scispace - formally typeset
Search or ask a question

Showing papers on "Transition state published in 1978"


Journal ArticleDOI
TL;DR: Quantitative studies of the energetics of enzymatic reactions and the corresponding reactions in aqueous solutions indicate that charge stabilization is the most important energy contribution in enzyme catalysis.
Abstract: Quantitative studies of the energetics of enzymatic reactions and the corresponding reactions in aqueous solutions indicate that charge stabilization is the most important energy contribution in enzyme catalysis. Low electrostatic stabilization in aqueous solutions is shown to be consistent with surprisingly large electrostatic stabilization effects in active sites of enzymes. This is established quantitatively by comparing the relative stabilization of the transition states of the reaction of lysozyme and the corresponding reaction is aqueous solution.

418 citations


BookDOI
01 Jan 1978
TL;DR: In this paper, the transition state is used as a basis for the design of enzymic inhibitors for enzyme-catalyzed reaction pathways, and transition state properties in Acyl and Methyl Transfer are investigated.
Abstract: 1 * Scope and Limitations of the Concept of the Transition State- 2 * Catalytic Power and Transition-State Stabilization- 3 * Quantum-Mechanical Approaches to the Study of Enzymic Transition States and Reaction Paths- 4 * Primary Hydrogen Isotope Effects- 5 * Secondary Hydrogen Isotope Effects- 6 * Solvent Hydrogen Isotope Effects- 7 * Heavy-Atom Isotope Effects in Enzyme-Catalyzed Reactions- 8 * Magnetic-Resonance Approaches to Transition-State Structure- 9 * Mapping Reaction Pathways from Crystallographic Data- 10 * Transition-State Properties in Acyl and Methyl Transfer- 11 * Transition States for Hydrolysis of Acetals, Ketals, Glycosides, and Glycosylamines- 12 * Decarboxylations of ?-Keto Acids and Related Compounds- 13 * The Mechanism of Phosphoryl Transfer- 14 * Intramolecular Reactions and the Relevance of Models- 15 * Transition-State Affinity as a Basis for the Design of Enzyme Inhibitors- 16 * Transition-State Theory and Reaction Mechanism in Drug Action and Drug Design- Author Index

236 citations


Journal ArticleDOI
TL;DR: In this paper, it was shown that the reaction coordinate is primarily a reorganization of heavy atoms since proton transfer from one oxygen to another has been shown to generate strongly curved Bronsted plots.
Abstract: The hydrolysis of many ortho esters, and some acetals and ketals, is general acid catalyzed, and in some examples these generate linear Bronsted plots over substantial ranges of catalyst acidity. This suggests that the reaction coordinate is primarily a reorganization of heavy atoms since proton transfer from one oxygen to another has been shown to generate strongly curved Bronsted plots. However, the isotopic fractionation factor for the catalytically active proton in these transition states is substantially less than 1.0; in several examples it is less than 0.5. Such values have been thought to require that the reaction coordinate be largely a motion of the hydrogen giving the low fractionation factor. This dilemma has been resolved by the observation and rationalization of fractionation factors as low as 0.28 for stable, hydrogen bridge-bonded complexes, AHA/sup -/. A similar, bounded coordinate is now suggested for the catalytically active protons in question. This permits the reaction coordinate to be pictured. 3 figures, 2 tables.

34 citations


Journal ArticleDOI
TL;DR: In this paper, two research groups have used heavy atom leaving group kinetic isotope effects to determine how the structure of an SN2 transition state is affected by a change in solvent.
Abstract: Two research groups have used heavy atom leaving group kinetic isotope effects to determine how the structure of an SN2 transition state is affected by a change in solvent. Two completely different...

27 citations


Journal ArticleDOI
TL;DR: In this paper, the BEBO method is used to calculate the energy of a quasi-thermodynamic cycle with six steps involved: desolvation and escape into the gas phase of MeX; desolation and escape of Nu- ; loss of an electron from Nu-; combination of Nu+MeX with MeX(g) to form a methyl radical transfer 'transition state'; placing an electron on the transition state; and transfer of the anionic transition state from the gas to the solvent.
Abstract: Free energies of activation for the reactions: Nu-+MeX → MeNu+X- (Nu = nucleophile, X = halogen) are calculated by a quasi-thermodynamic cycle. The six steps involved are: (i) desolvation and escape into the gas phase of MeX; (ii) desolvation and escape of Nu- ; (iii) loss of an electron from Nu-; (iv) combination of Nu.(g) with MeX(g) to form a methyl radical transfer 'transition state'; (v) placement of an electron on the 'transition state'; (vi) transfer of the anionic transition state from the gas phase to the solvent. The BEBO method is used to calculate the energetics of step (iv), and the BEBO exponents for various Nu and X are calculated from the measured or estimated rates of the symmetrical halide exchanges X-+MeX and Nu-+ MeNu. The energy of the system is plotted as a function of the fractional bond orders of the Nu...C and C...X partial bonds, and ΔG‡ is identified with the maximum value of this energy. An excellent correlation of calculated against experimental results is found for reactions in water and methanol, whilst interactions between polarizable HCONMe2 and polarizable SN2 transition states lead to small but regular discrepancies in HCONMe2. Observed nucleophilic and leaving group orders of reactivity are reproduced, as is the lack of a correlation between reactivity and selectivity. The computed transition state bond orders do not concur with predictions based on the Hammond postulate.

