scholarly journals Nonperfect Synchronization of Reaction Center Rehybridization in the Transition State of the Hydride Transfer Catalyzed by Dihydrofolate Reductase

2005 ◽  
Vol 127 (42) ◽  
pp. 14879-14886 ◽  
Author(s):  
Jingzhi Pu ◽  
Shuhua Ma ◽  
Mireia Garcia-Viloca ◽  
Jiali Gao ◽  
Donald G. Truhlar ◽  
...  
Keyword(s):  
Transition State ◽  
Reaction Center ◽  
Dihydrofolate Reductase ◽  
Hydride Transfer

scholarly journals The role of enzyme dynamics and tunnelling in catalysing hydride transfer: studies of distal mutants of dihydrofolate reductase

2006 ◽  
Vol 361 (1472) ◽  
pp. 1307-1315 ◽  
Author(s):  
Lin Wang ◽  
Nina M Goodey ◽  
Stephen J Benkovic ◽  
Amnon Kohen
Keyword(s):  
Temperature Dependence ◽  
Dihydrofolate Reductase ◽  
Isotope Effects ◽  
Hydride Transfer ◽  
Activation Parameters ◽  
Physical Nature ◽  
Enzyme Dynamics ◽  
Temperature Dependences ◽  
Donor Acceptor ◽  
Significant Temperature

Residues M42 and G121 of Escherichia coli dihydrofolate reductase ( ec DHFR) are on opposite sides of the catalytic centre (15 and 19 Å away from it, respectively). Theoretical studies have suggested that these distal residues might be part of a dynamics network coupled to the reaction catalysed at the active site. The ec DHFR mutant G121V has been extensively studied and appeared to have a significant effect on rate, but only a mild effect on the nature of H-transfer. The present work examines the effect of M42W on the physical nature of the catalysed hydride transfer step. Intrinsic kinetic isotope effects (KIEs), their temperature dependence and activation parameters were studied. The findings presented here are in accordance with the environmentally coupled hydrogen tunnelling. In contrast to the wild-type (WT), fluctuations of the donor–acceptor distance were required, leading to a significant temperature dependence of KIEs and deflated intercepts. A comparison of M42W and G121V to the WT enzyme revealed that the reduced rates, the inflated primary KIEs and their temperature dependences resulted from an imperfect potential surface pre-arrangement relative to the WT enzyme. Apparently, the coupling of the enzyme's dynamics to the reaction coordinate was altered by the mutation, supporting the models in which dynamics of the whole protein is coupled to its catalysed chemistry.

scholarly journals Kinetics and mechanism of acyl transfer reactions. Part 15. Quantumchemicalsimulation of mechanisms of reactions of N-ethylaniline sulfonation

2019 ◽  
Vol 57 (2) ◽  
pp. 19-27
Author(s):  
Ludmila B. Kochetova ◽  
◽  
Tatiana P. Kustova ◽  
Keyword(s):  
Water Molecule ◽  
Transition State ◽  
Reaction Center ◽  
Three Dimensional ◽  
Axial Direction ◽  
Acyl Transfer ◽  
Nucleophilic Attack ◽  
Specific Solvation ◽  
Benzenesulfonyl Chloride ◽  
Trigonal Bipyramidal

