Explore the vast range of titles available.

Solvent isotope effects have long been used as a mechanistic tool for determining enzyme mechanisms. Most commonly, macroscopic rate constants such as kcat and kcat/Km are found to decrease when the reaction is performed in D2O for a variety of reasons including the transfer of protons. Under certain circumstances, these constants are found to increase, in what is termed an inverse solvent kinetic isotope effect (SKIE), which can be a diagnostic mechanistic feature. Generally, these phenomena can be attributed to an inverse solvent equilibrium isotope effect on a rapid equilibrium preceding the rate-limiting step(s). This review surveys inverse SKIEs in enzyme-catalyzed reactions by assessing their underlying origins in common mechanistic themes. Case studies for each category are presented, and the mechanistic implications are put into context. It is hoped that readers may find the illustrative examples valuable in planning and interpreting solvent isotope effect experiments.

Thermochemical sulfate reduction experiments with simple amino acid and dilute concentrations of sulfate reveal significant degrees of mass-independent sulfur isotope fractionation. Enrichments of up to 13‰ for 33S are attributed to a magnetic isotope effect (MIE) associated with the formation of thiol-disulfide, ion-radical pairs. Observed 36S depletions in products are explained here by classical (mass-dependent) isotope effects and mixing processes. The experimental data contrasts strongly with multiple sulfur isotope trends in Archean samples, which exhibit significant 36S anomalies. These results support an origin other than thermochemical sulfate reduction for the mass-independent signals observed for early Earth samples.

Photosystem II (PSII) performs the solar-driven oxidation of water used to fuel oxygenic photosynthesis. The active site of water oxidation is the oxygen-evolving complex (OEC), a Mn₄CaO₅ cluster. PSII requires degradation of key subunits and reassembly of the OEC as frequently as every 20 to 40 min. The metals for the OEC are assembled within the PSII protein environment via a series of binding events and photochemically induced oxidation events, but the full mechanism is unknown. A role of proton release in this mechanism is suggested here by the observation that the yield of in vitro OEC photoassembly is higher in deuterated water, D₂O, compared with H₂O when chloride is limiting. In kinetic studies, OEC photoassembly shows a significant lag phase in H₂O at limiting chloride concentrations with an apparent H/D solvent isotope effect of 0.14 ± 0.05. The growth phase of OEC photoassembly shows an H/D solvent isotope effect of 1.5 ± 0.2. We analyzed the protonation states of the OEC protein environment using classical Multiconformer Continuum Electrostatics. Combining experiments and simulations leads to a model in which protons are lost from amino acid that will serve as OEC ligands as metals are bound. Chloride and D₂O increase the proton affinities of key amino acid residues. These residues tune the binding affinity of Mn2+/3+ and facilitate the deprotonation of water to form a proposed μ-hydroxo bridged Mn2+Mn3+ intermediate.

Ozonolysis of alkenes, an important nonphotolytic source of hydroxyl (OH) radicals in the atmosphere, proceeds through unimolecular decay of Criegee intermediates. Here, we report a large kinetic isotope effect associated with the rate-limiting hydrogen-transfer step that releases OH radicals for a prototypical Criegee intermediate, CH₃CHOO. IR excitation of selectively deuterated syn-CD₃CHOO is shown to result in deuterium atom transfer and release OD radical products. Vibrational activation of syn-CD₃CHOO is coupled with direct time-resolved detection of OD products to measure a 10-fold slower rate of unimolecular decay upon deuteration in the vicinity of the transition state barrier, which is confirmed by microcanonical statistical theory that incorporates quantum mechanical tunneling. The corresponding kinetic isotope effect of ∼10 is attributed primarily to the decreased probability of D-atom vs. H-atom transfer arising from tunneling. Master equation modeling is utilized to compute the thermal unimolecular decay rates for selectively and fully deuterated syn methyl-substituted Criegee intermediates under atmospheric conditions. At 298 K (1 atm), tunneling is predicted to enhance the thermal decay rate of syn-CH₃CHOO compared with the deuterated species, giving rise to a significant kinetic isotope effect of ∼50.

In aqueous acetic acid medium, the kinetics of oxidation of glycolic and lactic acid by ethylenediammonium dichromate [enH 2 Cr 2 O 7 ] have been explored. The oxidation product is the corresponding oxoacid. The conventional UV–vis spectrophotometric method is used to study the reaction kinetics. First-order kinetics has been observed concerning [enH 2 Cr 2 O 7 ] and with substrate the order is less than two. The fractional-order dependency with respect to substrate confirms the binding of oxidant and substrate to form a complex before rate-determining step. The rate of reaction increases with an increase in [H + ] concentration. The existence of primary kinetic isotope effect, k H / k D = 5.97 at 298K for glycolic acid (ratio of rate constants for protio- and deuterio-glycolic acid) indicated a C–H bond cleavage rather than C–C bond cleavage. Variation of solvent polarity is found to impose a remarkable impact on the rate of oxidation. From the experimental data, formation of an unstable cyclic transition state followed by intra-molecular proton transfer has been proposed. Under similar conditions oxidation of lactic acid was studied.

We present the discovery of an unusually large isotope effect in the structural relaxation and the glass transition temperature T g of water. Dielectric relaxation spectroscopy of low-density as well as of vapor-deposited amorphous water reveal T g differences of 10 ± 2 K between H ₂O and D ₂O, sharply contrasting with other hydrogen-bonded liquids for which H/D exchange increases T g by typically less than 1 K. We show that the large isotope effect and the unusual variation of relaxation times in water at low temperatures can be explained in terms of quantum effects. Thus, our findings shed new light on water's peculiar low-temperature dynamics and the possible role of quantum effects in its structural relaxation, and possibly in dynamics of other low-molecular-weight liquids. Significance Water is by far the most important and intriguing liquid. Despite the relative simplicity of its chemical structure there are many puzzling properties of water that remain the focus of active discussions. Our studies revealed an unusually strong isotope effect and an extraordinarily slow temperature variation of the structural relaxation of water at low temperatures. We show that the anomalous behavior of deeply supercooled water is affected by quantum effects, usually considered negligible for the glass transition. However, in water they are significant owing to the small mass of the molecule. The presented results might considerably change our understanding of water dynamics at low temperatures.

