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Hydrogenation and dehydrogenation reactions are fundamental in chemistry and essential for all living organisms. We employ density functional theory (DFT) to understand the reaction mechanism of the oxidative dehydrogenation (ODH) of the pyridyl-amine complex [FeIIIL3]3+ (L3, 1,9-bis(2′-pyridyl)-5-[(ethoxy-2″-pyridyl)methyl]-2,5,8-triazanonane) to the mono-imine complex [FeIIL4]2+ (L4, 1,9-bis(2′-pyridyl)-5-[(ethoxy-2″-pyridyl)methyl]-2,5,8-triazanon-1-ene) in the presence of dioxygen. The nitrogen radical [FeIIL3N8•]2+, formed by deprotonation of [FeIIIL3]3+, plays a crucial role in the reaction mechanism derived from kinetic studies. O2 acts as an oxidant and is converted to H2O. Experiments with the deuterated ligand L3 reveal a primary C-H kinetic isotope effect, kCH/kCD = 2.30, suggesting C-H bond cleavage as the rate-determining step. The DFT calculations show that (i) 3O2 abstracts a hydrogen atom from the α-pyridine aliphatic C-H moiety, introducing a double bond regio-selectively at the C7N8 position, via the hydrogen atom transfer (HAT) mechanism, (ii) O2 does not coordinate to the iron center to generate a high-valent Fe oxo species observed in enzymes and biomimetic complexes, and (iii) the experimental activation parameters (ΔH≠ = 20.38 kcal mol−1, ΔS≠ = −0.018 kcal mol−1 K−1) fall within in the range of values reported for HAT reactions and align well with the computational results for the activated complex [FeIIL3N8•]2+···3O2. [ABSTRACT FROM AUTHOR]

Carbon-14 (C-14) has been a major contributor to the human radioactive exposure dose, as it is released into the environment from the nuclear industry in larger quantities compared to other radionuclides. This most abundant nuclide enters the biosphere as organically bound C-14 (OBC-14), posing a potential threat to public health. Yet, it remains unknown how this relatively low radiotoxic nuclide induces health risks via chemical effects, such as isotope effect. By establishing a trophic transfer model involving algae (Scenedesmus obliquus), daphnia (Daphnia magna) and zebrafish (Danio rerio), we demonstrate that rapid incorporation and transformation of inorganic C-14 by algae into OBC-14 facilitates the blending of C-14 into the biomolecules of zebrafish. We find that internalized C-14 is persistently retained in the brain of zebrafish, affecting DNA methylation and causing alterations in neuropathology. Global isotope tracing metabolomics with C-14 exposure further reveals the involvement of C-14 in various critical metabolic pathways, including one-carbon metabolism and nucleotide metabolism. We thus characterize the kinetic isotope effects for 12C/14C in the key reactions of these metabolic pathways through kinetic experiments and density functional theory computations, showing that the isotopic substitution of carbon in biochemicals regulates metabolism by disrupting reaction ratios via isotope effects. Our results suggest that inorganic C-14 discharged by the nuclear industry can be biotransformed into OBC-14 to impact metabolism via isotope effects, providing new insights into understanding the health risk of C-14, which is traditionally considered as a low radiotoxic nuclide. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: Salimabromide, a unique and scarce marine tetracyclic polyketide, was synthesized in both racemic and optically active forms. A novel carboxylic acid‐directed method for tandem oxidative difunctionalization of olefins was developed, whereby the formation of bridged butyrolactone and enone moieties occurs concurrently. Density functional theory (DFT) calculations indicate that this reaction follows a [3+2] process rather than the [2+2] process. In the meantime, the distinctive benzo‐fused [4.3.1] carbon skeleton and highly hindered vicinal quaternary stereocenters were simultaneously constructed through a challenging intramolecular Giese‐Baran radical cyclization. Furthermore, deuterium kinetic isotopic effects were utilized to enhance the efficacy of this pivotal step. This represents a new illustration of the application of kinetic isotope effects in natural product synthesis. Then, the short asymmetric synthesis of (+)‐salimabromide (13 or 15 steps) was accomplished by combing this method with rhodium‐catalyzed enantioselective hydrogenation of a cycloheptenone derivative (97% ee) or conjugate addition of an aryl boronic acid with 2‐cyclohepten‐1‐one (> 99% ee). [ABSTRACT FROM AUTHOR]

The rational design of efficient bimetallic nanoparticle (NP) catalysts is challenging due to the lack of theoretical understanding of active components and insights into the mechanisms of a specific reaction. Here, we report the rational design of nanoreactors comprising hollow carbon sphere‐confined PtNi bimetallic NPs (PtNi@HCS) as highly efficient catalysts for hydrogen generation via ammonia borane hydrolysis in water. Using both density functional theory calculations and molecular dynamics simulations, the effects of an active PtNi combination and the critical synergistic role of a hollow carbon shell on the molecule diffusion adsorption behaviors are explored. Kinetic isotope effects and theoretical calculations allow the clarification of the mechanism, with oxidative addition of an O–H bond of water to the catalyst surface being the rate‐determining step. The remarkable catalytic activity of the PtNi@HCS nanoreactor was also utilized for successful tandem catalytic hydrogenation reactions, using in situ‐generated H2 from ammonia borane with high efficiency. The concerted design, theoretical calculations, and experimental work presented here shed light on the rational elaboration of efficient nanocatalysts and contribute to the establishment of a circular carbon economy using green hydrogen. [ABSTRACT FROM AUTHOR]

The distribution of stable isotopes in organic compounds within geochemical systems reflects the reactions they undergo, which are often kinetically governed and can be elucidated through quantification based on first principles: employing quantum chemical simulations to derive energy barriers and kinetic isotope effects (KIEs), followed by kinetic calculations using these parameters. In this paper, the distribution of 13C in hydrocarbon gases during the thermal generation and decomposition of ethane and propane has been addressed. The work is based on abundant and systematic isotopic data, including the compound- and position-specific 13C compositions, recent improvements in kinetic networks in hydrocarbon generation, and state-of-the-art quantum chemical methods that can process organic geochemical systems involving solid phases. Density Functional Theory computations validate the carbonium path of hydrocarbon generation and the free-radical path of their decomposition under geological conditions. The first step of each path (alkyl sidechain protonation for generation and hydrogen abstraction for decomposition) is the rate-limiting step and determines the 13C fractionations of gaseous hydrocarbons, with the reaction rate constrained by the concentration or accessibility of the active species (hydrated protons and surface free radicals in the two paths, respectively). Alkyl protonation has normal 13C KIEs, but hydrogen abstraction on the surfaces of solid organic matter has inverse ones (substituting 12C by 13C accelerates the reaction). These inverse KIEs explain three isotopic phenomena in gaseous hydrocarbons in their late thermal evolution: 1) the depletion of 13C in ethane and propane accompanied by their decreased fraction in hydrocarbon gases (isotope "rollover"); 2) the reversed 13C sequence with carbon number (δ13C methane > δ13C ethane > δ13C propane); and 3) the depletion of 13C in the center carbon atoms of residual propane. Isotopic fractionation between gaseous hydrocarbons upon generation is evaluated using the Successive Random Chain-Scission model. The covariation of δ13C in alkanes shows a depletion in CH 4 compared with the values expected from the reciprocal of the carbon numbers, indicating that this deviation may be intrinsic instead of mixing with microbial methane. The comparison of intramolecular 13C fractionation of propane between computational and observed data suggests the contribution of isoprenoids at the beginning of the generation, in addition to isotopic homogenization between the center and end carbon atoms through the ring closure of intermediate cations. The 13C–13C clumping exhibits a weak KIE in both the generation and decomposition of ethane; the clumping is essentially stochastically governed. This work demonstrates how first-principle calculations can provide significant insights into the details of geochemical reactions governing the isotopic distributions. [ABSTRACT FROM AUTHOR]

