Showing papers on "Transition state published in 1998"

Enzymatic Transition States and Transition State Analog Design

Abstract: All chemical transformations pass through an unstable structure called the transition state, which is poised between the chemical structures of the substrates and products. The transition states for chemical reactions are proposed to have lifetimes near 10(-13) sec, the time for a single bond vibration. No physical or spectroscopic method is available to directly observe the structure of the transition state for enzymatic reactions. Yet transition state structure is central to understanding catalysis, because enzymes function by lowering activation energy. An accepted view of enzymatic catalysis is tight binding to the unstable transition state structure. Transition state mimics bind tightly to enzymes by capturing a fraction of the binding energy for the transition state species. The identification of numerous transition state inhibitors supports the transition state stabilization hypothesis for enzymatic catalysis. Advances in methods for measuring and interpreting kinetic isotope effects and advances in computational chemistry have provided an experimental route to understand transition state structure. Systematic analysis of intrinsic kinetic isotope effects provides geometric and electronic structure for enzyme-bound transition states. This information has been used to compare transition states for chemical and enzymatic reactions; determine whether enzymatic activators alter transition state structure; design transition state inhibitors; and provide the basis for predicting the affinity of enzymatic inhibitors. Enzymatic transition states provide an understanding of catalysis and permit the design of transition state inhibitors. This article reviews transition state theory for enzymatic reactions. Selected examples of enzymatic transition states are compared to the respective transition state inhibitors.

Chemical reaction dynamics beyond the born-oppenheimer approximation

Abstract: ▪ Abstract To predict the branching between energetically allowed product channels, chemists often rely on statistical transition state theories or exact quantum scattering calculations on a single adiabatic potential energy surface. The potential energy surface gives the energetic barriers to each chemical reaction and allows prediction of the reaction rates. Yet, chemical reactions evolve on a single potential energy surface only if, in simple terms, the electronic wavefunction can evolve from the reactant electronic configuration to the product electronic configuration on a time scale that is fast compared to the nuclear dynamics through the transition state. The experiments reviewed here investigate how the breakdown of the Born-Oppenheimer approximation at a barrier along an adiabatic reaction coordinate can alter the dynamics of and the expected branching between molecular dissociation pathways. The work reviewed focuses on three questions that have come to the forefront with recent theory and exper...

Transition states for chemical reactions I. Geometry and classical barrier height

Abstract: A new computational procedure for the characterization of transition states for chemical reactions is proposed and tested. Previous calculations have frequently employed a single point high-level energy calculation at a transition state geometry obtained with a less expensive computational method, Energy[Method(1)]//Geom[Method(2)]. If we instead search the “inexpensive” intrinsic reaction coordinate (IRC) for the maximum of Energy[Method(1)] along this reaction path, the resulting “IRCMax method”, Max{Energy[Method(1)]}//IRC{Geom[Method(2)]}, reduces errors in transition state geometries by a factor of 4 to 5, and reduces errors in classical barrier heights by as much as a factor of 10. When applied to the CBS-4, G2(MP2), G2, CBS-Q, and CBS-QCI/APNO model chemistries, the IRCMax method reduces to the standard model for the reactants and products, and gives rms errors in the classical barrier heights for ten atom exchange reactions of 1.3, 1.2, 1.0, 0.6, and 0.3 kcal/mol, respectively.

Quantum theory of chemical reaction dynamics

Abstract: It is now possible to use rigorous quantum scattering theory to perform accurate calculations on the detailed state-to-state dynamics of chemical reactions in the gas phase. Calculations on simple reactions, such as H + D2 → HD + D and F + H2→ HF + H, compete with experiment in their accuracy. Recent advances in theory promise to extend such accurate predictions to more complicated reactions, such as OH + H2 → H2O + H, and even to reactions of molecules on solid surfaces. New experimental techniques for probing reaction transition states, such as negative-ion photodetachment spectroscopy and pump-probe femtosecond spectroscopy, are stimulating the development of new theories.