26 citations


Journal ArticleDOI
TL;DR: The regulatory behaviour of monomeric enzymes is discussed in the light of the concept of 'catalytic perfection' proposed by Albery & Knowles, which claims that an enzyme will be catalytically 'perfect' when its catalytic efficiency is maximum.
Abstract: Generalized microscopic reversibility implies that the apparent rate of any catalytic process in a complex mechanism is paralleled by substrate desorption in such a way that this ratio is held constant within the reaction mechanism [Whitehead (1976) Biochem. J. 159, 449--456]. The physical and evolutionary significances of this concept, for both polymeric and monomeric enzymes, are discussed. For polymeric enzymes, generalized microscopic reversibility of necessity occurs if, within the same reaction sequence, the substrate stabilizes one type of conformation of the active site only. Generalized microscopic reversibility suppresses the kinetic co-operativity of the slow transition model [Ainslie, Shill & Neet (1972) J. Biol. Chem. 247, 7088--7096]. This situation is obtained if the free-energy difference between the corresponding transition states of the two enzyme forms is held constant along the reaction co-ordinate. This situation implies that the 'extra costs' of energy (required to pass each energy barrier) that are not covered by the corresponding binding energies of the transition states vary in a similar way along the two reaction co-ordinates. The regulatory behaviour of monomeric enzymes is discussed in the light of the concept of 'catalytic perfection' proposed by Albery & Knowles [(1976) Biochemistry 15, 5631--5640]. These authors claim that an enzyme will be catalytically 'perfect' when its catalytic efficiency is maximum. If this situation occurs for a monomeric enzyme obeying either the slow transition or the mnemonical model, it can be shown that the kinetic co-operativity disappears. In other words, kinetic co-operativity of a monomeric enzyme is 'paid for' at the expense of catalytic efficiency, and the monomeric enzyme cannot be simultaneously co-operative and catalytically very efficient. This is precisely what has been found experimentally in a number of cases.

26 citations


Journal ArticleDOI
TL;DR: In this article, a criterion developed to decide between a bridged and a carbonium ion-like transition state is based on an internal comparison of the series and avoids resorting to external structural scales.

16 citations


Journal ArticleDOI
TL;DR: The effects of high hydraulic pressures on electrode reactions are complex because of the variation of reference electrode potentials with pressure so that only an apparent volume of activation can be directly measured experimentally, and dependence of coverage by adsorbed intermediates such as H, with pressure as mentioned in this paper.
Abstract: The effects of high hydraulic pressures on electrode reactions are complex because of (i) the variation of reference electrode potentials with pressure so that only an apparent volume of activation can be directly measured experimentally, and (ii) dependence of coverage by adsorbed intermediates, such as H, with pressure. Methods of dealing with these problems are treated and the significance of measured apparent volumes of activation for the hydrogen evolution reaction is discussed in terms of the nature of the transition state for proton transfer and neutralization. The negative true volumes of activation found for the cathodic evolution reaction under some conditions are attributed to increasing electrostriction of the proton in the complex as the transition state is formed. The significance of applications to ionic redox reactions is pointed out where pressure effects may be able to distinguish activation associated with long‐range Born polarization from that associated more specifically with reorganization of the primary solvation shell or inner coordination sphere of ions.

12 citations



Journal ArticleDOI
TL;DR: Methyl 4-methyl-5-oxo-hexanoate (4) and methyl 4methyl-6-phenyl-2H-pyran-2-one (6+7) were measured for reactions performed in benzene, diethyl ether, and tetrahydrofuran (with XCI).

