Transition state

About: Transition state is a research topic. Over the lifetime, 4978 publications have been published within this topic receiving 117965 citations. The topic is also known as: transition state of elementary reaction.

Testing electrostatic complementarity in enzyme catalysis: hydrogen bonding in the ketosteroid isomerase oxyanion hole.

Abstract: A longstanding proposal in enzymology is that enzymes are electrostatically and geometrically complementary to the transition states of the reactions they catalyze and that this complementarity contributes to catalysis. Experimental evaluation of this contribution, however, has been difficult. We have systematically dissected the potential contribution to catalysis from electrostatic complementarity in ketosteroid isomerase. Phenolates, analogs of the transition state and reaction intermediate, bind and accept two hydrogen bonds in an active site oxyanion hole. The binding of substituted phenolates of constant molecular shape but increasing p K a models the charge accumulation in the oxyanion hole during the enzymatic reaction. As charge localization increases, the NMR chemical shifts of protons involved in oxyanion hole hydrogen bonds increase by 0.50–0.76 ppm/p K a unit, suggesting a bond shortening of ˜0.02 A/p K a unit. Nevertheless, there is little change in binding affinity across a series of substituted phenolates (ΔΔG = −0.2 kcal/mol/p K a unit). The small effect of increased charge localization on affinity occurs despite the shortening of the hydrogen bonds and a large favorable change in binding enthalpy (ΔΔH = −2.0 kcal/mol/p K a unit). This shallow dependence of binding affinity suggests that electrostatic complementarity in the oxyanion hole makes at most a modest contribution to catalysis of ˜300-fold. We propose that geometrical complementarity between the oxyanion hole hydrogen-bond donors and the transition state oxyanion provides a significant catalytic contribution, and suggest that KSI, like other enzymes, achieves its catalytic prowess through a combination of modest contributions from several mechanisms rather than from a single dominant contribution.

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.

Variable reaction coordinate transition state theory: Analytic results and application to the C2H3+H→C2H4 reaction

Abstract: A novel derivation is provided for the canonical, microcanonical, and energy E and total angular momentum J resolved reactive flux within the variable reaction coordinate transition state theory (VRC-TST) formalism. The use of an alternative representation for the reaction coordinate velocity yields a new expression for the kinematic factor which better illustrates its dependence on the pivot point location, and which can be straightforwardly evaluated. Also, the use of a geometric approach in place of an earlier algebraic one clarifies the derivation as does the use of Lagrange multiplier methodology for the analytic integration over the total angular momentum. Finally, a quaternion representation for the fragment and line-of-centers orientations is employed in place of the Euler angle or internal/external rotational coordinates used in prior studies. The result is an efficient, and particularly easy to implement, methodology for performing variable reaction coordinate transition state theory calculations. Furthermore, the simplicity of the derivation allows for the straightforward generalization to alternative forms for the dividing surface, as is illustrated by deriving the expressions for the cases of elliptical and planar dividing surfaces. Application to the C2H3+H reaction yields results for the total rate coefficient that are generally only 15% greater than those obtained from related trajectory simulations, thereby demonstrating the accuracy of the VRC-TST formalism. Meanwhile, results for the two separate addition channels (frontside and backside) illustrate the difficulty of accurately apportioning the total flux and particularly the inadequacy of canonical predictions for the channel specific optimized dividing surfaces.

The nature of the transition state for enzyme-catalyzed phosphoryl transfer. Hydrolysis of O-aryl phosphorothioates by alkaline phosphatase.

Abstract: There has been much speculation that enzymes change the nature of the transition state for phosphoryl transfer from the dissociative transition state observed in solution reactions to an associative transition state at the enzyme's active site. This proposal can be tested by comparing linear free energy relationships (LFERs) for nonenzymatic and enzymatic reactions, provided that the specificity of the enzyme's binding site does not perturb the dependence of rate on the intrinsic reactivity of a series of substrates. The shallow binding groove of Escherichia coli alkaline phosphatase (AP) and its wide specificity suggest that this enzyme may be suited for such an approach. A second requirement of this approach is that the actual chemical step is rate-limiting. Comparisons of the reactions of aryl phosphorothioates and aryl phosphates support the previous conclusion that a nonchemical step limits kc,$& for reactions of aryl phosphates, but suggest that the chemical cleavage step is rate-limiting for the aryl phosphorothioates. We therefore determined the dependence of the rate of AP-catalyzed cleavage of a series of aryl phosphorothioates on the intrinsic reactivity of the substrates. The large negative values of group = -0.8 for the enzymatic reaction (kcat/&) and - 1.1 for the nonenzymatic hydrolysis reaction suggest that there is considerable dissociative character in both the enzymatic and nonenzymatic transition states. Despite the wide specificity of AP, certain substrates deviate from the LFER, underscoring that extreme care is required in applying LFERs to enzymatic reactions. The large negative value of Pleaving pup suggests that AP can achieve substantial catalysis via a transition state with dissociative character,

A Periodic DFT Study of Isobutene Chemisorption in Proton-Exchanged Zeolites: Dependence of Reactivity on the Zeolite Framework Structure

Abstract: Isobutene chemisorption within proton-exchanged zeolites is investigated using periodic density functional theory method. This allows us to consider the effect of the zeolite micropore dimension to reactivity. The isobutene reaction pathways that proceed through primary and tertiary carbocation-like transition states have been investigated. The results agree with predicted reactivity trends. Activation energies of isobutene chemisorption are estimated to be around 100 and 25 kJ/mol for primary and tertiary transition states, respectively. Destabilization of transition state complexes and products are as observed before. Interestingly, because of the steric constraints, the chemisorbed alkoxy species appeared to become as unstable as protonated hydrocarbons. The more significant result is the correlation of the zeolite micropore dimension with activation energies. Fluctuations of the activation energies are observed as a function of the match of the transition state structures with the zeolite cavities. We...