Showing papers on "Transition state published in 2017"
TL;DR: This model has been applied to reactions of all types in both organic and inorganic chemistry, including substitutions and eliminations, cycloadditions, and several types of organometallic reactions.
Abstract: The activation strain or distortion/interaction model is a tool to analyze activation barriers that determine reaction rates. For bimolecular reactions, the activation energies are the sum of the energies to distort the reactants into geometries they have in transition states plus the interaction energies between the two distorted molecules. The energy required to distort the molecules is called the activation strain or distortion energy. This energy is the principal contributor to the activation barrier. The transition state occurs when this activation strain is overcome by the stabilizing interaction energy. Following the changes in these energies along the reaction coordinate gives insights into the factors controlling reactivity. This model has been applied to reactions of all types in both organic and inorganic chemistry, including substitutions and eliminations, cycloadditions, and several types of organometallic reactions.
880 citations
TL;DR: The degree of rate control (DRC) is a mathematical approach for analyzing multistep reaction mechanisms that has proven very useful in catalysis research as discussed by the authors, which identifies the rate-controlling transition states and intermediates (i.e., those whose DRCs are large in magnitude).
Abstract: The “degree of rate control” (DRC) is a mathematical approach for analyzing multistep reaction mechanisms that has proven very useful in catalysis research. It identifies the “rate-controlling transition states and intermediates” (i.e., those whose DRCs are large in magnitude). Even in mechanisms with over 30 intermediates and transition states, these are generally just a few distinct chemical species whose energies, if they could be independently changed, would achieve a faster net reaction rate to the product of interest. For example, when there is a single “rate-determining step”, the DRC for its transition state (TS) is 1, which means (by definition) that if this TS’s energy could be decreased by kBT (where kB is Boltzmann’s constant and T is temperature), the net rate would increase by a factor of e. Because the (relative) energies of these key adsorbed intermediates and transition states can be adjusted by modifying the catalyst or solvent, or even a reactant’s molecular structure, the DRC values pr...
266 citations
TL;DR: In this paper, the Noyori asymmetric hydrogenation reaction was shown to behave in a chemically intact manner within the productive cycle or predominantly in a chemical intact way within productive cycles, and it was shown that the ligand is rather involved in the catalytic reaction via the stabilization of determining transition states through hydrogen bonding interactions.
Abstract: For years, following the ideas of Shvo and Noyori, the core assumption of metal–ligand bifunctional molecular catalysis has relied on the direct involvement of the chelating ligand in the catalytic reaction via a reversible proton (H+) transfer through cleavage/formation of one of its X–H bonds (X = O, N, C). A recently revised mechanism of the Noyori asymmetric hydrogenation reaction (Dub, P. A. et al. J. Am. Chem. Soc. 2014, 136, 3505) suggests that the ligand is rather involved in the catalytic reaction via the stabilization of determining transition states through N–H···O hydrogen-bonding interactions (HBIs) and not via a reversible H+ transfer, behaving in a chemically intact manner within the productive cycle or predominantly in a chemically intact manner within productive cycles. By reexamining selected examples of computational mechanistic studies involving bifunctional catalysts from the literature in the years between 2012–2017, the purpose of this work is to point out common misconceptions in m...
203 citations
TL;DR: The activation strain or distortion energy is the principal contribution to the activation barrier as mentioned in this paper, which is the sum of the energies to distort the reactants into geometries they have in transition states plus the energies of interaction between the two distorted molecules.
Abstract: The Activation Strain or Distortion/Interaction Model is a tool to analyze activation barriers that determine reaction rates. For bimolecular reactions, the activation energies are the sum of the energies to distort the reactants into geometries they have in transition states plus the energies of interaction between the two distorted molecules. The energy to distort the molecules is called the activation strain or distortion energy. This energy is the principal contribution to the activation barrier. The transition state occurs when this activation strain is overcome by stabilizing interaction energy. Following the changes in these energies along the reaction coordinate gives insights into the factors controlling reactivity. This model has been applied to reactions of all types in both organic and inorganic chemistry, including substitutions and eliminations, cycloadditions, and several types of organometallic reactions.