In this article, we present a meticulous computational study to foresee the effect of an oxygen-rich macrocycle on the reactivity for C–H activation. For this study, a widely studied nonheme Fe(IV)O molecule with a TMC (1,4,8,11-tetramethyl 1,4,8,11-tetraazacyclotetradecane) macrocycle that is equatorially attached to four nitrogen atoms (designated as N4) and acetonitrile as an axial ligand has been taken into account. For the goal of hetero-substitution, step-by-step replacement of the N4 framework with O atoms, i.e., N4, N3O1, N2O2, N1O3, and O4 systems, has been considered, and dihydroanthracene (DHA) has been used as the substrate. In order to neutralise the system and prevent the self-interaction error in DFT, triflate counterions have also been included in the calculations. The study of the energetics of these C–H bond activation reactions and the potential energy surfaces mapped therefore reveal that the initial hydrogen abstraction, which is the rate-determining step, follows the two-state reactivity (TSR) pattern, which means that the originally excited quintet state falls lower in the transition state and the product. The reaction follows the hydrogen atom transfer (HAT) mechanism, as indicated by the spin density studies. The results revealed a fascinating reactivity order, in which the reactivity increases with the enrichment of the oxygen atom in the equatorial position, namely the order follows N4 < N3O1 < N2O2 < N1O3 < O4. The impacts of oxygen substitution on quantum mechanical tunneling and the H/D kinetic isotope effect have also been investigated. When analysing the causes of this reactivity pattern, a number of variables have been identified, including the reactant-like transition structure, spin density distribution, distortion energy, and energies of the electron acceptor orbital, i.e., the energy of the LUMO (σ*z2), which validate the obtained outcome. Our results also show very good agreement with earlier combined experimental and theoretical studies considering TMC and TMCO-type complexes. The DFT predictions reported here will undoubtedly encourage experimental research in this biomimetic field, as they provide an alternative with higher reactivity in which heteroatoms can be substituted for the traditional nitrogen atom. [ABSTRACT FROM AUTHOR]

Activation of nitromethane to endow new reactivity is an interesting and meaningful but also challenging topic. Herein, we report an electrochemical activation of nitromethane to serve as both the heterocyclic skeleton and oxime sources for the construction of isoxazoline aldoximes. The isoxazoline aldoximes that are prepared by four steps with the reported strategy are synthesized in a single step from low‐cost and readily available nitromethane and olefins with moderate to excellent yields under our electrochemical conditions. The reaction also takes advantage of high atom‐economy and E‐selectivity. Moreover, the mechanism is studied by control experiments, a kinetic isotope effect (KIE) study, cyclic voltammogram (CV) experiments, and density functional theory (DFT) calculations. The mechanistic results reveal that nitromethane may be activated under electrochemical conditions to deliver a 1,2,5‐oxadiazole 2‐oxide intermediate, which undergoes [3+2] cycloaddition with olefins to yield isoxazoline aldoximes. [ABSTRACT FROM AUTHOR]

Elucidating the reaction mechanism in heterogeneous catalysis is critically important for catalyst development, yet remains challenging because of the often unclear nature of the active sites. Using a molecularly defined copper single‐atom catalyst supported by a UiO‐66 metal–organic framework (Cu/UiO‐66) allows a detailed mechanistic elucidation of the CO oxidation reaction. Based on a combination of in situ/operando spectroscopies, kinetic measurements including kinetic isotope effects, and density‐functional‐theory‐based calculations, we identified the active site, reaction intermediates, and transition states of the dominant reaction cycle as well as the changes in oxidation/spin state during reaction. The reaction involves the continuous reactive dissociation of adsorbed O2, by reaction of O2,ad with COad, leading to the formation of an O atom connecting the Cu center with a neighboring Zr4+ ion as the rate limiting step. This is removed in a second activated step. [ABSTRACT FROM AUTHOR]

Density functional theory calculations have been performed to probe the reaction mechanism of the recently reported twofold C−H annulation of arylformamides with alkynes by Ni−Al bimetallic catalysis. The main pathway consisted of the formyl C−H activation, phenyl C−H activation, migratory insertion, and reductive elimination steps in succession. The desired annulation product was found to be the equilibrium‐controlled product, while the minor hydrocarbamoylation product was the kinetics‐controlled product. Calculated free‐energy profiles indicated that the annulation and hydrocarbamoylation pathways could intersect with each other and merge into a mechanism unity, in which the reaction system entered the hydrocarbamoylation pathway in early stage and switched to the annulation pathway afterwards via suitable transition states. The modified mechanism picture demonstrated the phenyl C−H activation step to be the rate‐determining step with a free‐energy barrier of 27.7 kcal/mol. However, this barrier was only 19.4 kcal/mol on the basis of a single annulation pathway, which could not satisfactorily agree with the experimental conditions and kinetic isotope effects. In addition, the crucial role of the bifunctional secondary phosphine oxide ligand in promoting the reactivity and selectivity was elucidated in detail. [ABSTRACT FROM AUTHOR]

We report herein the design and development of Co/Al and Co/Mg bimetallic catalysts, supported by a phosphine/secondary phosphine oxide (PSPO) bifunctional ligand, for the site‐selective C−H alkenylation of nitrogen‐containing heteroarenes with alkynes. These catalysts enable the alkenylation of pyridine, pyridone, and imidazo[1,2‐a]pyridine derivatives at the C−H site proximal to the Lewis basic nitrogen or oxygen atom, which represents a selectivity profile distinct from that of the previously developed cobalt‐diphosphine/aluminum catalyst. The alkenylated products were obtained in moderate to good yields using various heterocycles and differently substituted internal alkynes. Kinetic isotope effect experiments suggest the irreversibility of the C−H activation step, the relevance of which to the rate‐limiting step depends on the reaction conditions. Density functional theory calculations indicate that ligand‐to‐ligand hydrogen transfer is the common mechanism of C−H activation. [ABSTRACT FROM AUTHOR]

Incorporating isotopically labelled materials in degradation experiments could help unravel the mechanism(s) of decomposition through use of the kinetic isotope effect. Characterizing synthesized isotopologues however requires an understanding of what observable signals are affected by the isotopic substitution. As vibrational spectroscopy can distinguish between isotopologues, it is an ideal characterization technique to evaluate isotopic variants. To this end, the vibrational spectra of HNIW and its deuterated (2H), 13C, 15N (all), 15N (nitro), and 18O isotopologues have been computationally predicted in the gas phase using density functional theory. These results are compared to experimentally measured FTIR/ATR and Raman spectra of both unsubstituted HNIW and 15N‐labeled HNIW in which the six nitro groups were synthetically tagged with 15N atoms (15Nnitro−HNIW). The experimental isotopic frequency shift for the −NO2 asymmetric stretching frequencies agrees with that theoretically calculated (∼35.7 cm−1 vs. 36.5 cm−1, respectively). Furthermore, analysis of the theoretically predicted frequency shifts for all isotopologues suggest the −NO2 bending modes are lower in frequency than previously reported. This assignment is supported by the experimentally measured isotopic shift of ∼10.1 cm−1 for these features (consistent with the predicted shift of ∼13.1 cm−1). This work expands our current understanding of the vibrational modes in HNIW as well as provides a method for future work on similar systems. [ABSTRACT FROM AUTHOR]

