Low Kinetic Isotope Effect Research Articles

Unprecedented Reactivities of Highly Reactive Manganese(III)-Iodosylarene Porphyrins in Oxidation Reactions.

We report that Mn(III)-iodosylarene porphyrins, [MnIII(Porp)(sArIO)]+, are capable of activating the C-H bonds of hydrocarbons, including unactivated alkanes such as cyclohexane, with unprecedented reactivities, such as a low kinetic isotope effect, a saturation behavior of reaction rates, and no electronic effect of porphyrin ligands on the reactivities of [MnIII(Porp)(sArIO)]+. In oxygen atom transfer (OAT) reactions, the sulfoxidation of para-X-substituted thioanisoles by [MnIII(Porp)(sArIO)]+ affords a very unusual behavior in the Hammett plot with the saturation behavior of reaction rates and no electronic effect of porphyrin ligands on reactivities. The reactivities and mechanisms of [MnIII(Porp)(sArIO)]+ are then compared with those of the corresponding MnIV(Porp)(O) complex. The present study reports the first example of highly reactive Mn(III)-iodosylarene porphyrins with unprecedented reactivities in C-H bond activation and OAT reactions.

Proton-coupled electron transfer as the mechanism of reaction between triplet state of kynurenic acid and tryptophan

Kynurenic acid (KNA−) is an endogenous UV-A chromophore of the human eye lens able to sensitize photodamages to eye lens proteins. In the present work, we studied in details the mechanism of reaction between KNA− triplet state (TKNA−) and tryptophan (Trp), the most effective quencher of TKNA− among aromatic and sulfur-containing amino acids, by nanosecond laser flash photolysis. Previous studies suggested electron transfer as the reaction mechanism without its direct spectroscopic confirmation. Time-resolved kinetics and spectral data of this work clearly evidence the formation of neutral tryptophanyl radicals immediately after the TKNA− quenching by Trp that indicates either hydrogen transfer or proton-coupled electron transfer (PCET) as the reaction mechanism. Low kinetic isotope effect for the quenching rate constant, kH2O/kD2O = 1.3, speaks in favor of PCET mechanism of the quenching reaction, which includes the diffusion-controlled electron transfer as the primary step and the proton transfer in the radical cage as the final step.

Catalytic C-H oxidations by nonheme mononuclear Fe(II) complexes of two pentadentate ligands: Evidence for an Fe(IV) oxo intermediate

The oxidation reactions of alkanes with hydrogen peroxide and peracids (peracetic acid (PAA) and m-chloroperoxybenzoic acid (mCPBA)) catalysed by two Fe(II) complexes of pentadentate {N5}-donor ligands have been investigated. Kinetic isotope effect experiments and the use of other mechanistic probes have also been performed. While the total yields of oxidized products are similar regardless of oxidant (e.g. 30–39% for oxidation of cyclohexane), the observed alcohol/ketone ratios and kinetic isotope effects differ significantly with different oxidants. Catalytic reactions in H2O2 medium are consistent with the involvement of hydroxyl radicals in the CH bond cleavage step, and resultant low kinetic isotope effect values. On the other hand, catalytic reactions performed using peracid media indicate the involvement of an oxidant different from the hydroxyl radical. For these reactions, the kinetic isotope effect values are relatively high (within a range of 4.2–5.1) and the C3/C2 selectivity parameters in adamantane oxidation are greater than 11, thereby excluding the presence of hydroxyl radicals in the CH bond cleavage step. A low spin Fe(III)-OOH species has been detected in the H2O2-based catalytic system by UV/Vis, mass spectrometry and EPR spectroscopy, while an Fe(IV)-oxo species is postulated to be the active oxidant in the peracid-based catalytic systems. Computational studies on the CH oxidation mechanism reveal that while the hydroxyl radical is mainly responsible for the H-atom abstraction in the H2O2-based catalytic system, it is the Fe(IV)-oxo species that abstracts the H-atom from the substrate in the peracid-based catalytic systems, in agreement with the experimental observations.