182 citations
TL;DR: This Review brings a new perspective to the study of chemical reactions in compressed fluid media by reviewing the substantial insight gained from more than 50 years of experimental studies on organic reactions in solution under pressure, and introducing a recently developed computational method, the XP-PCM (extreme pressure polarizable continuum model) method.
Abstract: This Review brings a new perspective to the study of chemical reactions in compressed fluid media. We begin by reviewing the substantial insight gained from more than 50 years of experimental studies on organic reactions in solution under pressure. These led to a proper estimation of the critical roles of volume of activation (Δ≠V) and reaction volume (ΔV) in understanding pressure effect on rates and equilibria of organic reactions. A recently developed computational method, the XP-PCM (extreme pressure polarizable continuum model) method, capable of carrying out quantum mechanical calculations of reaction pathways of molecules under pressure, is introduced. A case study of the Diels–Alder cycloaddition of cyclopentadiene with ethylene serves, in pedagogical detail, to describe the methodology. We then apply the XP-PCM method to a selection of other pericyclic reactions, including the parent Diels–Alder cycloaddition of butadiene with ethylene, electrocyclic ring-opening of cyclobutene, electrocyclic ring-closing of Z-hexatriene, the [1,5]-H shift in Z-pentadiene, and the Cope rearrangement. These serve as examples of some of the most common combinations of Δ≠V and ΔV. Interesting phenomena such as a shift in a transition state along a reaction coordinate, a switch of rate-determining step, and the possible turning of a transition state into a stable minimum are revealed by the calculations. A reaction volume profile, the change in the volume of the reacting molecules as the reaction proceeds, emerges as being useful.
86 citations
TL;DR: The mechanism and origins of the ligand-controlled stereoselectivity with density functional theory (DFT) calculations are explored and a concerted oxidative addition through a cyclic transition state, which provides stereoretention is determined.
Abstract: Nickel catalysts have shown unique ligand control of stereoselectivity in the Suzuki–Miyaura cross-coupling of boronates with benzylic pivalates and derivatives involving C(sp3)–O cleavage. The SIMes ligand (1,3-dimesityl-4,5-dihydroimidazol-2-ylidene) produces the stereochemically inverted C–C coupling product, while the tricyclohexylphosphine (PCy3) ligand delivers the retained stereochemistry. We have explored the mechanism and origins of the ligand-controlled stereoselectivity with density functional theory (DFT) calculations. The oxidative addition determines the stereoselectivity with two competing transition states, an SN2 back-side attack type transition state that inverts the benzylic stereogenic center and a concerted oxidative addition through a cyclic transition state, which provides stereoretention. The key difference between the two transition states is the substrate–nickel–ligand angle distortion; the ligand controls the selectivity by differentiating the ease of this angle distortion. For ...
83 citations
TL;DR: In this paper, the energy diagrams of the CO2 hydrogenation pathway over clean and one- or two-formate preadsorbed Cu(211) catalysts are obtained using density functional theory calculations and further employed for microkinetic modeling.
Abstract: The hydrogenation of CO2 to methanol over copper-based catalysts has attracted considerable attention recently. Among all the proposed reaction mechanisms, a large number of experimental and theoretical studies have focused on the one that includes a HCOO intermediate due to the fact that high coverages of formate over catalyst surfaces were observed experimentally. To systematically understand the influence of formate species coverage on the reaction kinetics of methanol synthesis, the energetics of the CO2 hydrogenation pathway over clean and one- or two-formate preadsorbed Cu(211) are obtained using density functional theory calculations, and these energetics are further employed for microkinetic modeling. We find that the adsorption energies of the intermediates and transition states involved in the reaction pathway are changed in the presence of spectating formate species, and consequently, the potential energy diagrams are varied. Microkinetic analysis shows that the turnover frequencies (TOFs) over...
