Determination Of Kinetic Isotope Effects Research Articles

Redox-Active Carboranyl Diphosphine as an Electron and Proton Transfer Agent.

In this work, we report the first example of the PCET reactivity for a boron cluster compound, the zwitterionic nido-carboranyl diphosphonium derivative 7-P(H)tBu2-10-P(H)iPr2-nido-C2B10H10. This main-group reagent efficiently transfers two electrons and two protons to quinones to yield hydroquinones and regenerate a neutral closo-carboranyl diphosphine, 1-PtBu2-2-PiPr2-closo-C2B10H10. As we have previously reported the conversion of this closo-carboranyl diphosphine into the zwitterionic nido- derivative upon reaction with main group hydrides, the transformation reported herein represents a complete synthetic cycle for the metal-free reduction of quinones, with the redox-active carboranyl diphosphine scaffold acting as a mediator. The proposed mechanism of this reduction, based on pKa determination, electrochemical studies, and kinetic isotope effect determination, involves the electron transfer from the nido- cluster to the quinone coupled with the delivery of protons.

Sharp Volcano-Type Synergy and Visible Light Acceleration in H2 Release upon B2(OH)4 Hydrolysis Catalyzed by Au-Rh@Click-Dendrimer Nanozymes

Hydrogen (H2) formation from hydrogen-rich precursors is a hot topic, whereby carbon-free energy perspectives, mechanistic features, and synthetic applications are actively searched. Here, we report oxygen atom uptake from water under ambient conditions, producing H2 in the presence of alloyed Au-Rh nanoparticle catalysts encapsulated in a “click”-dendrimer. These systems are named nanozymes (NZs) because their function and mechanism resemble those of hydrogenase enzymes. The Au-Rh NZs with variable proportions of Au and Rh exhibit positive sharp volcano-type synergy and visible light-induced acceleration. The best synergy in the dark is disclosed in Au4Rh1, achieving a turnover frequency (TOFs) of 5100 molH2 molcata–1 min–1 in dark, 3.4 times higher than the related Au NZ and 8.9 times higher than the related Rh NZ at 25 ± 1 °C. The catalytic activity of Au-Rh for H2 evolution is enhanced by visible light irradiation due to the Au plasmon, so that the synergistic effect in the dark and the visible light-induced rate enhancement cumulate for Au4Rh1, allowing for complete B2(OH)4 hydrolysis in 39 s at 25 ± 1 °C (TOFs = 6000 molH2 molcata–1 min–1). Upon increasing the Rh content, Au-Rh provides less synergy in the dark, whereas the light enhancement of the reaction rate increases, reaching a maximum for Au1Rh2. Experiments using D2O, including kinetic isotope effect determination, suggest that the rate-determining step of the reaction involves concerted O–H bond cleavage of water and support the proposed catalytic reaction mechanism.

N-Vinyl and N-Aryl Hydroxypyridinium Ions: Charge-Activated Catalysts with Electron-Withdrawing Groups.

Charge-enhanced Brønsted acid organocatalysts with electron-withdrawing substituents were synthesized, and their relative acidities were characterized by computations, 1:1 binding equilibrium constants (K1:1) with a UV-vis active sensor, 31P NMR shifts upon coordination with triethylphosphine oxide, and in one case by infrared spectroscopy. Pseudo-first-order rate constants were determined for the Friedel-Crafts alkylations of N-methylindole with trans-β-nitrostyrene and 2,2,2-trifluoroacetophenone and the Diels-Alder reaction of cyclopentadiene with methyl vinyl ketone. These results along with kinetic isotope effect determinations revealed that the rate-determining step in the Friedel-Crafts transformations can shift from carbon-carbon bond formation to proton transfer to the catalyst's conjugate base. This leads to an inverted parabolic reaction rate profile and slower reactions with more acidic catalysts in some cases. Electron-withdrawing groups placed on the N-vinyl and N-aryl substituents of hydroxypyridinium ion salts lead to enhanced acidities, more acidic catalysts than trifluoroacetic acid, and a linear correlation between the logarithms of the Diels-Alder rate constants and measured K1:1 values.

