Catalytic reaction mechanism of L-lactate dehydrogenase: anab initio study

Studies on the catalytic reaction mechanism of L-lactate dehydrogenase have been carried out by using quantum chemical ab initio calculation at HF/6-31G* level. It is found that the interconversion reaction of pyruvate to L-lactate is dominated by the hydride ion H_r transfer, and the transfers of the hydride ionH _r and protonH _r are a quasi-coupled process, in which the energy barrier of the transition state is about 168.37 kJ/mol. It is shown that the reactant complex is 87.61 kJ/mol lower, in energy, than the product complex. The most striking features in our calculated results are that pyridine ring of the model cofactor is a quasi-boat-like configuration in the transited state, which differs from a planar conformation in some previous semiempirical quantum chemical studies. On the other hand, the similarity in the structure and charge between theH _r transfer process and the hydrogen bonding with lower barrier indicates that the H_r transfer process occurs by means of an unusual manner. In addition, in the transition state the electrostatic interaction between the substrate and the active site of LDH is quite strong and the polarization of the carbonyl in the substrate is gradually enhanced accompanying the formation of the transition state. These calculated results are well in accord with the previous experimental studies, and indicate that the charge on the hydride ion H_r is only +0.13e in the transition state, which is in agreement with the reported semiempirical quantum chemical calculations.     

Catalytic reaction mechanism of L-lactate dehydrogenase: an ab initio study

Studies on the catalytic reaction mechanism of L-lactate dehydrogenase have been carried out by using quantum chemical ab initio calculation at HF/6-31G* level. It is found that the interconversion reaction of pyruvate to L-lactate is dominated by the hydride ion HR- transfer, and the transfers of the hydride ion HR and proton HR are a quasi-coupled process, in which the energy barrier of the transition state is about 168.37 kJ/mol. It is shown that the reactant complex is 87.61 kJ/mol lower, in energy, than the product complex. The most striking features in our calculated results are that pyridine ring of the model cofactor is a quasi-boat-like configuration in the transited state, which differs from a planar conformation in some previous semiempirical quantum chemical studies. On the other hand, the similarity in the structure and charge between the HR transfer process and the hydrogen bonding with lower barrier indicates that the HR transfer process occurs by means of an unusual manner. In addition,     

钐(II)类卡宾CH3SmCH2I与乙烯环丙烷化反应及溶剂化效应的理论研究

用密度泛函B3LYP方法研究了过渡金属钐类卡宾与乙烯的环丙烷化反应的机理. 对钐类卡宾试剂CH₃SmCH₂I和CH₂CH₂反应的反应物、中间体、过渡态和产物构型的全部结构几何参数进行了优化, 并计算了THF溶液的溶剂化效应, 用内禀反应坐标(IRC)计算和频率分析方法, 对过渡态进行了验证. 结果表明: CH₃SmCH₂I与CH₂CH₂环丙烷化反应按亚甲基转移机理(通道A)和卡宾金属化机理(通道B)都可以进行, 与锂类卡宾的反应机理相同, 通道A比通道B反应的势垒降低了14.65 kJ/mol. 溶剂化效应使通道B比通道A的反应势垒大幅度提高, 更有利于反应沿通道A进行, 而不利于通道B.     

A novel mechanism for the isomerization of N2O4 and its implication for the reaction with H2O and acid rain formation

We have discovered, by high‐level quantum‐chemical calculations, a new and predominant isomerization mechanism for N₂O₄ → ONONO₂ via a roaming‐like transition state occurring unimolecularly or bimolecularly during collision with H₂O. The new mechanism allows N₂O₄ to react with H₂O with a significantly lower barrier (< 13.1 kcal/mol) than the commonly known tight transition state (∼30‐45 kcal/mol) by concurrent stretching of the N N bond and rotation of one of the NO₂ groups to form trans‐ONONO₂, which then undergoes a rapid metathetical reaction with H₂O in the gas phase and in aqueous solution. The results have a significant implication for the hydrolysis of N₂O₄ in water to produce HONO and HNO₃. Rate constants for the isomerization and hydrolysis reactions have been predicted for atmospheric modeling applications.     