80 citations
TL;DR: The use of computed interaction energies and distances as parameters in multivariate correlations is introduced for postulating non-covalent interactions for two diverse catalytic systems with unique non- covalent interaction at the heart of each process.
Abstract: The use of computed interaction energies and distances as parameters in multivariate correlations is introduced for postulating non-covalent interactions. This new class of descriptors affords multivariate correlations for two diverse catalytic systems with unique non-covalent interactions at the heart of each process. The presented methodology is validated by directly connecting the non-covalent interactions defined through empirical data set analyses to the computationally derived transition states.
78 citations
TL;DR: Martinez-Nunez et al. as mentioned in this paper proposed a novel computational method for use in discovering reaction mechanisms and solving the kinetics of transition metal-catalyzed reactions, which does not rely on either chemical intuition or assumed a priori mechanisms.
Abstract: A novel computational method is proposed in this work for use in discovering reaction mechanisms and solving the kinetics of transition metal-catalyzed reactions. The method does not rely on either chemical intuition or assumed a priori mechanisms, and it works in a fully automated fashion. Its core is a procedure, recently developed by one of the authors, that combines accelerated direct dynamics with an efficient geometry-based post-processing algorithm to find transition states (Martinez-Nunez, E., J. Comput. Chem.2015, 36, 222–234). In the present work, several auxiliary tools have been added to deal with the specific features of transition metal catalytic reactions. As a test case, we chose the cobalt-catalyzed hydroformylation of ethylene because of its well-established mechanism, and the fact that it has already been used in previous automated computational studies. Besides the generally accepted mechanism of Heck and Breslow, several side reactions, such as hydrogenation of the alkene, emerged from our calculations. Additionally, the calculated rate law for the hydroformylation reaction agrees reasonably well with those obtained in previous experimental and theoretical studies.
77 citations
TL;DR: The results provide a foundation for exploiting electrostatic control of selectivity in other ion paired systems and show that changing the solvent dielectric to enforce ion pairing to a SbF6- counterion changes the regioselectivity by up to a factor of 12 depending on the substrate structure.
Abstract: Competing pathways in catalytic reactions often involve transition states with very different charge distributions, but this difference is rarely exploited to control selectivity. The proximity of a counterion to a charged catalyst in an ion paired complex gives rise to strong electrostatic interactions that could be used to energetically differentiate transition states. Here we investigate the effects of ion pairing on the regioselectivity of the hydroarylation of 3-substituted phenyl propargyl ethers catalyzed by cationic Au(I) complexes, which forms a mixture of 5- and 7-substituted 2H-chromenes. We show that changing the solvent dielectric to enforce ion pairing to a SbF6– counterion changes the regioselectivity by up to a factor of 12 depending on the substrate structure. Density functional theory (DFT) is used to calculate the energy difference between the putative product-determining isomeric transition states (ΔΔE‡) in both the presence and absence of the counterion. The change in ΔΔE‡ upon switch...
61 citations
TL;DR: In this paper, aldol condensations on microporous and mesoporous aluminosilicates (FER, TON, MFI, BEA, FAU, MCM-41) were investigated.
TL;DR: In this paper, the authors reported the high and stable ethene dimerization turnover rates conferred upon Ni-based active sites at subambient temperatures by the condensation of liquid ethenes reactants within ordered mesopores in Al-MCM-41.
TL;DR: Recent progress in the applications of quantum chemical methods for the modeling of homogeneous water oxidation catalysis, covering various transition metals, including manganese, iron, cobalt, nickel, copper, ruthenium, and iridium, is discussed.
Abstract: The design of efficient and robust water oxidation catalysts has proven challenging in the development of artificial photosynthetic systems for solar energy harnessing and storage. Tremendous progress has been made in the development of homogeneous transition metal complexes capable of mediating water oxidation. To improve the efficiency of the catalyst and to design new catalysts, a detailed mechanistic understanding is necessary. Quantum chemical model calculations have been successfully used to complement the experimental techniques to suggest a catalytic mechanism and to identify all stationary points including transition states for both O-O bond formation and O2 release. In this review, we discuss the recent progress in the applications of the quantum chemical methods for the modeling of homogeneous water oxidation catalysis, covering various transition metals, including Mn, Fe, Co, Ni, Cu, Ru, and Ir.