Ab Inito Modeling of Ethylbenzene Dehydrogenase Reaction Mechanism

Density functional theory calculations were performed to study the mechanism of ethylbenzene oxidation by ethylbenzene dehydrogenase (EBDH). EBDH is a bacterial molybdopterin enzyme capable of stereospecific anaerobic hydroxylation of alkylaromatic compounds to secondary alcohols. It is a key biocatalyst in the metabolism of ethylbenzene-degrading bacteria such as Aromatoleum aromaticum , which converts ethylbenzene to (S)-1-phenylethanol. The recently determined EBDH structure enabled the theoretical description of the ethylbenzene oxidation mechanism. In this work, theoretical calculations and kinetic isotopic experiments were conducted and combined in order to elucidate the reaction mechanism. We considered three aspects: (i) Does the reaction concur with one two-electron or two one-electron transfers? (ii) Is the active site His192 important for the reaction and what is its protonation state? (iii) What catalytic consequences have different possible arrangements of the molybdopterin ligand? The most important outcome of the calculations is that mechanisms involving two one-electron transfers and a radical-type intermediate have lower energy barriers than the corresponding two-electron transfer mechanisms and are, therefore, more plausible. The mechanism involves two transition states: radical-type TS1 associated with the C-H bond cleavage, and carbocation-type TS2 associated with the transfer of the second electron and OH rebound. Using models with protonated and nonprotonated His 192, we conclude that this amino acid takes part in the mechanism. However, as both models yielded plausible reaction pathways, its protonation state cannot be easily predicted. Qualitative agreement was reached between the calculated kinetic isotope effects (KIE) obtained for radical TS1 and the KIE measured experimentally at optimum pH, but we observed a very strong pH dependence of KIE throughout the investigated pH range (3.1 for pH 6, 5.9 for pH 7, up to 10.5 at pH 8.). This may be explained by assuming a gradual shift of the rate-determining step from TS1 associated with high KIE to TS2 associated with low KIE with lowered pH and an increasing contribution of proton/deuteron tunneling associated with high pH. Finally, models were calculated with different signs of the conformational twist of the pterin ligands, yielding only slightly different energy profiles of the reaction pathways.

Formation of the Active Species of Cytochrome P450 by Using Iodosylbenzene: A Case for Spin‐Selective Reactivity

The generation of the active species for the enzyme cytochrome P450 by using the highly versatile oxygen surrogate iodosylbenzene (PhIO) often produces different results compared with the native route, in which the active species is generated through O(2) uptake and reduction by NADPH. One of these differences that is addressed here is the deuterium kinetic isotope effect (KIE) jump observed during N-dealkylation of N,N-dimethylaniline (DMA) by P450, when the reaction conditions change from the native to the PhIO route. The paper presents a theoretical analysis targeted to elucidate the mechanism of the reaction of PhIO with heme, to form the high-valent iron-oxo species Compound I (Cpd I), and define the origins of the KIE jump in the reaction of Cpd I with DMA. It is concluded that the likely origin of the KIE jump is the spin-selective chemistry of the enzyme cytochrome P450 under different preparation procedures. In the native route, the reaction proceeds via the doublet spin state of Cpd I and leads to a low KIE value. PhIO, however, diverts the reaction to the quartet spin state of Cpd I, which leads to the observed high KIE values. The KIE jump is reproduced here experimentally for the dealkylation of N,N-dimethyl-4-(methylthio)aniline, by using intra-molecular KIE measurements that avoid kinetic complexities. The effect of PhIO is compared with N,N-dimethylaniline-N-oxide (DMAO), which acts both as the oxygen donor and the substrate and leads to the same KIE values as the native route.

Competitive reactions and diastereoselective C [sbnd]H bond activation in the McLafferty rearrangement of photoionized 3-methyl valeramide

