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

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 <sup>1</sup>H and <sup>13</sup>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 <sup>1</sup>H and <sup>13</sup>C chemical shifts for directly bonded <sup>13</sup>C–<sup>1</sup>H moieties. The key feature of this combined approach is that the quality of the structure determined is assessed <i>both</i> against experimental powder XRD data <i>and</i> against experimental solid-state NMR data, thus providing a very robust validation of the veracity of the structure.