Importance of Nuclear Quantum Effects for NMR Crystallography

The resolving power of solid-state nuclear magnetic resonance (NMR) crystallography depends heavily on the accuracy of computational predictions of NMR chemical shieldings of candidate structures, which are usually taken to be local minima in the potential energy. To test the limits of this approximation, we systematically study the importance of finite-temperature and quantum nuclear fluctuations for H-1, C-13, and N-15 shieldings in polymorphs of three paradigmatic molecular crystals: benzene, glycine, and succinic acid. The effect of quantum fluctuations is comparable to the typical errors of shielding predictions for static nuclei with respect to experiments, and their inclusion improves the agreement with measurements, translating to more reliable assignment of the NMR spectra to the correct candidate structure. The use of integrated machine-learning models, trained on first-principles energies and shieldings, renders rigorous sampling of nuclear fluctuations affordable, setting a new standard for the calculations underlying NMR structure determinations.