Computation of kinetic isotope effects for enzymatic reactions

We describe a computational approach,incorporating quantum mechanics into enzyme kinetics modeling with a special emphasis on computation of kinetic isotope effects.Two aspects are highlighted:(1) the potential energy surface is represented by a combined quantum mechanical and molecular mechanical(QM/MM) potential in which the bond forming and breaking processes are modeled by electronic structure theory,and(2) a free energy perturbation method in path integral simulation is used to determine both kinetic isotope effects(KIEs).In this approach,which is called the PI-FEP/UM method,a light(heavy) isotope is mutated into a heavy(light) counterpart in centroid path integral simulations.The method is illustrated in the study of primary and secondary KIEs in two enzyme systems.In the case of nitroalkane oxidase,the enzymatic reaction exhibits enhanced quantum tunneling over that of the uncatalyzed process in water.In the dopa delarboxylase reaction,there appears to be distinguishable primary carbon-13 and secondary deuterium KIEs when the internal proton tautomerism is in the N-protonated or in the O-protonated positions.These examples show that the incorporation of quantum mechanical effects in enzyme kinetics modeling offers an opportunity to accurately and reliably model the mechanisms and free energies of enzymatic reactions.

Equilibrium and kinetic Si isotope fractionation factors and their implications for Si isotope distributions in the Earth's surface environments

Several important equilibrium Si isotope fractionation factors among minerals,organic molecules and the H_4SiO_4 solution are complemented to facilitate the explanation of the distributions of Si isotopes in Earth's surface environments.The results reveal that,in comparison to aqueous H_4SiO_4,heavy Si isotopes will be significantly enriched in secondary silicate minerals.On the contrary,quadra-coordinated organosilicon complexes are enriched in light silicon isotope relative to the solution.The extent of ^(28)Si-enrichment in hyper-coordinated organosilicon complexes was found to be the largest.In addition,the large kinetic isotope effect associated with the polymerization of monosilicic acid and dimer was calculated,and the results support the previous statement that highly ^(28)Sienrichment in the formation of amorphous quartz precursor contributes to the discrepancy between theoretical calculations and field observations.With the equilibrium Si isotope fractionation factors provided here,Si isotope distributions in many of Earth's surface systems can be explained.For example,the change of bulk soil δ^(30)Si can be predicted as a concave pattern with respect to the weathering degree,with the minimum value where allophane completely dissolves and the total amount of sesquioxides and poorly crystalline minerals reaches their maximum.When,under equilibrium conditions,the well-crystallized clays start to precipitate from the pore solutions,the bulk soil δ^(30)Si will increase again and reach a constant value.Similarly,the precipitation of crystalline smectite and the dissolution of poorly crystalline kaolinite may explain the δ^(30)Si variations in the ground water profile.The equilibrium Si isotope fractionations among the quadracoordinated organosilicon complexes and the H_4SiO_4solution may also shed light on the Si isotope distributions in the Si-accumulating plants.

Rate Coecients and Kinetic Isotope E ects of Cl+XCl→XCl+Cl(X=H,D,Mu)Reactions from Ring Polymer Molecular Dynamics

The ring-polymer molecular dynamics(RPMD)was used to calculate the thermal rate coefficients and kinetic isotope effects of the heavy-light-heavy abstract reaction Cl+XCl→XCl+Cl(X=H,D,Mu).For the Cl+HCl reaction,the excellent agreement between the RPMD and experimental values provides a strong proof for the accuracy of the RPMD theory.And the RPMD results are also consistent with results from other theoretical methods including improved-canonical-variational-theory and quantum dynamics.The most novel finding is that there is a double peak in Cl+MuCl reaction near the transition state,leaving a free energy well.It comes from the mode softening of the reaction system at the peak of the potential energy surface.Such an explicit free energy well suggests strongly there is an observable resonance.And for the Cl+DCl reaction,the RPMD rate coefficient again gives very accurate results compared with experimental values.The only exception is at the temperature of 312.5 K,results from RPMD and all other theoretical methods are close to each other but slightly lower than the experimental value,which indicates experimental or potential energy surface deficiency.