TL;DR: The first proton transfer to form CHO from CO to be a critical step in C1 product formation is found and the corresponding barrier scales more favorably with the CO binding energy than for 211 and 111 transition metal surfaces, in the direction of improved activity.
Abstract: Single transition metal atoms embedded at single vacancies of graphene provide a unique paradigm for catalytic reactions. We present a density functional theory study of such systems for the electrochemical reduction of CO. Theoretical investigations of CO electrochemical reduction are particularly challenging in that electrochemical activation energies are a necessary descriptor of activity. We determined the electrochemical barriers for key proton–electron transfer steps using a state-of-the-art, fully explicit solvent model of the electrochemical interface. The accuracy of GGA-level functionals in describing these systems was also benchmarked against hybrid methods. We find the first proton transfer to form CHO from CO to be a critical step in C1 product formation. On these single atom sites, the corresponding barrier scales more favorably with the CO binding energy than for 211 and 111 transition metal surfaces, in the direction of improved activity. Intermediates and transition states for the hydroge...
TL;DR: A heterobimetallic Pd(II)/Cu(I) complex was prepared and characterized by X-ray diffraction analysis, which models the net stabilizing energy of the Pd-Cu interaction in the transition state of the transmetalation step in Pd/Cu-catalyzed cross-coupling reactions.
Abstract: A heterobimetallic Pd(II)/Cu(I) complex was prepared and characterized by X-ray diffraction analysis. The crystal structure shows a remarkably short Pd–Cu bond and a trigonal ipso carbon atom. The Pd–Cu interaction, as determined by energy-resolved collision-induced dissociation cross-section experiments, models the net stabilizing energy of the Pd–Cu interaction in the transition state of the transmetalation step in Pd/Cu-catalyzed cross-coupling reactions. The bonding situation in the bimetallic dinuclear complex has been studied by atoms-in-molecules analysis.
TL;DR: Houk's bifunctional Brønsted acid-hydrogen bonding model, which works for cinchonidine or cinchona alkaloid-urea catalyzed sulfa-Michael addition reactions, also applies to the catalytic system under investigation, and is shown to be in good accord with the observed value.
Abstract: The mechanism of the enantioselective sulfa-Michael addition reaction catalyzed by a cinchona alkaloid-squaramide bifunctional organocatalyst was studied using density functional theory (DFT). Four possible modes of dual activation mechanism via hydrogen bonds were considered. Our study showed that Houk’s bifunctional Bronsted acid–hydrogen bonding model, which works for cinchonidine or cinchona alkaloid-urea catalyzed sulfa-Michael addition reactions, also applies to the catalytic system under investigation. In addition, we examined the origin of the stereoselectivity by identifying stereocontrolling transition states. Distortion–interaction analysis revealed that attractive interaction between the substrates and catalyst in the C–S bond forming transition state is the key reason for stereoinduction in this catalytic reaction. Noncovalent interaction (NCI) analysis showed that a series of more favorable cooperative noncovalent interactions, namely, hydrogen bond, π-stacking, and C–H···π interaction and C...
TL;DR: In this article, the detailed mechanism of methanol decomposition on Pt3Ni(111) based on self-consistent periodic density functional theory calculations is reported, and the decomposition network is mapped to illustrate the reaction mechanisms.
Abstract: This work reports the detailed mechanism of methanol decomposition on Pt3Ni(111) based on self-consistent periodic density functional theory calculations. The geometries and energies of methanol and its intermediates are analyzed, and the decomposition network is mapped to illustrate the decomposition reaction mechanisms. On Pt3Ni(111), the less electronegative Ni atoms are more favorable for adsorbing radical intermediates and intermediates with lone-pair electrons (such as O-containing species). The possible pathways through initial scission of the O–H, C–H, and C–O bonds in methanol are studied and discussed based on the steric effect and electronic structure of the related transition states and the Bronsted-Evans–Polanyi (BEP) relationships. The initial scission of the O–H bond is the most favorable and bears the lowest energy barrier among the three decomposition modes (initial scission of O–H, C–H, and C–O bonds). The decomposition of the energy barrier analysis indicates that the high energy barrie...
