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The utility of bio-isosteres is broad in drug discovery and methodology herein enables the preparation of deuterium-labeled products is the most fundamental of known bio-isosteric replacements. As such we report the use of both [D1]-aldehydes and [D2]-isonitriles across 8 multicomponent reactions (MCRs) to give diverse arrays of deuterated products. A highlight is the synthesis of several FDA-approved calcium channel blockers, selectively deuterated at a t1/2 limiting metabolic soft-spot via use of [D1]-aldehydes. Surrogate pharmacokinetic analyses of microsomal stability confirm prolongation of t1/2 of the new deuterated analogs. We also report the first preparation of [D2]-isonitriles from [D3]-formamides via a modified Leuckart–Wallach reaction and their use in an MCR to afford products with [D2]-benzylic positions and likely significantly enhanced metabolic stability, a key parameter for property-based design efforts.

In aqueous acetic acid medium, the kinetics of oxidation of glycolic and lactic acid by ethylenediammonium dichromate [enH2Cr2O7] 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 [enH2Cr2O7] 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, kH/kD = 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. [ABSTRACT FROM AUTHOR]

Kinetic isotope effect (KIE) has emerged as a new topic in chemistry competitions both domestically and internationally in recent years. This paper elucidates the origins of first-order and second-order KIE, starting from the perspective of classical transition state theory, based on the potential energy curve and zero-point vibration energy. The role of KIE in the study of reaction mechanisms is briefly discussed. By analyzing relevant exam questions from both domestic and international chemistry competitions, the examination perspectives on KIE are identified, highlighting the continuity between domestic and international competitions. Finally, this paper offers reflections and suggestions for teaching KIE in the context of competitive exams, providing valuable insights and references for educators involved in competition training. [ABSTRACT FROM AUTHOR]

Olive oil phenols are recognized as molecules with numerous positive health effects, many of which rely on their antioxidative activity, i.e., the ability to transfer hydrogen to radicals. Proton-coupled electron transfer reactions and hydrogen tunneling are ubiquitous in biological systems. Reactions of olive oil phenols, hydroxytyrosol, tyrosol, oleuropein, oleacein, oleocanthal, homovanillyl alcohol, vanillin, and a few phenolic acids with a DPPH• (2,2-diphenyl-1-picrylhydrazyl) radical in a 1,4-dioxane:water = 95:5 or 99:1 v/v solvent mixture were studied through an experimental kinetic analysis and computational chemistry calculations. The highest rate constants corresponding to the highest antioxidative activity are obtained for the ortho-diphenols hydroxytyrosol, oleuropein, and oleacein. The experimentally determined kinetic isotope effects (KIEs) for hydroxytyrosol, homovanillyl alcohol, and caffeic acid reactions are 16.0, 15.4, and 16.7, respectively. Based on these KIEs, thermodynamic activation parameters, and an intrinsic bond orbital (IBO) analysis along the IRC path calculations, we propose a proton-coupled electron transfer mechanism. The average local ionization energy and electron donor Fukui function obtained for the phenolic compounds show that the most reactive electron-donating sites are associated with π electrons above and below the aromatic ring, in support of the IBO analysis and proposed PCET reaction mechanism. Large KIEs and isotopic values of Arrhenius pre-exponential factor AH/AD determined for the hydroxytyrosol, homovanillyl alcohol, and caffeic acid reactions of 0.6, 1.3, and 0.3, respectively, reveal the involvement of hydrogen tunneling in the process. [ABSTRACT FROM AUTHOR]

Impurity ion and isotope partitioning into carbonate minerals provide a window into the molecular processes occurring at the fluid-mineral interface during crystal growth. Here, we employ calcium isotope fractionation together with process-based modeling to elucidate the mechanisms by which two divalent cations with starkly contrasting compatibility, magnesium and manganese, inhibit calcite growth and incorporate into the mineral lattice. Calcite growth inhibition by Mg2+ is log-linear and KMg is on the order of 0.02–0.03 throughout the range of {Mg2+}/{Ca2+} studied here (0.01–2.6). Mn2+ exhibits much stronger log-linear growth rate inhibition at low Mn2+ concentrations (fluid {Mn2+}/{Ca2+} = 0.001–0.02). Mn2+ is readily incorporated into the calcite lattice to form a calcite-rhodochrosite solid solution, with large partition coefficients (KMn 4.6–15.6) inversely correlated to growth rate. For both Mn2+ and Mg2+, calcium isotope fractionation is found to be invariant with {Me2+}/{Ca2+} despite more than an order of magnitude decline in growth rate. This invariant Δ44/40Ca suggests that the presence of Mn2+ or Mg2+ does not significantly change the relative rates of Ca2+ attachment and detachment at kink sites during growth, indicative of a dominantly kink blocking inhibition mechanism. Because the partitioning behavior dictates that Mn2+ must attach to the surface significantly faster than Ca2+, attachment of Mn2+ is likely to be as a non-monomer species such as an ion pair or possibly a larger polynuclear cluster. We propose that calcite growth rate inhibition by Mn is determined by the kinetics of carbonate attachment at Mn-occupied kink sites, potentially due to slow re-orientation kinetics of carbonate ions that have formed an inner-sphere complex with Mn2+ at the surface but must reorient to incorporate into the lattice. We demonstrate that patterns in Mg2+ partitioning and inhibition behavior are broadly consistent with growth inhibition driven by slow Mg2+-aquo complex dehydration relative to Ca2+ but argue that this mechanism likely represents one endmember scenario, seen in Mg-calcite growth at low supersaturations and net precipitation rates. During growth at faster net precipitation rates, some portion of Mg2+ is likely incorporated as a partially hydrated or otherwise complexed species, but calcite growth remains significantly inhibited by the kinetics of CO32− attachment at Mg2+ kink sites. These findings suggest a hybrid classical/nonclassical growth mechanism whereby Ca2+ incorporates largely as a free ion at kink sites while Mn2+ and some portion of Mg2+ are incorporated via non-monomer attachment. This pattern may be generalizable; trace constituent cations with aquo-complex desolvation rates significantly slower than the mineral growth rate preferentially incorporate as a non-monomer species during otherwise classical crystal growth.