[Display omitted] • Cu/ZnO/Al 2 O 3 and Cu/Al 2 O 3 exhibit identical reaction orders for CO 2 hydrogenation. • Methanol synthesis and reverse water–gas shift occur on a common active site. • Active sites are saturated by H* and HCOOH** surface species during catalysis. • Competing pathways of CO 2 hydrogenation involve distinct rate-determining steps. • H 2 O preferentially inhibits methanol synthesis and alters its rate-determining step. We ally steady-state kinetics, kinetic isotope effects, and density functional theory (DFT) calculations to illustrate that Cu-based catalysts remain saturated by H-adatoms (H*) and molecular formic acid (HCOOH**) during CO 2 hydrogenation. High H* coverage under methanol synthesis conditions is evidenced by reverse water–gas shift (RWGS) rates that exhibit positive H 2 reaction orders only at P H2 ≲ 0.5 bar, above which methanol synthesis and RWGS rates exhibit first and zeroth order dependence on P H2 , respectively. HCOOH** also accumulates on the surface with increasing P CO2 as informed by the Langmuir-type dependence on P CO2 (0.25–23 bar) for both methanol synthesis and RWGS. As both HCOOH** and H* have one H-atom per site occupied, the two species share the same P H2 dependence and give rise to CO 2 reaction orders that are independent of P H2. Surface coverages determined based on kinetic analyses are further corroborated with DFT-derived adsorption energies that show favorable HCOOH** adsorbate–adsorbate interactions as well as repulsive interactions for bidentate formate (HCOO**) on H*-saturated surfaces. Methanol selectivity remains invariant with P CO2 and P CO despite CO inhibiting reaction rates, thereby demonstrating methanol synthesis and RWGS occur on the same active site. In contrast, water preferentially inhibits methanol synthesis rates, increases methanol synthesis H 2 reaction order from 1.0 to 1.5, and alters the methanol synthesis H 2 /D 2 kinetic isotope effect; the inhibitory effect of H 2 O thus cannot be attributed to competitive adsorption alone and instead reflects a change in the rate-determining step for methanol synthesis. The disparate kinetics of methanol synthesis and RWGS evince a branching pathway where methanol is formed from formates and CO is formed from carboxylates. The presented work thus identifies the relevant surface species, underscores the distinct catalytic role of water in branching methanol synthesis and RWGS pathways, and, in doing so, details a mechanistic picture that yields predictable rates and reaction orders for both methanol synthesis and RWGS on Cu-based CO 2 hydrogenation catalysts. [ABSTRACT FROM AUTHOR]

This study deals with the unprecedented reactivity of a [(cyclam)MnII(OTf) 2 ] (3 - cis ; OTf = CF 3 SO 3−) with O 2 , which, depending on the presence or absence of a hydrogen atom donor like 1-hydroxy-2,2,6,6-tetramethyl-piperidine (TEMPO-H), selectively generates di- μ -oxo Mn(III)Mn(IV) (1) or MnIV 2 (2) complexes, respectively. Both dimers have been characterized by different techniques including single-crystal X-ray diffraction, X-ray absorption spectroscopy, and electron paramagnetic resonance. Oxygenation reactions carried out with labeled 18O 2 and Resonance Raman spectroscopy unambiguously show that the oxygen atoms present in the MnIVMnIII dimer originate from O 2. Experimental evidences are provided for a novel method of dioxygen activation involving three Mn ions or two Mn ions and TEMPO-H to generate the bis(μ -oxo)dimanganese(IV) or bis(μ -oxo) dimanganese(III, IV) cores, respectively. An unprecedented reactivity of a [(cyclam)MnII(OTf) 2 ] complex with O 2 in presence or absence of a hydrogen atom donor like 1-hydroxy-2,2,6,6-tetramethyl-piperidine selectively generates di- μ -oxo Mn(IV)Mn(III) (1) or MnIV 2 (2) complexes, respectively. [Display omitted] • Dioxygen activation at a Mn(II) center • Formation of high-valent Mn(IV)oxo dimer by oxygen incorporation from dioxygen • Trinuclear Activation Mechanism for dioxygen activation • Negative kinetic isotope effect for H-atom abstraction reaction. • Detailed spectroscopic and mechanistic investigation [ABSTRACT FROM AUTHOR]

Nitrogen‐bearing rings are common features in the molecular structures of modern drugs, with chiral δ‐lactams being an important subclass due to their known pharmacological properties. Catalytic dearomatization of preactivated pyridinium ion derivatives emerged as a powerful method for the rapid construction of chiral N‐heterocycles. However, direct catalytic dearomatization of simple pyridine derivatives are scarce and methodologies yielding chiral δ‐lactams are yet to be developed. Herein, we describe an enantioselective C4‐dearomatization of methoxypyridine derivatives for the preparation of functionalised enantioenriched δ‐lactams using chiral copper catalysis. Experimental 13C kinetic isotope effects and density functional theory calculations shed light on the reaction mechanism and the origin of enantioselectivity. [ABSTRACT FROM AUTHOR]

High‐valent metal‐oxo species are typical catalytic cycle intermediates in mono‐oxygenases and dioxygenases and commonly react through oxygen atom transfer to substrates. In this work we study a biomimetic model complex with a 1,1'‐bis((3,5‐dimethylpyridin‐2‐yl)methyl)‐2,2'‐bipiperidine ligand system bound to a manganese(IV)‐oxo(hydroxo) species and study its formation from manganese(II)‐hydroxo and H2O2 as well as its reaction with (S)‐1‐phenylisochromane through dehydrogenative α‐oxygenation. The work utilizes density functional theory methods to explore its catalytic cycle and its reactivity patterns. We show that the manganese(IV)‐oxo(hydroxo) species is an active oxidant and preferentially the oxo group abstracts a hydrogen atom from substrate with barriers well lower in energy than those found for hydrogen atom abstraction by the hydroxo group. Interestingly, the rate‐determining step is the OH rebound rather than the hydrogen atom abstraction, which would imply they would have limited kinetic isotope effect for the replacement of the transferring hydrogen atom by deuterium. [ABSTRACT FROM AUTHOR]

Transition metal single atom catalysts (SACs) with M1-Nx coordination configuration have shown outstanding activity and selectivity for hydrogenation of nitroarenes. Modulating the atomic coordination structure has emerged as a promising strategy to further improve the catalytic performance. Herein, we report an atomic Co1/NPC catalyst with unsymmetrical single Co1-N3P1 sites that displays unprecedentedly high activity and chemoselectivity for hydrogenation of functionalized nitroarenes. Compared to the most popular Co1-N4 coordination, the electron density of Co atom in Co1-N3P1 is increased, which is more favorable for H2 dissociation as verified by kinetic isotope effect and density functional theory calculation results. In nitrobenzene hydrogenation reaction, the as-synthesized Co1-N3P1 SAC exhibits a turnover frequency of 6560 h−1, which is 60-fold higher than that of Co1-N4 SAC and one order of magnitude higher than the state-of-the-art M1-Nx-C SACs in literatures. Furthermore, Co1-N3P1 SAC shows superior selectivity (>99%) toward many substituted nitroarenes with co-existence of other sensitive reducible groups. This work is an excellent example of relationship between catalytic performance and the coordination environment of SACs, and offers a potential practical catalyst for aromatic amine synthesis by hydrogenation of nitroarenes. Modulating the atomic coordination structure has emerged as a promising strategy to further improve catalytic performance. Here, the authors report an atomic Co1/NPC catalyst with unsymmetrical single Co1N3P1 sites that displays high activity and chemoselectivity for hydrogenation of functionalized nitroarenes. [ABSTRACT FROM AUTHOR]