9 citations


Journal ArticleDOI
TL;DR: In this paper, the transition states and activation energies for isomerization to cyclobutane-1,3-dione and 2,4-dimethylene- 1, 3-dioxetane were determined.
Abstract: Alternative pathways for the thermolysis of diketene were investigated with a semiempirical SINDO method [1]. Transition states and activation energies for isomerization to cyclobutane-1,3-dione and 2,4-dimethylene-1,3-dioxetane were determined. The dissociation and formation of these three dimers into and from two ketenes was also calculated. The results disclose the possibility of existence of intermediates as well as the fragmentation into further products. Entropy appears as a major factor in this reaction at higher temperature.

Journal ArticleDOI
TL;DR: In this article, the rate constants for the reaction of [Fe(phen)3]2+(phen = 1,10-phenanthroline) with hydroxide ion in methanol-water and acetone-water mixtures were derived from known solubilities of naphthalene in these mixtures.
Abstract: Rate constants at 298 K are reported for the reaction of [Fe(phen)3]2+(phen = 1,10-phenanthroline) with hydroxide ion in methanol–water and acetone–water mixtures. From known solubilities of naphthalene in these mixtures, and using the method of Van Meter and Neumann, the effect of added solvent on the solvation of this iron complex has been calculated. Thence, the kinetic results have been split into the effects of solvent on the initial and transition states. The treatment of Van Meter and Neumann has been extended to an analysis of the effect of solvent on the transition state, using solubility data obtained from 2-naphthol in methanol–water mixtures. The results support a mechanism in which hydroxide attacks initially at the 2(9) position of the co-ordinated phen; considerable interaction between this carbon-bonded hydroxyl group and the central iron atom is indicated.

Book ChapterDOI
01 Jan 1978
TL;DR: The important relationship between enzyme catalysis and the enhanced affinity of an enzyme for its substrate in the transition state was first noted by Pauling in 1948 as mentioned in this paper, and attention has been focused on the design of stable analogs of transition states of enzyme reactions, since the structure of high affinity analogs can provide considerable insight into the structure and energy of enzyme transition states.
Abstract: The important relationship between enzyme catalysis and the enhanced affinity of an enzyme for its substrate in the transition state was first noted by Pauling in 1948.(1) In recent years, attention has been focused on the design of stable analogs of transition states of enzyme reactions, since the structure of high-affinity analogs can provide considerable insight into the structure and energy of enzyme transition states. The factors which give rise to enhanced transition-state analog binding can be complex, however, and many of the analogs which have been tested mimic intermediates rather than true transition states along the enzyme reaction path.(2–5)

Journal ArticleDOI
TL;DR: In this article, the conformational mobility plays a fundamental role in determining the variations of stereospecificity with varying reaction conditions, and the experimental data are interpreted in terms of anchimeric assistance given by the ester group to the reactions of the keto group in conformationally mobile δ-keto esters.

Journal ArticleDOI
TL;DR: The results of kinetic studies on the reaction of polar particles with polyfunctional molecules have been interpreted in terms of a multidipole transition-state model, the parent molecules and the transition states themselves being treated as collections of interacting point dipoles.
Abstract: 1. The results of kinetic studies on the reaction of polar particles with polyfunctional molecules have been interpreted in terms of a multidipole transition-state model, the parent molecules and the transition states themselves being treated as collections of interacting point dipoles. 2. Comparison with experimental data shows that a theoretical treatment based on this model can account for the reduction in rate constant, the increase in the activation energy and the preexponential factor, and the appearance of a compensation effect observed on passing from cumyl peroxide radical reactions with monoatomic esters to cumyl peroxide radical reactions with polyatomic esters.

Journal ArticleDOI
TL;DR: In this paper, the rate constants for the reaction of [Fe(phen)3]2+(phen = 1,10-phenanthroline) with hydroxide ion in methanol-water and acetone-water mixtures were derived from known solubilities of naphthalene in these mixtures.
Abstract: Rate constants at 298 K are reported for the reaction of [Fe(phen)3]2+(phen = 1,10-phenanthroline) with hydroxide ion in methanol–water and acetone–water mixtures. From known solubilities of naphthalene in these mixtures, and using the method of Van Meter and Neumann, the effect of added solvent on the solvation of this iron complex has been calculated. Thence, the kinetic results have been split into the effects of solvent on the initial and transition states. The treatment of Van Meter and Neumann has been extended to an analysis of the effect of solvent on the transition state, using solubility data obtained from 2-naphthol in methanol–water mixtures. The results support a mechanism in which hydroxide attacks initially at the 2(9) position of the co-ordinated phen; considerable interaction between this carbon-bonded hydroxyl group and the central iron atom is indicated.