Effects of the Hydrophobicity of the Reactants on Diels-Alder Reactions in Water

Abstract: To assess the importance of the hydrophobicity of different parts of diene and dienophile on the aqueous acceleration of Diels-Alder reactions, second-order rate constants have been determined for the reactions of cyclopentadiene (1), 2,3-dimethyl-1,3-butadiene (4), and 1,3-cyclohexadiene (6) with N-methyl-, N-ethyl-, N-propyl-, and N-butylmaleimide (2a-d) in different solvents. All these reactions are accelerated in water relative to organic solvents as a result of enhanced hydrogen bonding and enforced hydrophobic interactions during the activation process. The beneficial influence of water as compared to 1-propanol on the rate of the Diels-Alder reaction of 4 with 2a-d increases linearly with the length of the alkyl chain of 2. In contrast, for the reaction of both 1 and 6 with 2a-d, no such effect was observed. This difference can be explained by a hydrophobic interaction between the methyl groups of 4 and the N-alkyl group of 2 during the activation process. In the reactions of 1 and 6, lacking the methyl substituents, this interaction is not possible and elongation of the alkyl chain from ethyl onward does not result in an additional acceleration by water. The enhanced hydrophobicity near the reaction center of dienes 4 and 6 compared to 1 results in an increased aqueous acceleration of the Diels-Alder reactions of the former dienes with 2a. These data indicate that an increase in the hydrophobicity close to the reaction center in the diene has a much more pronounced effect on the rate acceleration in water than a comparable increase in hydrophobicity in the dienophile further away from the reaction center. The Gibbs energies of transfer of initial state and activated complex of the Diels-Alder reactions under study have been determined. As expected, for all reactions the initial state in water is destabilized compared to that in 1-propanol. This destabilization becomes more pronounced when the nonpolar character of diene (close to the reaction center) or dienophile (distant from the reaction center) is increased. Likewise, an increase in the nonpolar character of 2 results in a destabilization of the activated complex. In contrast, addition of methyl or methylene units to the diene is not accompanied by a significant destabilization of the activated complex in water as compared to 1-propanol. We conclude that hydrophobic groups near the reaction center seem to lose their hydrophobic character completely in the activated complex of the Diels-Alder reaction, whereas more distant groups retain their nonpolar character throughout the reaction.

Femtosecond Real-Time Probing of Reactions. 23. Studies of Temporal, Velocity, Angular, and State Dynamics from Transition States to Final Products by Femtosecond-Resolved Mass Spectrometry

Abstract: In this contribution, we give a full account of the approach of femtosecond, time-resolved mass spectrometry in molecular beams for the studies of the elementary steps of complex reactions and the application to different systems. The level of complexity varies from diatomics to polyatomics, from direct-mode to complex-mode, from one-center, to two-center, to four-center, and from uni- to bimolecular reactions. The systems studied are iodine, cyanogen iodide, methyl iodide, iodobenzene, 1,2-diiodotetrafluoroethane, mercury iodide, benzene· iodine complexes, and methyl iodide dimers. By resolving the femtosecond dynamics and simultaneously observing the evolution of velocity, angular, and state distribution(s) of the reaction, we are able to study multiple reaction paths, the nature of transition-state geometry and dynamics, coherent wave-packet motion, evolution of energy disposal, and the nonconcerted motion in multicenter reactions. These phenomena and concepts are elucidated in dissociation, elimination, and charge-transfer reactions and in the inelastic and reactive pathways of bimolecular reactions. Theoretical phenomenology, using frontier orbitals and molecular dynamics, are invoked to provide a relationship between the observed dynamics and molecular structures.

Theoretical Study of the Mechanism of Zeolite-Catalyzed Isomerization Reactions of Linear Butenes

Abstract: Density functional theory is used to study the mechanism of double-bond isomerization and skeletal isomerization of linear butenes catalyzed by a protonated zeolite, which is simulated by a cluster consisting of two Si and one Al tetrahedra. The study includes complete geometry optimization and characterization of reactants, products, reaction intermediates and transition states, and calculation of the activation energies for the different processes involved. It is shown that the double bond isomerization proceeds by a concerted mechanism which does not involve the formation of either ionic or covalent alkoxy intermediates. According to this concerted mechanism, in one step the acid OH group of the zeolite protonates the double bond of adsorbed but-1-ene and the basic neighboring O atom of the cluster abstracts a hydrogen from the olefin, restoring the zeolite active site and yielding adsorbed but-2-ene. However, the mechanism of skeletal isomerization of linear butenes consists of three elementary steps:...