Density functional theory investigations were performed to address the C–H activation reactivity and the influence of quantum mechanical tunneling catalyzed by a non-heme iron(IV)-oxo complex, namely [FeIVOdpaq-X]+, where the macrocyclic ligand dpaq represents {2-[bis(pyridine-2-yl-methyl)]amino-N-quinolin-8-yl-acetamido}. Counter ion and solvent corrections were incorporated in the computation to avoid self-interaction error. To find the impact of the indirectly linked substituents to the central metal atom, Fe, the macrocyclic ligand dpaq was substituted at the 5-position of its quinoline moiety represented as dpaq-X and the reactivity and hydrogen tunneling were compared with the parent ligand dpaq-H. Here, both electron-donating, e.g. –N(CH3)2 and –OMe, and electron-withdrawing, e.g. –NO2 and –SO2CF3, substituents compared to hydrogen were considered. The reactions displayed exchange interaction favouring two-state reactivity (TSR) as the S = 2 state was found for the excited state in the reactant, which crossed the S = 1 path (initially the ground state) during the progress of the reaction. This was further verified by the tunneling corrected kinetic isotope effect (KIE), which closely matched with the experiment (32) in the S = 2 state (22), whereas the S = 1 KIE (∼69) was found to be very far from that experimentally observed. More than 90% of all the C–H activation reactions proceeded through quantum mechanical tunneling even at room temperature. As the substituent group became more electron-donating, both the tunneling contributions and the kinetic isotope effect increased, which supported the anti-electrophilic tunneling control reactivity premise. The presented consequences may further expose the possibility for the rational design of metal-based catalysts with systematic ligand/substituent tuning that can be performed efficiently through quantum mechanical tunneling. [ABSTRACT FROM AUTHOR]

Metal–TEMPO hybrids are a family of novel and promising catalysts for aerobic oxidation of alcohols, yet the underlying mechanisms have not been understood theoretically. Using density functional theory, we probe the hydrogen abstraction mechanisms of FeCl3/TEMPO on two characteristic substrates, 9,10-dihydroanthracene and benzyl alcohol. We found that the low spin state of FeCl3/TEMPO is more favourable, and that the N atom is the preferred hydrogen acceptor. Moreover, dispersion interactions assist the reaction, as well as nuclear tunnelling, which even at room temperature can speed up the process by almost two orders of magnitude. We also predict that pronounced kinetic isotope effects (KIE) could be observed due to tunnelling. Our findings provide insights into improving the substrate scope and the development of new transformations for the FeCl3/TEMPO system. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: The development of catalytic aerobic epoxidation by numerous metal complexes in the presence of aldehyde as a sacrificial reductant (Mukaiyama epoxidation) has been reported, however, comprehensive examination of oxygen atom transfer mechanism involving free radical and highly reactive intermediates has yet to be presented. Herein, meso‐tetrakis(pentafluorophenyl) porphyrinatooxidovanadium(IV) (VOTPFPP) was prepared and proved to be efficient toward aerobic olefin epoxidation in the presence of isobutyraldehyde. In situ electron paramagnetic resonance spectroscopy (in situ EPR) showed the generation, transfer pathways and ascription of free radicals in the epoxidation. According to the spectral and computational studies, the side‐on vanadium‐peroxo complexes are considered as the active intermediate species in the reaction process. In the cyclohexene epoxidation catalyzed by VOTPFPP, the kinetic isotope effect value of 1.0 was obtained, indicating that epoxidation occurred via oxygen atom transfer mechanism. The mechanism was further elucidated using isotopically labeled dioxygen experiments and density functional theory (DFT) calculations. [ABSTRACT FROM AUTHOR]

Microbial production and consumption of methane are widespread in natural and artificial environments, with important economic and climatic implications. Attempts to use the isotopic composition of methane to identify its sources are complicated by incomplete understanding of the mechanisms of variation in methane's isotopic composition. Knowledge of the equilibrium isotope fractionations among the large organic intracellular intermediates in the microbial pathways of methane production and consumption must form the basis of any exploration of the mechanisms of isotopic variation, but estimates of these equilibrium isotope fractionations are currently unavailable. To address this gap, we calculated the equilibrium isotopic fractionation of carbon ( 13 C/ 12 C) and hydrogen (D/H) isotopes among compounds in the anaerobic methane metabolisms, as well as the abundance of double isotope substitutions ("clumping," i.e., a single 13 C–D bond or two 12 C–D bonds) in these compounds. The isotope fractionation factors were calculated using density functional theory at the M06-L/def2-TZVP level of theory with the SMD implicit solvation model, which we recently tested against measured equilibrium isotope fractionations. The computed 13 β and 2 β values decrease with decreasing oxidation state of the carbon atom in the molecules, resulting in a preference for enrichment in 13 C and D in the molecules with more oxidized carbon. Using the computed β values, we calculated the equilibrium isotope fractionation factors in the prominent methanogenesis pathways (hydrogenotrophic, methylotrophic and acetoclastic) and in the pathway for anaerobic oxidation of methane (AOM) over a temperature range of 0–700 °C. Our calculated equilibrium fractionation factors compare favorably with experimental constraints, where available, and were then used to investigate the relation between the apparent isotope fractionation during methanogenesis or AOM and the thermodynamic drive for these reactions. We show that a detailed map of the equilibrium fractionation factors along these metabolic pathways allows for an evaluation of the contribution of equilibrium and kinetic isotope effects to apparent isotope fractionations observed in laboratory, natural and artificial settings. The comprehensive set of equilibrium isotope fractionation factors calculated in this study provides a firm basis for future explorations of isotope effects in methane metabolism. [ABSTRACT FROM AUTHOR]

The use of alkyl chlorides in Pd-catalyzed Mizoroki–Heck coupling reactions remains an unsolved problem despite their significant potential for synthetic utility and applicability. The combination of the high thermodynamic barrier of alkyl chloride activation and kinetic propensity of alkylpalladium complexes to undergo undesired β-hydride elimination provides significant challenges. Herein, a variety of alkyl chlorides, even tertiary chlorides, are shown to efficiently participate in Mizoroki–Heck cross-coupling reactions with excellent functional group compatibility under mild reaction conditions via photoinduced Pd catalysis. The reaction is applied to late-stage functionalizations of diverse biologically significant scaffolds and iterative double Mizoroki–Heck annulations, affording high molecular complexity in a single step. Notably, studies on the kinetic isotope effects in combination with density functional theory (DFT)-computations completely exclude the involvement of a previously proposed β-hydride elimination in the catalytic cycle, revealing that the chlorine atom transfer process is the key catalytic turnover step. This distinctive single-electron transfer mediated reaction pathway resolves a longstanding challenge in traditional two-electron based Pd-catalyzed Mizoroki–Heck cross-coupling with alkyl electrophiles, wherein the β-hydride elimination is involved in the formation of both the desired product and undesired by-products. The use of alkyl chlorides in Pd-catalyzed Mizoroki–Heck coupling reactions remains an unsolved problem despite their significant synthetic potential. Here, the authors show that alkyl chlorides can efficiently participate in Mizoroki–Heck cross-coupling reactions with excellent functional group compatibility via photoinduced Pd catalysis. [ABSTRACT FROM AUTHOR]

Kinetic isotope effect (KIE) reveals the transition state structure of an elementary reaction and can be predicted by quantum chemical calculation. Density Functional Theory calculation of an enzymatic reaction with large numbers of atoms is computationally prohibitive, especially if explicit solvent effect is considered. Cutoff method, which simplifies an entire molecule to a cluster around a target position, can simplify position-specific equilibrium isotope effect calculation for a large organic molecule. It should also be applicable to KIE calculation of an enzymatic reaction and allow us to introduce explicit solvent molecules to the system. If this treatment is feasible and trustable, it will provide an efficient method to estimate a number of KIEs produced by enzyme reactions. Obviously, its robustness must be tested. Here, using NO 3 − reduction by the active site of periplasmic dissimilatory nitrate reductase (Nap) in Rhodobacter sphaeroides as an example, we built 17 models to test the influence of cutoff size, implicit, and explicit solvent effects on KIE calculation. The results show that to estimate the KIE value of an enzymatic reaction accurately and efficiently, we can first simplify the reaction model to a cutoff model with 3 proximal bonds to the active position. Then, incorporating implicit-plus-explicit solvent models can simulate a reaction environment more realistically, which is necessary for accuracy. Our calculated ln KIE values for nitrate Nap reduction at 25 °C are −32.4 ± 1.8‰ for 15N and −20.9 ± 0.4 ‰ for 18O, respectively, with a ln18 KIE /ln15 KIE ratio of 0.65 ± 0.05. Although additional reservoir-transport processes need to be considered, our calculation results are consistent with calibrated isotope effects from laboratory experiments, suggesting that the transition state we calculated depicts the general reaction mechanism of NO 3 − reduction by Nap. [ABSTRACT FROM AUTHOR]

