The kinetic isotope effect in the photochlorination of methane

The kinetic isotope effect for the photochemically initiated chlorination of methane-d₂ has been determined. The value is k_H/k_D = 12·1 at 0°C., and the variation with temperature is given by k_H/k_D = 1·09 exp (1300/RT. The results are considered in terms of a semiempirical potential energy surface, and the general subject of the magnitudes of primary kinetic isotope effects is discussed.     

Anomalous kinetic hydrogen isotope effect in the oxidation of formate by bromine: Tunneling via an intermediate

Rates of oxidation of XCOO^? (X = H, D) by Br₂ in acid aqueous media were measured between 274 and 332 K. The derived Arrhenius parameters for both reactions where θ = 4.575T × 10^?3 kcal/mol, with (k_H/k_D)_298K = 2.85, reveal a primary isotope effect, but the difference (E_D - E_H) = 3.29 kcal/mol and the ratio A_D/A_H = 91 fall beyond the limits imposed by semiclassical transition-state theory, suggesting tunneling or a multiple-stage mechanism. However, it can be shown that either tunneling in a single step or a three-step, internal return mechanism can be ruled out as alternative models, since both require unreasonable kinetic parameters to fit the data. The simplest scheme accounting for the present observations involves tunneling in the decomposition of a charge transfer complex in equilibrium with the reactants.     

Anomalously large kinetic isotope effect

Activated diffusion of water between macromolecules in swollen cellulose is accompanied by anomalously high kinetic isotope effects of oxygen. The separation factor of heavy-oxygen water (H₂ ¹⁸O /H₂ ¹⁶O) is thousands of permilles instead of tens of permilles according to modern Absolute Rate Theory. This anomalous separation under usual conditions is disguised by the opposing process of very fast equalization to equilibrium through water-filled cellulose pores. This process is quicker by approximately 3 orders of magnitude than diffusion through the cellulose body. As a consequence, this opposition-directed equalization virtually eliminates the results of isotope separation. To reveal this anomaly it is necessary to suppress equalization, which was the primary problem for both discovery of this anomaly and its investigation. The method of investigating the anomalous separation in cellulose was developed with suppression of this negative influence. Discussion of the theoretical nature of the anomalous kinetic isotope effect is presented. This theoretical study would probably permit the discovery and use for isotope separation of the anomalously high isotope effect for other chemical elements, in particular, for those heavier than oxygen.      

PCET in the oxidation of ascorbate. Dramatic change of the kinetic isotope effect on the change in solvent polarity

The first step in the oxidation of ascorbate with substituted nitrosobenzenes is a proton-coupled electron transfer (PCET) reaction and the observed kinetic isotope effects in the reaction, k_H2O/k_D2O, change dramatically with a change in solvent polarity, in line with known theoretical predictions.     

Quantum-mechanical calculations on the kinetic hydrogen isotope effect

Conclusions Study has been made of the relation between the magnitude of the kinetic isotope effect and the free energy of reaction, account being taken of the anharmonicity of proton vibrations and the possibility of adiabatic transitions between the vibrational levels. Calculated values are compared with the results of measurements on proton transfer between ethyl nitroacetate and various bases in aqueous solution.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 11, pp. 2414–2418, November, 1979.     

Oxygen kinetic isotope effects upon catalytic water oxidation by a monomeric ruthenium complex

Oxygen isotope fractionation is applied for the first time to probe the catalytic oxidation of water using a widely studied ruthenium complex, [Ru(II)(tpy)(bpy)(H(2)O)](ClO(4))(2) (bpy = 2,2'-bipyridine; tpy = 2,2';6",2"-terpyridine). Competitive oxygen-18 kinetic isotope effects ((18)O KIEs) derived from the ratio of (16,16)O(2) to (16,18)O(2) formed from natural-abundance water vary from 1.0132 ± 0.0005 to 1.0312 ± 0.0004. Experiments were conducted with cerium(IV) salts at low pH and a photogenerated ruthenium(III) tris(bipyridine) complex at neutral pH as the oxidants. The results are interpreted within the context of catalytic mechanisms using an adiabatic formalism to ensure the highest barriers for electron-transfer and proton-coupled electron-transfer steps. In view of these contributions, O-O bond formation is predicted to be irreversible and turnover-limiting. The reaction with the largest (18)O KIE exhibits the greatest degree of O-O coupling in the transition state. Smaller (18)O KIEs are observed due to multiple rate-limiting steps or transition-state structures which do not involve significant O-O motion. These findings provide benchmarks for systematizing mechanisms of O-O bond formation, the critical step in water oxidation by natural and synthetic catalysts. In addition, the measurements introduce a new tool for calibrating computational studies using relevant experimental data.     

