Organic NMR crystallography: enabling progress for applications to pharmaceuticals and plant cell walls

Abstract

The application of NMR crystallography to organic molecules is exemplified by two case studies. For the tosylate salt of the active pharmaceutical ingredient, Ritlectinib, solid-state NMR spectra are presented at a ¹H Larmor frequency of 1 GHz and a magic-angle spinning (MAS) frequency of 60 kHz. Specifically, ¹⁴N–¹H heteronuclear multiple-quantum coherence (HMQC) and ¹H–¹H double-quantum (DQ) single-quantum (SQ) correlation experiments are powerful probes of hydrogen bonding interactions. A full assignment of the ¹H, ¹³C and ¹⁴N/¹⁵N chemical shifts is achieved using also ¹H–¹³C cross polarization (CP) HETCOR spectra together with gauge-including projector augmented wave (GIPAW) DFT calculation for the geometry-optimised X-ray diffraction crystal structure that is reported here (CCDC 2352028). In addition, GIPAW calculations are presented for the ¹³C chemical shifts in the two polymorphs of cellulose for which diffraction structures are available. For both case studies, a focus is on the discrepancy between experiment and GIPAW calculation.