Amine Boranes Dehydrogenation Mediated by an Unsymmetrical Iridium Pincer Hydride: (PCN) vs (PCP) Improved Catalytic Performance

The IrIII hydride (tBuPCN)IrHCl (1) containing the tridendate unsymmetrical pincer ligand tBuPCN– {tBuPCN(H) = 1-[3-[(di-tert-butylphosphino)methyl]phenyl]-1H-pyrazole} has been exploited as ammonia borane (NH3BH3, AB) and amine boranes dehydrogenation catalyst in THF solution at ambient temperature. 1 releases one H2 equivalent per AB equivalent, with concomitant cyclic poly(aminoboranes) formation [B-(cyclotriborazanyl)-amine-borane (BCTB) and cyclotriborazane (CTB)] as the final “spent fuel”. 1 has been found to have superior catalytic activity than its symmetrical analogue (tBuPCP)IrHCl, with recorded TOF values of 580 h–1 (AB in THF) and 401 h–1 (DMAB in toluene) at ambient temperature. The reaction has been analyzed experimentally through multinuclear [11B, 31P{1H}, 1H] NMR and IR spectroscopy, kinetic rate measurements, and kinetic isotope effect determination with deuterated AB isotopologues. The hydride/borohydride intermediate (tBuPCN)IrH(η2-BH4) (2) is the catalyst resting state formed during t...

Kinetic Isotope Effect Determination Probes the Spin of the Transition State, Its Stereochemistry, and Its Ligand Sphere in Hydrogen Abstraction Reactions of Oxoiron(IV) Complexes.

This Account outlines interplay of theory and experiment in the quest to identify the reactive-spin-state in chemical reactions that possess a few spin-dependent routes. Metalloenzymes and synthetic models have forged in recent decades an area of increasing appeal, in which oxometal species bring about functionalization of hydrocarbons under mild conditions and via intriguing mechanisms that provide a glimpse of Nature's designs to harness these reactions. Prominent among these are oxoiron(IV) complexes, which are potent H-abstractors. One of the key properties of oxoirons is the presence of close-lying spin-states, which can mediate H-abstractions. As such, these complexes form a fascinating chapter of spin-state chemistry, in which chemical reactivity involves spin-state interchange, so-called two-state reactivity (TSR) and multistate reactivity (MSR). TSR and MSR pose mechanistic challenges. How can one determine the structure of the reactive transition state (TS) and its spin state for these mechanisms? Calculations can do it for us, but the challenge is to find experimental probes. There are, however, no clear kinetic signatures for the reactive-spin-state in such reactions. This is the paucity that our group has been trying to fill for sometime. Hence, it is timely to demonstrate how theory joins experiment in realizing this quest. This Account uses a set of the H-abstraction reactions of 24 synthetic oxoiron(IV) complexes and 11 hydrocarbons, together undergoing H-abstraction reactions with TSR/MSR options, which provide experimentally determined kinetic isotope effect (KIEexp) data. For this set, we demonstrate that comparing KIEexp results with calculated tunneling-augmented KIE (KIETC) data leads to a clear identification of the reactive spin-state during H-abstraction reactions. In addition, generating KIEexp data for a reaction of interest, and comparing these to KIETC values, provides the mechanistic chemist with a powerful capability to identify the reactive-TS in terms of not only its spin state but also its geometry and ligand-sphere constitution. Since tunneling "cuts through" barriers, it serves as a chemical selectivity factor. Thus, we show that in a family of oxoirons reacting with one hydrocarbon, the tunneling efficiency increases as the ligands become better electron donors. This generates counterintuitive-reactivity patterns, like antielectrophilic reactivity, and induces spin-state reactivity reversals because of differing steric demands of the corresponding 2S+1TS species, etc. Finally, for the same series, the Account reaches intuitive understanding of tunneling trends. It is shown that the increase of ligand's donicity results in electrostatic narrowing of the barrier, while the decrease of donicity and increase of bond-order asymmetry in the TS (inter alia due to Bell-Evans-Polanyi effects) broadens the barrier. Predictions are made that usage of powerful electron-donating ligands may train H-abstractors to activate the strongest C-H bond in a molecule. The concepts developed here are likely to be applicable to other oxometals in the d- and f-blocks.

RuII(tpy)(bpy)Cl]+-Catalyzed reduction of carbon dioxide. Mechanistic insights by carbon-13 kinetic isotope effects.

In this work, we examine the use of competitive 13C kinetic isotope effects (13C KIEs) on CO2 reduction reactions that produce CO and formic acid as a means to formulate reaction mechanisms. The findings reported here mark a further advancement in the combined 13C KIE measurements and theoretical calculations methodology for probing CO2 conversion reactions.

Kinetic Studies on Formic Acid Dehydrogenation Catalyzed by an Iridium Complex towards Insights into the Catalytic Mechanism of High-Pressure Hydrogen Gas Production.