The formation of H 2 CO 3 and HCO 3 − from CO 2 is common in aqueous environmental systems and occurs via the CO 2 hydration and hydroxylation reactions. The reactions are especially important in the context of CaCO 3 mineral precipitation. The reactions carry with them equilibrium and kinetic isotope fractionations that impact paleoclimate proxy records. Herein, quantum mechanical calculations of dissolved inorganic carbon species embedded in H 2 O clusters are analyzed under a transition state theory framework to predict kinetic isotope fractionations associated with the reactions. Experimental measurements of reaction energetics and equilibrium isotope fractionations are well-reproduced by the models which suggests the computational methods are justified. The CO 2 hydration reaction discriminates against 13C by 19–23‰ and against 18O by 14–15‰ at 25 °C. The CO 2 hydroxylation reaction discriminates against 13C by 26–31‰ and against 18O by 27–30‰ at 25 °C. Our analyses of the model isotopic fractionations lead to the conclusion that hydrogen-bonds and C(CO 2)-O(H 2 O or OH−) distances influence the calculated values. We infer that when the model H-bond patterns more realistically represent the aqueous species, the accuracy and precision of equilibrium fractionation factor prediction is improved. Implications for coral carbonate paleothermometry are discussed. Results indicate that hydration and hydroxylation δ13C-δ18O slopes bound the values of slopes form corals and abiotic precipitation experiments, albeit with key uncertainties related to precipitation fractionations. The process of regressing molecular model fractionation results against H-bond patterns as presented here is a promising way to improve isotope fractionation calculations in aqueous systems. [ABSTRACT FROM AUTHOR]

A RuII complex, [RuII(tpphz)(bpy)2]2+ (1) (tpphz = tetrapyridophenazine, bpy = 2,2′-bipyridine), whose tpphz ligand has a pyrazine moiety, is converted efficiently to [RuII(tpphz-HH)(bpy)2]2+ (2) having a dihydropyrazine moiety upon photoirradiation of a water–methanol mixed solvent solution of 1 in the presence of an electron donor. In this reaction, the triplet metal-to-ligand charge-transfer excited state (3MLCT*) of 1 is firstly formed upon photoirradiation and the 3MLCT* state is reductively quenched with an electron donor to afford [RuII(tpphz˙−)(bpy)2]+, which is converted to 2 without the observation of detectable reduced intermediates by nano-second laser flash photolysis. The inverse kinetic isotope effect (KIE) was observed to be 0.63 in the N–H bond formation of 2 at the dihydropyrazine moiety. White-light (380–670 nm) irradiation of a solution of 1 in a protic solvent, in the presence of an electron donor under an inert atmosphere, led to photocatalytic H2 evolution and the hydrogenation of organic substrates. In the reactions, complex 2 is required to be excited to form its 3MLCT* state to react with a proton and aldehydes. In photocatalytic H2 evolution, the H–H bond formation between photoexcited 2 and a proton is involved in the rate-determining step with normal KIE being 5.2 on H2 evolving rates. Density functional theory (DFT) and time-dependent DFT (TD-DFT) calculations on the reaction mechanism of H2 evolution from the ground and photo-excited states of 2 were performed to have a better understanding of the photocatalytic processes. [ABSTRACT FROM AUTHOR]

The addition of Sb−H bonds to alkynes was reported recently as a new hydroelementation reaction that exclusively yields anti‐Markovnikov Z‐olefins from terminal acetylenes. We examine four possible mechanisms that are consistent with the observed stereochemical and regiochemical outcomes. A comprehensive analysis of solvent, substituent, isotope, additive, and temperature effects on hydrostibination reaction rates definitively refutes three ionic mechanisms involving closed‐shell charged intermediates. Instead the data support a fourth pathway featuring open‐shell neutral intermediates. Density‐functional theory (DFT) calculations are consistent with this model, predicting an activation barrier that is in agreement with the experimental value (Eyring analysis) and a rate limiting step that is congruent with the experimental kinetic isotope effect. We therefore conclude that hydrostibination of arylacetylenes is initiated by the generation of stibinyl radicals, which then participate in a cycle featuring SbII and SbIII intermediates to yield the observed Z‐olefins as products. This mechanistic understanding will enable rational evolution of hydrostibination as a synthetic methodology. [ABSTRACT FROM AUTHOR]

Using density functional theory calculations (at the B97‐D2//BP86 level) and measurements of kinetic isotope effects, we explored the mechanism of [RuH2(PPh3)3(CO)] (22) in catalytic acceptor‐less dehydrogenation of methanol to formaldehyde. 22 is found to exhibit a similar activity as the previously studied [RuH2(H2)(PPh3)3] (1 b) complex. On the computed pathway, η2→η1 slippage of Ru‐bound formaldehyde prior to decoordination is indicated to be rate‐limiting, consistent with the low kH/kD KIE of 1.3 measured for this reaction. We also explored computationally the possibility of achieving complete dehydrogenation of methanol (into CO2 and H2), through subsequent decarbonylation of formaldehyde and water‐gas shift reaction of the resulting carbonyl complex. Complete pathways of this kind are traced for 22 and for [RuH2(PPh3)2(CO)2]. An alternative mechanism, involving a gem‐diol intermediate (obtained upon attack of OH− to coordinated formaldehyde), has also been investigated. All these pathways turned out to be unfavourable kinetically, in keeping with the lack of CO2 evolution experimentally observed in this system. Our calculations show that the reactions are hampered by the low electrophilicities of the CO and HCHO ligands, making OH− uptake unfavourable. Consequently, the subsequent intermediates are too high‐lying on the reaction profiles, thus leading to high kinetic barriers and preventing full dehydrogenation of methanol to occur by this kind of mechanism. [ABSTRACT FROM AUTHOR]

[Display omitted] • Reaction kinetics of C-Cl hydrogenolysis of chlorobenzene are first-order in chlorobenzene, half-order in hydrogen, and inverse-first-order in HCl. • Kinetic study, including kinetic isotope effect measurement, and DFT calculations all suggest C-Cl activation is kinetically relevant. • DFT calculations show the Pd surface saturates with Cl* coverage less than 0.5 ML. • The reaction appears to require only one site because Cl* and Ph* bind non-competitively. Chlorinated organic compounds are ubiquitous chemical intermediates, final products, and waste streams found in multiple industries. These compounds must often be dechlorinated prior to disposal to avoid negative consequences for environmental and human health. In this work, we employ kinetic experiments and density functional theory (DFT) to examine Pd-catalyzed chlorobenzene hydrogenolysis, which is highly selective for the formation of benzene (>95 %). Kinetic data (353 K, 10–101 kPa H 2 , 0.2–1.1 kPa C 6 H 2 Cl, 0.5–1 kPa HCl) on 5 wt% Pd/C catalysts revealed rates that are first-order, half-order, and inverse first-order with respect to PhCl, H 2 , and HCl, respectively. These kinetic trends are consistent with PhCl dechlorination as the kinetically relevant step occurring at a single site on surfaces saturated by Cl adatoms (Cl*) in equilibrium with H 2 and HCl, consistent with previous reports in the literature. However, the nature of this C−Cl bond activation has not been well-described in the prior literature, because forming adsorbed Ph* and Cl* typically requires two sites, yet the kinetic trends suggest that only a single site is needed. Here, we resolve this inconsistency using theory, which shows that Cl* saturates Pd surfaces at a Cl*:Pd surf ratio of ca. 0.3–0.4. This low saturation coverage enables Ph* (and other species) to bind interstitially among the Cl* adatoms without requiring Cl* desorption. Theory furthermore confirms that the reaction occurs through a rate-determining PhCl dechlorination, without any C–H activation of the phenyl ring. This non-competitive binding of Ph* among Cl* adatoms can be described as a two-site mechanism that agrees with the kinetic, isotopic, and theoretical data from this and prior work. [ABSTRACT FROM AUTHOR]