Theoretical study on the atmospheric reaction of CH3SH with O2

A detailed study on the reaction mechanism of CH₃SH with O₂ was carried out using quantum chemical methods. Eleven singlet pathways and four triplet pathways were found based on CCSD(T)//M06-2x calculations. The nature of chemical bonding evolution was also studied using electron localization function and atoms in molecules analysis. Moreover, reaction rate constants were calculated between 200 and 800 K at the level of the transition state theory by Wigner tunneling correction. The results suggest that the main products should be CH₂SO, H₂O, CH₃OH, SO, CH₄, and SO₂, respectively, basically coinciding with the experimental results. The corresponding feasible pathways are channels R7, R8, and R9, respectively, with an effective energy barrier of 56.21 kJ/mol. Obviously, given the low energy barrier similar to the main paths mentioned above, the products CH₂SH and HO₂ should assume a definite proportion in all possible products, although such species were not yet detected in experiment.     

Multicomponent QM study on the reaction of HOSO + NO2 with H2O: Nuclear quantum effect on structure and reaction energy profile

The hydrogen transfer reaction in the reaction of HOSO + NO₂ with and without H₂O have been investigated using multicomponent quantum-mechanics method, which can directly take nuclear quantum effect (NQE) of light nuclei into account. For the case of the reaction without H₂O, our calculation reveals that the reaction leading to trans-HONO is preferred. For the reaction with H₂O, water-non-mediated and water-mediated (hydrogen-relay) hydrogen transfer mechanism are investigated. The NQE of hydrogen nucleus lowers the relative energy of the stationary point structures and reduces the activation barrier of the reactions. The largest stabilization is found in the transition state structure of the hydrogen-relay type reaction. H/D isotope effects for the reactions are also analyzed. In particular, H/D isotope effect on the activation barrier is analyzed in detail with the aid of the active strain model.     

Bis-ortho-substitution by methyl groups dramatically increases the racemization barrier of Tröger bases

We have shown through racemization kinetics studies that the enantiomerization barriers of the bis‐ortho‐methyl substituted Tröger bases 2 and 3 in acidic media are raised by 30 kJ mol^?1 relative to the parent compound 1 , that is 130.4(4) and 131.6(4) kJ mol^?1, respectively (105 °C, pH 1, ethylene glycol). The enantiomerization barrier of para‐methoxy‐para‐nitro substituted Tröger base 4 was determined by dynamic capillary electrophoresis to 96.3(2) kJ mol^?1 (25 °C, pH 2.2, H₂O), which is lower by 5 kJ mol^?1 relative to 1 . The influence of deutero‐substitution on the racemization rates was also studied. The influence of steric and electronic factors on the enantiomerization barrier was investigated by quantum‐mechanical (DFT) calculations. It is shown that enantiomerization takes place in two steps: ring‐opening and further interconversion of the monocyclic intermediate. For the interconversion to occur a transition state has to be passed which is sensitive to steric effects. Ortho‐substitution by methyl groups significantly increases the energy of this state. Thus, compounds 2 and 3 are the simplest Tröger bases which are configurationally stable in acidic media.     

Theoretical studies of cyclopropylsilylenes: The structures and stability of cyclopropylsilylene C3H5SiH

Ab initio molecular orbital calculations at the G2(MP2) level have been carried out on cyclopropylsilylene C₃H₅SiH. Four equilibrium structures were located. Like H₂Si, the ground state of C₃H₅SiH is singlet and the triplet is the low‐lying excited state. The singlet–triplet separation energy is 127.9 kJ/mol. The cis‐trans isomerization path of singlet cyclopropylsilylene was investigated by intrinsic reaction coordinate (IRC) calculations. The calculations show that no gauche conformers exist along the potential energy curve of the cis‐trans isomerization and the isomerization happens with a barrier of 30.1 kJ/mol. Changes (ΔH and ΔG) in thermodynamic functions, equilibrium constant K(T), and A factor and reaction rate constant k(T) in Eyring transition state theory of the cis‐trans isomerization were also calculated. © 2001 John Wiley & Sons, Inc. Int J Quantum Chem, 2001     

HMB体系分子内质子传递的量子化学计算研究

首次利用量子化学半经验AM1方法和从头算HF/6-31G方法对一种新型的苝醌类光? 艏?PQP)-菌生素(HMB)的结构及其分子内质子传递(IPT)进行了理论计算研究，并? 捎弥鸩皆黾硬嗔吹姆椒ㄉ杓屏艘幌盗心Ｐ突衔镆钥悸歉鞑嗔炊訦MBIPT的影响，? 峁推p醌(PQ)的IPT作了对比。同于HMB只有一个分子内氢键，此项研究对解释PQP的光敏活性有十分重要的意义。本研究主要结论：(1)基态时HMB的IPT势垒只有10.0180kJ/mol(反式)和37.9819kJ/mol(顺式)，分子中存在着快速的IPT。(2)侧链对HMB的IPT势垒影响较小，IPT主要受它的大共轭结构和共振模式的影响。(3)过渡态时质子的电荷增加，质子传递势垒与它的电荷变化成线性关系，此关系可推广到其它质子传递体系。(4)HMB的IPT势垒和IPT过程中羟基氧氢键以及氢键的键长变化均成较好的线性关系。(5)虽然只有一个IPT模式，HMB的IPT以及共振模式仍然和PQ十分相似，这是HMB保持光敏活性的基础。     

