Synergy of Solid-State NMR, Single-Crystal X-ray Diffraction, and Crystal Structure Prediction Methods: A Case Study of Teriflunomide (TFM)
Tomasz Pawlak, Isaac Sudgen, Grzegorz Bujacz, Dinu Iuga, Steven P. Brown, Marek J. Potrzebowski
Abstract
= 2 molecules, while in the room-temperature structure, there is disorder that is modeled with ∼50% occupancy between torsion angles of -7.8 and 28.6°. These observations are consistent with a broad energy minimum as revealed by DFT calculations. PISEMA solid-state NMR experiments show a reduction in the C-H dipolar coupling in comparison to the static limit for the aromatic CH moieties of 75% and 51% at 20 and 40 °C, respectively, that is indicative of ring flips at the higher temperature. Our study shows the power of combining experiments, namely DSC, X-ray diffraction, and MAS NMR, with DFT calculations and CSP to probe and understand the solid-state landscape, and in particular the role of dynamics, for pharmaceutical molecules.