Dissociative photoionization of 3-methyl valeramide is characterized by various degradations of the alkyl backbone, initiated by competitive intramolecular hydrogen migrations. The dominating pathway corresponds to butene elimination via the McLafferty rearrangement. At photon energies ( E hν) close to the ionization threshold, the McLafferty rearrangement is followed by a second hydrogen transfer, known as [McLafferty + 1] reaction. The methyl group at C(3) in combination with diastereospecific labeling at C(4) permits steric differentiation of the two γ-H(D)-atoms at C(4) according to the relative orientations of the stereogenic centers. Investigation of the syn- and anti-[4-D 1]-diastereomers shows a strong preference for activation of the anti-γ-hydrogen in the McLafferty rearrangement. A straightforward analysis of the product distribution is impossible, because also C(4′) allows for a [1,5]-H shift, and the contributions of both sites are additionally superimposed by [McLafferty + 1] products. Photoionization studies of six isotopomers, employing tunable synchrotron radiation, combined with kinetic modeling enable a deconvolution of the branching ratios and a determination of the corresponding steric and kinetic isotope effects operative in the McLafferty rearrangement. The kinetic isotope effects (KIEs) are more or less independent of E hν. The initiating [1,5]-H shifts feature very low KIEs, especially for the C(4) H bond activation, whereas the subsequent hydrogen atom transfers in the course of the [McLafferty + 1] processes are affected by substantial KIEs. Interestingly, the steric effect (SE) decreases considerably at low E hν (SE = 1.8, 2.6, and 2.8 at E hν = 9.6, 10, and 11 eV, respectively), which can be explained by more pronounced epimerization prior to dissociation at lower energies.

Synthesis, structure, and catalytic activity of mononuclear iron and (mu-Oxo)diiron complexes with the ligand 2,6-bis(N-methylbenzimidazol-2-yl)pyridine.

Iron complexes including polyimidazole and exchangeable ligands are studied with the aim of modeling the structural and functional features of the non-heme iron centers of dinuclear proteins, such as methane monooxygenase. In [Fe(2)OL(2)(MeOH)(2)(NO(3))(2)](NO(3))(2) (1) (L = 2,6-bis(N-methylbenzimidazol-2-yl)pyridine), each Fe(III) is in a distorted octahedral environment and has a donor set of N(3)O(3) which includes three N atoms from L and three O atoms from a nitrate, micro-oxo, and methanol. In complex [FeLCl(3)] (2) (L = 2,6-bis(N-methylbenzimidazol-2-yl)pyridine), Fe(III) is coordinated to three nitrogen atoms from L and three chloride ions. Complex 1 efficiently catalyzed the oxidation of cyclohexane with 51% conversion to cyclohexanol. It also catalyzed the epoxidation of styrene, cyclohexane, 2-methyl-2-butene, and cis- and trans-2-heptene with 51-84% conversions and high selectivity (71-99%) for epoxide products. Complex 2, however, has no specific reactivity toward these substrates. From the alcohol/ketone (A/K) ratio close to 1 in the oxidation of cyclohexane, the low KIE (kinetic isotope effect K(H)/K(D) ratio = 1.8) for cyclohexanol formation, and the nonstereospecificity of the oxidation of cis-dimethylcyclohexane, it can be concluded that long-lived alkyl radicals are involved in the oxidation catalyzed by complex 1. On the other hand, the stereospecific epoxidation of alkenes, the stereoselective oxidation of cumene, and the high degree of retention of configuration in the oxidation of cis- and trans-2-heptene suggest that a nonradical species, probably a metal-based intermediate, is involved in the oxidation of alkenes and cumene.

Kinetic isotope effects for hydrogen diffusion in bulk nickel and on nickel surfaces

Diffusion coefficients for H, D, and T on a Ni(100) surface and in bulk Ni are calculated using variational transition state theory with semiclassical ground-state transmission coefficients using two potential energy surfaces obtained by the embedded atom method (EAM). The original EAM potential reproduces experimental bulk diffusion coefficients, but greatly overestimates the diffusion coefficients for H and D on Ni(100). By refining the empirical potential parameters, a new EAM potential is developed that accurately reproduces both the bulk and surface diffusion coefficients. The variational transition state theory calculations are used to analyze the unusually low (compared to gas phase) H/D kinetic isotope effects for diffusion in bulk and on the Ni(100) surface. For the temperature range for which experiments have been carried out, quantum mechanical tunneling contributes negligibly to the diffusion and, in these cases, the kinetic isotope effect is determined largely by the change in zero-point energy between the reactant equilibrium binding sites and the transition state. A near equality of the reactant and transition state zero-point energies leads to the unusually low kinetic isotope effects. Using the same refined EAM potential energy surface, the energetics of diffusion on the Ni(111) and Ni(110) surfaces are also presented. The barriers for diffusion on these two surfaces are sufficiently low, about 1.0 kcal/mol, that the approximation of uncorrelated hops needed to relate the computed hopping rate to the diffusion coefficient is suspect. Although diffusion coefficients were not computed, based upon an analysis of the zero-point energies at the reactants and saddle points, we predict that the H/D kinetic isotope effects for diffusion on these two surfaces will also be close to unity.