Kinetic studies on the catalytic reaction mechanism of formic acid (FA) dehydrogenation were performed in the presence of a water-soluble iridium complex bearing a 4,4'-dihydroxy-2,2'-bipyridine ligand. Determination of kinetic isotope effects revealed that a shift of the rate-limiting step at low and high concentrations of FA can be caused by the pH dependence of the reaction steps. The proposed equation for the reaction rate corresponds well with the experimental results concerning the shift phenomena. Towards industrial application in future hydrogen fueling stations, this will able the design of a dehydrogenation system catalyzed by the iridium complex.

Solvent-Slaved Motions in the Hydride Tunneling Reaction Catalyzed by Human Glycolate Oxidase

Enzyme motions facilitate many hydride-transfer reactions involving quantum mechanical (QM) tunneling. The evidence mainly comes from the determination of kinetic isotope effects (KIEs) and their temperature dependence that have been used to reveal interesting characteristics of human glycolate oxidase (HsGOX). Previous studies have shown that HsGOX oxidizes glycolate to glyoxylate via a hydride-transfer mechanism to an enzyme-associated FMN. Here, we investigate the temperature effect on the anaerobic rate of flavin reduction (kred) for HsGOX with glycolate and [2R-2H]glycolate. While the kred values for HsGOX are temperature-dependent, their KIEs on the kred values (Dkred) do not change as the temperature is varied. This is consistent with the involvement of QM hydride tunneling in the highly optimized active site of HsGOX. We show that the enzyme motions are slaved by the fluctuations in the bulk solvent after determining the kred and Dkred for HsGOX at various solvent viscosities and constant temperat...

Chemical Hydrogen Storage: Ammonia Borane Dehydrogenation Catalyzed by NP3Ruthenium Hydrides (NP3=N(CH2CH2PPh2)3)

Two novel RuII hydrides containing the tripodal polyphosphine ligand NP3 (N(CH2CH2PPh2)3) have been prepared and characterized: (κ4-NP3)Ru(H)2 (1) and [(κ4-NP3)Ru(H)(η2-H2)]BArCl4 (2; ArCl=3,5-dichlorophenyl, C6H3Cl2). The classical and nonclassical nature of the hydride ligand in 1 and 2, respectively, has been confirmed by solution NMR studies and single-crystal X-ray diffraction. The reaction of 1 and 2 with excess ammonia borane (NH3⋅BH3, AB) has been analyzed experimentally through variable-temperature multinuclear (11B, 31P, 1H) NMR spectroscopy, kinetic rate measurements, and kinetic isotope effect determination with deuterated AB isotopologues. Both complexes are active in AB dehydrogenation, with release of two H2 equivalents per AB equivalent, with concomitant polyborazylene and cyclic polyaminoborane formation as the final “spent fuel”. A DFT modeling of the AB first dehydrogenation step has been finally performed, at the M06//6-31G* level of theory. The combination of the kinetic and computational data reveals that the initial AB activation step is different for the two catalysts: a simultaneous BH/NH activation occurs in the presence of 1, whereas the NH activation only is the rate-determining step if 2 is employed as a catalyst.

Mechanistic Elucidation of Intramolecular Aminoalkene Hydroamination Catalyzed by a Tethered Bis(ureate) Complex: Evidence for Proton-Assisted C–N Bond Formation at Zirconium

A broad mechanistic investigation regarding hydroamination reactions catalyzed by a tethered bis(ureate) zirconium species, [ureate(2-)]Zr(NMe(2))(2)(HNMe(2)), is described. The cyclization of both primary and secondary aminoalkene substrates gives similar kinetic profiles, with zero-order dependence on substrate concentration up to ∼60-75% conversion, followed by first-order dependence for the remainder of the reaction. The addition of 2-methylpiperidine changes the observed substrate dependence to first order throughout the reaction, but does not act as a competitive inhibitor. The reactions are first order in precatalyst up to loadings of ∼0.15 M, indicating that a well-defined, mononuclear catalytic species is operative. Several model complexes have been structurally characterized, including dimeric imido and amido species, and evaluated for catalytic performance. These results indicate that imido species need not be invoked as catalytically relevant intermediates, and that the mono(amido) complex [ureate(2-)]Zr(NMe(2))(Cl)(HNMe(2)) is much less active than its bis(amido) counterpart. Structural evidence suggests that this is due to differences in coordination geometry between the mono- and bis(amido) complexes, and that an equatorial amido ligand is required for efficient catalytic turnover. On the basis of the determination of kinetic isotope effects and stoichiometric reactivity, the catalytic turnover-limiting step is proposed to be a concerted C-H, C-N bond-forming process with a highly ordered, unimolecular transition state (ΔS(‡) = -21 ± 1 eu). In addition to this key bond-forming step, the catalytic cycle involves an on-cycle pre-equilibrium between six- and seven-coordinate intermediates, leading to the observed switch from zero- to first-order kinetics.