• Decomposition of HCOOH on TiO 2 surfaces forms CO and H 2 O products. • Inactive bidentate formates (*HCOO*) saturate all Ti 5c centers at conditions of catalysis (423–463 K). • HCOOH adsorbs molecularly at a proton (HCOOH-H*) in this *HCOO*-template. • HCOOH-H* eliminates H 2 O by reacting with a Ti 5c -O 2c pair, made available by the momentary reprotonation of *HCOO*. • The reprotonation of *HCOO* is less facile on rutile than on anatase TiO 2 , causing its lower reactivity at these conditions. Mechanistic details of HCOOH decomposition routes provide valuable insights into reactions involving bound formates as intermediates or spectators; these routes are also widely used as a probe of the acid-base properties of oxide surfaces. The identity and kinetic relevance of bound intermediates, transition states, and elementary steps are reported here for HCOOH dehydration on anatase and rutile TiO 2 surfaces through complementary kinetic, isotopic, spectroscopic and theoretical assessments. Five-coordinate exposed Ti 5c centers are saturated with bidentate formates (*HCOO*) at catalytic conditions (423–463 K; 0.1–3 kPa HCOOH), as evident from infrared spectra collected during catalysis and the amounts of HCOOH and CO evolved upon heating the TiO 2 samples containing pre-adsorbed HCOOH-derived species. These *HCOO* species are inactive but form a stable "surface template" that contains stochiometric protons onto which HCOOH binds molecularly (HCOOH-H*) to form a coexisting adlayer. H 2 O elimination from HCOOH-H* is the sole kinetically-relevant step. DFT-derived barriers show that this step involves its reaction with Ti 5c -O 2c that acts as a Lewis acid-base pair. Such route, in turn, requires the access of HCOOH-H* to a Ti 5c center, which is made available through a momentary reprotonation of a *HCOO*. This step is much less facile on rutile than on anatase due to stronger acid strength of its Ti 5c centers that binds *HCOO* species more strongly and its shorter Ti 5c -Ti 5c distances that induce greater repulsions between co-adsorbed HCOOH* formed upon reprotonation step. These differences account for low dehydration reactivity of rutile at these temperatures. This mechanistic interpretation is in full accord with DFT-derived barriers, binding energies, and kinetic isotope effects that quantitatively agree with the values from regressed kinetic and thermodynamic parameters, with in-situ infrared spectra that identify HCOOH-H* species as the sole reactive intermediates, and with the differences in turnover rates between anatase and rutile catalysts. These dehydration routes are also consistent with the surface chemistry expected for Lewis acid-base pairs on stoichiometry TiO 2 surfaces without requiring the presence or involvement of reduced centers or titanols in the catalytic cycle. The reaction routes described in this work show how strongly-bound species, evident in presence and unreactive nature from in-situ infrared spectra, provide an organic "permanent" template for reactions of weakly-bound species that are often invisible in spectroscopy. [ABSTRACT FROM AUTHOR]

In this work, the aromatic hydroxylation mechanism of the [Cu2(H-XYL)O2]2+ complex mediated by a peroxo dicopper core and Cu-ligand effects are investigated by using hybrid density functional theory (DFT) and the broken symmetry B3LYP method. Based on the calculated free-energy profiles, we proposed two available mechanisms. The first reaction steps of both mechanisms involve concerted O--O bond cleavage and C--O bond formation and the second step involves the Wagner--Meerwein rearrangement of the substrate by a [1,2] H shift (HA shift from CA to CC) or (HA shift from CA to OA) across the phenyl ring to form stable dienone intermediates, and this is followed by the protonation of bridging oxygen atoms to produce the final hydroxylated dicopper(II) product. The HA shift from CA to CC mechanism is the energetically most favorable, in which the first reaction step is the rate-limiting reaction, with a calculated free-energy barrier of 19.0 kcal mol-1 and a deuterium kinetic isotope effect of 1.0, in agreement with experimental observations. The calculation also shows that the reaction started from the Ptype species of [Cu2(H-XYL)O2]2+ which is capable of mediating the direct hydroxylation of aromatic substrates without the intermediacy of an O-type species. Finally, we designed some new complexes with different Cu-ligands and found the complex that computationally possesses a higher activity in mediating the hydroxylation of the ligand based aromatic substrate; here, Cu loses a pyridyl ligand donor by dissociation, compared to the [Cu2(H-XYL)O2]2+ complex. [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 FROM AUTHOR]

Quantum mechanical (QM) semiempirical methods (SMs), combined with molecular mechanics (MM) force fields, are extensively used in theoretical studies of enzymatic reactions. Despite being several orders of magnitude faster than ab initio methods, their correctness is essential to be used in calculations requiring statistical simulations. Herein, a wide range of SMs are examined, from those based on s and p orbitals, sp-SMs (MNDO, AM1, PM3 and RM1), to those including d orbitals, spd-SMs, either based on approximations to the Hartree–Fock theory (MNDO/d, PM6 and AM1/d-PhoT) or derived from density functional theory (DFTB3). These QM Hamiltonians are used within a multiscale QM/MM additive scheme, to clarify their usefulness in mechanistic studies of phosphoryl-transfer reactions. The SN2-like reaction of the adenylyl group transfer catalysed by 4′-O-Nucleotidyltransferase (ANT4′) was selected as a benchmark. Geometrical characteristics of stationary structures, the shape of potential energy surfaces together with the barrier heights and kinetic isotope effects (KIEs), obtained with the different SMs/MM methods were compared with results obtained at higher M06-2X/MM level of theory. Critical limitations of the sp-SMs in the present mechanistic study were detected. The spd-SMs describe the reaction as a concerted process, same as the reference method M06-2X, but none of them is free of limitations. PM6 reproduces the biased trend of previous sp-SMs stabilizing structures of phosphorous atoms with certain pentavalent character, while AM1/d-PhoT and DFTB3 describe TSs more dissociative than M06-2X, which determines the lower quality of the computed primary and secondary 16O/18O KIEs. Efforts to improve the SMs can be guided by the exposure of their limitations, which were supported by the results of a second studied phosphoryl-transfer reactions; the hydrolysis of phosphodiester bond at the 3′-end of the viral DNA (vDNA). Thus, for instance, further increases in SMs accuracy can be achieved by improving the training and survey reference data sets, a more complete set of parameters for describing intermolecular interactions or further developments of spd-SMs. [ABSTRACT FROM AUTHOR]

In this study, density functional theory (DFT) calculations were performed to gain insight into the possible reaction mechanism and substituent effects of benzene arylation at the molecular level. The results showed that both [Me3Si]+[WCA]− and [Et3Si]+[WCA]− promoted the reaction. The whole catalytic cycle generally involved three processes, namely, carbocation formation, Wheland intermediate formation, and catalyst regeneration. For the second process, the stepwise mechanism (C−C coupling followed by proton transfer) was shown to be preferred over the concerted mechanism, with successive [1,2]/[1,4]‐proton transfer as the preferred pathway. C−C coupling, rather than C−H insertion, was shown to be the rate‐determining step of the reaction, which was consistent with the kinetic isotope effect experimental results. Bond dissociation energy calculations showed that the ortho‐TMS substituent played a major role in activating the C−F bond to facilitate phenyl cation formation, leading to the most weakly C−Cl bonded intermediate, which facilitated the C−C coupling. Ortho‐phenyl substituents resulted in more severe steric hindrance of fluoride abstraction and a weaker C−H⋅⋅⋅π interaction in the C−C coupling transition state compared with meta‐phenyl substituents. Better stabilization of the cation center by an electron‐rich meta‐substituent was concluded to be the main reason for the better yield obtained compared with substrates containing an electron‐deficient meta‐substituent. [ABSTRACT FROM AUTHOR]