TL;DR: This work uses computational chemistry to determine the rate constants and product yields for the reactions of BrHg˙ with the atmospherically abundant radicals NO2 and HOO and will provide guidance for atmospheric modelers and experimental kineticists.
Abstract: We use computational chemistry to determine the rate constants and product yields for the reactions of BrHg˙ with the atmospherically abundant radicals NO2 and HOO. The reactants, products, and well-defined transition states are characterized using CCSD(T) with large basis sets. The potential energy profiles for the barrierless addition of HOO and NO2 to BrHg˙ are characterized using CASPT2 and RHF-CCSDT, and the rate constants are computed as a function of temperature and pressure using variational transition state theory and master equation simulations. The calculated rate constant for the addition of NO2 to BrHg˙ is larger than that for the addition of HOO by a factor of up to two under atmospheric conditions. For the reaction of HOO with BrHg˙ the addition reaction entirely dominates competing HOO + BrHg˙ reaction channels. The addition of NO2 to BrHg˙ initially produces both BrHgNO2 and BrHgONO, but after a few seconds under atmospheric conditions the sole product is syn-BrHgONO. A previously unsuspected reaction channel for BrHg˙ + NO2 competes with the addition to yield Hg + BrNO2. This reaction reduces the mercury oxidation state in BrHg˙ from Hg(i) to Hg(0) and slows the atmospheric oxidation of Hg(0). While the rate constant for this reduction channel is not well-constrained by the present calculations, it may be as much as 18% as large as the oxidation channel under some atmospheric conditions. As no experimental kinetic or product yield data are available for the reactions studied here, this work will provide guidance for atmospheric modelers and experimental kineticists.
01 Jan 2017
TL;DR: In this paper, the authors predict the kinetics of 3O+C2H4 using an ab initio transition state theory based master equation (AITSTME) approach that includes an a priori description of ISC.
Abstract: The reaction of atomic oxygen with ethylene is a fundamental oxidation step in combustion and is prototypical of reactions in which oxygen adds to double bonds. For 3O+C2H4 and for this class of reactions generally, decomposition of the initial adduct via spin-allowed reaction channels on the triplet surface competes with intersystem crossing (ISC) and a set of spin-forbidden reaction channels on the ground-state singlet surface. The two surfaces share some bimolecular products but feature different intermediates, pathways, and transition states. In addition, the overall product branching is therefore a sensitive function of the ISC rate. The 3O+C2H4 reaction has been extensively studied, but previous experimental work has not provided detailed branching information at elevated temperatures, while previous theoretical studies have employed empirical treatments of ISC. Here we predict the kinetics of 3O+C2H4 using an ab initio transition state theory based master equation (AITSTME) approach that includes an a priori description of ISC. Specifically, the ISC rate is calculated using Landau–Zener statistical theory, consideration of the four lowest-energy electronic states, and a direct classical trajectory study of the product branching immediately after ISC. The present theoretical results are largely in good agreement with existing low-temperature experimental kinetics and molecular beam studies.more » Good agreement is also found with past theoretical work, with the notable exception of the predicted product branching at elevated temperatures. Above ~1000 K, we predict CH2CHO+H and CH2+CH2O as the major products, which differs from the room temperature preference for CH3+HCO (which is assumed to remain at higher temperatures in some models) and from the prediction of a previous detailed master equation study.« less
TL;DR: In this article, the authors investigated the mechanism of NO heterogeneous reduction with the presence of CO using density functional theory (DFT), where the zigzag and armchair configurations composed with several aromatic ring clusters were selected as the carbonaceous surfaces.
TL;DR: These studies on imine/chiral phosphoric acid complexes show that an appropriate combination of highly developed NMR and theoretical methods can provide detailed insights into the complicated structures, exchange kinetics, and H-bonding properties of chiral ion pairs.