This research investigates the impact of deuteration on the operational lifetime of blue organic light‐emitting diodes (OLEDs). Our study focuses on the kinetic isotope effect (KIE) and how it enhances device lifetime. Specifically, we examine the effects of deuteration on OLEDs with emitters based on common polycyclic aromatic hydrocarbons by deuterating anthracene‐based host materials. Our findings show that the deuterated analogues with incremental deuterium substitutions exhibit similar electroluminescence (EL) performances but progressively prolonged device lifetimes as a function of deuteration, indicating a cumulative enhancement effect. We observed a twofold increase in device lifetime with partial deuterium substitutions, while highly deuterated hosts realized up to a fourfold improvement. Furthermore, we found that device degradation is initiated from the interface of the hole transport layer (HTL) and emitting layer (ETL), and deuteration can mitigate the degraded reactions in the devices, thereby improving operational stability. These results provide insight into how deuteration can increase the operational lifetime of OLEDs, which has important implications for developing more efficient and durable OLED materials. [ABSTRACT FROM AUTHOR]

Olive oil phenols are recognized as molecules with numerous positive health effects, many of which rely on their antioxidative activity, i.e., the ability to transfer hydrogen to radicals. Proton-coupled electron transfer reactions and hydrogen tunneling are ubiquitous in biological systems. Reactions of olive oil phenols, hydroxytyrosol, tyrosol, oleuropein, oleacein, oleocanthal, homovanillyl alcohol, vanillin, and a few phenolic acids with a DPPH• (2,2-diphenyl-1-picrylhydrazyl) radical in a 1,4-dioxane:water = 95:5 or 99:1 v/v solvent mixture were studied through an experimental kinetic analysis and computational chemistry calculations. The highest rate constants corresponding to the highest antioxidative activity are obtained for the ortho-diphenols hydroxytyrosol, oleuropein, and oleacein. The experimentally determined kinetic isotope effects (KIEs) for hydroxytyrosol, homovanillyl alcohol, and caffeic acid reactions are 16.0, 15.4, and 16.7, respectively. Based on these KIEs, thermodynamic activation parameters, and an intrinsic bond orbital (IBO) analysis along the IRC path calculations, we propose a proton-coupled electron transfer mechanism. The average local ionization energy and electron donor Fukui function obtained for the phenolic compounds show that the most reactive electron-donating sites are associated with π electrons above and below the aromatic ring, in support of the IBO analysis and proposed PCET reaction mechanism. Large KIEs and isotopic values of Arrhenius pre-exponential factor AH/AD determined for the hydroxytyrosol, homovanillyl alcohol, and caffeic acid reactions of 0.6, 1.3, and 0.3, respectively, reveal the involvement of hydrogen tunneling in the process.

The pharmacokinetics of pharmaceutical drugs can be improved by replacing C−H bonds with the more stable C−D bonds at the α‐position to heteroatoms, which is a typical metabolic site for cytochrome P450 enzymes. However, the application of deuterated synthons is limited. Herein, we established a novel concept for preparing deuterated reagents for the successful synthesis of complex drug skeletons with deuterium atoms at the α‐position to heteroatoms. (dn‐Alkyl)diphenylsulfonium salts prepared from the corresponding nondeuterated forms using inexpensive and abundant D2O as the deuterium source with a base, were used as electrophilic alkylating reagents. Additionally, these deuterated sulfonium salts were efficiently transformed into dn‐alkyl halides and a dn‐alkyl azide as coupling reagents and a dn‐alkyl amine as a nucleophile. Furthermore, liver microsomal metabolism studies revealed deuterium kinetic isotope effects (KIE) in 7‐(d2‐ethoxy)flavone. The present concept for the synthesis of deuterated reagents and the first demonstration of a KIE in a d2‐ethoxy group will contribute to drug discovery research based on deuterium chemistry. [ABSTRACT FROM AUTHOR]

5′-18O labeled RNA oligos are important probes to investigate the mechanism of 2′-O-transphosphorylation reactions. Here we describe a general and efficient synthetic approach to the phosphoramidite derivatives of 5′-18O labeled nucleosides starting from the corresponding commercially available 5′-O-DMT protected nucleosides. Using this method, we prepared 5′-18O-guanosine phosphoramidite in 8 steps (13.2% overall yield), 5′-18O-adenosine phosphoramidite in 9 steps (10.1% overall yield) and 5′-18O-2′-deoxyguanosine phosphoramidite in 6 steps (12.8% overall yield). These 5′-18O labeled phosphoramidites can be incorporated into RNA oligos by solid phase synthesis for determination of heavy atom isotope effects in RNA 2′-O-transphosphorylation reactions. [ABSTRACT FROM AUTHOR]

Glutathione S-transferases are a family of detoxifying enzymes that catalyze the conjugation of reduced glutathione (GSH) with different xenobiotic compounds using either Ser, Tyr, or Cys as a primary catalytic residue. We identified a novel GST in the genome of the shrimp pathogen V. parahaemolyticus FIM- S1708+, a bacterial strain associated with Acute Hepatopancreatic Necrosis Disease (AHPND)/Early Mortality Syndrome (EMS) in cultured shrimp. This new GST class was named Gtt2. It has an atypical catalytic mechanism in which a water molecule instead of Ser, Tyr, or Cys activates the sulfhydryl group of GSH. The biochemical properties of Gtt2 from Vibrio parahaemolyticus (VpGSTT2) were characterized using kinetic and crystallographic methods. Recombinant VpGSTT2 was enzymatically active using GSH and CDNB as substrates, with a specific activity of 5.7 units/mg. Low affinity for substrates was demonstrated using both Michaelis-Menten kinetics and isothermal titration calorimetry. The crystal structure showed a canonical two-domain structure comprising a glutathione binding G-domain and a hydrophobic ligand H domain. A water molecule was hydrogen-bonded to residues Thr9 and Ser 11, as reported for the yeast Gtt2, suggesting a primary role in the reaction. Molecular docking showed that GSH could bind at the G-site in the vicinity of Ser11. G-site mutationsT9A and S11A were analyzed. S11A retained 30% activity, while T9A/S11A showed no detectable activity. VpGSTT2 was the first bacterial Gtt2 characterized, in which residues Ser11 and Thr9 coordinated a water molecule as part of a catalytic mechanism that was characteristic of yeast GTT2. The GTT2 family has been shown to provide protection against metal toxicity; in some cases, excess heavy metals appear in shrimp ponds presenting AHPND/EMS. Further studies may address whether GTT2 in V. parahaemolyticus pathogenic strains may provide a competitive advantage as a novel detoxification mechanism.

In this study, the reactivity of the alkyl nitrenes, generated from the substituted hydroxylamine precursors, was determined using the same rhodium catalyst. The results revealed that in competitive C–H insertion experiments, the regioselectivity between benzylic and tertiary C–H bonds could be modulated by adding Brønsted acids or changing the substituents on oxygen. This study enhances our understanding of the metallonitrene structures and provides valuable insights for further development of selective N-heterocycle syntheses.

