Quantum-corrected NMR crystallography at scale

Abstract

Structure determination by chemical-shift-driven NMR crystallography relies on comparing chemical shieldings measured in solid-state NMR experiments with simulations. However, computational cost limits the accuracy of shielding predictions, that usually rely on low-level electronic-structure approximations and neglect thermal and quantum mechanical nuclear motion, leading to large errors, especially for highly informative hydrogen-bonded protons. To address these limitations, we introduce a quantum-nuclei-corrected (QNC-NMR) approach. We generate inexpensively quantum ensembles using PET-MOLS, a novel machine-learning learning model of the interatomic potential transferable across molecular crystals. Using them as inputs to a chemical-shift model results in a two-fold improvement of the agreement with experiments for hydrogen-bonded protons, without the need for empirical corrections. The ability to sample structures consistent with the experimental conditions enables further refinement of the shielding model by finetuning it against measured shieldings. The favorable scaling with system size allows similar improvements for amorphous materials that are otherwise inaccessible to explicit DFT simulations.