Issue 3, 2021

Machine learning meets mechanistic modelling for accurate prediction of experimental activation energies

Abstract

Accurate prediction of chemical reactions in solution is challenging for current state-of-the-art approaches based on transition state modelling with density functional theory. Models based on machine learning have emerged as a promising alternative to address these problems, but these models currently lack the precision to give crucial information on the magnitude of barrier heights, influence of solvents and catalysts and extent of regio- and chemoselectivity. Here, we construct hybrid models which combine the traditional transition state modelling and machine learning to accurately predict reaction barriers. We train a Gaussian Process Regression model to reproduce high-quality experimental kinetic data for the nucleophilic aromatic substitution reaction and use it to predict barriers with a mean absolute error of 0.77 kcal mol−1 for an external test set. The model was further validated on regio- and chemoselectivity prediction on patent reaction data and achieved a competitive top-1 accuracy of 86%, despite not being trained explicitly for this task. Importantly, the model gives error bars for its predictions that can be used for risk assessment by the end user. Hybrid models emerge as the preferred alternative for accurate reaction prediction in the very common low-data situation where only 100–150 rate constants are available for a reaction class. With recent advances in deep learning for quickly predicting barriers and transition state geometries from density functional theory, we envision that hybrid models will soon become a standard alternative to complement current machine learning approaches based on ground-state physical organic descriptors or structural information such as molecular graphs or fingerprints.

Graphical abstract: Machine learning meets mechanistic modelling for accurate prediction of experimental activation energies

Supplementary files

Article information

Article type
Edge Article
Submitted
04 9 2020
Accepted
02 11 2020
First published
05 11 2020
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY license

Chem. Sci., 2021,12, 1163-1175

Machine learning meets mechanistic modelling for accurate prediction of experimental activation energies

K. Jorner, T. Brinck, P. Norrby and D. Buttar, Chem. Sci., 2021, 12, 1163 DOI: 10.1039/D0SC04896H

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

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