Rhenium Hydride/Boron Lewis Acid Cocatalysis of Alkene Hydrogenations: Activities Comparable to Those of Precious Metal Systems

Dibromonitrosyl(dihydrogen)rhenium(I) complexes [ReBr(2)(NO)(PR(3))(2)(η(2)-H(2))] (1; R = iPr, a; Cy, b) and Me(2)NH·BH(3) (DMAB) catalyze at either 90 °C or ambient temperature under 10 bar of H(2) the hydrogenation of various terminal and cyclic alkenes (1-hexene, 1-octene, cyclooctene, styrene, 1,5-cyclooctadiene, 1,7-octadiene, α-methylstyrene). Maximum turnover frequency (TOF) values of 3.6 × 10(4) h(-1) at 90 °C and 1.7 × 10(4) h(-1) at 23 °C were achieved in the hydrogenation of 1-hexene. The extraordinary catalytic performance of the 1/DMAB system is attributed to the formation of five-coordinate rhenium(I) hydride complexes [Re(Br)(H)(NO)(PR(3))(2)] (2; R = iPr, a; Cy, b) and the action of the Lewis acid BH(3) originating from DMAB. The related 2/BH(3)·THF catalytic system also exhibits under the same conditions high activity in the hydrogenation of various alkenes with a maximum turnover number (TON) of 1.2 × 10(4) and a maximum TOF of 4.0 × 10(4) h(-1). For the hydrogenations of 1-hexene with 2a and 2b, the effect of the strength of the boron Lewis acid was studied, the acidity being in the following order: BCl(3) > BH(3) > BEt(3) ≈ BF(3) > B(C(6)F(5))(3) > BPh(3) ≫ B(OMe)(3). The order in catalytic activity was found to be B(C(6)F(5))(3) > BEt(3) ≈ BH(3)·THF > BPh(3) ≫ BF(3)·OEt(2) > B(OMe)(3) ≫ BCl(3). The stability of the catalytic systems was checked via TON vs time plots, which revealed the boron Lewis acids to cause an approximate inverse order with the Lewis acid strength: BPh(3) > BEt(3) ≈ BH(3)·THF > B(C(6)F(5))(3). For the 2a/BPh(3) system a maximum TON of 3.1 × 10(4) and for the 2a/B(C(6)F(5))(3) system a maximum TOF of 5.6 × 10(4) h(-1) were obtained in the hydrogenation of 1-hexene. On the basis of kinetic isotope effect determinations, H(2)/D(2) scrambling, halide exchange experiments, Lewis acid variations, and isomerization of terminal alkenes, an Osborn-type catalytic cycle is proposed with olefin before H(2) addition. The active rhenium(I) monohydride species is assumed to be formed via reversible bromide abstraction with the "cocatalytic" Lewis acid. Homogeneity of the hydrogenations was tested with filtration and mercury poisoning experiments. These "rhenium(I) hydride/boron Lewis acid" systems demonstrate catalytic activities comparable to those of Wilkinson- or Schrock-Osborn-type hydrogenations accomplished with precious metal catalysts.

An assessment of the relative contributions of redox and steric issues to laccase specificity towards putative substrates

