Metadynamics with Discriminants: a Tool for Understanding Chemistry

TL;DR

This paper presents an extension of a method to identify low-dimensional variables for studying chemical reactions, enabling analysis of multiple pathways and reactivity without detailed mechanistic information.

Contribution

The authors introduce a new approach that uses simple equilibrium statistics to study complex chemical reactions and select reaction pathways without prior mechanistic data.

Findings

Analyzed the stereochemistry of SN2 reactions and explained chirality inversion.

Investigated regioselectivity in hydrobromination, linking empirical rules to kinetics.

Demonstrated the method's ability to handle multiple reaction pathways.

Abstract

We introduce an extension of a recently published method\cite{Mendels2018} to obtain low-dimensional collective variables for studying multiple states free energy processes in chemical reactions. The only information needed is a collection of simple statistics of the equilibrium properties of the reactants and product states. No information on the reaction mechanism has to be given. The method allows studying a large variety of chemical reactivity problems including multiple reaction pathways, isomerization, stereo- and regiospecificity. We applied the method to two fundamental organic chemical reactions. First we study the \ce{S_N2} nucleophilic substitution reaction of a \ce{Cl} in \ce{CH_2 Cl_2} leading to an understanding of the kinetic origin of the chirality inversion in such processes. Subsequently, we tackle the problem of regioselectivity in the hydrobromination of propene revealing that the nature of empirical observations such as the Markovinikov's rules lies in the chemical kinetics rather than the thermodynamic stability of the products.