Intramolecular carbon isotope of propane from coal-derived gas reservoirs of sedimentary basins:Implications for source,generation and post-generation of hydrocarbons

An intramolecular isotopic study was conducted on natural gases collected from coal-derived gas reser-voirs in sedimentary basins of China to determine their position-specific isotope distributions.The propane from the Turpan-Hami Basin exhibited negativeΔc-T(δ13Ccentral-δ13Cterminal)values ranging from-3.9‰to-0.3‰,with an average of-2.1‰.Propane from the Ordos Basin,Sichuan Basin,and Tarim Basin showed positiveΔC-T values,with averages of 1.3‰,5.4‰and 7.6‰,respectively.Positionspecific carbon isotope compositions reveal the precursors and the propane generation pathways in the petroliferous basins.Propane formed from the thermal cracking of TypeⅢkerogen has largerδ13Ccentral andδ13Cterminal values than propane from TypeⅠ/Ⅱkerogen.The precursor for natural gases collected in this study is identified to be TypeⅢkerogen.Comparing our data to calculated results for thermal cracking of TypeⅢkerogen,we found that propane from the low-maturity gas reservoir in the Turpan Basin was generated via the i-propyl radical pathway,whereas propane from the Sulige tight gas reservoir in the Ordos Basin was formed via the n-propyl radical pathway.δ13Cterminal values covered a narrow range across basins,in contrast toδ13Ccentral.The terminal carbon position in propane is less impacted by microbial oxidation and more relevant to maturity levels and precursors.Thus,δ13Cterminal has a good potential to infer the origin and maturity level of natural gas.In examining post-generation processes,we proposed an improved identification strategy for microbial oxidation of natural gases,based on the position-specific carbon isotope distributions of propane.Samples from the Liaohe Depression of the Bohai Bay Basin and the Sichuan Basin were detected of post-generation microbial oxidation.Overall,position-specific carbon isotope composition of propane provides new insights into the generation mechanism and post-generation processes of natural gas in the geological period at the atomic level.

The role of proton dynamics on the catalyst-electrolyte interface in the oxygen evolution reaction

The development of non‐precious metal catalysts that facilitate the oxygen evolution reaction(OER)is important for the widespread application of hydrogen production by water splitting.Various perovskite oxides have been employed as active OER catalysts,however,the underlying mechanism that occurs at the catalyst‐electrolyte interface is still not well understood,prohibiting the design and preparation of advanced OER catalysts.Here,we report a systematic investigation into the effect of proton dynamics on the catalyst‐electrolyte interfaces of four perovskite catalysts:La_(0.5)Sr_(0.5)CoO_(3‐δ)(LSCO),LaCoO_(3),LaFeO_(3),and LaNiO_(3).The pH‐dependent OER activities,H/D kinetic isotope effect,and surface functionalization with phosphate anion groups were investigated to elucidate the role of proton dynamics in the rate‐limiting steps of the OER.For oxides with small charge‐transfer energies,such as LSCO and LaNiO_(3),non‐concerted proton‐coupled electron transfer steps are involved in the OER,and the activity is strongly controlled by the proton dynamics on the catalyst surface.The results demonstrate the important role of interfacial proton transfer in the OER mechanism,and suggest that proton dynamics at the interface should carefully be considered in the design of future high‐performance catalysts.

A hybrid nickel/iron-pyromellitic acid electrocatalyst for oxygen evolution reaction

