Improving Confidence in Crystal Structure Solutions Using NMR Crystallography: The Case of beta-Piroxicam

NMR crystallographic techniques are used to validate a structure of beta-piroxicam determined from powder Xray diffraction (PXRD) with a relatively poor R-factor. Geometry optimization of PXRD- and single-crystal XRD-derived structures results in convergence to the same energy of the structures, with minimal atomic displacements, and good agreement of gauge-included projector augmented wave (GIPAW) calculated and experimentally determined NMR and N-15 chemical shifts, and N-14 quadrupolar H-1, C-13, and N-15 chemical shifts, and N-14 quadrupolar parameters. Calculations on isolated molecules combined with 2D magic-angle spinning (MAS) H-1 double-quantum (DQ) and N-14-H-1 NMR experiments confirm the 3D packing arrangement of beta-piroxicam. NMR crystallography is shown to be an effective means of validating crystal structures that might otherwise be considered sceptically on the basis of diffraction data alone.