Methane clumped isotope compositions signify the relative natural abundances of rare, doubly substituted isotopic species of methane (13CH 3 D and 12CH 2 D 2) and have emerged as a new isotopic tool to trace the sources, sinks, and lifecycles of methane in the environment. Such measurements can identify equilibration (or re-equilibration) temperatures if found to be in isotopic equilibrium or non-equilibrium processes (e.g., kinetically controlled reactions or mixing) if not in isotopic equilibrium. Naturally occurring thermogenic methane—formed by the thermally activated breakdown of larger organic molecules—has been found to have clumped isotope compositions consistent with equilibrium at reasonable gas formation temperatures in some settings and non-equilibrium processes occurring during either formation, migration, storage, or extraction in others. To explore the potential controls on the isotopic composition of thermogenic methane, we conducted isothermal time-series ethane pyrolysis experiments at 550 and 600 °C to measure methane and ethane 13C/12C and D/H fractionations and methane clumped isotope compositions (resolved 13CH 3 D and 12CH 2 D 2). We explore the effects of modifying the initial clumped isotope composition of ethane and the addition of water vapor to pyrolysis experiments. We observe that ethane and methane 13C/12C are controlled by kinetic isotope effects and Rayleigh distillation processes. In contrast, ethane and methane D/H and methane clumped isotope compositions appear to be controlled by a combination of these processes and hydrogen isotope exchange. The hydrogen isotope exchange processes lead to isotopic equilibrium as reaction completion is approached for both D/H (ethane/methane) and methane clumped isotope compositions. We develop a chemical model based on a mass balance approach that accounts for inheritance vs. hydrogen-abstraction formation pathways for singly and doubly substituted isotopologues of ethane and methane that is compared to the experimental data. The model allows the determination of carbon and hydrogen kinetic isotope effects associated with ethane cracking and hydrogen abstraction reactions that, where applicable, we compare to prior theoretical constraints. From the comparison of the model to the experimental data, we infer that the kinetically controlled ethane and methane bulk isotope compositions and methane clumped isotope compositions are controlled by kinetic isotope effects (both primary and secondary) associated with both C C bond and C H bond cleavage reactions. Specifically, the methane clumped isotope compositions likely result from a combination of clumped isotope effects associated with ethane breakdown and/or assembly of methane isotopologues (expressed in terms of γ-factor parameters ≠ 1) and combinatorial effects that arise probabilistically. We discuss our experimental results in the context of recent pyrolysis experiments and observations of naturally occurring thermogenic methane. We consider a proposal consistent with observations from nature that the hydrogen isotope exchange reactions that promote equilibration of methane isotopic molecules at or near formation temperature may be facilitated by free radicals generated by pyrolysis reactions. In this framework, isotope exchange effectively ceases when pyrolysis effectively ceases locking in compositions that can be consistent with peak formation temperatures. [ABSTRACT FROM AUTHOR]

The reaction HO + SO → H + SO2 (Rt) and its reverse (R‐t) play an important role in environment and the combustion of sulfur‐containing fuels. However, their kinetics is of high uncertainty as its reaction profile is complicated with multiple deep complexes and channels. In this work, the kinetics and mechanisms of Rt and R‐t are studied comprehensively based on a newly developed full‐dimensional accurate potential energy surface (PES) with the aid of machine learning. This highly accurate PES is interfaced with the software Gaussian. Then reliable information, including the energy, structures, and vibrational frequencies of the stationary points, as well as the minimum energy path and variational analysis can be efficiently determined. The variational transition state theory (VTST) and Rice−Ramsperger−Kassel−Marcus (RRKM) theory are employed to obtain the rate coefficients of each elementary reaction. The temperature‐ and pressure‐dependent rate coefficients of Rt are derived by the RRKM‐based master equation with hindered rotor and free rotor model considered. In addition, the effect of isotope substitution for the hydrogen is investigated on the reaction kinetics. Meanwhile, the quasi‐classical trajectory (QCT) calculation is performed on the PES‐2020 to obtain the temperature‐dependent reaction kinetics. [ABSTRACT FROM AUTHOR]

The oxidation of Mandelic acids to the corresponding oxoacids with ethylenediammonium dichromate (EDDC) in aqueous acetic acid has been studied. The reaction is first order with respect to [EDDC] and less than two order observed for mandelic acids and [H+]. The oxidation of a-deuteriomandelic acid shows the presence of a primary kinetic isotope effect (kH/kD=6.01 at 298K). The reaction has been found to be catalyzed by [H+] ions. The various thermodynamic parameters for the oxidation have been reported and discussed along with the validity of the isokinetic relationship. With a negative reaction constant (r), the reaction displayed a strong correlation with the Hammett values. All of the chosen Mandelic acids are oxidised by the same process, according to the Exner plot. [ABSTRACT FROM AUTHOR]

The kinetic isotope effect (KIE) is beneficial to improve the performance of luminescent molecules and relevant light-emitting diodes. In this work, the influences of deuteration on the photophysical property and stability of luminescent radicals are investigated for the first time. Four deuterated radicals based on biphenylmethyl, triphenylmethyl, and deuterated carbazole were synthesized and sufficiently characterized. The deuterated radicals exhibited excellent redox stability, as well as improved thermal and photostability. The appropriate deuteration of relevant C-H bonds would effectively suppress the non-radiative process, resulting in the increase in photoluminescence quantum efficiency (PLQE). This research has demonstrated that the introduction of deuterium atoms could be an effective pathway to develop high-performance luminescent radicals. [ABSTRACT FROM AUTHOR]

The mechanism and the reactive species involved in the oxidation of alkenes, and alcohols with H2O2, catalysed by an in situ prepared mixture of a MnII salt, pyridine‐2‐carboxylic acid and a ketone is elucidated using substrate competition experiments, kinetic isotope effect (KIE) measurements, and atom tracking with 18O labelling. The data indicate that a single reactive species engages in the oxidation of both alkenes and alcohols. The primary KIE in the oxidation of benzyl alcohols is ca. 3.5 and shows the reactive species to be selective despite a zero order dependence on substrate concentration, and the high turnover frequencies (up to 30 s−1) observed. Selective 18O labelling identifies the origin of the oxygen atoms transferred to the substrate during oxidation, and is consistent with a highly reactive, e. g., [MnV(O)(OH)] or [MnV(O)2], species rather than an alkylperoxy or hydroperoxy species. [ABSTRACT FROM AUTHOR]

Basic isotope dynamics equations based on maintaining deuterium equilibrium were used to analyze the dynamics of nitrite-dependent anaerobic methane oxidation (NDAMO) in two laboratory experiments with different initial substrate concentrations and deuterium isotope variables. Notably, the initial amount of water in a closed vessel was reduced by a factor of about 2.8 in the second experiment. According to the model, methane was completely consumed, while nitrite ions were still present in excessive amounts at the end of the first experiment and methane was present, while nitrite ions were completely exhausted at the end of the second experiment. Concentrations of the substrates containing a single deuterium atom (СН4 and NH ), the product (Н2О), and the biomass of anaerobic methanotrophic (ANME) microorganisms (C5H7NO2) were taken as isotope variables in the model. Stoichiometric reaction equations were derived to describe the redistribution of deuterium between the reaction substrates, product (water), and biomass. Isotope fractionation was shown to proceed in the course of a microbiological reaction in water. As a result, the substrates become enriched in deuterium, while water and the biomass become depleted of deuterium. The fractionation process ended after t ≥ 17 h in the first experiment, which was accompanied by a slight drop in deuterium in the biomass and water. In the second experiment, fractionation ended after t ≥ 140 h, the deuterium content decreased significantly in both water and the biomass, and its decrease depended on the initial concentration of deuterium-containing water. This was due to dilution of the water in the vessel with deuterium-depleted water generated in the NDAMO process. The paper additionally summarizes the results of modeling the dynamics of 11 biological processes in a long-term study, in which stable carbon isotopes have mainly been measured. Isotope fractionation factors used in the simulation were described. [ABSTRACT FROM AUTHOR]

