Exploiting the Synergy of Powder X-ray Diffraction and Solid-State NMR Spectroscopy in Structure Determination of Organic Molecular Solids

[Image: see text] We report a strategy for structure determination of organic materials in which complete solid-state nuclear magnetic resonance (NMR) spectral data is utilized within the context of structure determination from powder X-ray diffraction (XRD) data. Following determination of the crystal structure from powder XRD data, first-principles density functional theory-based techniques within the GIPAW approach are exploited to calculate the solid-state NMR data for the structure, followed by careful scrutiny of the agreement with experimental solid-state NMR data. The successful application of this approach is demonstrated by structure determination of the 1:1 cocrystal of indomethacin and nicotinamide. The (1)H and (13)C chemical shifts calculated for the crystal structure determined from the powder XRD data are in excellent agreement with those measured experimentally, notably including the two-dimensional correlation of (1)H and (13)C chemical shifts for directly bonded (13)C–(1)H moieties. The key feature of this combined approach is that the quality of the structure determined is assessed both against experimental powder XRD data and against experimental solid-state NMR data, thus providing a very robust validation of the veracity of the structure.