is a very useful tool in isotope tracing studies. This technique was applied to a quantitative study of a site-specific deuterium affiliation among the substrate, the medium, and a product (glycerol), in glucose fermentation with yeast. The quality of the results depends on the quantitative 2H NMR analysis of glycerol. After comparing several potential analysis probe molecules, the derivative of glycerol, 2,2-dimethyl-1,3-dioxolane-4-methanol, was chosen as the most advantageous. Using this probe in a set of isotope-labeling experiments, we describe how a complete quantitative site-specific hydrogen isotope transfer model, which connects the site-specific isotopic ratios of the substrate, the medium, and the products, can be established. This model can provide information on complex hydrogen transfer mechanisms during biochemical reactions and can be useful for the prediction of site-specific hydrogen isotopic ratios at natural abundance of the products, based on that of the substrate or reactants and the medium.

Wine Polyphenols and Optimal Nutrition

One of the key elements of Mediterranean diet is the use of wine, usually taken with foods. Besides the evidence from human experience and ancient medicine, modern experimental data support the notion that the most striking effect of wine in protecting against cardiovascular disease involves the reduction of oxidative damage to plasma lipoproteins. This oxidative damage is thought to be mediated by eating foods containing oxidized lipids. In fact, eating a meal containing oxidized lipids increases the plasma level of lipid hydroperoxides and increases the susceptibility to oxidation of LDL. The postprandial increase of LDL-, an oxidatively modified form of LDL, where apoB is unfolded and sinking in the core of the particle, is a valuable biomarker for this food-derived oxidative stress in plasma. Wine, taken with foods minimizes the postprandial rise of lipid hydroperoxides and LDL- and abolishes the increase of LDL oxidability. Among wine antioxidants, the best candidates for providing an antioxidant effect are procyanidins. These compounds are considered better antioxidants than the corresponding monomers containing catechol groups. This is due to the hydrogen transfer mechanism for the radical-scavenging reaction, which renders the reaction more specific for peroxyl radicals and pH independent. Moreover, the fast intramolecular disproportion among aroxyl radicals pulls the antioxidant reaction by both decreasing the oxidation potential and increasing the rate of the reaction. Apparently, wine procyanidins are active in preventing lipid oxidation of foods while in the digestive tract, thus preventing the postprandial plasma rise in oxidants. The likely limited bioavailability of these compounds, therefore, does not affect their relevance as key elements for optimizing nutrition and reducing risk of atherogenesis. Accordingly, studies with rabbits fed a high cholesterol diet show that grapeseed procyanidins are strongly protective not only in terms of reducing plasma lipid peroxides, but they also markedly inhibit lipid-laden foam-cell deposition. Drinking wine at meals provides this kind of protection, and the final benefits are realized by the prevention of the development of atheromatous lesions even under conditions of hypercholesterolemia.

Studies on the mechanism of metal-catalyzed hydrogen transfer from alcohols to ketones.

The mechanism of metal-catalyzed hydrogen transfer from alcohols to ketones has been studied. Hydrogen transfer (H-transfer) from (S)-alpha-deutero-alpha-phenylethanol ((S)-1) to acetophenone was used as a probe to distinguish between selective carbon-to-carbon H-transfer and nonselective transfer involving both oxygen-to-carbon and carbon-to-carbon H-transfer. The progress of the reaction was monitored by the decreasing enantiomeric excess of (S)-1. After complete racemization, the alcohol was analyzed for its deuterium content in the alpha-position, which is a measure of the degree of selectivity in the H-transfer. A number of different rhodium, iridium, and ruthenium complexes (in total 21 complexes) were investigated by using this probe. For all rhodium complexes a high degree of retention of deuterium at alpha-carbon (95-98%) was observed. Also most iridium complexes showed a high degree of retention of deuterium. However, the results for the ruthenium complexes show that there are two types of catalysts: one that gives a high degree of deuterium retention at alpha-carbon and another that gives about half of the deuterium content at alpha-carbon (37-40%). Two different mechanisms are proposed for transition-metal-catalyzed hydrogen transfer, one via a monohydride (giving a high D content) and another via a dihydride (giving about half of D content). As comparison non-transition-metal-catalyzed hydrogen transfer was studied with the same probe. Aluminum- and samarium-catalyzed racemization of (S)-1 gave 75-80% retention of deuterium in the alpha-position of the alcohol, and involvement of an electron transfer pathway was suggested to account for the loss of deuterium.

Chiral NADH models with restricted or blocked rotation at the amide function: attempts to interpret the mechanism of the enantioselective hydrogen transfer to methyl benzoylformate

Various NADH models with the following characteristics were studied and compared with previously reported models: (1) use of ( S)-phenylalaninol as chiral auxiliary; (2) orientation in or out of the plane of the amide carbonyl. Despite the occurrence of apparently similar characteristics, they gave very different results in the asymmetric reduction of methyl benzoylformate. A detailed NMR study was performed in order to explain the behaviour of these models.