Abstract: ConspectusOver the years, the field of enantioselective organocatalysis has seen unparalleled growth in the development of novel synthetic applications with respect to mechanistic investigations. Reaction optimization appeared to be rather empirical than rational. This offset between synthetic development and mechanistic understanding was and is generally due to the difficulties in detecting reactive intermediates and the inability to experimentally evaluate transition states. Thus, the first key point for mechanistic studies is detecting elusive intermediates and characterizing them in terms of their structure, stability, formation pathways, and kinetic properties. The second key point is evaluating the importance of these intermediates and their properties in the transition state.In the past 7 years, our group has addressed the problems with detecting elusive intermediates in organocatalysis by means of NMR spectroscopy and eventually theoretical calculations. Two main activation modes were extensively ...
TL;DR: An acylation mechanism is proposed through four possible model transition states (TS) of mycobacterium tuberculosis, namely four membered-ring ( TS-4,TS-4-His and TS- 4-water ) and six membered -ring (TS-6-water) transition states, to pave the way for an improved understanding of the LDT/carbapenem acylated reaction at a molecular level.
TL;DR: In this article, the double-ended and single-ended growing string methods are implemented using a hybrid coordinate system, then benchmarked for a test set of 43 elementary reactions occurring on surfaces.
Abstract: The computational challenge of fast and reliable transition state and reaction path optimization requires new methodological strategies to maintain low cost, high accuracy, and systematic searching capabilities. The growing string method using internal coordinates has proven to be highly effective for the study of molecular, gas phase reactions, but difficulties in choosing a suitable coordinate system for periodic systems has prevented its use for surface chemistry. New developments are therefore needed, and presented herein, to handle surface reactions which include atoms with large coordination numbers that cannot be treated using standard internal coordinates. The double-ended and single-ended growing string methods are implemented using a hybrid coordinate system, then benchmarked for a test set of 43 elementary reactions occurring on surfaces. These results show that the growing string method is at least 45% faster than the widely used climbing image-nudged elastic band method, which also fails to converge in several of the test cases. Additionally, the surface growing string method has a unique single-ended search method which can move outward from an initial structure to find the intermediates, transition states, and reaction paths simultaneously. This powerful explorative feature of single ended-growing string method is demonstrated to uncover, for the first time, the mechanism for atomic layer deposition of TiN on Cu(111) surface. This reaction is found to proceed through multiple hydrogen-transfer and ligand-exchange events, while formation of H-bonds stabilizes intermediates of the reaction. Purging gaseous products out of the reaction environment is the driving force for these reactions. © 2017 Wiley Periodicals, Inc.
TL;DR: A computational toolkit is described that automates the density functional theory (DFT) based screening of chiral ligands for transition-metal-catalyzed reactions with well-defined reaction mechanisms but multiple stereocontrolling transition states.
Abstract: A computational toolkit (AARON: An automated reaction optimizer for new catalysts) is described that automates the density functional theory (DFT) based screening of chiral ligands for transition-metal-catalyzed reactions with well-defined reaction mechanisms but multiple stereocontrolling transition states. This is demonstrated for the Rh-catalyzed asymmetric hydrogenation of (E)-β-aryl-N-acetyl enamides, for which a new C2 -symmetric phosphorus ligand is designed.
TL;DR: The findings reveal that the widespread consensus mechanism of H2 splitting characterizes activation processes corresponding to high-energy transition states and, accordingly, is not operative for H2-activating systems.