Unlocking of the extremely inert C=O bond during electrochemical CO2 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. [ABSTRACT FROM AUTHOR]

[Display omitted] • The selectivity of ethanol oxidation is dependent on the valence band potential. • The rate-limiting step involves α-C–H bond breaking and rehybridization of α-C. • The oxidation process is proceeded by photogenerated holes rather than·OH. • Alcohol oxidation occurs on a single reaction site of the photocatalysts. • No cooperativity of multiple sites involves the alcohol oxidation. Operando spectroelectrochemical spectroscopy is employed to investigate the selectivity of ethanol oxidation on hematite and titania photoanodes. High selectivity of acetaldehyde formation from ethanol oxidation has been identified using the hematite photoanode, whilst modest selectivity and over-oxidation of acetaldehyde are observed using titania photoanodes. This difference in the acetaldehyde selectivity is correlated with the valence band potential. The valence band potential is also associated with the activation energy required for the over-oxidation of acetaldehyde. The activation energy of acetaldehyde oxidation by the photogenerated holes in hematite is 427 meV whilst only 45 meV is required for titania. Kinetic isotope effect shows that the rate-limiting step of ethanol oxidation on hematite and titania involves α-C–H bond breaking, and solvent molecules are important to assist the rehybridization of this α-C. The spectral analyses emphasize the importance of considering the band potential upon the selectivity of alcohol oxidation on a broad scope. [ABSTRACT FROM AUTHOR]

Quantum mechanics revolutionized chemists' understanding of molecular structure. In contrast, the kinetics of molecular reactions in solution are well described by classical, statistical theories. To reveal how the dynamics of chemical systems transition from quantum to classical, we study femtosecond proton transfer in a symmetric molecule with two identical reactant sites that are spatially apart. With the reaction launched from a superposition of two local basis states, we hypothesize that the ensuing motions of the electrons and nuclei will proceed, conceptually, in lockstep as a superposition of probability amplitudes until decoherence collapses the system to a product. Using ultrafast spectroscopy, we observe that the initial superposition state affects the reaction kinetics by an interference mechanism. With the aid of a quantum dynamics model, we propose how the evolution of nuclear wavepackets manifests the unusual intersite quantum correlations during the reaction. [ABSTRACT FROM AUTHOR]

Impurity ion and isotope partitioning into carbonate minerals provide a window into the molecular processes occurring at the fluid-mineral interface during crystal growth. Here, we employ calcium isotope fractionation together with process-based modeling to elucidate the mechanisms by which two divalent cations with starkly contrasting compatibility, magnesium and manganese, inhibit calcite growth and incorporate into the mineral lattice. Calcite growth inhibition by Mg2+ is log-linear and K Mg is on the order of 0.02–0.03 throughout the range of {Mg2+}/{Ca2+} studied here (0.01–2.6). Mn2+ exhibits much stronger log-linear growth rate inhibition at low Mn2+ concentrations (fluid {Mn2+}/{Ca2+} = 0.001–0.02). Mn2+ is readily incorporated into the calcite lattice to form a calcite-rhodochrosite solid solution, with large partition coefficients (K Mn 4.6–15.6) inversely correlated to growth rate. For both Mn2+ and Mg2+, calcium isotope fractionation is found to be invariant with {Me2+}/{Ca2+} despite more than an order of magnitude decline in growth rate. This invariant Δ44/40Ca suggests that the presence of Mn2+ or Mg2+ does not significantly change the relative rates of Ca2+ attachment and detachment at kink sites during growth, indicative of a dominantly kink blocking inhibition mechanism. Because the partitioning behavior dictates that Mn2+ must attach to the surface significantly faster than Ca2+, attachment of Mn2+ is likely to be as a non-monomer species such as an ion pair or possibly a larger polynuclear cluster. We propose that calcite growth rate inhibition by Mn is determined by the kinetics of carbonate attachment at Mn-occupied kink sites, potentially due to slow re-orientation kinetics of carbonate ions that have formed an inner-sphere complex with Mn2+ at the surface but must reorient to incorporate into the lattice. We demonstrate that patterns in Mg2+ partitioning and inhibition behavior are broadly consistent with growth inhibition driven by slow Mg2+-aquo complex dehydration relative to Ca2+ but argue that this mechanism likely represents one endmember scenario, seen in Mg-calcite growth at low supersaturations and net precipitation rates. During growth at faster net precipitation rates, some portion of Mg2+ is likely incorporated as a partially hydrated or otherwise complexed species, but calcite growth remains significantly inhibited by the kinetics of CO 3 2− attachment at Mg2+ kink sites. These findings suggest a hybrid classical/nonclassical growth mechanism whereby Ca2+ incorporates largely as a free ion at kink sites while Mn2+ and some portion of Mg2+ are incorporated via non-monomer attachment. This pattern may be generalizable; trace constituent cations with aquo-complex desolvation rates significantly slower than the mineral growth rate preferentially incorporate as a non-monomer species during otherwise classical crystal growth. [ABSTRACT FROM AUTHOR]

This study investigates the use of multi-element compound-specific isotope analysis (ME-CSIA) to monitor degradation processes of methoxychlor, a persistent organochlorine insecticide. Laboratory experiments examined the kinetics, release of transformation products, and carbon and chlorine isotope effects during methoxychlor degradation through alkaline hydrolysis, oxidation with alkaline-activated persulfate, and biotic reductive dechlorination. Results showed that hydrolysis and oxidation did not cause significant carbon and chlorine isotope fractionation, indicating that C-H rather than C-Cl bond cleavage was the rate-determining step. Conversely, biotic reductive dechlorination by a field-derived microcosm under strictly anoxic conditions displayed significant carbon (ε C = -0.9 ± 0.3 ‰) and chlorine (ε Cl = -1.9 ± 1.0 ‰) isotope fractionation. Its corresponding calculated dual isotope slope (Λ C/Cl = 0.4 ± 0.1) and apparent kinetic isotope effects (AKIE C = 1.014 ± 0.005 and AKIE Cl = 1.006 ± 0.003) indicate a C-Cl bond cleavage as the rate-determining step, highlighting the difference with respect to the other studied degradation mechanisms. Changes in the microbial community diversity revealed that families such as Dojkabacteria, Anaerolineaceae, Dysgonomonadaceae, Bacteroidetes vadinHA17, Pseudomonadaceae, and Spirochaetaceae, may be potential agents of methoxychlor reductive dechlorination under anoxic conditions. This study advances the understanding of degradation mechanisms of methoxychlor and improves the ability to track its transformation in contaminated environments, including for the first time an isotopic perspective., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

The utility of bio-isosteres is broad in drug discovery and methodology herein enables the preparation of deuterium-labeled products is the most fundamental of known bio-isosteric replacements. As such we report the use of both [D 1 ]-aldehydes and [D 2 ]-isonitriles across 8 multicomponent reactions (MCRs) to give diverse arrays of deuterated products. A highlight is the synthesis of several FDA-approved calcium channel blockers, selectively deuterated at a t 1/2 limiting metabolic soft-spot via use of [D 1 ]-aldehydes. Surrogate pharmacokinetic analyses of microsomal stability confirm prolongation of t 1/2 of the new deuterated analogs. We also report the first preparation of [D 2 ]-isonitriles from [D 3 ]-formamides via a modified Leuckart-Wallach reaction and their use in an MCR to afford products with [D 2 ]-benzylic positions and likely significantly enhanced metabolic stability, a key parameter for property-based design efforts., (Copyright © 2024, Schofield et al.)