Reaction pathways involving quantum tunneling of protons are fundamental to chemistry and biology. They are responsible for essential aspects of interstellar synthesis, the degradation and isomerization of compounds, enzymatic activity, and protein dynamics. On‐surface conditions have been demonstrated to open alternative routes for organic synthesis, often with intricate transformations not accessible in solution. Here, we investigate a hydroalkoxylation reaction of a molecular species adsorbed on a Ag(111) surface by scanning tunneling microscopy complemented by X‐ray electron spectroscopy and density functional theory. The closure of the furan ring proceeds at low temperature (down to 150 K) and without detectable side reactions. We unravel a proton‐tunneling‐mediated pathway theoretically and confirm experimentally its dominant contribution through the kinetic isotope effect with the deuterated derivative. [ABSTRACT FROM AUTHOR]

Mononuclear nonheme MnIII‐peroxo complexes are important intermediates in biology, and take part in oxygen activation by photosystem II. Herein, we present work on two isomeric biomimetic side‐on MnIII‐peroxo intermediates with bispidine ligand system and reactivity patterns with aldehydes. The complexes are characterized with UV/Vis and mass spectrometric techniques and reaction rates with cyclohexane carboxaldehyde (CCA) are measured. The reaction gives an unusual regioselectivity switch from aliphatic to aldehyde hydrogen atom abstraction upon deuteration of the substrate, leading to the corresponding carboxylic acid product for the latter, while the former gives a deformylation reaction. Mechanistic details are established from kinetic isotope effect studies and density functional theory calculations. Thus, replacement of C−H by C−D raises the hydrogen atom abstraction barriers and enables a regioselectivity switch to a competitive pathway that is slightly higher in energy. [ABSTRACT FROM AUTHOR]

The diiron active site is pivotal in catalyzing transformations in both biological and chemical systems. Recently, a range of biomimetic diiron catalysts have been synthesized, drawing inspiration from the active architecture of soluble methane monooxygenase (sMMO). These catalysts have been successfully deployed for the dehydrogenation of indolines, marking a significant advancement in the field. Using density functional theory (DFT) calculations, we have identified a novel mechanistic pathway that governs the dehydrogenation of indolines catalyzed by a biomimetic diiron complex. Specifically, this reaction is facilitated by the transfer of a hybrid atom from the C 1 position of the substrate to the distal oxygen atom of the Fe(III)Fe(III)-1,1-μ-hydroperoxy active species. This transfer serves as the rate-limiting step for the heterolytic cleavage of the O O bond, ultimately generating the substrate cation. The mechanism we propose aligns well with mechanistic investigations incorporating both kinetic isotope effect (KIE) measurements and evaluations of stereochemical selectivity. This research contributes to the broader scientific understanding of catalysis involving biomimetic diiron complexes and offers valuable insights into the catalytic behaviors of non-heme diiron metalloenzymes. In this study, DFT calculations were performed to identify a novel mechanistic pathway that governs the dehydrogenation of indolines catalyzed by a biomimetic diiron complex. Specifically, this reaction is facilitated by the transfer of a hybrid atom from the C 1 position of the substrate to the distal oxygen atom of the Fe(III)Fe(III)-1,1-μ-hydroperoxy active species. [Display omitted] • The biomimetic diiron complex catalyzes the dehydrogenation of indolines via a novel mechanistic pathway. • The reaction proceeds by hybrid transfer from substrate to the Fe(III)Fe(III)-1,1-μ-hydroperoxy active species. • This research expands our understanding on the catalysis of biomimetic diiron complexes and non-heme diiron metalloenzymes. [ABSTRACT FROM AUTHOR]

Understanding the reaction mechanism underlying the functionalization of C−H bonds by an enzymatic process is one of the most challenging issues in catalysis. Here, combined approaches using density functional theory (DFT) analysis and transient kinetics were employed to investigate the reaction mechanism of C−H bond oxidation in d‐glucose, catalyzed by the enzyme pyranose 2‐oxidase (P2O). Unlike the mechanisms that have been conventionally proposed, our findings show that the first step of the C−H bond oxidation reaction is a hydride transfer from the C2 position of d‐glucose to N5 of the flavin to generate a protonated ketone sugar intermediate. The proton is then transferred from the protonated ketone intermediate to a conserved residue, His548. The results show for the first time how specific interactions around the sugar binding site promote the hydride transfer and formation of the protonated ketone intermediate. The DFT results are also consistent with experimental results including the enthalpy of activation obtained from Eyring plots, as well as the results of kinetic isotope effect and site‐directed mutagenesis studies. The mechanistic model obtained from this work may also be relevant to other reactions of various flavoenzyme oxidases that are generally used as biocatalysts in biotechnology applications. Which is the first step on the path? Combined approaches using density functional theory (DFT) analysis and transient kinetics were employed to investigate the reaction mechanism of C−H bond oxidation in d‐glucose, catalyzed by the enzyme pyranose 2‐oxidase (P2O) (see figure). [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 FROM AUTHOR]

Abstract: A combination of experimental 13C kinetic isotope effects (KIEs) and high‐level density functional theory (DFT) calculations is used to distinguish between “enamine” and “enol” mechanisms in the Michael addition of acetone to trans‐β‐nitrostyrene catalyzed by Jacobsen's primary amine thiourea catalyst. In light of the recent findings that the widely used 18O‐incorporation probe for these mechanisms is flawed, the results described in this communication demonstrate an alternative probe to distinguish between these pathways. A key advantage of this probe is that quantitative mechanistic information is obtained without modifying experimental conditions. This approach is expected to find application in resolving mechanistic debates, while providing valuable information about the key transition state of organocatalyzed reactions involving the α‐functionalization of carbonyls. [ABSTRACT FROM AUTHOR]

Abstract: C−H activations with challenging arylacetamides were accomplished by versatile ruthenium(II) biscarboxylate catalysis. The distal C−H functionalization offers ample scope—including twofold oxidative C−H functionalizations and alkyne hydroarylations—through facile base‐assisted internal electrophilic‐type substitution (BIES) C−H ruthenation by weak O‐coordination. [ABSTRACT FROM AUTHOR]

Multiple proton transfer (PT) is an essential process in long-range proton transport such as proton relay in enzymes. 7-Hydroxyquinoline (7HQ) undergoes alcohol-mediated PT in both the excited and ground states, and this system has been investigated as a biomimetic model. In the present study, the reaction pathway of triple PT in a 7HQ-methanol cluster, 7HQ·(MeOH)2, in the ground state has been investigated using density functional theory calculations to clarify the reaction mechanism and the origin of the experimentally observed kinetic isotope effect (KIE). The PT takes place in an asynchronous concerted fashion, in which the oxygen atom in 7HQ first accepts a proton from the directly hydrogen-bonded MeOH. The rate constants and primary H/D KIEs have been estimated with canonical variational transition state theory in combination with the small curvature tunneling approximation. The tunneling effect on the PT rate is significant, and the KIE is much greater than 1 at room temperature. The rule of the geometric mean for the KIEs breaks down because of the asynchronicity in the motions of 3 protons and tunneling effect. In addition, the rate constant is smaller, the KIE is larger, and the activation energy is higher compared with the experimental values in heptane solution, suggesting that the PT dynamics in solution is governed by not only the intrinsic PT process but also thermal fluctuation of the solute and solvent molecules, which plays an important role in the configurational change of the 7HQ·(MeOH)2 complex. [ABSTRACT FROM AUTHOR]

