title: NMR crystallography of ezetimibe co-crystals.
abstract: An efficient, simplified protocol for solvent-drop assisted co-crystal preparation of ezetimibe (a drug for the treatment of primary hypercholesterolemia) with both imidazole and l-proline has been derived. The structures of the white powders were successfully solved via "NMR crystallography" combining solid-state NMR, powder X-ray diffraction and DFT chemical shift computations. Detailed insights into the likely crystallization mechanism were obtained from competition experiments, where efficient co-crystallization was feasible using ezetimibe monohydrate as precursor indicating that the crystal water acts as "molecular catalyst". It was also found that co-crystallization of imidazole is favored over l-proline, thus suggesting a clear preference of neutral hydrogen bonds compared to charge-assisted motifs.
authors.affiliation: Institut für Physikalische Chemie, Westfälische Wilhelms-Universität Münster, Corrensstr. 28, D-48149 Münster, Germany.
authors.forename: David
authors.initials: D
authors.lastname: Lüdeker
authors.affiliation: Institut für Physikalische Chemie, Westfälische Wilhelms-Universität Münster, Corrensstr. 28, D-48149 Münster, Germany. Electronic address: gbrunklaus@uni-muenster.de.
authors.forename: Gunther
authors.initials: G
authors.lastname: Brunklaus
mesh_terms: D018360:Crystallography, X-Ray; D000069438:Ezetimibe / Q000737:chemistry*; D007093:Imidazoles / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008968:Molecular Conformation; D011392:Proline / Q000737:chemistry
chemical_list: D007093:Imidazoles; C029899:imidazole; D011392:Proline; D000069438:Ezetimibe
keywords: Co-crystals; DFT computation; Ezetimibe; Imidazole; NMR crystallography; Pharmaceuticals; Powder X-ray diffraction; Solid-state NMR; l-proline