Symmetrical Transition State Research Articles

Comparison of the energetics of the uncatalyzed and glutamate dehydrogenase catalyzed .alpha.-imino acid-.alpha.-amino acid interconversion

The thermodynamic and activation parameters for the reduction of delta 1-pyrroline-2-carboxylic acid (an alpha-imino acid) by reduced nicotinamide adenine dinucleotide phosphate (NADPH) are compared with those for the reduction of the same imino acid by the glutamate dehydrogenase-NADPH complex. The enthalpies of activation and standard free energy changes for these two reactions are found to be virtually the same. The catalysis by the enzyme, expressed as the ratio of the reactivity of the enzyme--NADPH complex to that of NADPH itself in reducing the iminium ion, is entirely accounted for by a more favorable entropy of activation with enzyme--NADPH as the reductant. This entropic driving force is large enough to overcome the exergonic formation of the binary complex and still lead to considerable catalysis by glutamate dehydrogenase. Comparison of delta S not equal to and delta So values for the reduction of the iminium ion by NADPH suggests that the solvation of the transition state resembles that of the reactants, even though the substituent effects on rate have shown that the hydride transfer from the reduced coenzyme is complete at the transition state [Srinivasan, R., Medary, R. T., Fisher, H. F., Norris, D. J., & Stewart, R. (1982) J. Am. Chem. Soc. 104, 807]. The delta Go and delta S not equal to/delta So values for the reduction by the enzyme--NADPH complex indicate that this reaction has a fairly symmetric transition state, the solvation properties of which are intermediate between those of the reactants and those of the products.(ABSTRACT TRUNCATED AT 250 WORDS)

Molecular mechanics calculations on aliphatic amines

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTMolecular mechanics calculations on aliphatic aminesS. Profeta Jr. and N. L. AllingerCite this: J. Am. Chem. Soc. 1985, 107, 7, 1907–1918Publication Date (Print):April 1, 1985Publication History Published online1 May 2002Published inissue 1 April 1985https://doi.org/10.1021/ja00293a019RIGHTS & PERMISSIONSArticle Views273Altmetric-Citations141LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (1 MB) Get e-Alerts Get e-Alerts

An MNDO SCF-MO study of the mechanism of the Cannizzaro reaction

The mechanism of the Cannizzaro reaction has been studied using the MNDO SCF-MO method. A hydride transfer between the intermediate (1) to the aldehyde (2)(R =R1=H) was calculated to proceed via a symmetrical transition state with a barrier of 72 kJ mol–1. Alternative mechanisms involving a single-electron transfer between (1) and (2) are predicted to be less favourable, particularly for aliphatic aldehydes. A radical chain mechanism involving a single-electron-transfer step is proposed as an alternative. Mechanisms involving dianions are discussed, in which single-electron transfers are particularly favourable, and radicals such as H˙ should be formed at high pH. Primary hydrogen kinetic isotope effects are calculated for all the steps involving hydrogen transfers and the results discussed in terms of the symmetry and properties of the transition states.

Variation of transition-state structure as a function of the nucleotide in reactions catalyzed by dehydrogenases. 2. Formate dehydrogenase.