A theoretical approach to the complexation and decomplexation processes in the reaction C60 + He ⇌ (He@C60)

To theoretically investigate the complexation and decomplexation processes in the reaction C₆₀ + He ? (He@C₆₀), four possible reaction paths are assumed, so that while He approaches and penetrates the C₆₀ cage (a) a pentagon, (b) a hexagon, (c) a short bond, or (d) a long bond will be expanded on its original sphere or plane to form a window. The computation is performed by the quantum chemical method EHMO/ASED. The results show that the probability of completing this reaction in terms of the tunnel effect can be neglected and the reaction is completed by overcoming a potential barrier of the reaction. It is easily completed by opening a planar window than by opening a shperical window. The probability through reaction path (b) with a barrier of 1247.94 kJ/mol is larger than that through reaction path (a) with a barrier of 1438.26 kJ/mol. The probability through reaction path (d) is the largest with a barrier of 1076.78 kJ/mol, when the planar expansion forming a window of a 9-membered ring is at the optimized value of 0.40 å. When He deviates the center and approaches the C₆₀ cage, there will be a charge distribution on C₆₀ with changing in size and even in sign along the longitude corresponding to the symmetry axis, but the absolute value gradually decreases. This situation is similar to the charge transfer on carbons in sraight-chain polyene. © 1995 John Wiley & Sons, Inc.     

Theoretical studies of mechanisms of cycloaddition reaction between difluoromethylene carbene and acetone

Mechanisms of the cycloaddition reaction between singlet difluoromethylene carbene and acetone have been investigated with the second‐order Møller–Plesset (MP2)/6‐31G* method, including geometry optimization and vibrational analysis. Energies for the involved stationary points on the potential energy surface (PES) are corrected by zero‐point energy (ZPE) and CCSD(T)/6‐31G* single‐point calculations. From the PES obtained with the CCSD(T)//MP2/6‐31G* method for the cycloaddition reaction between singlet difluoromethylene carbene and acetone, it can be predicted that path B of reactions 2 and 3 should be two competitive leading channels of the cycloaddition reaction between difluoromethylene carbene and acetone. The former consists of two steps: (i) the two reactants first form a four‐membered ring intermediate, INT2, which is a barrier‐free exothermic reaction of 97.8 kJ/mol; (ii) the intermediate INT2 isomerizes to a four‐membered product P_2b via a transition state TS2b with an energy barrier of 24.9 kJ/mol, which results from the methyl group transfer. The latter proceeds in three steps: (i) the two reactants first form an intermediate, INT1c, through a barrier‐free exothermic reaction of 199.4 kJ/mol; (ii) the intermediate INT1c further reacts with acetone to form a polycyclic intermediate, INT3, which is also a barrier‐free exothermic reaction of 27.4 kJ/mol; and (iii) INT3 isomerizes to a polycyclic product P₃ via a transition state TS3 with an energy barrier of 25.8 kJ/mol. © 2006 Wiley Periodicals, Inc. Int J Quantum Chem, 2007     

Mechanism of Ethylene Migratory Insertion and Dimerization Catalyzed by δ‐Alkyl Platinum Complexes–A DFT Study

The mechanism of ethylene insertion reactions catalyzed by cationic δ‐alkyl platinum complexes has been studied at the B3LYP level of density functional theory. The initial steps of the reactions proceed via the coordination of ethylene to the reactants L₂Pt(II)R⁺, where L₂=none, (NH₃)₂, (CHNH)₂; R=H, CH₃, C₂H₅ in which ethylene coordinates strongly to the complexes PtCH⁺₃ and PtC₂H⁺₅ (coordination energies (CE) are 296.52 and 229.28 kJ/mol, respectively), while nitrogen‐containing ligands decrease the energies: Pt(NH₃)₂CH⁺₃ (CE: 180.04 kJ/mol), Pt(NH₃)₂C₂H⁺₅ (CE: 97.86 kJ/mol), Pt(CHNH)₂CH⁺₃ (CE : 176.31 kJ/mol) and Pt(CHNH)₂C₂H⁺₅ (CE: 91.00 kJ/mol). Moreover, ethylene insertion into the Pt‐alkyl bond, which is the rate‐determining step, is endothermic with barrier heights for L₂PtCH₃(C₂H₄)⁺ decreasing in the order: PtCH⁺₃ (164.18 kJ/mol)>(NH₃)₂ PtCH⁺₃ (129.95 kJ/mol)>(CHNH)₂ PtCH⁺₃ (115.27 kJ/mol), which has the same tendency for the ethyl case. The insertion product will continually undergo β‐hydride elimination, which is exothermic. On the other hand, the effects of solvent (dichloromethane, THF and benzene) are investigated with PCM method, but the inclusion of the effects in the computations only slightly affects the results. Beside that, a complete catalytic cycle for ethylene dimerization is studied in detail and the calculations agree well with known energetic and recognized tendencies.     