Previous experimental studies have shown that addition of H and Mu atoms to pyrazine in aqueous solution leads to different reaction products. H adds to the N atom of the pyrazine ring, whereas Mu adds preferentially to the C atom. In this work, to explain this anomalous isotope effect, we performed reaction path analyses for the H/Mu + pyrazine·(H 2 O) n ( n = 0–2) reactions at the density functional theory level by considering microsolvation effects. Without water microsolvation, the barrier height of the addition to N is always lower than that of the addition to C. However, the barrier height of the addition to N is slightly higher than that of the addition to C when the N atom of the pyrazine ring is pre-solvated by water through an N⋯H−O hydrogen bond. Thermal rate constants are calculated within a variational transition state theory framework including quantum tunneling corrections and are compared with the experimental results. [ABSTRACT FROM AUTHOR]

The mechanism of the hydroxylation of benzene by an iron(II) bis(NHC) complex, [Fe II (NCCN)(CH 3 CN) 2 ](PF 6 ) 2 ( 1 ; NCCN = bis( o -imidazol-2-ylidenepyridine)methane), in the presence of hydrogen peroxide was investigated. The invariance of the catalytic system towards the presence of radical scavengers and an inverse intermolecular kinetic isotope effect (KIE) allow to rule out a hydrogen abstraction pathway. Additionally, using 1,3,5-[D 3 ]benzene as substrate, NIH-shift products were detected, resembling the reactivity of naturally occurring enzymes and some molecular biomimetic iron complexes. Supported by density functional theory calculations, the aromatic hydroxylation reaction is proposed to proceed via an iron-arene σ-complex as intermediate species. [ABSTRACT FROM AUTHOR]

High-valent Cu and Fe species, which are generated from dioxygen activation in metalloenzymes, carry out the functionalization of strong C-H bonds. Understanding the atomic details of the catalytic mechanism has long been one of the main objectives of bioinorganic chemistry. Large H/D kinetic isotope effects (KIEs) were observed in the C-H activation by high-valent non-heme Cu or Fe complexes in enzymes and their synthetic models. The H/D KIE depends significantly on the transition state properties, such as structure, energies, frequencies, and shape of the potential energy surface, when the tunneling effect is large. Therefore, theoretical predictions of kinetic parameters such as rate constants and KIEs can provide a reliable link between atomic-level quantum mechanical mechanisms and experiments. The accurate prediction of the tunneling effect is essential to reproduce the kinetic parameters. The rate constants and HD/KIE have been calculated using the variational transition-state theory including multidimensional tunneling based on DFT potential energy surfaces along the reaction coordinate. Excellent agreement was observed between the predicted and experimental results, which assures the validity of the DFT potential energy surfaces and, therefore, the proposed atomic-level mechanisms. The [Cu(μ-O)], [Fe(μ-O)], and Fe(IV)-oxo species were employed for C-H activation, and their role as catalysts was discussed at an atomic level. [ABSTRACT FROM AUTHOR]

Isotopes are indispensable tools for elucidating catalytic reaction mechanisms. Yet, computational isotopic studies in heterogeneous catalysis remain scarce, especially when compared with other subfields of chemistry. In this review, we discuss isotope effects from a computational viewpoint, focusing specifically on heterogeneous catalysts. First, we review methods for predicting kinetic and equilibrium isotope effects of individual elementary steps, as well as for simulating the apparent kinetic isotope effects of multistep reactions. Second, we discuss the influence of the often-neglected catalytic environment, such as the presence of different binding sites and non-zero adsorbate coverages. Third, we present case studies illustrating possible pitfalls when performing isotope studies and how computations can help avoid them. Finally, we share our outlook on possible future applications of isotope effects. Throughout the review, we highlight the promising synergies that can be gained by combining experiments and computations. [Display omitted] • Showed how to compute isotope effects for elementary steps and multistep reactions. • Shed light on how the catalytic environment influences isotope effects. • Highlighted challenges in isotopic studies and discussed how computations can help. • Discussed promising alternative applications of isotope effects in catalysis. [ABSTRACT FROM AUTHOR]

Determination of experimental kinetic isotope effects (KIE) is one of the most useful tools for the exploration of reaction mechanisms in organometallic chemistry. The approach has been further strengthened during the last decade with advances in modern computational chemistry. This allows for the calculation of a theoretical KIE that can often be compared directly to the experimental value. This combined experimental/theoretical approach can be particularly useful in cases where the value of the experimental KIE is not directly associated with one particular reaction step (e.g., in a catalytic reaction). The approach is highlighted by using recent examples from both stoichiometric and catalytic reactions, homogeneous and heterogeneous catalysis, and enzyme catalysis to illustrate the expected accuracy and utility of this approach. [ABSTRACT FROM AUTHOR]

Kinetic and isotopic data on Pt clusters and activation free energy barriers from density functional theory (DFT) on Pt(1 1 1) are used to assess the elementary steps involved in NO–H 2 reactions. Pt clusters 1–10 nm in diameter gave similar turnover rates, indicating that these elementary steps are insensitive to surface-atom coordination. N–O cleavage occurs after sequential addition of two chemisorbed H-atoms (H * ) to NO * which are quasi-equilibrated with H 2 and NO co-reactants. The first step is equilibrated and forms HNO * , while the second addition is irreversible and forms * HNOH * ; this latter step limits NO–H 2 rates and forms OH * and NH * intermediates that undergo fast reactions to give H 2 O, N 2 O, NH 3 , and N 2 . These conclusions are consistent with (i) measured normal H/D kinetic isotope effects; (ii) rates proportional to H 2 pressure, but reaching constant values at higher pressures; (iii) fast H 2 –D 2 equilibration during catalysis; and (iv) DFT-derived activation barriers. These data and calculations, taken together, rule out N–O cleavage via NO * reactions with another NO * (forming O * and N 2 O) or with vicinal vacancies (forming N * and O * ), which have much higher barriers than H * -assisted routes. The cleavage of N–O bonds via * HNOH * intermediates is reminiscent of C–O cleavage in CO–H 2 reactions (via * HCOH * ) and of O–O cleavage in O 2 –H 2 reactions (via OOH * or * HOOH * ). H * -addition weakens the multiple bonds in NO, CO, and O 2 and allows coordination of each atom to metal surfaces; as a result, dissociation occurs via such assisted routes at all surface coverages relevant in the practice of catalysis. [ABSTRACT FROM AUTHOR]

Experimental 13C kinetic isotope effects have been used to interrogate the rate-limiting step of the Michael addition of glycinate imines to benzyl acrylate catalyzed by a chiral 2,3-bis(dicyclohexylamino) cyclopropenimine catalyst. The reaction is found to proceed via rate-limiting carbon-carbon bond formation. The origins of enantioselectivity and a key noncovalent CH---O interaction responsible for transition state organization are identified on the basis of density functional theory calculations and probed using experimental labeling studies. The resulting high-resolution experimental picture of the enantioselectivity-determining transition state is expected to guide new catalyst design and reaction development. [ABSTRACT FROM AUTHOR]

Highlights: [•] Theoretical mechanisms of CH3OCl/CD3OCl with Cl− are investigated by DFT. [•] Anti-E2 elimination is dominant channel competing SN2 and Syn-E2 channels. [•] Rate constants and kinetic isotope effects are calculated by direct dynamic. [•] Vibrational contribution is the dominant factor for kinetic isotope effects. [ABSTRACT FROM AUTHOR]

Modern DFT functional as well as the continuum solvation model have been applied in order to theoretically predict carbon, chlorine and hydrogen kinetic isotope effects (KIEs) during aerobic degradation of four hexachlorocyclohexane isomers (α, β, δ and γ). A small model of the hexachlorocyclohexane dehydrochlorinase (LinA) active site comprising its catalytic dyad has been constructed based on the receptor-ligand complexes suggested by docking studies and compared to the respective reaction modeled in aqueous solution. In-depth analysis of chlorine and hydrogen KIEs patterns clearly indicates different transition states in aqueous solution and in the model mimicking the protein active site. Although all isomers seem to undergo a concerted E2 mechanism, the contribution of proton transfer and carbon-chlorine leaving group bond stretch in the transition states differs for the different isomers giving rise to totally different magnitudes of predicted isotope effects. Copyright © 2013 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]