Laccases catalyze the one-electron oxidation of a broad range of substrates coupled to the 4 electron reduction of O2 to H2O. Phenols are typical substrates, because their redox potentials (ranging from 0.5 to 1.0 V vs. NHE) are low enough to allow electron abstraction by the T1 Cu(II) that, although a relatively modest oxidant (in the 0.4-0.8 V range), is the electron-acceptor in laccases. The present study comparatively investigated the oxidation performances of Trametes villosa and Myceliophthora thermophila laccases, two enzymes markedly differing in redox potential (0.79 and 0.46 V). The oxidation efficiency and kinetic constants of laccase-catalyzed conversion of putative substrates were determined. Hammett plots related to the oxidation of substituted phenols by the two laccases, in combination with the kinetic isotope effect determination, confirmed a rate-determining electron transfer from the substrate to the enzyme. The efficiency of oxidation was found to increase with the decrease in redox potential of the substrates, and the Marcus reorganisation energy for electron transfer to the T1 copper site was determined. Steric hindrance to substrate docking was inferred because some of the phenols and anilines investigated, despite possessing a redox potential compatible with one-electron abstraction, were scarcely oxidised. A threshold value of steric hindrance of the substrate, allowed for fitting into the active site of T. villosa laccase, was extrapolated from structural information provided by X-ray analysis of T. versicolor lac3B, sharing an identity of 99% at the protein level, thus enabling us to assess the relative contribution of steric and redox properties of a substrate in determining its susceptibility to laccase oxidation. The inferred structural threshold is compatible with the distance between two phenylalanine residues that mark the entrance to the active site. Interaction of the substrate with other residues of the active site is commented on.

Kinetic Isotope Effects in Complex Reaction Networks: Formic Acid Electro‐Oxidation

The determination of kinetic isotope effects (KIEs) for different reaction pathways and steps in a complex reaction network, where KIEs may affect the overall reaction in various different ways including dominant and minority pathways or the buildup of a reaction-inhibiting adlayer, is demonstrated for formic acid electrooxidation on a Pt film electrode by quantitative electrochemical in situ IR spectroscopic measurements under controlled mass-transport conditions. The ability to separate effects resulting from different contributions--which is not possible using purely electrochemical kinetic measurements--allows conclusions on the nature of the rate-limiting steps and their transition state in the individual reaction pathways. The potential-independent values of approximately 1.9 for the KIE of formic acid dehydration (CO(ad) formation) in the indirect pathway and approximately 3 for the CO(ad) coverage-normalized KIE of formic acid oxidation to CO2 (direct pathway) indicate that 1) C-H bond breaking is rate-limiting in both reaction steps, 2) the transition states for these reactions are different, and 3) the configurations of the transition states involve rather strong bonds to the transferred D/H species, either in the initial or in the final state, for the direct pathway and--even more pronounced--for formic acid dehydration (CO(ad) formation).

Synthesis and Use of Deuterated Palmitic Acids to Decipher the Cryptoregiochemistry of a Δ13 Desaturation

The synthesis of two hexadeuterated palmitic acids differing in the position of the diagnostic labels, and their use to decipher the cryptoregiochemistry of a Delta13 desaturation are described. A dithiane and a triple bond functionalities were used to introduce the diagnostic (C13 or C14) and tagging (C8 and C9) labels, respectively, in the palmitic acid skeleton. Using these probes, the cryptoregiochemistry of the Delta13 desaturation involved in the biosynthesis of Thaumetopoea pityocampa sex pheromone was studied by means of kinetic isotope effect determinations. Transformation of both (Z)-11-hexadecenoic and 11-hexadecynoic acids into (Z, Z)-11,13-hexadecadienoic and (Z)-13-hexadecen-11-ynoic acids, respectively, is initiated by abstraction of the hydrogen atom at the C13 position, followed by the fast elimination of the C14 hydrogen to give the double bond.

Deuterium kinetic isotope effects and mechanism of the thermal isomerization of bicyclo[4.2.0]oct-7-ene to 1,3-cyclooctadiene.

The thermal conversion of cis-bicyclo[4.2.0]oct-7-ene to cis,cis-1,3-cyclooctadiene might involve a direct disrotatory ring opening, or it might possibly take place by way of cis,trans-1,3-cyclooctadiene. This cis,trans-diene might possibly form the more stable cis,cis isomer through a [1,5] hydrogen shift or a trans-to-cis isomerization about the trans double bond. Deuterium kinetic isotope effect determinations for the isomerizations of 2,2,5,5-d(4)-bicyclo[4.2.0]oct-7-ene and 7,8-d(2)-bicyclo[4.2.0]oct-7-ene rule out these two alternatives because the observed effects are much smaller than would be anticipated for these mechanisms: k(H)/k(D)(d(4)) at 250 degrees C is 1.17 (1.04 per D), and k(H)/k(D)(d(2)) at 238 degrees C is 1.20 (1.10 per D). The direct disrotatory ring opening route remains the preferred mechanism.

QM/MM determination of kinetic isotope effects for COMT-catalyzed methyl transfer does not support compression hypothesis.

