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

Abstract

NMR crystallographic techniques are used to validate a structure of -piroxicam determined from powder X-ray diffraction (PXRD) with a relatively poor R-factor. Geometry optimisation of PXRD-and singlecrystal 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 1 H, 13 C and 15 N chemical shifts and 14 N quadrupolar parameters. Calculations on isolated molecules combined with 2D magic-angle spinning (MAS) 1 H doublequantum (DQ) and 14 N-1 H NMR experiments confirm the 3D packing arrangement of -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.

NMR Crystallography of the Polymorphs of Metergoline

“…This approach was the subject of recent reviews by Ashbrook et al [5] and by Bryce [6]. Additionally, some of its notable applications were most recently discussed by Brown et al [7] and by Emsley et al [8]. Our group successfully employed NMR crystallography in the structural elucidation/refinement of framework materials [9], bioactive compounds [10], and drugs [11][12][13].…”

Resolving alternative organic crystal structures using density functional theory and NMR chemical shifts

“…Such structural relaxation is particularly valuable where structures have been derived from powder diffraction, either as part of the renement process, 30,31 or, for example, to conrm the validity of structures which are potentially suspect as suggested by high R factors. 32 Measurement of 13 C and 1 H NMR chemical shis is only needed in the relatively small number of cases where the structural relaxation results in different local minima, and where the differences are structurally signicant, Fig. 3 (a, top) Overlaid full-cell geometry-optimised crystal structures of SANYIP and SANYIP02 show minor differences apart from the position of the hydrogen atom of a hydroxyl group (this H atom is highlighted in magenta for SANYIP).…”

14N1H HMQC Solid-State NMR as a Powerful Tool to Study Amorphous Formulations – an Exemplary Study of Paclitaxel Loaded Polymer Micelles

“…29 So far, the majority of 14 N-1 H HMQC experiments was acquired for highly ordered, crystalline compounds. 28,[30][31][32][33][34][35][36][37][38][39] In contrast, disordered systems with significant differential dynamics are more challenging systems and there are thus very seldom reports employing the 14 N-1 H HMQC experiment for their characterization. However, the characterization of disordered and amorphous materials could substantially benefit from the additional 14 N second-order isotropic quadrupolar shifts (see SI for detailed equations) as opposed to the 15 N isotropic chemical shifts alone.…”