Transition‐state optimization on free energy surface: Toward solution chemical reaction ergodography

Abstract: To obtain a transition state (TS) in solution chemical reaction, a new TS optimization method has been proposed on a multidimensional free energy surface (FES). Analogous to the method for the Born–Oppenheimer potential energy surface using ab initio molecular orbital calculation, the present method utilizes force and Hessian on the FES, which can be calculated by molecular dynamics method and the free energy perturbation theory. Furthermore, on the basis of the method, we have proposed the definition of the intrinsic reaction coordinate (IRC) on the FES. According to not only the estimation of the computational demand but also the comparison of the numerical accuracy, we conclude that our method should be more efficient than such other methods that utilize only the free energy. Finally, it is discussed that the TS optimization and the IRC on the FES should become very important tools to develop a new research field called the solution chemical reaction ergodography. © 1998 John Wiley & Sons, Inc. Int J Quant Chem 70: 95–103, 1998

Interpretation of activation volumes for water exchange reactions revisited : Ab initio calculations for Al3+, Ga3+, and In3+, and new experimental data

Abstract: The water exchange mechanisms on the hexaaqua ions of Al3+, Ga3+, and In3+ in aqueous solution have been modeled by using ab initio calculations at the Hartree−Fock level. As an approximation aqua clusters in vacuo involving seven water molecules were considered. For species with five, six, or seven water molecules in the first coordination shell of the cation, stable intermediates and transition states have been optimized and characterized from vibrational analyses. Water exchange reaction pathways could then be proposed via interconnected intermediates and transition states. The calculations provide theoretical evidence for a break in kinetic behavior between Al3+ and Ga3+ on one side and In3+ on the other. Hexaaqua complexes of Al3+ and Ga3+ show no tendency to increase their coordination number over six and, despite the high positive charge on the central ion, water exchange proceeds via a D mechanism involving a pentacoordinated intermediate [M(OH2)5·(OH2)]3+. This is in agreement with experimental v...

Theoretical Prediction and Experimental Tests of Conformational Switches in Transition States of Diels−Alder and 1,3-Dipolar Cycloadditions to Enol Ethers

Abstract: Transition structures for the cycloadditions of butadiene, acrolein, nitrosoethylene, and methylenenitrone to 1-butene, silyl vinyl ether, and methyl vinyl ether have been located using ab initio RHF theory with the 3-21G basis set and with density functional theory using the Becke3LYP functional and the 6-31G* basis set. The computational results show that there is a switch in the conformation of the enol ether from syn (COCC = 0°), which is favored by 2.3 kcal/mol in the reactant, to anti (COCC = 180°), which is favored by 1.2−6.6 kcal/mol in the various transition structures studied here. The results are consistent with the experimental stereoselectivities in reactions of chiral enol ethers observed by Denmark and Reissig. The preference of the anti conformation in the transition structures is due primarily to electrostatic effects and, to a lesser extent, steric effects. The preference is predicted to be influenced significantly by polar solvents. The magnitude of this preference was calculated theore...

B3LYP-DFT characterization of the potential energy surface of the CH(X 2Π)+C2H2 reaction

Abstract: The potential energy surface for the reaction of doublet methylidyne with acetylene has been investigated in detail using the B3LYP-DFT/6-31G** quantum chemical method. Three barrierless entrance channels lead to the formation of initially highly excited C3H3 radicals, the most stable of which is the 2-propynyl radical (propargyl). Other C3H3 isomers characterized include 1-propynyl, as well as the cyclic structures cycloprop-2-enyl and cycloprop-1-enyl which were not considered in a previous theoretical study by Walch. All identified C3H3 isomers can interconvert via transition states lying well below the entrance and exit channels. The dissociation pathways of the C3H3 radicals leading to various C3H2 isomers+H have been identified. The energetically most favorable of these exit channels was found to be the formation of singlet cyclopropenylidene+H. Other favored routes are formation of triplet prop-2-ynylidene+H and of singlet propadienylidene+H. Also identified are pathways leading to linear-C3H+H2. T...

