A reaction density functional theory study of the solvent effect in prototype S<sub>N</sub>2 reactions in aqueous solution

Cheng, Cai; Tang, Weiqiang; Qiao, Chongzhi; Peng, Jiang; Lu, Changjie; Zhao, Teng; Liu, Honglai

doi:10.1039/c9cp03888d

Cited by 16 publications

(30 citation statements)

References 53 publications

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“…In this shell, the favoured orientations at any point are globally pointing toward the closest chlorine atom, except in a small region located close to the plane of the bisector of the Cl-Cl bond where the preferred orientations are pointing outward. Thus, the orientations in the first solvation shell are consistent with the usual charge picture of the transition state in which each chlorine is globally anionic and the CH 3 fragment is almost neutral39,49,78 .…”

supporting

confidence: 79%

“…when minimising equation 9 allows to account for the mutual polarisation of the solute and the solvent environment. This is a clear improvement with respect to methods that consist in a single QM calculation in vacuum followed by a single liquid state theory calculation such 10 as RxDFT [38][39][40] . Indeed, such methods neglect the polarisation of the solute by the solvent density which is properly accounted with the present approach.…”

Section: ⌦mentioning

confidence: 99%

“…We examine the reaction free energy of the symmetrical S N 2 reaction between chloromethane and chloride in water. We chose the same reaction coordinate, r, as many other studies 39,49,75,76,78,80 that is the difference between the two carbon chlorine distances r =…”

Section: S N 2 Reactionmentioning

confidence: 99%

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Tackling Solvent Effects by Coupling Electronic and Molecular Density Functional Theory

Jeanmairet

Levesque

Borgis

2020

J. Chem. Theory Comput.

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Solvation effects can have a tremendous influence on chemical reactions. However, precise quantum chemistry calculations are most often done either in vacuum neglecting the role of the solvent or using continuum solvent model ignoring its molecular nature. We propose a new method coupling a quantum description of the solute using electronic density functional theory with a classical grand-canonical treatment of the solvent using molecular density functional theory. Unlike previous work, both densities are minimised self-consistently, accounting for mutual polarisation of the molecular solvent and the solute. The electrostatic interaction is accounted using the full electron density of the solute rather than fitted point charges. The introduced methodology represents a good compromise between the two main strategies to tackle solvation effects 1 in quantum calculation. It is computationally more effective than a direct quantummechanics/molecular mechanics coupling, requiring the exploration of many solvent configurations. Compared to continuum methods it retains the full molecular-level description of the solvent. We validate this new framework onto two usual benchmark systems: a water solvated in water and the symmetrical nucleophilic substitution between chloromethane and chloride in water. The prediction for the free energy profiles are not yet fully quantitative compared to experimental data but the most important features are qualitatively recovered. The method provides a detailed molecular picture of the evolution of the solvent structure along the reaction pathway.

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supporting

confidence: 79%

Section: ⌦mentioning

confidence: 99%

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Tackling Solvent Effects by Coupling Electronic and Molecular Density Functional Theory

Jeanmairet

Levesque

Borgis

2020

J. Chem. Theory Comput.

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“…Nucleophilic substitution, having equation X − + RY → RX + Y − where X = halide, R = alkyl group and Y = leaving group, is an extensively studied reaction, [25][26][27][28][29][30] via a single transition state with a concerted ligand switch. Most theoretical studies have been in the gas phase, 25,26 others in implicit solvent, 27,28 and more recent studies in explicit solvent. 31,32 We employ four different Hamiltonians and three free-energy methods.…”

Section: Introductionmentioning

confidence: 99%

Comparison of Free-Energy Methods to Calculate the Barriers for the Nucleophilic Substitution of Alkyl Halides by Hydroxide