The first ionization constants of phosphoric acid and acetic acid have been measured in H 2 O and D 2 O from T  = 373 K to T  = 573 K and p  = 11.5 and 20 MPa to yield accurate values of the deuterium isotope effect. Sequential conductivity measurements using a unique high-precision flow-through AC conductance instrument were made on dilute ( m  ≤ 10 –2  mol·kg −1 ) aqueous solutions of phosphoric acid, acetic acid, potassium dihydrogenphosphate, sodium acetate, potassium hydroxide, sodium hydroxide, hydrochloric acid, potassium chloride and sodium chloride in light and heavy water under the same experimental conditions (temperature, pressure, flow-rate), so that systematic experimental errors between the two solvents would cancel. The experimental molar conductivities of potassium dihydrogenphosphate, sodium acetate, hydrochloric acid, and the corresponding chloride salts were used to calculate the molar conductivities for the fully dissociated acids [λ(D + ), λ(D 2 PO 4 − ) and λ(CH 3 COO − )]. Together with the molar conductivities measured for partially ionized acids, Λ(D 3 PO 4 ) and Λ(CH 3 COOD), these yielded values for the degree of dissociation, α, and the ionization constants, p K a1 . The iterative process was repeated at each temperature in both H 2 O and D 2 O where the Fuoss-Hsia-Fernández-Prini (“FHFP”) and the Quint-Viallard (“QV”) equations were used to correct for ionic strength. The resulting values of p K a1 for phosphoric acid in H 2 O agree with those reported from conductivity studies by previous works over the entire temperature range and with low temperature potentiometric studies to within the combined experimental uncertainties. The results for p K a1 above 298.15 K in D 2 O are the first to be reported in the literature. The new values for p K a (CH 3 COOD) yield more accurate values for the deuterium isotope effect on the ionization constant of acetic acid than those reported in our previous work (Erickson et al. in J. Phys. Chem. B. 123:9503–9506, 2019). The single-ion limiting conductivities for dihydrogenphosphate and acetate in D 2 O, λ(D 2 PO 4 − ) and λ(CH 3 COO − ), were found to be the same as those in H 2 O once corrected for viscosity effects, confirming previous observations for other ions.

Stable carbon isotope (δ 13 C) rollover of natural gas has attracted recent attention due to its association with highly productive shale gas. However, the mechanistic causes of δ 13 C rollover are not fully understood. In this investigation, pyrolysis was carried out using calcareous shale and carbonaceous mudstone under high water pressure (WP) (i.e., 5 × 10 6 –1.2 × 10 8  Pa). It was found that WP induced the isotope rollover of gaseous hydrocarbons. For both sapropelic and humic organic matter, the δ 13 C rollover of CH 4 (methane), C 2 H 6 (ethane), and C 3 H 8 (propane) occurred when the WP ranged from 3.25 × 10 7 to 1.2 × 10 8  Pa. This result can be explained by high WP conditions retarding oil cracking, and enhancing hydrocarbon expulsion and oil generation. The promotion of oil generation resulted in increasing trends of vitrinite reflectance, and inhibition of gaseous hydrocarbons generation resulted in decrease in δ 13 C 1 values with increase in WP. Good functions were found between water pressure and the calculated carbon kinetic isotope effect (KIE) for 12 CH 4 and 13 CH 4 produced from sapropelic and humic organic matter. Further calculations showed that the increments of activation volume ( Δ V 12 CH 4 ‡ – Δ V 13 CH 4 ‡ ) were linearly correlated with the kinetic isotope effect of methane ( Δ KIE ) produced from sapropelic and humic organic matter, indicating that WP may affect the KIE of 12 CH 4 and 13 CH 4 by changing the Δ V ‡ of 12 CH 4 and 13 CH 4 . Overall, these findings suggest that WP affects the carbon isotope fractionation of gaseous hydrocarbons due to the different thermodynamic properties of 12 CH 4 and 13 CH 4 .

Theoretical treatment of ozone forming reaction is developed within the framework of mixed quantum/classical dynamics. Formation and stabilization steps of the energy transfer mechanism are both studied, which allows simultaneous capture of the delta zero-point energy effect and η-effect and identification of the molecular level origin of mass-independent isotope fractionation. The central role belongs to scattering resonances; dependence of their lifetimes on rotational excitation, asymmetry; and connection of their vibrational wave functions to two different reaction channels. Calculations, performed within the dimensionally reduced model of ozone, are in semiquantitative agreement with experiment.

This review is giving a short introduction to the techniques used to investigate isotope effects on NMR chemical shifts. The review is discussing how isotope effects on chemical shifts can be used to elucidate the importance of either intra- or intermolecular hydrogen bonding in ionic liquids, of ammonium ions in a confined space, how isotope effects can help define dimers, trimers, etc., how isotope effects can lead to structural parameters such as distances and give information about ion pairing. Tautomerism is by advantage investigated by isotope effects on chemical shifts both in symmetric and asymmetric systems. The relationship between hydrogen bond energies and two-bond deuterium isotope effects on chemical shifts is described. Finally, theoretical calculations to obtain isotope effects on chemical shifts are looked into.