AM1 studies on the potential energy surface for the proton transfer in protonated water clusters,H+(H2O)n

The potential energy surfaces for the proton transfer processes in H⁺(H₂O)_n with n=2 ～ 11 have been studied using the semiempirical AM1 method. Two model systems were adopted: branched and linear systems. The branched system showed a tendency to form a bulk cluster, while the linear system showed a tendency toward a constant barrier height with increasing number of water molecules in the model system. The potential energy surfaces were discussed using Marcus theory. In the case of H⁺ (H₂O)_n with n=10 and 11, the intrinsic barrier to the proton transfer was found to be around 1.0 kcal/mol.     

Bio‐Inspired Transition Metal–Organic Hydride Conjugates for Catalysis of Transfer Hydrogenation: Experiment and Theory

Taking inspiration from yeast alcohol dehydrogenase (yADH), a benzimidazolium (BI⁺) organic hydride‐acceptor domain has been coupled with a 1,10‐phenanthroline (phen) metal‐binding domain to afford a novel multifunctional ligand ( L ^BI+) with hydride‐carrier capacity ( L ^BI++H^?? L ^BIH). Complexes of the type [Cp*M( L ^BI)Cl][PF₆]₂ (M=Rh, Ir) have been made and fully characterised by cyclic voltammetry, UV/Vis spectroelectrochemistry, and, for the Ir^III congener, X‐ray crystallography. [Cp*Rh( L ^BI)Cl][PF₆]₂ catalyses the transfer hydrogenation of imines by formate ion in very goods yield under conditions where the corresponding [Cp*Ir( L ^BI)Cl][PF₆] and [Cp*M(phen)Cl][PF₆] (M=Rh, Ir) complexes are almost inert as catalysts. Possible alternatives for the catalysis pathway are canvassed, and the free energies of intermediates and transition states determined by DFT calculations. The DFT study supports a mechanism involving formate‐driven Rh?H formation (90 kJ mol^?1 free‐energy barrier), transfer of hydride between the Rh and BI⁺ centres to generate a tethered benzimidazoline (BIH) hydride donor, binding of imine substrate at Rh, back‐transfer of hydride from the BIH organic hydride donor to the Rh‐activated imine substrate (89 kJ mol^?1 barrier), and exergonic protonation of the metal‐bound amide by formic acid with release of amine product to close the catalytic cycle. Parallels with the mechanism of biological hydride transfer in yADH are discussed.     

Molecule dynamics and combined QM/MM study on one-carbon unit transfer reaction catalyzed by GAR transformylase

Both a molecule dynamic study and a combined quantum mechanics and molecule mechanics (QM/MM) study on Glycinamide ribonucleotide transformylase (GAR Tfase) catalytic mechanism are presented. The results indicate a direct one-carbon unit transfer process but not a stepwise mechanism in this reaction. The residues near the active center can fix the cofactor (N10-formyltetrahydrofolate) and GAR in proper relative positions by a H-bond network. The transition state and the minimum energy pathway are located on the potential energy surface. After all the residues (including H₂O molecules) are removed from the system the activation energy has increased from 145.1 kJ/mol to 243.3 kJ/mol, and the formly transfer reaction is very hard to achieve. The interactions between coenzyme, GAR and residues near the reactive center are discussed as well.     

Molecular structure study of 1,2,3-trimethyldiaziridine by means of gas electron diffraction method

The molecular structure of 1,2,3-trimethyldiaziridine has been determined from the gas-phase electron diffraction data supplemented spectral and quantum chemical calculations. The configuration of studied compound incorporates trans-position of methyl groups attached to nitrogen atoms of diaziridine cycle. The following principal structural parameters were determined (r_h1 bond lengths in Å, bond angles in degrees with 3σ in parentheses): r(N–C), 1.489(9); r(N–N), 1.480(15); r(C–C), 1.503(15); ∠NCN, 61.5(9); ∠(H₃C)CN, 124.0(15). The obtained structural parameters of 1,2,3-trimethyldiaziridine were compared with those for structural analogues. The gaseous standard enthalpy of formation of 1,2,3-trimethyldiaziridine was estimated to be 176.2?±?5.0 kJ/mol.