The migration of protons during the oxygen evolution reaction(OER)is a key factor that affects the performance of OER catalysts.To enhance proton transportation,we designed a catalyst based on nickel/iron-pyromellitic acid(NiFe-PMA)prepared by the electrochemical deposition method.This catalyst exhibited a low overpotential of 188 mV at a current density of 10 mA·cm^(-2),a Tafel slope of 28.2 mV·dec^(-1),and long-term stability for 30 days with a current of 50 mA·cm^(-2).We characterized the NiFe-PMA catalyst using various techniques,including Fourier transform infrared(FTIR)spectroscopy,Raman spectroscopy,X-ray photoelectron spectroscopy(XPS),X-ray absorption spectroscopy(XAS),transmission electron microscopy(TEM),scanning electron microscopy(SEM),and inductively coupled plasma-optical emission spectrometry(ICP-OES).Our results showed that NiFe-PMA contains nickel,iron atoms,and both coordinated and uncoordinated carboxylate groups.Additionally,XPS data confirmed that carboxylate ligands could adjust the outer electronic structure of metal ions,resulting in the high valence state of Ni in NiFe-PMA.The result of XAS indicated that the nickel atoms present in the catalyst might be easier to maintain a higher chemical state.Further investigations using kinetic isotope effects(KIEs)and proton inventory revealed that the uncoordinated carboxylic protons played a crucial role in receiving protons during the OER,which promoted the proton transfer of the rate-determining step of the OER.Our novel electrocatalysts provide a new strategy for designing more active and cost-effective catalysts for the OER.

Spin polarization strategy to deploy proton resource over atomic-level metal sites for highly selective CO_(2) electrolysis

Unlocking of the extremely inert C=O bond during electrochemical CO_(2) reduction demands subtle regulation on a key“resource”,protons,necessary for intermediate conversion but also readily trapped in water splitting,which is still challenging for developing efficient single-atom catalysts limited by their structural simplicity usually incompetent to handle this task.Incorporation of extra functional units should be viable.Herein,a proton deployment strategy is demonstrated via“atomic and nanostructured iron(A/N-Fe)pairs”,comprising atomically dispersed iron active centers spin-polarized by nanostructured iron carbide ferromagnets,to boost the critical protonation steps.The as-designed catalyst displays a broad window(300 mV)for CO selectivity>90%(98%maximum),even outperforming numerous cutting-edge M–N–C systems.The well-placed control of proton dynamics by A/N-Fe can promote*COOH/*CO formation and simultaneously suppress H2 evolution,benefiting from the magnetic-proximity-induced exchange splitting(spin polarization)that properly adjusts energy levels of the Fe sites’d-shells,and further those of the adsorbed intermediates’antibonding molecular orbitals.

C-S coupling with nitro group as leaving group via simple inorganic salt catalysis

An efficient and practical synthetic protocol to synthesize nonsymmetrical aryl thioethers by nucleophilic aromatic substitution(S_NAr)reaction of nitroarenes by thiols with potassium phosphate as the catalyst is described.Various moderate to strong electron-withdrawing functional groups are tolerated by the system to provide thioethers in a good to excellent yields.We also showed that the present method allows access to 3 drug examples in a short reaction time.Finally,mechanistic studies suggest that the reaction may form the classic Meisenheimer complex through a two-step additionelimination mechanism.

Unusual reaction of a tungsten alkylidyne complex with water.Formation,characterization,and crystal structures of oxo trimers

The reaction of the alkyl alkylidyne W（CH2CMe3）3（=CSiMe3） （1） with H20 in THF and with D20 in benzene-d6 gave two new trimeric oxo complexes： W3O3（μ=O）3（CH2CMe3）6（THF）3 （2） and [W303（μ=O）3（Ch2CMe3）6（D2O）3] 2benzene-d6 （3.2benzened6）, respectively, each containing two alkyl ligands per W atom. This is in contrast to the dimer W2o（β-O）（CH2CMe3）6, containing three alkyl ligands per W atom, from the previously reported reaction of the alkyl alkylidyne analog W（CH2CMe3）3- （=-CCMe3） with H2O. In the reaction of 1 with D20 in THF, an unstable intermediate W2O2（μ-O）（CD2SiMe3）2（CH2CMe3）4 （4-d4） was identified. Kinetic studies of the reactions of 1 with excess H2O and D2O in THF-ds, yielding 4 and 4-d4, respectively, give a kinetic isotope effect （KIE） of 3.46（3） at 298（1） K, suggesting that the disappearance of 1 is a rate-determining step.