Dynamic exit-channel pathways of the microsolvated HOO−(H2O) + CH3Cl SN2 reaction: Reaction mechanisms at the atomic level from direct chemical dynamics simulations

In previous work, ion imaging experiments and direct chemical dynamics simulations with DFT/B97-1 were performed to study the atomic-level dynamics of the F− + CH3I → FCH3 + I− SN2 reaction at different collision energies.

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Chemical Dynamics Simulations of X–+ CH3Y → XCH3+ Y–Gas-Phase SN2 Nucleophilic Substitution Reactions. Nonstatistical Dynamics and Nontraditional Reaction Mechanisms

The Journal of Physical Chemistry A ◽

10.1021/jp211387c ◽

2012 ◽

Vol 116 (12) ◽

pp. 3061-3080 ◽

Cited By ~ 108

Author(s):

Paranjothy Manikandan ◽

Jiaxu Zhang ◽

William L. Hase

Keyword(s):

Nucleophilic Substitution ◽

Gas Phase ◽

Reaction Mechanisms ◽

Chemical Dynamics ◽

Substitution Reactions ◽

Nucleophilic Substitution Reactions ◽

Dynamics Simulations

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A Paramedic Treatment for Modeling Explicitly Solvated Chemical Reaction Mechanisms

10.26434/chemrxiv.6045422.v1 ◽

2018 ◽

Author(s):

Yasemin Basdogan ◽

John Keith

Keyword(s):

Reaction Mechanism ◽

Chemical Reaction ◽

Reaction Mechanisms ◽

Reaction Pathway ◽

Optimization Procedure ◽

Cost Effective ◽

Chemical Reaction Mechanisms ◽

Solvent Molecules ◽

Dynamics Simulations ◽

Mbh Reaction

<div> <div> <div> <p>We report a static quantum chemistry modeling treatment to study how solvent molecules affect chemical reaction mechanisms without dynamics simulations. This modeling scheme uses a global optimization procedure to identify low energy intermediate states with different numbers of explicit solvent molecules and then the growing string method to locate sequential transition states along a reaction pathway. Testing this approach on the acid-catalyzed Morita-Baylis-Hillman (MBH) reaction in methanol, we found a reaction mechanism that is consistent with both recent experiments and computationally intensive dynamics simulations with explicit solvation. In doing so, we explain unphysical pitfalls that obfuscate computational modeling that uses microsolvated reaction intermediates. This new paramedic approach can promisingly capture essential physical chemistry of the complicated and multistep MBH reaction mechanism, and the energy profiles found with this model appear reasonably insensitive to the level of theory used for energy calculations. Thus, it should be a useful and computationally cost-effective approach for modeling solvent mediated reaction mechanisms when dynamics simulations are not possible. </p> </div> </div> </div>

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A QM/MM Evaluation of the Missing Step in the Reduction Mechanism of HMG-CoA by Human HMG-CoA Reductase

Processes ◽

10.3390/pr9071085 ◽

2021 ◽

Vol 9 (7) ◽

pp. 1085

Author(s):

Paula Mihaljević-Jurič ◽

Sérgio F. Sousa

Keyword(s):

Mevalonate Pathway ◽

Atomic Level ◽

Amino Acid Residues ◽

Protonation State ◽

Primary Target ◽

Cholesterol Levels ◽

The Subject ◽

Electron Reduction ◽

Dynamics Simulations ◽

Coa Reductase

Statins are important drugs in the regulation of cholesterol levels in the human body that have as a primary target the enzyme β-hydroxy-β-methylglutaryl-CoA reductase (HMGR). This enzyme plays a crucial role in the mevalonate pathway, catalyzing the four-electron reduction of HMG-CoA to mevalonate. A second reduction step of this reaction mechanism has been the subject of much speculation in the literature, with different conflicting theories persisting to the present day. In this study, the different mechanistic hypotheses were evaluated with atomic-level detail through a combination of molecular dynamics simulations (MD) and quantum mechanics/molecular mechanics (QM/MM) calculations. The obtained Gibbs free activation and Gibbs free reaction energy (15 kcal mol−1 and −40 kcal mol−1) show that this hydride step takes place with the involvement of a cationic His405 and Lys639, and a neutral Glu98, while Asp715 remains in an anionic state. The results provide an atomic-level portrait of this step, clearly demonstrating the nature and protonation state of the amino acid residues involved, the energetics associated, and the structure and charge of the key participating atoms in the several intermediate states, finally elucidating this missing step.

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