Secondary alpha-D3 kinetic isotope effects calculated by the hybrid AM1/TIP3P/CHARMM method for the reaction of S-adenosylmethionine with catecholate anion in aqueous solution and catalyzed by rat liver catechol O-methyltransferase at 298 K are 0.94 and 0.85, respectively, in good accord with experiment. The large inverse effect for the enzymatic reaction is not due to compression but arises from significant increases in the stretching and bending force constants involving the isotopically substituted atoms of the transferring methyl group as between the reactant complex and the transition structure, larger than for the reaction in water.

Oxidation of Non‐Phenolic Substrates with the Laccase/N‐Hydroxyacetanilide System: Structure of the Key Intermediate from the Mediator and Mechanistic Insight.

We have investigated the reactivity and mechanistic features in the oxidation of non-phenolic substrates by the enzyme laccase under mediation by N-hydroxyacetanilide, NHA. A radical route of hydrogen-abstraction by the N–O˙ reactive intermediate of the mediator, formed in a preliminary oxidative interaction with the enzyme, seems the more viable oxidation mechanism, in keeping with analogous conclusions reached for other laccase/N–OH-type mediators. The evaluated value of the energy of the O–H bond of NHA corroborates the occurrence of hydrogen-abstraction from the benzylic substrates by the N–O˙ intermediate of NHA. The occurrence of an alternative ionic route through the oxoammonium ion (NO+) of mediator NHA is ruled out by experimental evidence acquired through an Hammett structure/reactivity correlation in the oxidation of substituted benzyl alcohols, as well as by kinetic isotope effect determinations. The NO+ species of NHA, being a one-electron oxidant of moderate strength, could in principle even be responsible for an alternative electron-transfer route of oxidation of the substrates. This hypothesis could also be dismissed through the use of probe substrates and intermolecular selectivity determinations.

Oxidation of non-phenolic substrates with the laccase/N-hydroxyacetanilide system: Structure of the key intermediate from the mediator and mechanistic insight

We have investigated the reactivity and mechanistic features in the oxidation of non-phenolic substrates by the enzyme laccase under mediation by N-hydroxyacetanilide, NHA. A radical route of hydrogen-abstraction by the N–O˙ reactive intermediate of the mediator, formed in a preliminary oxidative interaction with the enzyme, seems the more viable oxidation mechanism, in keeping with analogous conclusions reached for other laccase/N–OH-type mediators. The evaluated value of the energy of the O–H bond of NHA corroborates the occurrence of hydrogen-abstraction from the benzylic substrates by the N–O˙ intermediate of NHA. The occurrence of an alternative ionic route through the oxoammonium ion (NO+) of mediator NHA is ruled out by experimental evidence acquired through an Hammett structure/reactivity correlation in the oxidation of substituted benzyl alcohols, as well as by kinetic isotope effect determinations. The NO+ species of NHA, being a one-electron oxidant of moderate strength, could in principle even be responsible for an alternative electron-transfer route of oxidation of the substrates. This hypothesis could also be dismissed through the use of probe substrates and intermolecular selectivity determinations.

Reactivity of isobutane in fluorosulfonic based superacids

AbstractThe behavior of isobutane in DSO3F containing various amounts of SbF5 has been studied in relation to the acid strength of the superacid system. In contrast to the DF–SbF5 system, H/D exchange occurs only in the weakest superacid via deprotonation of the t‐butyl ion intermediate formed by an oxidative process. Kinetic isotope effect determination shows that the slow step is hydride transfer. At higher acidity, the increasing stability of this intermediate impedes isotopic exchange. Copyright © 2002 John Wiley & Sons, Ltd.

A simple method for the precise and simultaneous determination of primary and multiple secondary kinetic deuterium isotope effects in organic reactions at natural abundance

AbstractA method for the determination of kinetic isotope effects (KIEs) in organic reactions using natural abundance deuterium NMR is proposed. The method consists of the determination of the site‐specific H/D isotopic ratios of the starting reactant and the product in a reaction run under pseudo‐first‐order kinetic conditions. Using simple and easy experimental procedures, primary and/or multiple secondary KIEs can be measured simultaneously with high precision. The application of this approach to different types of reaction is described. The primary and α‐secondary KIEs for C—H(D) bond breaking of —CDH— can be measured separately. The uncertainty in the determination of small secondary KIEs can reach less than 1%. The results show that some remote secondary KIEs are not negligible. The advantages and limitations of the method are discussed. One of its merits is that the method can even be used in complex situations when there are branch reactions and when the reaction is reversible. The performance depends essentially on the signal separation in the NMR spectra. Copyright © 2001 John Wiley & Sons, Ltd.