Since hydride transfer is completely rate limiting for yeast formate dehydrogenase [Blanchard, J.S., & Cleland, W. W. (1980) Biochemistry 19, 3543], the intrinsic isotope effects on this reaction are fully expressed. Primary deuterium, 13C, and 18O isotope effects in formate and the alpha-secondary deuterium isotope effect at C-4 of the nucleotide have been measured for nucleotide substrates with redox potentials varying from -0.320 (NAD) to -0.258 V (acetylpyridine-NAD). As the redox potential gets more positive, the primary deuterium isotope effect increases from 2.2 to 3.1, the primary 13C isotope effect decreases from 1.042 to 1.036, the alpha-secondary deuterium isotope effect drops from 1.23 to 1.06, and Vmax decreases. The 18O isotope effects increase from 1.005 to 1.008 per single 18O substitution in formate (these values are dominated by the normal isotope effect on the dehydration of formate during binding; pyridinealdehyde-NAD gives an inverse value, possibly because it is not fully dehydrated during binding). These isotope effects suggest a progression toward earlier transition states as the redox potential of the nucleotide becomes more positive, with NAD having a late and acetyl-pyridine-NAD a nearly symmetrical transition state. By contrast, the I2 oxidation of formate in dimethyl sulfoxide has a very early transition state (13k = 1.0154; Dk = 2.2; 18k = 0.9938), which becomes later as the proportion of water in the solvent increases (13k = 1.0265 in 40% dimethyl sulfoxide and 1.0362 in water). alpha-secondary deuterium isotope effects with formate dehydrogenase are decreased halfway to the equilibrium isotope effect when deuterated formate is the substrate, showing that the bending motion of the secondary hydrogen is coupled to hydride transfer in the transition state and that tunneling of the two hydrogens is involved. The 15N isotope effect of 1.07 for NAD labeled at N-1 of the nicotinamide ring suggests that N-1 becomes pyramidal during the reaction. 18O fractionation factors for formate ion relative to aqueous solution are 1.0016 in sodium formate crystal, 1.0042 bound to Dowex-1, and 1.0040 as an ion pair (probably hydrated) in CHCl3. The CO2 analogue azide binds about 10(4) times better than the formate analogue nitrate to enzyme-nucleotide complexes (even though the Ki values for both and the affinity for formate vary by 2 orders of magnitude among the various nucleotides), but the ratio is not sensitive to the redox potential of the nucleotide. Thus, not the nature of the transition state but rather the shape of the initial binding pocket for formate is determining the relative affinity.(ABSTRACT TRUNCATED AT 400 WORDS)

Mechanism of proline transport in Escherichia coli K12. III. Inhibition of membrane potential-driven proline transport by syn-coupled ions and evidence for symmetrical transition states of the 2H+/proline symport carrier.

Specific inhibition of 2H+/proline symport by syn-coupled ions (Na+, Li+, and H+) was investigated using cytoplasmic membrane vesicles prepared from the proline carrier-overproducing strain MinS/ pLC4 -45 of Escherichia coli K12. The 2H+/proline symport driven by the membrane potential generated via respiration with 20 mM ascorbate/Tris, 0.1 mM phenazine methosulfate was specifically inhibited by Na+. The inhibition by Na+ was described by a fully noncompetitive mechanism, and the apparent Ki for Na+ was 15 mM. A linear correlation between the apparent Vmax and the apparent Kd was observed. Li+ stimulated the transport activity 2-fold at 10 mM and inhibited it at concentrations above 50 mM. H+ caused fully noncompetitive inhibition of 2H+/proline symport, and its apparent Ki was 0.6 microM. These results indicate that the concentrations of Na+ and H+ strictly and independently regulate the amount of the active C state carrier responsible for 2H+/proline symport driven by the membrane potential by inhibiting the transition from the C* state carrier which exhibits Na+- and H+-dependent binding of proline and is predominant in nonenergized conditions.

The reinvestigation of the kinetics of the reactions of fluorodi(4-nitrophenyl)ethanes with sodium methoxide in methanol

The procedure previously described for the preparation of 1-fluoro-2,2,-di(4-nitrophenyl)ethane actually yields 1,1,2-tri-(4-nitrophenyl)ethane. 1-Fluoro-2,2-di(4-nitrophenyl)ethane has been prepared and rate constants, isotope effects, and activation parameters for the β-elimination reaction with methoxide ion in methanol are reported. These parameters indicate a concerted E2 mechanism, with a fairly symmetrical transition state. The subsequent dimerization reaction of the olefin product to yield 1,1,3,3-tetra(4-nitrophenyl)butene-1 is described.The reaction of 1,1,1-trifluoro-2,2-di(4-nitrophenyl)ethane with methoxide ion in methanol has been reinvestigated and the reaction of the first product 1,1-difluoro-2,2-di(4-nitrophenyl)ethylene with excess methoxide, to give di(4-nitrophenyl)ketene dimethylacetal in a multistep reaction, is reported.

