Crystal Structures of Two Important Pharmaceuticals Solved by 3D Precession Electron Diffraction Tomography

The crystal structures of two important marketed pharmaceuticals, namely, ramelteon (RAM) and tolvaptan (TOL), were determined for the first time using 3D precession electron diffraction tomography (PEDT) on 500 nm-sized crystals. The results were compared with the same structures determined by sing...

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Bibliographic Details
Published in:Organic process research & development 2018-10, Vol.22 (10), p.1365-1372
Main Authors: Das, Partha P, Mugnaioli, Enrico, Nicolopoulos, Stavros, Tossi, Camilla, Gemmi, Mauro, Galanis, Athanasios, Borodi, Gheorghe, Pop, Mihaela M
Format: Article
Language:English
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Summary:The crystal structures of two important marketed pharmaceuticals, namely, ramelteon (RAM) and tolvaptan (TOL), were determined for the first time using 3D precession electron diffraction tomography (PEDT) on 500 nm-sized crystals. The results were compared with the same structures determined by single-crystal X-ray diffraction on subsequently grown 50–200 μm single crystals, indicating a good match of molecular conformation, crystal packing, and unit cell parameters. The X-ray crystal structures were used to validate the developed workflow of data acquisition and structure solution with electron diffraction. This study highlights that 3D PEDT alone is able to provide accurate crystal structures from pharmaceutical nanocrystals that will suffice for most practical applications when no larger crystals can be grown.
ISSN:1083-6160
1520-586X
DOI:10.1021/acs.oprd.8b00149