Angew Chem Int Ed Engl. 2024 Oct 15:e202410308. doi: 10.1002/anie.202410308. Online ahead of print.
ABSTRACT
With the rise of machine learning (ML), the modeling of chemical systems has reached a new era and has the potential to revolutionize how we understand and predict chemical reactions. Here, we probe the historic dependence on utilizing enantiomeric excess (ee) as a target variable and discuss the benefits of using relative Gibbs free activation energies (ΔΔG≠), grounded firmly in transition-state theory, emphasizing practical benefits for chemists. This perspective is intended to discuss best practices that enhance modeling efforts especially for chemists with an experimental background in asymmetric catalysis that wish to explore modelling of their data. We outline the enhanced modeling performance using ΔΔG≠, escaping physical limitations, addressing temperature effects, managing non-linear error propagation, adjusting for data distributions and how to deal with unphysical predictions,in order to streamline modeling for the practical chemist and provide simple guidelines to strong statistical tools. For this endeavor, we gathered ten datasets from the literature covering very different reaction types. We evaluated the datasets using fingerprint-, descriptor-, and graph neural network-based models. Our results highlight the distinction in performance among varying model complexities with respect to the target representation, emphasizing practical benefits for chemists.
PMID:39405467 | DOI:10.1002/anie.202410308
