Revving up 13C NMR shielding predictions across chemical space: benchmarks for atoms-in-molecules kernel machine learning with new data for 134 kilo molecules

Abstract

The requirement for accelerated and quantitatively accurate screening of nuclear magnetic resonance spectra across the small molecules chemical compound space is two-fold: (1) a robust ‘local’ machine learning (ML) strategy capturing the effect of the neighborhood on an atom’s ‘near-sighted’ property—chemical shielding; (2) an accurate reference dataset generated with a state-of-the-art first-principles method for training. Herein we report the QM9-NMR dataset comprising isotropic shielding of over 0.8 million C atoms in 134k molecules of the QM9 dataset in gas and five common solvent phases. Using these data for training, we present benchmark results for the prediction transferability of kernel-ridge regression models with popular local descriptors. Our best model, trained on 100k samples, accurately predicts isotropic shielding of 50k ‘hold-out’ atoms with a mean error of less than 1.9 ppm. For the rapid prediction of new query molecules, the models were trained on geometries from an inexpensive theory. Furthermore, by using a Δ-ML strategy, we quench the error below 1.4 ppm. Finally, we test the transferability on non-trivial benchmark sets that include benchmark molecules comprising 10–17 heavy atoms and drugs.