Steric, Quantum, and Electrostatic Effects on S_N2 Reaction Barriers in Gas Phase

Abstract

Biomolecular nucleophilic substitution reactions, SN2, are fundamental and commonplace in chemistry. It is the well documented experimental finding in the literature that vicinal substitution with bulkier groups near the reaction center significantly slows the reaction due to steric hindrance, but theoretical understanding in the quantitative manner about factors dictating the SN2 reaction barrier height is still controversial. In this work, employing the new quantification approach that we recently proposed for the steric effect from the density functional theory framework, we investigate the relative contribution of three independent effects, steric, electrostatic, and quantum, to the SN2 barrier heights in gas phase for substituted methyl halide systems, R1R2R3CX, reacting with fluorine anion where R1, R2, and R3 denote substituting groups and X=F or Cl. We found that in accordance with the experimental finding, for these systems the steric effect dominates the transition state barrier, contributing positively to barrier heights, but this contribution is largely compensated by the negative, stabilizing contribution from the quantum effect due to the exchange-correlation interactions. Moreover, we find that it is the component from the electrostatic effect that is linearly correlated with the SN2 barrier height for the systems investigated in the present study. In addition, we compared our approach with the conventional method of energy decomposition in density functional theory, as well as examined the steric effect from the wavefunction theory for these systems via the natural bond orbital analysis.

Regioselectivity of catechol O-methyltransferase confers enhancement of catalytic activity

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Synthesis and characterization of ethylenediaminium nitrophenolate

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Computational Study of Chemical Reactivity Using Information-Theoretic Quantities from Density Functional Reactivity Theory for Electrophilic Aromatic Substitution Reactions

“…[19][20][21][22][23][24][25][26][27][28][29][30][31] In this work, we will examine the role of these quantities and relationships for a number of electrophilic aromatic substitution reactions. In particular, we are interested to see (i) what the performance of applying Hirshfeld charge and information gain in predicting the reaction barrier height of these reactions is; (2) whether the electrostatic component is still the dominant contributor to the barrier height; and (3) if there exist similar strong linear correlations from the information-theoretic quantities for these systems with transition state involved.…”

“…At first, we examine the behavior of employing both Hirshfeld charge and information gain as descriptors to predict reaction barrier heights. Secondly, with the tools we recently developed in quantifying chemical effects such as steric effect under the framework of density functional reactivity theory, [19][20][21][22][23][24][25][26][27][28][29][30][31] we decompose the barrier height and determine the energy components that play dominant and indispensable roles in contributing to the barrier heights of these reactions. Finally, we reveal the scaling properties of information-theoretic quantities in these systems with respect to the electronic population at both molecular and atoms-in-molecules levels.…”