Lack of kinetic hydrogen isotope effect in acetylene pyrolysis

Second order rate constants for C₂H₂ or C₂D₂ polymerizations into vinylacetylene and higher C_nH_n products have been measured in a static reactor by dynamic mass spectrometry between 770–980 K. They are nearly identical within experimental error (±50%). It is shown that these results are consistent with the participation of thermally equilibrated vinylidene H₂C ? C: as a reactive intermediate: (1) since this assumption only introduces a modest reverse equilibrium isotope effect (K_iH/K_iD ca. 0.48 in this range) into overall rate constants. At the same time they seem to discriminate in general against alternative mechanisms in which the required H-atom transfers take place in rate determining steps. Present evidence, in conjunction with an updated analysis of relevant issues such as experimental and theoretical vs. termochemical estimates of the heat of formation of H₂C?C:, the nature of the transition states of singlet vinylidene addition reactions and the likelihood of discrete biradical intermediates in C₂H₂ dimerization, seems to lend further support to the notion that acetylene behaves as a singlet carbene at high temperatures.     

Measurement of the kinetic isotope effect for the oxidation of NADH at a poly(aniline)-modified electrode

Kinetic isotope measurements using [4,4-2H2]NADH and [4-1H, 4-2H]NADH have been used to investigate the mechanism of the electrochemical oxidation of NADH at poly(aniline)-poly(vinyl sulfonate)-modified electrodes. The experiments show a primary kinetic isotope effect for the reaction of 4.2. This is consistent with literature values for the corresponding isotope effect for the oxidation of NADH by two-electron oxidants in homogeneous solution. The result demonstrates that transfer of H from NADH to the modified electrode occurs in the rate-limiting step within the reaction complex.     

Deuterium kinetic isotope effect in the oxidation of sodium (2-D2)propionate with permanganate in water solutions

Kinetic parameters characterizing the oxidation of sodium(2-¹H₂) propionate and the oxidation of sodium (2-²H₂) propionate with permanganate in water solutions have been determined and compared with kinetic parameters derived from the investigation of the deuterium isotope effect on the activation parameters in the permanganate and manganate oxidation of sodium (2-³H₂) propionate in water solutions of sodium hydroxide.     

Primary kinetic isotope effect in the nitrosation of 1,3- dialkylureas

In the nitrosation mechanism of 1,3 dialkylureas, the existence of protonic transfer to the solvent as a rate-limiting step was confirmed when a primary kinetic isotope effect was observed in these reactions.     

Theoretical analysis of the kinetic isotope effect on carboxylation in RubisCO

Ribulose-1,5-bisphosphate carboxylase/oxygenase (RubisCO) fixes atmospheric carbon dioxide into bioavailable sugar molecules. It is also well known that a kinetic isotope effect (KIE; CO₂ carbon atoms) accompanies the carboxylation process. To describe the reaction and the KIE α, two different types of molecular dynamics (MD) simulations (ab initio MD and classical MD) have been performed with an Own N-layered Integrated molecular Orbitals and molecular Mechanics (ONIOM)-hybrid model. A channel structure for CO₂ transport has been observed during the MD simulation in RubisCO, and assuming the reaction path from the inlet to the product through the coordinate complex with Mg²⁺, simulations have been performed on several molecular configuration models fixing several distances between CO₂ and ribulose-1,5-bisphosphate along the channel. Free energy analysis and diffusion coefficient analysis have been evaluated for different phases of the process. It is confirmed that the isotopic fractionation effect for CO₂ containing either ¹³C or ¹²C would appear through the transiting path in the channel structure identified in RubisCO. The estimated isotope fractionation constant was quite close to the experimental value.     

Kinetics and kinetic isotope effect in pentavalent plutonium disproportionation activated by power ultrasound

A kinetic isotope effect in Pu(V) disproportionation has been observed in nitric acid solution under the effect of power ultrasound with intensity 0.9W·cm^–2 and frequency 22 kHz. The isotope separation coefficient for²⁴²Pu/²³⁹Pu isotopes was found to be 1.0081 at 20°C. Without sonication the k.i.e. was not observed. The rate constant of Pu(V) disproportionation was found to be accelerated under sonication. The rate constant determined was (5.7±0.6)·10^–3 1²·mol^–2·s^–1 atl=0.9 W·cm^–2,v=22 kHz, [HNO₃]=0.5 mol·l^–1 andT=20°C. It is supposed that the acceleration of Pu(V) disproportionation and the kinetic isotope effect are due to the activation of plutonoyl groups in the interface between the cavitation bubble and the bulk solvent.     