Central-force models for proton-transfer reactions

A general central-force model is used to calculate free-energy changes and Brönsted exponents for proton-transfer reactions. The exponents assume different values for the separate variations of the acidic and basic reactants, the value being always greater for the former type of variation, and a symmetrical transition state does not correspond to an exponent equal to one-half. The results cast some doubt on the procedure commonly adopted for using the curvature of Brönsted plots to deduce the energy of solvent reorganisation in the transition state.

A unimolecular reaction ABC→A+B+C involving three product molecules and a single transition state. Photodissociation of glyoxal: HCOHCO→H2+CO+CO

Following an earlier proposal [Y. Osamura and H. F. Schaefer, J. Chem. Phys. 74, 4576 (1981)], the unimolecular reaction HCOHCO→H2+CO+CO has been examined via nonempirical molecular electronic structure theory. Specifically, the constrained symmetric (point group C2v) transition state for this ABC→A+B+C reaction has been located at several levels of self-consistent-field (SCF) theory. Four different basis sets of contracted Gaussian functions were used: an STO-3G minimum basis, the small split valence 3-21G basis, the standard C(9s 5p/4s 2p) double zeta (DZ) set, and a double zeta plus polarization (DZ+P) basis. Vibrational analyses of the four stationary point structures (all of which are geometrically similar) yield a remarkable variety of results. The STO-3G stationary point has three imaginary vibrational frequencies, 3-21G has one imaginary frequency (and thus is a genuine transition state), while the DZ and DZ+P structures yield two imaginary vibrational frequencies. For the latter two cases, one of the two imaginary vibrations is a very small bending frequency, while the larger frequency clearly connects glyoxal with the three products H2+CO+CO. This suggests the existence of a slightly nonplanar true transition state. To our knowledge such a unimolecular transition state is without precedent. Configuration interaction (CI) suggests that the barrier for this ABC→A+B+C reaction is competitive with that for HCOHCO→H2CO+CO.

Model Calculations of Isotope Effects. IV. Transition State Structures and the Question of Tunnelling in Proton Transfer Reactions

Model calculations of primary hydrogen isotope effects in proton transfer reactions are reported. The geometries and force fields of transition state models have been systematically varied with respect to both reactant-like and product-like character and to tight against loose character. The models include both hypothetical cut-off molecules and 2-nitropropane. Values of kH/kD greater than 17 are calculated for loose, symmetrical transition states in which the sum of the bond orders pertaining to the transferring proton is set at 0.6, and higher than normal values of (ED-EH) and ADIAH are also associated with such transition states. It is suggested that transition state looseness is a consequence of repulsive donor-acceptor steric interactions, and that several sets of experimental results which have hitherto been rationalized by the invocation of proton tunnelling may equally well be explained by postulating loose transition states.

Large kinetic isotope effects with unsymmetrical transition states

The results of a series of calculations for a wide, unrestricted variation in the force constants for the making and breaking bonds and their interaction constant are presented for the abstraction reactions of CH 2D 2 with Cl atoms. A wide range of asymmetrical force constants leads to a high kinetic isotope effect as has been pointed out by others for a more restricted range of consideration. These results pointedly contradict the assumed connection between a high kinetic isotope effect and a symmetrical transition state. It is found by examining the atomic displacements of the normal mode that the motion of the H or D atom in the real stretch of the transition state will often have little influence on the isotope effect because the mode can be dominated by end group motions. It is further found that a 3-center model multiplied by a constant factor to account for the contributions of the other vibrations is capable of very satisfactorily reproducing the more rigorous 6-center calculations.

Calculations of steric effects. Part 3. The anion-catalysed substitution of alkylmercury(II) bromides by mercury(II) bromide in ethanol

The steric effect of a neopentyl (Pe) group compared with that of the methyl group has been calculated for both the one-bromide ion and two-bromide ion catalysed reactions of alkylmercury(II) bromides with mercury(II)bromides in ethanol. For the case of one-anion catalysis, calculations were carried out with three model transition states, an open model, an unsymmetrical cyclic model with one bridging bromide ion, and the symmetrical bicyclic model with two bridging bromide ions suggested by Jensen and Rickborn. It is shown that only the Jensen and Rickborn model yields calculated rate ratios kPe/kMe that are in accord with experiment. Calculations on the two-anion catalysed reactions were carried out on a symmetrical cyclic transition state with one bridging bromide ion, and good agreement between calculated and observed rate ratios was obtained.