Abstract: Using a set of state-of-the-art quantum chemical techniques we scrutinized the characteristically different reactivity of frustrated and classical Lewis pairs towards molecular hydrogen. The mechanisms and reaction profiles computed for the H2 splitting reaction of various Lewis pairs are in good agreement with the experimentally observed feasibility of H2 activation. More importantly, the analysis of activation parameters unambiguously revealed the existence of two reaction pathways through a low-energy and a high-energy transition state. An exhaustive scrutiny of these transition states, including their stability, geometry and electronic structure, reflects that the electronic rearrangement in low-energy transition states is fundamentally different from that of high-energy transition states. Our findings reveal that the widespread consensus mechanism of H2 splitting characterizes activation processes corresponding to high-energy transition states and, accordingly, is not operative for H2-activating systems. One of the criteria of H2-activation, actually, is the availability of a low-energy transition state that represents a different H2 splitting mechanism, in which the electrostatic field generated in the cavity of Lewis pair plays a critical role: to induce a strong polarization of H2 that facilities an efficient end-on acid-H2 interaction and to stabilize the charge separated “H+–H−” moiety in the transition state.
TL;DR: To gain an understanding of the substitution effect on the unimolecular reaction rate coefficients for Criegee intermediates (CIs), ab initio calculations for CH2OO, CH3CHOO, (CH3)2COO,CH3CH2ChOO, Ch2CHCHOO and CHCCHOO found that for single bonded substitutions, the hydrogen transfer reaction dominates for the syn-conformers, while the OO bending reaction dominates For both syn and anti-
Abstract: To gain an understanding of the substitution effect on the unimolecular reaction rate coefficients for Criegee intermediates (CIs), we performed ab initio calculations for CH2OO, CH3CHOO, (CH3)2COO, CH3CH2CHOO, CH2CHCHOO and CHCCHOO. The energies of the CIs, products and transition states were calculated with QCISD(T)/CBS//B3LYP/6-311+G(2d,2p), while the rate coefficients were calculated with anharmonic vibrational correction by using second order vibrational perturbation theory. It was found that for single bonded substitutions, the hydrogen transfer reaction dominates for the syn-conformers, while the OO bending reaction dominates for the anti-conformers. However once a double bond or a triple bond is added, the OO bending reaction dominates for both syn and anti-conformers. The rate coefficients for OO bending reaction show a significant increase when adding a methyl group or ethyl group. On the other hand, the addition of unsaturated vinyl and acetylene groups usually results in a slower thermal decomposition compared to the substitution with saturated carbon groups. Interestingly, for syn_Syn-CH2CHCHOO, a special five member ring closure reaction forming dioxole was calculated to have an extremely fast rate coefficient of 9312 s−1 at room temperature.
TL;DR: The current findings provide a route for modeling this reaction inside the SpnF active site and inferring the catalytic architecture of possible Diels-Alderases, and find that the line between the recently proposed bis-pericyclic routes is blurred, and favorable transition states of both types may coexist.
Abstract: The Diels–Alder reaction is a cornerstone of modern organic synthesis. Despite this, it remains essentially inaccessible to biosynthetic approaches. Only a few natural enzymes catalyze even a formal [4 + 2] cycloaddition, and it remains uncertain if any of them proceed via the Diels–Alder mechanism. In this study, we focus on the [4 + 2] cycloaddition step in the biosynthesis of spinosyn A, a reaction catalyzed by SpnF enzyme, one of the most promising “true Diels–Alderase” candidates. The four currently proposed mechanisms (including the Diels–Alder one) for this reaction in water (as a first-order approximation of the enzymatic reaction) are evaluated by an exhaustive quantum mechanical search for possible transition states (728 were found in total). We find that the line between the recently proposed bis-pericyclic [J. Am. Chem. Soc. 2016, 138 (11), 3631] and Diels–Alder routes is blurred, and favorable transition states of both types may coexist. Application of the Curtin–Hammett principle, however, r...
TL;DR: The catalytic cycle for the serine protease α-chymotrypsin was investigated in an attempt to determine the suitability of using the semiempirical method PM7 in the program MOPAC for investigating enzyme-catalyzed reactions, and the result leads to the recommendation that PM7 and related methods, such as PM6-D3H4, are appropriate for modeling similar enzyme- catalyzing reactions.