Olefin Epoxidation by Methyltrioxorhenium: A Density Functional Study on Energetics and Mechanisms.

Abstract: A spiro attack on a peroxo group is calculated to be the preferred reaction pathway for olefin epoxidation with the catalytic system CH3 ReO3 /H2 O2 (see picture). This finding is supported by density functional calculations on more than ten transition states for the most probable mechanisms. Hydration has significant effects on various reaction species: it stabilizes the intermediates and destabilizes, with one exception, the transition states.

On the Reactivity of Ti+(4F,2F). Reaction of Ti+ with OH2

Abstract: The reaction of Ti+(4F,2F) + OH2 has been studied in detail for both doublet and quartet spin states. The only exothermic products are TiO+(2Δ) and H2; formation of several endothermic products is also examined. An in-depth analysis of the reaction paths leading to each of the observed products is given, including various singlet, triplet, and quartet minima, several important transition states, and a discussion of the two H2 elimination mechanisms proposed in the literature. The experimentally observed spin-forbidden crossing is given a possible explanation. Throughout this work comparison to experimental results in energetics, reaction products, and suggested mechanisms has been central.

Rate constant of the HONO + HONO → H2O + NO + NO2 reaction from ab initio MO and TST calculations

Abstract: Kinetics and mechanism for the bimolecular decomposition of HONO have been studied by ab initio molecular orbital (G2M) and transition-state theory calculations. The reaction can take place by the interaction of a cis and a trans isomer or two cis or two trans isomers, via four-, five-, and six-member ring transition states, with decreasing reaction barriers as the size of the ring increases. The lowest energy path with a 13.7 kcal/mol barrier was found to occur by the six-member ring TS1 formed by the reaction of cis- and trans-HONO. A similar six-member ring TS (TS2) formed by two cis isomers has a barrier height of 15.1 kcal/mol, which is very close to the 5-ring TS formed by two trans isomers, 15.7 kcal/mol. The total rate constant computed with the ab initio MO results, including the three reaction channels mentioned above and an additional channel involving a five-member ring TS formed by a cis- and a trans isomer with a 17.7 kcal/mol barrier, can be represented by the three-parameter expression for...

A Model Study of the Enzyme-Catalyzed Cytosine Methylation Using ab Initio Quantum Mechanical and Density Functional Theory Calculations: pKa of the Cytosine N3 in the Intermediates and Transition States of the Reaction

Abstract: The reaction mechanism of the DNA (cytosine-5)-methyltransferase-catalyzed cytosine methylation was investigated using ab initio quantum mechanical (at the MP2/6-31+G*//HF/6-31+G* and MP2/6-31+G*//HF/3-21+G* levels) and density functional theory calculations (Becke3LYP/6-31+G*) in the gas phase and in solution. The effects of aqueous solvation on the reaction energies were included by using an isodensity surface-polarized continuum model. The quantum mechanical model consisted of 1-methylcytosine (the model of the target cytosine), methylthiolate (the model of the side chain of the catalytic cysteine), and trimethylsulfonium (the model of the methyl-donating AdoMet). In addition, an approach is presented to estimate the pKa of the cytosine N3 in the reaction intermediates and transition states and on the calculated reaction profiles. The approach involves calculation of the gas-phase proton affinities and solvation energies of the neutral and protonated forms of the molecules using ab initio quantum mecha...

Amination of Ketene: A Theoretical Study

Abstract: The reactions of NH3, (NH3)2, and (H3N·H2O) with ketene have been studied by ab initio calculations. Attack by the dimer (NH3)2 or by (H3N·H2O) through six-membered cyclic transition states is found to be favored, with a preference of 12.8 kcal/mol for initial addition of (NH3)2 to the CO bond of the ketene giving the enol amide, as compared to initial addition to the CC bond to give the more stable amide directly. These results are in contrast to previous theoretical studies for the reaction of monomeric NH3 with ketene, in which direct addition to the CC bond was reported to be favored, and for the reaction of ketene with (H2O)2, in which addition to the CO bond is calculated to be only 1.9 kcal/mol more favorable than addition to the CC bond. The barrier via 10ts for the NH3-catalyzed rearrangement of the enol amide/ NH3 complex 6 to the amide is 16.5 kcal/mol above that of 6, consistent with the experimental observation of an intermediate in ketene amination, and the barrier for reversion of 6 to the ...