Kinetics of oxidation of secondary alcohols by chloramine T

The kinetics of oxidation by chloramine T(CAT) of secondary alcohols with propan-2-ol as reference compound have been studied in aqueous acidic and aqueous acetic acid media. In the presence of strong mineral acid in aqueous medium the rate law is found to be –d[CAT]/dt=k[CAT][Alcohol][H+].2 The rate law, a low kinetic isotope effect, and the effect of solvent polarity on the rate are consistent with a mechanism involving a rate determining interaction of either the protonated chloramine T (CATH2+) or H2OCl+ with the secondary alcohol giving alkyl hypochlorite followed by a fast decomposition to ketone. The observed order of 1.5 in [HCl] is interpreted by a simultaneous oxidation by molecular chlorine or HOCl and CATH2+. At low percentages of acetic acid (10% and 20% v/v) the reaction exhibits a second-order dependence on CAT and first-order in alcohol. Dichloramine T (DCT) formed in a disproportionation step is possibly the active oxidant under these conditions. At 50% HOAc(v/v)a fractional order dependence on [Alcohol] and first-order in [CAT] are observed. Further increase in percentage of acetic acid increases the order in alcohol and a limiting value of 1 is reached in 90% HOAc(v/v). These results are indicative of the formation of a complex, the stability of which is solvent dependent. The concentration dependence on alcohol varies in buffered acetic acid in the presence of chloride and the rate law is rationalised by a concurrent oxidation by DCT and molecular chlorine.

The preparation and properties of tris(triphenylphosphine)halogenorhodium(I) and some reactions thereof including catalytic homogeneous hydrogenation of olefins and acetylenes and their derivatives

Tris(triphenylphosphine)chlororhodium(I), RhCl(PPh3)3, has been prepared by the interaction of an excess of triphenylphosphine with rhodium(III) chloride hydrate in ethanol; the corresponding bromide and iodide are also described. The dissociation of the complex in various solvents has been investigated, and its reactions with hydrogen, ethylene, and carbon monoxide and aldehydes studied. Dihydrido- and ethylene complexes have been isolated and studied by nuclear magnetic resonance (n.m.r.) spectroscopy. Approximate values for the formation constants of ethylene and propylene complexes have been obtained; the latter is lower by a factor of over 103. By electron spin resonance spectroscopy, the complex RhCl(PPh3)3 has been shown to contain trace amounts of a paramagnetic species, probably a rhodium(II) complex.In homogeneous solution the tris(triphenylphosphine) complexes are exceedingly active catalysts for the rapid and homogeneous hydrogenation, at ca. 1 atmosphere of hydrogen pressure and room temperature, of unsaturated compounds containing isolated olefinic and acetylenic linkages.The rates of hydrogenation of hept-1-ene, cyclohexene and hex-1-yne have been studied quantitatively and the dependence on factors such as substrate and catalyst concentration, temperature, and pressure determined. The data can be accommodated by a rate expression of the form: Rate =Kp[S][A]//1 +K1p+K2[S] where [S] and [A] are the olefin and catalyst concentrations, respectively, and p is the concentration of hydrogen in solution.From the data for cyclohexene the activation energy for the rate determining step is Ea= 22·9 kcal. mole–1(ΔH‡= 22·3 kcal. mole–1) and the value of ΔS‡= 12·9 e.u.It is shown that the rate of hydrogen–deuterium exchange under selected conditions is quite slow compared with the rates of hydrogenation of olefins and, furthermore, that when H2–D2 mixtures are used in the reactions, alkanes and dideuteroalkanes are the major products. Reductions of maleic and fumaric acids with deuterium shows that cis-addition occurs preferentially. Similarly, in the reduction of hex-2-yne to n-hexane, cis-hex-2-ene is found to be the major olefin intermediate.A mechanism for the hydrogenation is proposed in which the metal complex serves as a template to which a hydrogen molecule and an olefin molecule are briefly co-ordinated before transfer of one to the other takes place. The low kinetic isotope effect (rate H2/rate D2= 0·9) suggests that synchronous breaking of Rh–H bonds and making of C–H bonds takes place in the transition state involving two simultaneous three-centre interactions.