The kinetic isotope effect (KIE) is beneficial to improve the performance of luminescent molecules and relevant light-emitting diodes. In this work, the influences of deuteration on the photophysical property and stability of luminescent radicals are investigated for the first time. Four deuterated radicals based on biphenylmethyl, triphenylmethyl, and deuterated carbazole were synthesized and sufficiently characterized. The deuterated radicals exhibited excellent redox stability, as well as improved thermal and photostability. The appropriate deuteration of relevant C-H bonds would effectively suppress the non-radiative process, resulting in the increase in photoluminescence quantum efficiency (PLQE). This research has demonstrated that the introduction of deuterium atoms could be an effective pathway to develop high-performance luminescent radicals.

Low-temperature (–90°C) ozonolysis of tris(trimethylsilyl)silane gave tris(trimethylsilyl)silanol and 1,1,1-trimethyl-2,2-bis(trimethylsiloxy)disilan-2-ol. The primary isotope effect in the reaction of tris(trimethylsilyl)silane with ozone at –90°C is equal to 5.5 and is consistent with the theoretical value calculated at the B3LYP/6-31+G(2d,p) level of theory assuming abstraction of H(D) from the Si–H(D) bond by ozone. Possible reaction mechanisms, namely radical, ionic, and ozone insertion into the Si–H bond, are discussed. [ABSTRACT FROM AUTHOR]

The development of proton exchange membrane water electrolysis (PEMWE) offers an updating potential for electrolytic hydrogen isotope separation. However, it has a significantly lower separation factor than the traditional alkaline water electrolysis. In this study, we propose gold as a promising cathodic catalyst for efficient hydrogen isotope separation in PEMWE. Au/C has a protium-to-deuterium (H/D) separation factor of 7.47 in PEMWE, about twice that of Pt/C. In addition, the full cell's electrochemical performance is comparable to that of its Pt/C counterpart. The separation mechanism in PEMWE is explained by the transitional hydrogen evolution reaction mechanism from Heyrovsky to Tafel for Pt and the unchangeable Volmer mechanism for Au. The high separation factor for Au is also calculated by the H/D zero-point vibrational energy difference between transition state and reaction state through a simple density functional theory calculation. This work offers an effective strategy to improve hydrogen isotope separation efficiency in PEMWE. Au/C has a high hydrogen isotope separation factor of 7.5 in the PEMWE cell through the Volmer mechanism, about twice that of Pt/C which follows the Tafel mechanism. [Display omitted] • The electrolytic hydrogen isotope separation factor of Au/C was nearly twice that of Pt/C. • Au/C was employed as a cathodic catalyst in a PEM water electrolyzer for the first time. • The hydrogen isotope separation mechanism for Pt was elucidated by the HER mechanism transition. • The high separation factor for Au was confirmed by the ZPE difference between H and D. [ABSTRACT FROM AUTHOR]

Proton-coupled electron transfer (PCET) is key to the activation of the blue light using flavin (BLUF) domain photoreceptors. Here, to elucidate the photocycle of the central FMN-Gln-Tyr motif in the BLUF domain of OaPAC, we eliminated the intrinsic interfering W90 in the mutant design. We integrated the stretched exponential function into the target analysis to account for the dynamic heterogeneity arising from the active-site solvation relaxation and the flexible H-bonding network as shown in the molecular dynamics simulation results, facilitating a simplified expression of the kinetics model. We find that, in both the functional wild-type (WT) and the nonfunctional Q48E and Q48A, forward PCET happens in the range of 105 ps to 344 ps, with a kinetic isotope effect (KIE) measured to be ~1.8 to 2.4, suggesting that the nature of the forward PCET is concerted. Remarkably, only WT proceeds with an ultrafast reverse PCET process (31 ps, KIE = 4.0), characterized by an inverted kinetics of the intermediate FMNH_. Our results reveal that the reverse PCET is driven by proton transfer via an intervening imidic Gln. [ABSTRACT FROM AUTHOR]

Compound-specific stable isotope analysis provides an alternative method to insight into the biotransformation mechanisms of diffuse organic pollutants in the environment, e.g., the endocrine disruptor herbicide atrazine. Biotic hydrolysis process catalyzed by chlorohydrolase AtzA and TrzN plays an important role in the detoxification of atrazine, while the catalytic mechanism of AtzA is still speculative. To investigate the catalytic mechanism of AtzA and answer whether both enzymes catalyze hydrolytic dechlorination of atrazine by the same mechanism, in this study, apparent kinetic isotope effects (AKIE) for carbon and nitrogen were observed by three atzA-harboring bacterial isolates and their membrane-free extracts. The AKIEs obtained from atzA-harboring bacterial isolates (AKIEC = 1.021 ± 0.010, AKIEN = 0.992 ± 0.003) were statistically different from that of trzN-harboring strains (AKIEC = 1.040 ± 0.006, AKIEN = 0.983 ± 0.006), confirming the different activation mechanisms of atrazine preceding to nucleophilic aromatic substitution of Cl atom in actual enzymatic reaction catalyzed by AtzA and TrzN, despite the limitation of variable dual-element isotope plots. The lower degree of normal carbon and inverse nitrogen isotope fractionation observed from atzA-harboring strains, suggesting AtzA catalyzing hydrolytic dechlorination of atrazine by coordination of Cl and one aromatic N to the Fe2+ drawing electron density from carbon-chlorine bond that facilitating the nucleophilic attack, rather than in TrzN case that protonation of aromatic N increasing nucleophilic substitution of Cl atom. This study suggests considering the potential influences of phylogenetic diversity of bacterial isolates and evolution of enzymes on the applications of CSIA method in future study. [ABSTRACT FROM AUTHOR]