Transition States for Alkane Oxidations by Dioxiranes

Abstract: The mechanism of the oxygen insertion by dioxiranes into alkane C−H bonds has been investigated theoretically. Becke3LYP hybrid DFT calculations with the 6-31G* basis set on the reactions of dioxirane and cyanodioxirane with methane and on the reactions of cyanodioxirane with ethane, propane, and isobutane predict that the reactions are concerted with highly asynchronous transition states. The transition states have considerable diradical character, but are polarized as well. Substituent effects, stereoselectivity, and the possibility of the formation of radical pairs are discussed.

A New Look at the Diels–Alder Transition State

Abstract: The chronology of π-orbital mixing in the Diels-Alder cycloaddition of butadiene and ethylene differs for the two main interactions, the HOMOdiene -LUMOdieneophile and HOMOdienophile -LUMOdiene interactions. The C2-C3 π bond of the cycloadduct is already well developed at the level of the transition state, which is reminiscent of a late transition state.

Variational transition state theory and tunneling calculations with reorientation of the generalized transition states for methyl cation transfer

Abstract: The new RODS algorithm based on optimizing the orientation of the dividing suface at each point along the reaction path in order to maximize the free energy of the generalized transition state containing that point has been used to carry out variational transition state calculations and tunneling calculations for two reactions with high-frequency vibrations strongly coupled to the reaction coordinate, (Cl-)(CH3NH3+) → ClCH3(NH3) and ClCH3 + NH3, and CH3Cl(H2O) + NH3(H2O) → (CH3NH3+)(Cl-)(H2O)2. These reactions, both of which involve the transfer of a methyl cation between Cl- and NH3, show much larger variational-transition-state and tunneling effects than were observed in previous studies of the transfer of methyl cations between anionic centers. However, they are hard to study because the adiabatic potential energy curves of both reactions and, as a consequence, the corresponding free energy of activation profiles show big dips when the minimum energy path (MEP) is followed using standard methods, even ...

Geminal Bond Participation and Reactivities of Z- vs E-1-Substituted Butadienes in the Diels−Alder Reactions

Abstract: A bond model for the transition states of organic reactions was proposed to investigate the interactions of bonds at the transition states. The application to the Diels−Alder reaction between butadiene and ethylene disclosed the significant participation of geminal σ bonds at the reacting centers of the diene. It was found that the electron delocalization from the geminal σ bonds at the Z-positions to the π bond in the dienophile is bonding while that from the σ bonds at the E-positions is antibonding. The finding led to the prediction that electron-donating σ bonds at the Z-positions should enhance the reactivity more than those at the E-positions. The prediction of the relative reactivities of Z- vs E-1-substituted butadienes was confirmed by the calculated activation energies of the reactions.

Factors Governing the Enhanced Reactivity of Five-Membered Cyclic Phosphate Esters

Abstract: Ab initio calculations and continuum dielectric methods have been employed to map out the lowest activation free-energy profiles for the alkaline hydrolysis of a five-membered cyclic phosphate, methyl ethylene phosphate (MEP), its acyclic analog, trimethyl phosphate (TMP), and its six-membered ring counterpart, methyl propylene phosphate (MPP). The rate-limiting step for the three reactions was found to be hydroxyl ion attack at the phosphorus atom of the triester. By performing constrained optimization along the reaction coordinate, defined as the phosphorus to incoming hydroxyl oxygen distance, and computing the solvation free energies of the resulting stationary points, the rate-limiting transition states have been relocated in solution. Dihedral ring constraints in the five-membered ring leading to a more solvent-exposed hydroxyl group and, thus, better solvation of the cyclic transition state compared to its acyclic counter-part was found to be the dominant factor governing the rate enhancement of cy...