et al. 2020

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Calculating the free energy barriers of liquid-phase chemical reactions with explicit solvent is a considerable challenge. Most methods use the energy and entropy (EE) of minimized single-point geometries of the reactants and transition state in implicit solvent using normal mode analysis (NMA). Explicit-solvent methods instead make use of the potential of mean force (PMF). Here we propose a new EE method to calculate the Gibbs free energy of reactants and transition states in explicit solvent by combining quantum mechanics/molecular mechanics (QM/MM) molecular dynamics simulations with Multiscale Cell Correlation (MCC). We apply it to six nucleophilic substitution reactions of the hydroxide transfer to methyl-and ethyl halides in water, where the halides are F, Cl and Br. We compare EE-MCC Gibbs free energy barriers using two Hamiltonians, self-consistent charge density functional based tight binding (SCC-DFTB) and B3LYP/6-31+G* Density Functional Theory (DFT) with respective PMF values, EE-NMA values using B3LYP/6-31+G* and M06/6-31G* DFT in implicit solvent and experimental values derived via Transition State Theory. The barriers using SCC-DFTB are found to agree well with PMF and experiment and previous computational studies, being slightly higher but improving on the lower values obtained for the implicit solvent. Achieving convergence over many degrees of freedom remains a challenge for EE-MCC in explicit-solvent QM/MM systems, particularly for the more expensive B3LYP/6-31+G* and M06/6-31G* DFT methods, but the insightful decomposition of entropy over all degrees of freedom should make EE-MCC a valuable tool for deepening the understanding of chemical reactions.

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“…The self-consistent optimisation of electronic density ρ e (r) and the solvent density ρ(r, Ω) when minimising equation 8 allows to account for the mutual polarisation of the solute and the solvent environment. This is a clear improvement with respect to methods that consists in single QM calculation in vacuum followed by a single liquid state theory calculation such as RxDFT [38][39][40]. Indeed, such methods neglect the polarisation of the solute by the solvent density which is properly accounted with the present approach.…”

Section: Theorymentioning

confidence: 89%

Tackling solvent effect by coupling electronic and molecular Density Functional Theory

Jeanmairet,

Levesque,

Borgis

2020

Preprint

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Solvation effect might have a tremendous influence on chemical reactions. However, precise quantum chemistry calculations are most often done either in vacuum neglecting the role of the solvent or using continuum solvent model ignoring its molecular nature. We propose a new method coupling a quantum description of the solute using electronic density functional theory with a classical grand-canonical treatment of the solvent using molecular density functional theory. Unlike previous work, both densities are minimised self consistently, accounting for mutual polarisation of the molecular solvent and the solute. The electrostatic interaction is accounted using the full electron density of the solute rather than fitted point charges. The introduced methodology represents a good compromise between the two main strategies to tackle solvation effect in quantum calculation. It is computationally more effective than a direct quantum-mechanics/molecular mechanics coupling, requiring the exploration of many solvent configurations. Compared to continuum methods it retains the full molecular-level description of the solvent. We validate this new framework onto two usual benchmark systems: a water solvated in water and the symmetrical nucleophilic substitution between chloromethane and chloride in water. The prediction for the free energy profiles are not yet fully quantitative compared to experimental data but the most important features are qualitatively recovered. The method provides a detailed molecular picture of the evolution of the solvent structure along the reaction pathway.

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A reaction density functional theory study of the solvent effect in prototype S_N2 reactions in aqueous solution

Abstract: Reaction density functional theory (RxDFT), combining quantum DFT with classical DFT, has been employed to investigate the solvent effect and free energy profiles of SN2 reactions in aqueous solution.

Cited by 16 publications

References 53 publications

Tackling Solvent Effects by Coupling Electronic and Molecular Density Functional Theory

Tackling Solvent Effects by Coupling Electronic and Molecular Density Functional Theory

Comparison of Free-Energy Methods to Calculate the Barriers for the Nucleophilic Substitution of Alkyl Halides by Hydroxide

Tackling solvent effect by coupling electronic and molecular Density Functional Theory

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A reaction density functional theory study of the solvent effect in prototype SN2 reactions in aqueous solution

Abstract: Reaction density functional theory (RxDFT), combining quantum DFT with classical DFT, has been employed to investigate the solvent effect and free energy profiles of SN2 reactions in aqueous solution.

Cited by 16 publications

References 53 publications

Tackling Solvent Effects by Coupling Electronic and Molecular Density Functional Theory

Tackling Solvent Effects by Coupling Electronic and Molecular Density Functional Theory

Comparison of Free-Energy Methods to Calculate the Barriers for the Nucleophilic Substitution of Alkyl Halides by Hydroxide

Tackling solvent effect by coupling electronic and molecular Density Functional Theory

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Product

Resources

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A reaction density functional theory study of the solvent effect in prototype S_N2 reactions in aqueous solution