Stable carbon isotope (δ13C) rollover of natural gas has attracted recent attention due to its association with highly productive shale gas. However, the mechanistic causes of δ13C 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 × 106–1.2 × 108 Pa). It was found that WP induced the isotope rollover of gaseous hydrocarbons. For both sapropelic and humic organic matter, the δ13C rollover of CH4 (methane), C2H6 (ethane), and C3H8 (propane) occurred when the WP ranged from 3.25 × 107 to 1.2 × 108 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 δ13C1 values with increase in WP. Good functions were found between water pressure and the calculated carbon kinetic isotope effect (KIE) for 12CH4 and 13CH4 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 12CH4 and 13CH4 by changing the Δ V ‡ of 12CH4 and 13CH4. Overall, these findings suggest that WP affects the carbon isotope fractionation of gaseous hydrocarbons due to the different thermodynamic properties of 12CH4 and 13CH4. [ABSTRACT FROM AUTHOR]

The cumulative effects of deuteration on the device lifetime of blue OLEDs with emitters based on common polycyclic aromatic hydrocarbons were studied using two anthracene‐based host materials. Their deuterated analogues with incremental deuterium substitutions exhibited similar EL efficiencies but progressively prolonged device lifetimes as a function of deuteration. [ABSTRACT FROM AUTHOR]

Herein, we present work on the catalyst development and the kinetics of acetone-butanol-ethanol (ABE) condensation. After examining multiple combinations of metal and basic catalysts reported in the literature, Cu supported on calcined hydrotalcites (HT) was found to be the optimal catalyst for the ABE condensation. This catalyst gave a six-fold increase in reaction rates over previously reported catalysts. Kinetic analysis of the reaction over CuHT and HT revealed that the rate-determining step is the C−H bond activation of alkoxides that are formed from alcohols on the Cu surface. This step is followed by the addition of the resulting aldehydes to an acetone enolate formed by deprotonation of the acetone over basic sites on the HT surface. The presence of alcohols reduces aldol condensation rates, as a result of the coverage of catalytic sites by alkoxides.

Kinetic isotope effects occurring during carbonate precipitation impact the accuracy of paleoclimate records. One rate-limiting process is CO 2 absorption, which, at high pH, primarily proceeds through hydroxylation, where aqueous CO 2 and OH− react to form HCO 3 −. In this study, we investigated the triple oxygen isotope fractionation (18O/16O and 17O/16O) associated with the hydroxylation reaction. We experimentally determined the extent of the kinetic isotope effects superimposed on the reacting CO 2 and OH− during hydroxylation, using high-pH precipitation reactions. These results were compared to the equilibrium triple oxygen isotope fractionation between H 2 O and OH− modeled using quantum chemical computations. Our quantum chemical modeling confirms the previously suggested equilibrium θ eq. H2O/OH- of 0.5296 at 25 °C. Our empirical data show a kinetic isotope effect superimposed on the OH− involved in the hydroxylation reaction of approximately −16.4‰ for the fractionation of 18O/16O and a corresponding slope of 0.514 in triple oxygen isotope space. The θ effective H2O/OH- for the fractionation between water and the reacting OH− is 0.523. In order to identify and potentially correct kinetic isotope effects in carbonates, it is important to understand the fractionations occurring during precipitation. Our results enable a more accurate modeling of kinetic isotope effects in triple oxygen isotope space, particularly the slope of hydroxylation. The θ hydroxylation is dependent on the isotope composition of the ambient water, CO 2 , and the temperature. We estimate that θ hydroxylation is approximately 0.532 for carbonates growing in 25 °C seawater. [Display omitted] • Kinetic isotopes effects are superimposed on OH− and CO 2 during CO 2 hydroxylation. • We quantified the fractionations via experiments and theoretical modeling. • Our results estimate the hydroxylation slope in triple oxygen isotope space. [ABSTRACT FROM AUTHOR]

Various (pentamethylcyclopentadienyl)‐rhodium(III) complexes comprising aromatic bidentate ligands [(Cp*)Rh(L)Cl]+ (Cp* = pentamethylcyclopentadienyl, L = 2,2′‐bipyridine, 1,10‐phenanthroline, and their derivatives) were prepared to compare their reactivities of chemical cofactor regeneration. When the catalytic NADH regeneration was performed with sodium formate−, the reaction rates were compared with six Rh(III) complexes. The kinetics of the reactions including kinetic isotope effects are also studied in the chemical NADH regeneration. The Rh(III) complexes react with formate efficiently to afford the intermediates [(Cp*)Rh(L)(H)]+ and CO2. The electronic and steric effects of the ligands of the Rh complexes were observed on the reaction rates. The overall reaction rates of the NADH regeneration were also obtained using DCOO− in H2O. Such H/D exchange rates of [(Cp*)Rh(L)(H)]+ and the observation of a deuterium kinetic isotope provide valuable mechanistic insight into the catalytic NADH regeneration. [ABSTRACT FROM AUTHOR]

We present direct observation of ultrafast proton rocking in the central motif of a BLUF domain protein scaffold. The mutant design has taken consideration of modulating the proton‐coupled electron transfer (PCET) driving forces by replacing Tyr in the original motif with Trp, in order to remove the interference of a competing electron transfer pathway. Using femtosecond pump–probe spectroscopy and detailed kinetics analysis, we resolved an electron‐transfer‐coupled Grotthuss‐type forward and reverse proton rocking along the FMN–Gln–Trp proton relay chain. The rates of forward and reverse proton transfer are determined to be very close, namely 51 ps vs. 52 ps. The kinetic isotope effect (KIE) constants associated with the forward and reverse proton transfer are 3.9 and 5.3, respectively. The observation of ultrafast proton rocking is not only a crucial step towards revealing the nature of proton relay in the BLUF domain, but also provides a new paradigm of proton transfer in proteins for theoretical investigations. [ABSTRACT FROM AUTHOR]

Catalyst‐controlled vinylogous aza‐MBH reactions of vinylcyclopentenone were performed, and it was found that the α‐adducts were exclusively obtained by DABCO‐catalysis, while the γ‐adducts were the major products by DMAP‐catalysis. We report here that the rate‐determining step of the DABCO‐catalyzed α‐selective reactions is the Mannich‐type C−C bond forming step, while that of the DMAP‐catalyzed γ‐selective reactions seems to be the β‐elimination step. [ABSTRACT FROM AUTHOR]

