Homogeneous catalyst graph neural network: A human-interpretable graph neural network tool for ligand optimization in...

Optimization of metal-ligand asymmetric catalysts is usually done by empirical trials, where the ligand is arbitrarily modified, and the new catalyst is re-evaluated in the lab. This procedure is not efficient and alternative strategies are highly desirable. We propose the Homogeneous Catalyst Graph Neural Network (HCat-GNet), a machine learning model capable of aiding ligand optimization. This method trains models to predict the enantioselectivity of asymmetric reactions using only the SMILES representations of the participant molecules. HCat-GNet allows high interpretability indicating from which atoms the model gathers the most predictive information, thus showing which atoms within the ligand most affect the increase or decrease in the reaction's selectivity. The validation of the model's selectivity predictions is made using a new class of ligand for rhodium-catalyzed asymmetric 1,4-addition, demonstrating the ability of HCat-GNet to extrapolate into unknown chiral ligand space. Validation with other benchmark asymmetric reaction datasets demonstrates its generality when modeling different reactions.