Insights on the mechanism of amine oxidation catalyzed by D-arginine dehydrogenase through pH and kinetic isotope effects

The mechanism of amine oxidation catalyzed by D-arginine dehydrogenase (DADH) has been investigated using steady-state and rapid reaction kinetics, with pH, substrate and solvent deuterium kinetic isotope effects (KIE) as mechanistic probes, and computational studies. Previous results showed that 85-90% of the flavin reduction reaction occurs in the mixing time of the stopped-flow spectrophotometer when arginine is the substrate, precluding a mechanistic investigation. Consequently, leucine, with slower kinetics, has been used here as the flavin-reducing substrate. Free energy calculations and the pH profile of the K(d) are consistent with the enzyme preferentially binding the zwitterionic form of the substrate. Isomerization of the Michaelis complex, yielding an enzyme-substrate complex competent for flavin reduction, is established due to an inverse hyperbolic dependence of k(cat)/K(m) on solvent viscosity. Amine deprotonation triggers the oxidation reaction, with cleavage of the substrate NH and CH bonds occurring in an asynchronous fashion, as suggested by the multiple deuterium KIE on the rate constant for flavin reduction (k(red)). A pK(a) of 9.6 signifies the ionization of a group that facilitates flavin reduction in the unprotonated form. The previously reported high-resolution crystal structures of the iminoarginine and iminohistidine complexes of DADH allow us to propose that Tyr(53), on a mobile loop covering the active site, may participate in substrate binding and facilitate flavin reduction.     

Measurement of the alpha-secondary kinetic isotope effect for the reaction catalyzed by mammalian protein farnesyltransferase

Protein farnesytransferase (FTase) catalyzes the transfer of a 15-carbon prenyl group from farnesyl diphosphate (FPP) to the cysteine residue of target proteins and is a member of the newest class of zinc metalloenzymes that catalyze sulfur alkylation. Common substrates of FTase include oncogenic Ras proteins, and therefore inhibitors are under development for the treatment of various cancers. An increased understanding of the salient features of the chemical transition state of FTase may aid in the design of potent inhibitors and enhance our understanding of the mechanism of this class of zinc enzymes. To investigate the transition state of FTase we have used transient kinetics to measure the alpha-secondary 3H kinetic isotope effect at the sensitive C1 position of FPP. The isotope effect for the FTase single turnover reaction using a peptide substrate that is farnesylated rapidly is near unity, indicating that a conformational change, rather than farnesylation, is the rate-limiting step. To look at the chemical step, the kinetic isotope effect was measured as 1.154 +/- 0.006 for a peptide that is farnesylated slowly, and these data suggest that FTase proceeds via a concerted mechanism with dissociative character.     

The kinetic deuterium isotope effect in the thermal dehydration of boric acid

The kinetic deuterium isotope effect in the thermal dehydration process from H₃BO₃ to HBO₂(III) was determined using simultaneous TG and DSC. The rate constant ratio of H₃BO₃ to D₃BO₃ obtained by the analysis of isothermal TG and DSC curves was found to be smaller than unity. Both activation energy, E, and frequency factor, A, for the dehydration of H₃BO₃ proved to be larger than those of D₃BO₃, using non-isothermal TG and DSC. The origin of the deuterium kinetic isotope effect in the thermal dehydration of boric acid is also briefly discussed.     

Vibrational analysis of a rate-slowing conformational kinetic isotope effect

An enthalpy-entropy approach to analyzing a rate-slowing conformational kinetic isotope effect (CKIE) in a deuterated doubly-bridged biaryl system is described. The computed isotope effect (k_H/k_D?=?1.075, 368?K) agrees well with the measured value (k_H/k_D?=?1.06, 368?K). The rate-slowing (normal isotope effect) nature of the computed CKIE is shown to originate from a vibrational entropy contribution defined by the twenty lowest frequency normal modes in the ground state and transition state structures. This normal entropy contribution is offset by an inverse vibrational enthalpy contribution, which also arises from the twenty lowest frequency normal modes. Zero point vibrational energy contributions are found to be relatively small when all normal modes are considered. Analysis of the H_ZPE, H_vib, and S_vib energy terms arising from the low frequency vibrational modes reveals their signs and magnitudes are determined by larger vibrational energy differences in the labeled and unlabeled ground state structures.     

Carbon-13 kinetic isotope effect of the decarbonylation of oxalic acid

Carbon-13 intramolecular kinetic isotope effects in the decarbonylation of oxalic acid dihydrate of natural isotopic composition by SO₃ and by fuming sulphuric acid at room temperature and decarbonylation of oxalic acid dihydrate by 100% H₃PO₄ in the temperature interval 80–150°C have been determined. The obtained isotopic and kinetic results have been compared with the earlier¹³C experimental and theoretical studies in other solvents.     

Computational evidence that the inverse kinetic isotope effect for reductive elimination of methane from a tungstenocene methyl-hydride complex is associated with the inverse equilibrium isotope effect for formation of a sigma-complex intermediate

Calculations on [H2Si(C5H4)2]W(Me)H demonstrate that the interconversion between [H2Si(C5H4)2]W(Me)H and the sigma-complex [H2Si(C5H4)2]W(sigma-HMe) is characterized by normal kinetic isotope effects for both reductive coupling and oxidative cleavage; the equilibrium isotope effect, however, is inverse and is the origin of the inverse kinetic isotope effect for the overall reductive elimination of methane.