[Display omitted] • "Degree of rate control" (DRC) analysis reviewed. • Provides quantitative approach for analyzing kinetics of multi-step mechanisms. • DRCs offer simple, intuitive route to optimize catalysts. • Simple equations connect experimental observables to DRCs. • This includes: surface coverages, activation energy, reaction orders, kinetic isotope effect and Tafel slope. "Degree of rate control" (DRC) analysis provides a quantitative approach for analysing the kinetics of multi-step reaction mechanisms that has been widely applied to both heterogeneous and homogeneous catalysis research, as well as electrocatalysis. The DRC of any given transition state or intermediate is defined as a partial derivative such that it approximately equals the fractional increase in net rate to the product of interest per differential decrease in its standard-state free energy for that species (÷RT), holding constant the standard-state free energies of all other transition states and intermediates. Even very complex mechanisms usually have only a few species with non-zero DRCs and are thus the species whose interactions with the catalyst most strongly affect the net rate. These key DRC values thus offer a simple and intuitive route to optimize catalyst materials, especially with the assistance of computational methods like density functional theory (DFT). These high-DRC species are also the species whose energetics must be most accurately measured or calculated to achieve an accurate kinetic model for any reaction mechanism. In simple cases with a single "rate-determining step", the DRC for its transition state (TS) is + 1. Catalyst-bound intermediates, on the other hand, often have negative DRCs equal to a small integer times their fractional occupancy of catalyst sites. The apparent activation energy equals a weighted average of the standard-state enthalpies (relative to reactants) of all the species (intermediates, transition states and products) in the reaction mechanism, each weighted by its DRC (+RT). It has been shown that the apparent transfer coefficient in electrocatalysis, an inverted form of the Tafel slope, is a weighted average of the number of electrons transferred to generate each intermediate or product species in the mechanism, weighted again by the DRC. Quantitative analysis of kinetic isotope effects (KIEs, or the ratio of net rates for different reactant isotopes) in complex mechanisms has shown that the logarithm of the KIE equals the weighted average over all species in the mechanism of the difference between the two isotopes in their standard-state free energies (÷RT), again weighted by the DRC. The reaction orders with respect to fluid-phase concentrations of reactants, products and intermediates have also been proven to be directly related to DRCs. Thus, there are numerous experimental observables which equate to short linear combinations of DRCs, so that combinations of experimental measurements might provide access to DRC values. Since its invention for transition states in 1994 and its generalization to include intermediates in 2009, the DRC has thus far mainly been calculated for microkinetic models based either entirely on DFT or on DFT with the key energies (i.e., those for high-DRC species) being fine-tuned to match experiments. The relationships summarized above provide new opportunities for using experiments earlier in the development and optimization of microkinetic models that require input from computational catalysis. [ABSTRACT FROM AUTHOR]

A series of Rh-based intermetallic compounds supported on silica was prepared and tested in alkene hydrogenation at room temperature. H2 and D2 were used as the hydrogen sources and the kinetic isotope effect (KIE) in hydrogenation was studied. In styrene hydrogenation, the KIE values differed strongly depending on the intermetallic phase, and some intermetallic compounds with Sb and Pb exhibited remarkably high KIE values (>28). An extraordinarily high KIE value of 91, which has never been reported in catalytic reactions at room temperature, was observed particularly for RhPb2/SiO2. RhPb2/SiO2 also showed high KIE values in the hydrogenation of other unsaturated hydrocarbons such as phenylacetylene and cyclohexene. The density functional theory calculation focused on the surface diffusion of hydrogen suggested no contribution of the quantum tunneling effect to the high KIE values observed. A kinetic study revealed that the dissociative adsorption of H2 (D2) was the rate-determining step in the styrene hydrogenation over RhPb2/SiO2. We propose that the large KIE originates from the quantum tunneling occurring at the hydrogen adsorption process with the aid of the specific surface structure of the intermetallic compound and adsorbate alkene.

ABSTRACT Analysis of nitrogen isotope fractionation effects is useful for tracing biogeochemical nitrogen cycle processes. Nitrification can cause large nitrogen isotope effects through the enzymatic oxidation of ammonia (NH3) via nitrite (NO2−) to nitrate (NO3−) (15εNH4+→NO2- and 15εNO2-→NO3-). The isotope effects of ammonia-oxidizing bacteria (AOB) and archaea (AOA) and of nitrite-oxidizing bacteria (NOB) have been analyzed previously. Here, we studied the nitrogen isotope effects of the complete ammonia oxidizer (comammox) Nitrospira inopinata that oxidizes NH3 to NO3−. At high ammonium (NH4+) availability (1 mM) and pH between 6.5 and 8.5, its 15εNH4+→NO2- ranged from −33.1 to −27.1‰ based on substrate consumption (residual substrate isotopic composition) and −35.5 to −31.2‰ based on product formation (cumulative product isotopic composition), while the 15εNO2-→NO3- ranged from 6.5 to 11.1‰ based on substrate consumption. These values resemble isotope effects of AOB and AOA and of NOB in the genus Nitrospira, suggesting the absence of fundamental mechanistic differences between key enzymes for ammonia and nitrite oxidation in comammox and canonical nitrifiers. However, ambient pH and initial NH4+ concentrations influenced the isotope effects in N. inopinata. The 15εNH4+→NO2- based on product formation was smaller at pH 6.5 (−31.2‰) compared to pH 7.5 (−35.5‰) and pH 8.5 (−34.9‰), while 15εNO2-→NO3- was smaller at pH 8.5 (6.5‰) compared to pH 7.5 (8.8‰) and pH 6.5 (11.1‰). Isotopic fractionation via 15εNH4+→NO2- and 15εNO2-→NO3- was smaller at 0.1 mM NH4+ compared to 0.5 to 1.0 mM NH4+. Environmental factors, such as pH and NH4+ availability, therefore need to be considered when using isotope effects in 15N isotope fractionation models of nitrification. IMPORTANCE Nitrification is an important nitrogen cycle process in terrestrial and aquatic environments. The discovery of comammox has changed the view that canonical AOA, AOB, and NOB are the only chemolithoautotrophic organisms catalyzing nitrification. However, the contribution of comammox to nitrification in environmental and technical systems is far from being completely understood. This study revealed that, despite a phylogenetically distinct enzymatic repertoire for ammonia oxidation, nitrogen isotope effects of 15εNH4+→NO2- and 15εNO2-→NO3- in comammox do not differ significantly from those of canonical nitrifiers. Thus, nitrogen isotope effects are not suitable indicators to decipher the contribution of comammox to nitrification in environmental samples. Moreover, this is the first systematic study showing that the ambient pH and NH4+ concentration influence the isotope effects of nitrifiers. Hence, these key parameters should be considered in comparative analyses of isotope effects of nitrifiers across different growth conditions and environmental samples.

Deuterated drugs (heavy drugs) have recently been spotlighted as a new modality for small-molecule drugs because the pharmacokinetics of pharmaceutical drugs can be enhanced by replacing C-H bonds with more stable C-D bonds at metabolic positions. Therefore, deuteration methods for drug candidates are a hot topic in medicinal chemistry. Among them, the H/D exchange reaction (direct transformation of C-H bonds to C-D bonds) is a useful and straightforward method for creating novel deuterated target molecules, and over 20 reviews on the synthetic methods related to H/D exchange reactions have been published in recent years. Although various deuterated drug candidates undergo clinical trials, approved deuterated drugs possess CD 3 groups in the same molecule. However, less diversification, except for the CD 3 group, is a problem for future medicinal chemistry. Recently, we developed various deuterated alkyl (d n -alkyl) sulfonium salts based on the H/D exchange reaction of the corresponding hydrogen form using D 2 O as an inexpensive deuterium source to introduce CD 3 , CH 3 CD 2 , and ArCH 2 CD 2 groups into drug candidates. This concept summarises recent reviews related to H/D exchange reactions and novel reagents that introduce the CD 3 group, and our newly developed electrophilic d n -alkyl reagents are discussed., (© 2024 The Authors. ChemMedChem published by Wiley-VCH GmbH.)