Determination of molecular symmetries by force field calculations and evaluation of symmetric and nonsymmetric conformational transition states avoiding complete point-by-point mapping

In connection with the application of force field calculations to the derivation of molecular symmetries some remarks of caution are given. Frequently used energy minimisation procedures cannot decrease molecular symmetries; only an increase of symmetry can occur. This phenomenon can be used for the calculation of symmetric conformational transition states without using point-by-point mapping techniques. A procedure for the economic calculation of general conformational transition states is described which avoids exhaustive mapping of interconversion paths.

Existence of symmetric transition states for cycloaddition reactions

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTExistence of symmetric transition states for cycloaddition reactionsJames W. McIver Jr.Cite this: J. Am. Chem. Soc. 1972, 94, 13, 4782–4783Publication Date (Print):June 1, 1972Publication History Published online1 May 2002Published inissue 1 June 1972https://doi.org/10.1021/ja00768a085RIGHTS & PERMISSIONSArticle Views76Altmetric-Citations18LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (282 KB) Get e-Alerts Get e-Alerts

SN2 Reactions in Dipolar Aprotic Solvents. Chlorine Isotopic Exchange Reactions of 2-Arylethyl Chlorides, Chloromethyl Aryl Ethers, and Chloromethyl Aryl Sulfides in Acetonitrile

Abstract The SN2 reactions having a symmetrical transition state were studied in a dipolar aprotic solvent. A good Hammett correlation was found for the chlorine isotopic exchange reactions in acetonitrile between tetraethylammonium chloride and three types of substituted methyl chlorides, 2-arylethyl chlorides, chloromethyl aryl ethers, and chloromethyl aryl sulfides. The reaction constant was positive for 2-arylethyl chlorides and negative for the methyl chlorides possessing an α-heteroatom. The presence of oxygen and sulfur atom on the α-position to the reaction center resulted in a rate enhancement of about 105 times and 103 times, respectively. Features of the transition states of these SN2 reactions are discussed.

Computations on quantum-mechanical tunnelling in proton-transfer reactions in solution

Experimental data on six proton-transfer reactions are fitted, with the aid of computer programmes, to the theoretical equations for quantum-mechanical tunnelling through parabolic energy barriers (with ΔH°= 0). Values for the widths and heights of energy-barriers calculated for various reactions are compared. A correlation is noted between the ΔpK of the reaction, which is related to the symmetry of the transition state, and the difference in barrier-heights for H+- and D+-transfer, which is related to the zero-point energies of the vibrations involving H or D in the transition state. When the ΔpK is zero, indicating a symmetrical transition state, the difference in barrier-heights reaches a maximum value of around 1.1 kcal mole–1, indicating that the zero-point energies in the transition state are small.

Model calculations of primary hydrogen isotope effects

Model calculations of primary hydrogen isotope effects for four and five-centre transition states, taking account of bending vibrations and proton tunnelling, are reported. The results reinforce those based on consideration of stretching vibrations alone, and suggest that both zero-point energy and tunnelling contributions are at a maximum for a symmetrical transition state. For proton transfer to halide ions, large isotope effects persist for product-like transition states owing to the low frequency of hydrogen bending vibrations. Swain's relation between deuterium and tritium isotope effects is well obeyed. It seems better to consider the reaction co-ordinate mode for an atom transfer reaction as deriving from a translation rather than from a vibration in the reactants.

Kinetic protium‐deuterium isotope effect in an intramolecular 1–5 shift of hydrogen

AbstractThe thermal isomerization of 5,8‐dideuterocycloocta‐1,3,6‐triene to the 1,3,5‐isomer has been studied. From the rate, as compared with that of the unlabelled compound, and from the distribution of the label in the rearranged material, values were obtained for the primary and secondary kinetic isotope effects. The large value of 5.0 at 120° for the former tallies with a nearly symmetrical transition state.