The RHF/6-31G(d) quantum chemical simulation of the mechanism of the interaction of the secondary fatty aromatic amine N-ethylaniline with benzenesulfonyl chloride under conditions of non-specific water solvation, using the continuum model of the solvent, as well as of sulfonylation reactions of N-ethylaniline solvation complexes containing one water molecule, modeled specific solvation of N-ethylaniline with water, and one molecule of water and one of dioxane, which simulate the solvation of the amine with aqueous dioxane. Three-dimensional potential energy surface of these processes is calculated. It is shown that in the case of a reaction proceeding under conditions of non-specific solvation of reagents, the route with axial attack of the N-ethylaniline molecule to the sulfonyl reaction center is realized, in the two other cases the reactions proceed along a single route, starting as an axial attack of the nucleophile, which goes further with decreasing of the attack angle as reagent molecules approach each other. It was established that all the simulated reactions proceed in accordance with bimolecular coordinated mechanism of nucleophilic substitution SN2, which implies the formation of a single transition state in the reaction path. It was found that geometrical configuration of the reaction center in the transition state of N-ethylaniline reaction with benzenesulfonyl chloride under non-specific solvation by water is close to trigonal-bipyramidal, which is determined by the axial direction of the nucleophilic attack, in the two other cases it is medium between the trigonal-bipyramidal and tetragonal-pyramidal, which is associated with the change in the angle of N-ethylaniline attack as the reactant molecules approach each other. In a reaction involving N-ethylaniline monohydrate, a water molecule forms a 6-membered cyclic structure with reagent molecules in the transition state, in which the transfer of a proton from N-ethylaniline amino group to a hydrogen chloride molecule occurs via a relay mechanism involving the water molecule. The activation energy values of the studied processes were calculated; it is shown that both specific and universal solvation significantly lower the energy barrier of the reaction compared to the reaction occurring in gas phase, which is consistent with the data obtained earlier for related processes.

Kinetics and mechanism of acyl transfer reactions. Part 16. Quantum chemical simulation of mechanism of N-methylaniline sulfonation in aqueous 1,4-dioxane

2020 ◽  
Vol 61 (1) ◽  
pp. 1-8
Author(s):  
Ludmila B. Kochetova ◽  
◽  
Tatiana P. Kustova ◽  
Keyword(s):  
Water Molecule ◽  
Transition State ◽  
Reaction Center ◽  
Quantum Chemical ◽  
Acyl Transfer ◽  
Nucleophilic Attack ◽  
Quantum Chemical Simulation ◽  
Specific Solvation ◽  
Benzenesulfonyl Chloride ◽  
Chemical Simulation

The RHF/6-31G(d) quantum chemical simulation of the mechanism of the secondary fatty aromatic amine N-methylaniline interaction with benzenesulfonyl chloride under conditions of N-methylaniline specific solvation by one water molecule and one 1,4-dioxane molecule, and under conditions of N-methylaniline specific solvation by two water molecules and one 1,4-dioxane molecule. Three-dimensional potential energy surfaces of the processes pointed out are computed. It is shown that in the both cases a single route of the reactions is realized, starting as an axial nucleophilic attack, which goes further with decreasing of the attack angle as reagent molecules approach each other. It was established that both simulated reactions proceed in accordance with bimolecular concerted mechanism of nucleophilic substitution SN2, which implies the formation of a single transition state in the reaction path. It was found that geometrical configuration of the reaction center in the transition states of the reactions is medium between the trigonal-bipyramidal and tetragonal-pyramidal, which is associated with the change in the angle of N-methylaniline attack as the reactant molecules approach each other. In the benzenesulfonyl chloride reaction with N-methylaniline, solvated by one water molecule and one 1,4-dioxane molecule, the transition state is solvated only by 1,4-dioxane molecule, while water molecule moves away from the reaction center, whereas in the benzenesulfonyl chloride reaction with N-methylaniline, solvated by two water molecule and one 1,4-dioxane molecule the transition state is solvated by 1,4-dioxane molecule and one water molecule that forms hydrogen bond with chlorine atom and promote the S–Cl-bond loosening. The activation energies of the reactions were calculated; it is shown that specific solvation increases the reactions energetic barrier as compared with the reaction in gaseous phase, that is caused by the partial dehydratation of N-methylaniline molecule before the transition state formation. A decrease of the activation energy of the reaction with participation of N-methylaniline, solvated by two water molecule and one 1,4-dioxane molecule as compared with the cases of non-specific solvation of the reactants and N-methyl-aniline solvation by one water molecule and one 1,4-dioxane molecule is caused by the existence of the second water molecule in the system, forming a bond with amine group and facilitating N–H bond break.

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