Abstract: The catalytic cycle for the serine protease α-chymotrypsin was investigated in an attempt to determine the suitability of using the semiempirical method PM7 in the program MOPAC for investigating enzyme-catalyzed reactions. All six classical intermediates were modeled using standard methods, and were characterized as stable minima on the potential energy surface. Using a modified saddle point optimization method, five transition states were located and verified both by vibrational and by intrinsic reaction coordinate analysis. Some individual features, such as the hydrogen bonds in the oxyanion hole, the nature of various electrostatic interactions, and the role of Met192, were examined. This involved designing and running computational experiments to model mutations that would allow features of interest, in particular the energies involved, to be isolated. Three features within the enzyme were examined in detail: the reaction site itself, where covalent bonds were made and broken, the electrostatic effects of the buried aspartate anion, a passive but essential component of the catalytic triad, and the oxyanion hole, where hydrogen bonds help stabilize charged intermediates. With one minor exception, all phenomena investigated agreed with previously-reported descriptions. This result, along with the fact that all the techniques used were relatively straightforward, leads to the recommendation that PM7 and related methods, such as PM6-D3H4, are appropriate for modeling similar enzyme-catalyzed reactions.
TL;DR: In this paper, a key common C-C bond formation step in a family of enzymes that is responsible for the biosynthesis of 60% of all natural products is studied. And the authors employ hybrid quantum mechanics-molecular mechanics free energy simulations to show that this energy tuning is achieved by modulation of electrostatic interactions.
Abstract: Electrostatic interactions play a major role in stabilizing transition states in enzymes. A crucial question is how general this electrostatic stabilization principle is. To address this point, we study a key common C–C bond formation step in a family of enzymes that is responsible for the biosynthesis of 60% of all natural products. In these terpene cyclases, we have previously shown that the enzymes gain chemical control by raising the energy of initial carbocation intermediates along the reaction coordinate to bypass the formation of unwanted side products. Here we employ hybrid quantum mechanics–molecular mechanics free energy simulations to show that this energy tuning is achieved by modulation of electrostatic interactions. The tempering of electrostatic interactions allows enzymatically directed chemical control that slows down the reaction temporarily by introducing thermodynamic and activation barriers. We show that this electrostatic control in terpene cyclases is achieved by a unique binary act...
TL;DR: QM/MM calculations to the asymmetric ring-opening reaction of cyclohexene oxide with aniline catalyzed by a two-dimensional metal-organic framework that contains a Cu-paddlewheel unit show that the Cu-PDW unit does not maintain a symmetric geometry during the reaction but rather is flexible enough to detach a carboxylate ligand from the copper center, thereby facilitating the reaction.
Abstract: We applied QM/MM calculations to the asymmetric ring-opening reaction of cyclohexene oxide with aniline catalyzed by a two-dimensional metal–organic framework (MOF) that contains a Cu-paddlewheel (Cu-PDW) unit, aiming to elucidate the reaction mechanism and to identify the factors that determine the enantioselectivity of the reaction. Our QM/MM calculations show that the reaction consists of two major steps. In the first step, ring-opening of the epoxide moiety occurs that leads to an intermediate having an alkoxide ion, and the strong binding of the alkoxide to the Cu(II) center results in cleavage of one of the four coordination bonds of the copper with carboxylate ligands. In the second step of the reaction, there is a proton transfer from aniline to a distant site—i.e., the alkoxide oxygen atom—to form the β-amino alcohol product, and the carboxylate ligands of the Cu-PDW unit assist this process. The first ring-opening step was calculated as the rate-limiting step, and the enantioselectivity arises from different degrees of CH–π interactions between aniline and a naphthol group in the transition states. The transition state for the ring-opening step in the formation of the (R,R)-isomer is stabilized by CH–π interactions, whereas such interactions are absent in the transition state for the (S,S)-isomer formation. Interestingly, QM/MM calculations also show that the Cu-PDW unit does not maintain a symmetric geometry during the reaction but rather is flexible enough to detach a carboxylate ligand from the copper center, thereby facilitating the reaction. These results illuminate the utility of multiscale QM/MM computations in identifying critical factors determining the reactivity and selectivity of MOF-catalyzed reactions.