QM/MM Simulations for Diels−Alder Reactions in Water:  Contribution of Enhanced Hydrogen Bonding at the Transition State to the Solvent Effect†

2002 ◽  
Vol 106 (33) ◽  
pp. 8078-8085 ◽  
Author(s):  
Jayaraman Chandrasekhar ◽  
Shane Shariffskul ◽  
William L. Jorgensen
Keyword(s):  
Hydrogen Bonding ◽  
Transition State ◽  
Solvent Effect ◽  
Diels Alder

scholarly journals Accurate Diels-Alder Energies and Endo Selectivity in Ionic Liquids Using the OPLS-VSIL Force Field

2020 ◽  
Vol 21 (4) ◽  
pp. 1190 ◽  
Author(s):  
Caroline Velez ◽  
Brian Doherty ◽  
Orlando Acevedo
Keyword(s):  
Free Energy ◽  
Ionic Liquid ◽  
Hydrogen Bonding ◽  
Ionic Liquids ◽  
Transition State ◽  
Force Field ◽  
Reaction Medium ◽  
Alder Reaction ◽  
Diels Alder ◽  
Diels Alder Reaction

Our recently developed optimized potentials for liquid simulations-virtual site ionic liquid (OPLS-VSIL) force field has been shown to provide accurate bulk phase properties and local ion-ion interactions for a wide variety of imidazolium-based ionic liquids. The force field features a virtual site that offloads negative charge to inside the plane of the ring with careful attention given to hydrogen bonding interactions. In this study, the Diels-Alder reaction between cyclopentadiene and methyl acrylate was computationally investigated in the ionic liquid 1-butyl-3-methylimidazolium hexafluorophosphate, [BMIM][PF6], as a basis for the validation of the OPLS-VSIL to properly reproduce a reaction medium environment. Mixed ab initio quantum mechanics and molecular mechanics (QM/MM) calculations coupled to free energy perturbation and Monte Carlo sampling (FEP/MC) that utilized M06-2X/6-31G(d) and OPLS-VSIL gave activation free energy barriers of 14.9 and 16.0 kcal/mol for the endo-cis and exo-cis Diels-Alder reaction pathways, respectively (exptl. ΔH‡ of 14.6 kcal/mol). The endo selectivity trend was correctly predicted with a calculated 73% endo preference. The rate and selectivity enhancements present in the endo conformation were found to arise from preferential hydrogen bonding with the exposed C4 ring hydrogen on the BMIM cation. Weaker electronic stabilization of the exo transition state was predicted. For comparison, our earlier ±0.8 charge-scaled OPLS-2009IL force field also yielded a ΔG‡ of 14.9 kcal/mol for the favorable endo reaction pathway but did not adequately capture the highly organized solvent interactions present between the cation and Diels-Alder transition state.

Hydrophobic and Hydrogen-Bonding Effects on the Rate of Diels−Alder Reactions in Aqueous Solution

1996 ◽  
Vol 61 (16) ◽  
pp. 5492-5497 ◽  
Author(s):  
Thomas R. Furlani ◽  
Jiali Gao
Keyword(s):  
Aqueous Solution ◽  
Hydrogen Bonding ◽  
Diels Alder

Solvent effect in the Diels-Alder reaction

1983 ◽  
Vol 93 ◽  
pp. 255-260 ◽  
Author(s):  
L. Pardo ◽  
V. Branchadell ◽  
A. Oliva ◽  
J. Bertrán
Keyword(s):  
Solvent Effect ◽  
Alder Reaction ◽  
Diels Alder ◽  
Diels Alder Reaction

Ab initio Cs transition state for the Diels-Alder reaction of acetylene and butadiene

1990 ◽  
Vol 55 (12) ◽  
pp. 3804-3807 ◽  
Author(s):  
James M. Coxon ◽  
Stephen T. Grice ◽  
Robert G. A. R. Maclagan ◽  
D. Quentin McDonald
Keyword(s):  
Transition State ◽  
Ab Initio ◽  
Alder Reaction ◽  
Diels Alder ◽  
Diels Alder Reaction

Solvent effect on the initial state and transition state of anation of pentaammine-aquachromium(III) ion by thiocyanate

1993 ◽  
Vol 18 (1) ◽  
pp. 110-112 ◽  
Author(s):  
Olga A. ◽  
J�n Benko ◽  
Ol'ga Voll�rov� ◽  
Vladislav Holba
Keyword(s):  
Transition State ◽  
Solvent Effect ◽  
Initial State

Studies of hydrogen bonding—XXVII. NMR studies of hydrogen bonding and solvent effect

1976 ◽  
Vol 32 (4) ◽  
pp. 723-730 ◽  
Author(s):  
Thor Gramstad ◽  
Ole Riis Simonsen
Keyword(s):  
Hydrogen Bonding ◽  
Solvent Effect ◽  
Nmr Studies

scholarly journals A crystallographic study of the Toho-1 β-lactamase acylation mechanism

2014 ◽  
Vol 70 (a1) ◽  
pp. C1207-C1207
Author(s):  
Leighton Coates
Keyword(s):  
Hydrogen Bonding ◽  
Transition State ◽  
Active Site ◽  
Catalytic Mechanism ◽  
Substrate Binding ◽  
Ligand Complex ◽  
Transition State Analog ◽  
Hydrogen Bonding Interactions ◽  
Active Site Region ◽  
Neutron Crystallography

β-lactam antibiotics have been used effectively over several decades against many types of highly virulent bacteria. The predominant cause of resistance to these antibiotics in Gram-negative bacterial pathogens is the production of serine β-lactamase enzymes. A key aspect of the class A serine β-lactamase mechanism that remains unresolved and controversial is the identity of the residue acting as the catalytic base during the acylation reaction. Multiple mechanisms have been proposed for the formation of the acyl-enzyme intermediate that are predicated on understanding the protonation states and hydrogen-bonding interactions among the important residues involved in substrate binding and catalysis of these enzymes. For resolving a controversy of this nature surrounding the catalytic mechanism, neutron crystallography is a powerful complement to X-ray crystallography that can explicitly determine the location of deuterium atoms in proteins, thereby directly revealing the hydrogen-bonding interactions of important amino acid residues. Neutron crystallography was used to unambiguously reveal the ground-state active site protonation states and the resulting hydrogen-bonding network in two ligand-free Toho-1 β-lactamase mutants which provided remarkably clear pictures of the active site region prior to substrate binding and subsequent acylation [1,2] and an acylation transition-state analog, benzothiophene-2-boronic acid (BZB), which was also isotopically enriched with 11B. The neutron structure revealed the locations of all deuterium atoms in the active site region and clearly indicated that Glu166 is protonated in the BZB transition-state analog complex. As a result, the complete hydrogen-bonding pathway throughout the active site region could then deduced for this protein-ligand complex that mimics the acylation tetrahedral intermediate [3].

An Experimental Study of the Solvent Effect on Rate and Selectivity in a Concentrated Diels−Alder Reaction

1999 ◽  
Vol 3 (6) ◽  
pp. 471-475 ◽  
Author(s):  
Madoc Sheehan ◽  
Paul Sharratt
Keyword(s):  
Experimental Study ◽  
Solvent Effect ◽  
Alder Reaction ◽  
Diels Alder ◽  
Diels Alder Reaction
Sign in / Sign up

Export Citation Format

Share Document