Fragment-Based Electronic Structure Approach for Computing Nuclear Magnetic Resonance Chemical Shifts in Molecular Crystals

First-principles chemical shielding tensor predictions play a critical role in studying molecular crystal structures using nuclear magnetic resonance. Fragment-based electronic structure methods have dramatically improved the ability to model molecular crystal structures and energetics using high-level electronic structure methods. Here, a many-body expansion fragment approach is applied to the calculation of chemical shielding tensors in molecular crystals. First, the impact of truncating the many-body expansion at different orders and the role of electrostatic embedding are examined on a series of molecular clusters extracted from molecular crystals. Second, the ability of these techniques to assign three polymorphic forms of the drug sulfanilamide to the corresponding experimental C-13 spectra is assessed. This challenging example requires discriminating among spectra whose C-13 chemical shifts differ by only a few parts per million (ppm) across the different polymorphs. Fragment-based PBE0/6-311+G(2d,p) level chemical shielding predictions correctly assign these three polymorphs and reproduce the sulfanilamide experimental C-13 chemical shifts with 1 ppm accuracy. The results demonstrate that fragment approaches are competitive with the widely used gauge-invariant projector augmented wave (GIPAW) periodic density functional theory calculations.