The overall rate constant for H‐abstraction (kH) from CH3CH2CH2Cl and D‐abstraction (kD) from CD3CH2CD2Cl by chlorine atoms is described by the formulas: kH=(6.48−1.19+1.45)×10−12·(T298)(1.81±0.15)·exp(597±62)Tcm3molecule−1s−1and kD=(1.45−0.27+0.33)×10−12·exp(801±62)Tcm3molecule−1s−1, respectively. The results of the experiment show that the value of the kinetic isotope effect (kH/kD) for the overall rate constants is also temperature dependent in the temperature range of 298–550 K and can be expressed as kHkD=(4.34−1.27+1.80)·(T298)−0.88±0.26·exp(−195±105T). The titled reaction was also studied theoretically for the same range of temperatures and with both isotope substituents, just like in the experiment. The computations were made using the MP2 method and the aug‐cc‐pVDZ basis set. This paper presents detailed results relating to structural parameters of each of the compounds, complexes, and all energy stages important to the reaction mechanism analysis. It also describes all possible individual channels of the process and their feasibilities. In addition, a kinetic analysis of the process was carried out with branching ratio calculations. The results presented here have been compared with those discussed in a paper published earlier, in which the same process was investigated. [ABSTRACT FROM AUTHOR]

Structure determination of proteins and enzymes by X-ray crystallography remains the most widely used approach to complement functional and mechanistic studies. Capturing the structures of intact redox states in metalloenzymes is critical for assigning the chemistry carried out by the metal in the catalytic cycle. Unfortunately, X-rays interact with protein crystals to generate solvated photoelectrons that can reduce redox active metals and hence change the coordination geometry and the coupled protein structure. Approaches to mitigate such site-specific radiation damage continue to be developed, but nevertheless application of such approaches to metalloenzymes in combination with mechanistic studies are often overlooked. In this review, we summarize our recent structural and kinetic studies on a set of three heme peroxidases found in the bacterium Streptomyces lividans that each belong to the dye decolourizing peroxidase (DyP) superfamily. Kinetically, each of these DyPs has a distinct reactivity with hydrogen peroxide. Through a combination of low dose synchrotron X-ray crystallography and zero dose serial femtosecond X-ray crystallography using an X-ray free electron laser (XFEL), high-resolution structures with unambiguous redox state assignment of the ferric and ferryl (FeIV = O) heme species have been obtained. Experiments using stopped-flow kinetics, solvent-isotope exchange and site-directed mutagenesis with this set of redox state validated DyP structures have provided the first comprehensive kinetic and structural framework for how DyPs can modulate their distal heme pocket Asp/Arg dyad to use either the Asp or the Arg to facilitate proton transfer and rate enhancement of peroxide heterolysis. [ABSTRACT FROM AUTHOR]

The objective of this work is to propose a more effective way to prepare an in-house CO2 with known triple oxygen isotope compositions. The major experimental steps include: (1) the O2 is combusted to CO2 on a graphite rod at 750 °C with Pt-catalyst for 3–4 min; and (2) converted CO2 is subsequently purified by two cryogenic traps. The results show high reproducibility of δ13C and δ18O values of the converted CO2 within 0.010–0.020 ‰ and 0.006–0.010 ‰ (1σ, SD), and the identical δ18O value within error with that of the original O2. Additionally, we have measured the triple oxygen isotope compositions of converted CO2 using an O2–CO2 Pt-catalyzed oxygen-isotope equilibration method. The measured δ17O values of CO2 show high reproducibility within 0.006 ‰ (1σ, SD), and are identical within error with the original O2 as well. Notably, our experiments also found that the O2 with heavier oxygen isotope ratios (δ18O > 40 ‰, VSMOW) might have a lesser conversion efficiency, and this effect, combined with the lighter isotope preferential fractionations during the reaction processes of O2 to CO and CO to CO2, may explain the observed lower 17O/16O and 18O/16O ratios of the converted CO2 relative to the original O2. [ABSTRACT FROM AUTHOR]

The production of H2 from non-fossil sources is a key research challenge to contributing solving the forthcoming energy problem. Aqueous solutions of tetrahydroxydiboron have very recently appeared as a H2 source, from which both hydrogen atoms are provided by water, in the presence of highly sophisticated nanocatalysts. Herein, commercial and cheap Pd/C is shown to be an efficient and recyclable catalyst for H2 evolution upon tetrahydroxydiboron hydrolysis. [ABSTRACT FROM AUTHOR]

The reactions of carbonyl oxide Criegee intermediates with acids proceed predominantly by an insertion mechanism. We characterise the products from one of the simplest reactions of carbonyl oxides with inorganic acids, CH2OO + hydrogen chloride, which occurs via a 1,2-insertion in the H–Cl bond. Reactions of both HCl and DCl isotopologues yield product signal at the mass of the insertion product chloro(hydroperoxy)methane and a dissociative ionisation peak at the mass of the protonated (or deuteronated) Criegee intermediate. The isotopic composition of the insertion product has been measured for reaction mixtures where both HCl isotopologues are present, and the H/D ratio of the product is consistently higher (by a factor of 1.6 ± 0.3) than that of the reactants. This isotope selectivity in the products has smaller uncertainty than the ratio of measured rate coefficients and suggests a normal (kH > kD) kinetic isotope effect in the reaction. Theoretical kinetics calculations predict a small normal kinetic isotope effect for the overall reaction (kH / kD = 1.35 at 20 Torr N2 and kH / kD = 1.2 at 1 atm N2) but predict a substantial inverse kinetic isotope effect (kD > kH) for the stabilisation fraction, in disagreement with the experimental observation. [ABSTRACT FROM AUTHOR]

Model calculations are performed to investigate the kinetic isotope effect of hydrogen and deuterium atom diffusion on hexagonal ice and amorphous solid water. Comparisons with experimental results by Kuwahata et al. (Phys. Rev. Lett., Sep. 2015, 115 (13), 133201) at 10 K are made. The experimentally derived kinetic isotope effect on amorphous solid water is reproduced by transition state theory. The experimentally found kinetic isotope effect on hexagonal ice is much larger than on amorphous solid water and is not reproduced by transition state theory. Additional calculations using model potentials are made for the hexagonal ice, but the experimental kinetic isotope effect is not fully reproduced. A strong influence of temperature is observed in the calculations. The influence of tunnelling is discussed in detail and related to the experiments. The calculations fully support the claims by the Kuwahata et al. (Phys. Rev. Lett., Sep. 2015, 115 (13), 133201) that on amorphous solid water the diffusion is predominantly by thermal hopping while on the polycrystalline ice tunnelling diffusion contributes significantly.