     

DFT Study on the Gold(I)-Catalyzed Dehydrogenative Heterocyclization of 2-(1-Alkynyl)-2-alken-1-ones to form 2,3-Furan-Fused Carbocycles: Effects of Additives C5H5NO vs. PhNO

A computational study with the M06/B3LYP density functional is carried out to explore the effects of additives C₅H₅NO vs. PhNO on the gold-catalyzed dehydrogenative heterocyclization of 2-(1-alkynyl)-2-alken-1-ones to form 2,3-furan-fused carbocycles. The following three conclusions are obtained based on our theoretical calculations. (a) The Au(I) catalyst plays a crucial role on the intramolecular cyclization reaction. (b) Both additives C₅H₅NO and PhNO as the proton shuttle can assist proton-transfer through a two-step proton-transfer mechanism including the protonation of additive and the deprotonation of additive-H⁺, whereas the catalytic capability of PhNO is weaker than that of C₅H₅NO (energy barrier: 90.6 vs. 33.2 kJ/mol). (c) C₅H₅NO-H⁺ has stronger stability comparing with PhNO-H⁺ because the basicity of C₅H₅NO is stronger than that of PhNO, which cause that the energy barrier of ts3 + PhNO-H⁺ (131.5 kJ/mol) is higher than that of ts3 + C₅H₅NO-H⁺ (60.5 kJ/mol) in the intermolecular addition. Therefore, the base strength is the primary factor that controls the catalytic capability of additives C₅H₅NO vs. PhNO. These studies are expected to improve our understanding of Au(I)-catalyzed reactions involving additive as the cocatalyst and to provide guidance for the future design of new catalysts and new reactions.     

Can hydridic-to-protonic hydrogen bonds catalyze hydride transfers in biological systems?

Catalysis of hydride transfer by hydridic-to-protonic hydrogen (HHH) bonding in α-hydroxy carbonyl isomerization reactions was examined computationally in the lithium salts of 7-substituted endo-3-hydroxybicyclo[2.2.1]hept-5-en-2-ones. The barrier for intramolecular hydride transfer in the parent system was calculated to be 17.2 kcal/mol. Traditional proton donors, such as OH and NH(3)(+), stabilized the metal cation-bridged transition state by 1.4 and 3.3 kcal/mol, respectively. Moreover, among the conformers of the OH systems, the one in which the proton donor is able to interact with the migrating hydride (H(m)) has an activation barrier lower by 1.3 and 1.7 kcal/mol than the other possible OH conformers. By contrast, the presence of an electronegative group such as F, which disfavors the migration electronically by opposing development of hydridic charge, destabilizes the hydride migration by 1.5 kcal/mol relative to the epimeric exo system. In both ground and transition states the H(m)···H distance decreased with increasing acidity of the proton donor, reaching a minimum of 1.58 ? at the transition state for NH(3)(+). Both Mulliken and NPA charges show enhancement of negative character of the migrating hydride in the cases in which HHH bonding is possible.     

Ab initio study on the mechanism of reaction HNCO+NH2

Ab initio UMP2 and UQCISD(T) calculations, with 6-311G** basis sets, were performed for the titled reactions. The results show that the reactions have two product channels: NH₂+ HNCO?NH₃+NCO (1) and NH₂+HNCO?N₂H₃+CO (2), where reaction (1) is a hydrogen abstraction reaction via an H-bonded complex (HBC), lowering the energy by 32.48 kJ/mol relative to reactants. The calculated QCISD(T)//MP2(full) energy barrier is 29.04 kJ/mol, which is in excellent accordance with the experimental value of 29.09 kJ/mol. In the range of reaction temperature 2300–2700 K, transition theory rate constant for reaction (1) is 1.68×10¹¹–3.29×10¹¹ mL·mol^-1·s^-1, which is close to the experimental one of 5.0×10¹¹mL·mol^-1·s^-1or less. However, reaction (2) is a stepwise reaction proceeding via two orientation modes,cis andtrans, and the energy barriers for the rate-control step at our best calculations are 92.79 kJ/mol (forcis-mode) and 147.43 kJ/mol (fortrans-mode), respectively, which is much higher than reaction (1). So reaction (1) is the main channel for the titled reaction.