Transfer Hydrogenation of Carbonyl Compounds Catalyzed by a Ruthenium−Acetamido Complex: Evidence for a Stepwise Hydrogen Transfer Mechanism

The ruthenium−acetamido complex, prepared from the reaction of [(PCy3)2(CO)(CH3CN)2RuH]+BF4- with KOH in 2-propanol, was found to be an effective catalyst for the transfer hydrogenation of carbonyl compounds and imines. Observation of both the inverse deuterium isotope effect and the competitive inhibition by added phosphine provided strong evidence for a stepwise mechanism of proton and hydride transfer via a coordinatively unsaturated ruthenium−amido species.

A Langmuir–Hinshelwood model for a hydrogen transfer mechanism in the selective hydrogenation of acetylene over a Pd/γ-Al 2O 3 catalyst prepared by the sol–gel method

This study represents an effort to fit a Langmuir–Hinshelwood-type mechanism which involves a proposed hydrogen transfer step from a carbonaceous deposit with observed rate data, spectroscopic data, and reported literature results on a supported Pd/γ-Al 2O 3 catalyst prepared by the sol–gel method. Our data was taken in a differential reactor as the temperature was varied from 100 to 225°C in six increments. A change in the apparent reactant orders and activation energies support a multiple mechanism rate expression. Our data correlates best with an expression composed of two mechanisms: a competitive, low-temperature mechanism (mechanism I) with an activation energy of 29 kJ/mol, and a non-competitive, high-temperature mechanism (mechanism II) with an activation energy of 168 kJ/mol. Both mechanisms were fit using an enthalpy of adsorption of −124 kJ/mol for acetylene. The enthalpy of the hydrogen transfer was found to be 133 kJ/mol, indicating an endothermic process. Mechanism II is predicted to emerge and dominate at high temperatures.

Enthalpy Surfaces for Hydrogen Atom Transfer in a Molecular Crystal

The mechanism of the intermolecular photoinitiated hydrogen transfer in fluorene crystal doped with acridine molecules is studied theoretically. For this reaction, extensive experimental data in a ...

Nature of hydrogen transfer in soybean lipoxygenase 1: separation of primary and secondary isotope effects.

Previous measurements of the kinetics of oxidation of linoleic acid by soybean lipoxygenase 1 have indicated very large deuterium isotope effects, but have not been able to distinguish the primary isotope effect from the alpha-secondary effect. To address this question, singly deuterated linoleic acid was prepared, and enantiomerically resolved using the enzyme itself. Noncompetitive measurements of the primary deuterium isotope effect give a value of ca. 40 which is temperature-independent. The enthalpy of activation is low and isotope-independent, and there is a large isotope effect on the Arrhenius prefactor. A very large apparent secondary isotope effect (ca. 2.1) is measured with deuterium in the primary position, but a greatly reduced value (1.1) is observed with protium in the primary position. Mutagenesis of the active site leads to a significant reduction in k(cat) and perturbed isotope effects, in particular, a secondary effect of 5.6 when deuterium is in the primary position. The anomalous secondary isotope effects are shown to arise from imperfect stereoselectivity of hydrogen abstraction which, for the mutant, is attributed to a combination of inverse substrate binding and increased flexibility at the reactive carbon. After correction, a very large primary (76-84) and small secondary (1.1-1.2) kinetic isotope effects are calculated for both mutant and wild-type enzymes. The weight of the evidence is taken to favor hydrogen tunneling as the primary mechanism of hydrogen transfer.

The protection of polyunsaturated fatty acids in micellar systems against UVB-induced photo-oxidation by procyanidins from Vitis vinifera L., and the protective synergy with vitamin E

The protective effect of procyanidins (catechin oligomers) from Vitis vinifera seeds on the UVB-promoted photo-oxygenation of polyunsaturated fatty acids (PUFAs) (linoleic, linolenic and arachidonic acids, 35 mM) has been studied in 0.5 mM sodium dodecylsulfate micelles exposed to UVB radiation (1-8 J cm-2) and determined qualitatively by Fourier transform infrared spectroscopy (FT-IR) and quantitatively by UV spectroscopy (conjugated dienes and total lipid hydroperoxides). Procyanidins (1-10 muM) strongly and dose-dependently inhibit the formation of PUFA hydroperoxides (IC50 = 4-6 muM), with a potency comparable to that of vitamin E. In these micellar systems, a strong co-operative interaction (synergistic effect) between procyanidins and vitamin E (1:1 molar ratio) in PUFA protection was demonstrated; this, as shown by electron spin resonance (ESR) studies, is a result of the ability of procyanidins to regenerate alpha-tocopherol from the alpha-tocopheroxyl radical (generated by a UV Solar Simulator), through a hydrogen transfer mechanism. HPLC monitoring of vitamin E in PUFAs micelles oxidatively stressed by UVB, confirms that procyanidins save vitamin E from consumption. All these findings, if properly extrapolated to an in vivo situation, indicate that this class of radical scavengers can be used as adjuvants of physical/chemical sunscreens in skin protection from photodamage.

Influence of gaseous hydrogen on the hydrogen transfer reaction between phenanthrene and hydrogen donors

Transfer hydrogenation of phenanthrene was performed in the presence of superbases or strong acids and gaseous hydrogen. The influence of hydrogen on the yield of these reactions was discussed with respect to the mechanism of hydrogen transfer.