Startseite Challenging structure determination from powder diffraction data: two pharmaceutical salts and one cocrystal with Z′ = 2
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Challenging structure determination from powder diffraction data: two pharmaceutical salts and one cocrystal with Z′ = 2

  • Carina Schlesinger , Michael Bolte und Martin U. Schmidt EMAIL logo
Veröffentlicht/Copyright: 15. November 2018
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Zeitschrift für Kristallographie - Crystalline Materials
Aus der Zeitschrift Zeitschrift für Kristallographie - Crystalline Materials Band 234 Heft 4

Abstract

Structure solution of molecular crystals from powder diffraction data by real-space methods becomes challenging when the total number of degrees of freedom (DoF) for molecular position, orientation and intramolecular torsions exceeds a value of 20. Here we describe the structure determination from powder diffraction data of three pharmaceutical salts or cocrystals, each with four molecules per asymmetric unit on general position: Lamivudine camphorsulfonate (1, P 21, Z=4, Z′=2; 31 DoF), Theophylline benzamide (2, P 41, Z=8, Z′=2; 23 DoF) and Aminoglutethimide camphorsulfonate hemihydrate [3, P 21, Z=4, Z′=2; 31 DoF (if the H2O molecule is ignored)]. In the salts 1 and 3 the cations and anions have two intramolecular DoF each. The molecules in the cocrystal 2 are rigid. The structures of 1 and 2 could be solved without major problems by DASH using simulated annealing. For compound 3, indexing, space group determination and Pawley fit proceeded without problems, but the structure could not be solved by the real-space method, despite extensive trials. By chance, a single crystal of 3 was obtained and the structure was determined by single-crystal X-ray diffraction. A post-analysis revealed that the failure of the real-space method could neither be explained by common sources of error such as incorrect indexing, wrong space group, phase impurities, preferred orientation, spottiness or wrong assumptions on the molecular geometry or other user errors, nor by the real-space method itself. Finally, is turned out that the structure solution failed because of problems in the extraction of the integrated reflection intensities in the Pawley fit. With suitable extracted reflection intensities the structure of 3 could be determined in a routine way.

Keywords: pharmaceutical compound; powder diffraction data; real-space method; structure determination

Acknowledgements

The authors thank Jacco van de Streek (Avant-garde Materials Simulation, Merzhausen) for finally solving structure 3 from powder diffraction data and helpful discussions, Franziska Fischer (formerly at Bundesanstalt für Materialforschung, Berlin) for indexing, structure solution and Rietveld refinement of compound 2. Silke D. Gumbert, Lukas Tapmeyer and Isolda M. Stais are acknowledged for the crystallisation and Edith Alig (all of them Goethe University, Frankfurt) for recording the X-ray powder patterns of 1 and 3. The authors thank Christoph Saal (Merck KGaA, Darmstadt) for providing the starting materials for 1 and 3. Carina Schlesinger thanks the Fond der Chemischen Industrie for a generous scholarship.

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Supplementary Material

The online version of this article offers supplementary material (https://doi.org/10.1515/zkri-2018-2093).

Received: 2018-05-02
Accepted: 2018-10-24
Published Online: 2018-11-15
Published in Print: 2019-04-24

©2019 Walter de Gruyter GmbH, Berlin/Boston

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  2. Graphical Synopsis
  3. Inorganic Crystal Structures
  4. Density functional theory calculations of merohedric twinning in KLiSO4
  5. Low-temperature anharmonicity and symmetry breaking in the sodalite |Na8I2|[AlSiO4]6
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  10. Challenging structure determination from powder diffraction data: two pharmaceutical salts and one cocrystal with Z′ = 2
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https://doi.org/10.1515/zkri-2018-2093
Schlagwörter für diesen Artikel
pharmaceutical compound; powder diffraction data; real-space method; structure determination

Artikel in diesem Heft

  1. Frontmatter
  2. Graphical Synopsis
  3. Inorganic Crystal Structures
  4. Density functional theory calculations of merohedric twinning in KLiSO4
  5. Low-temperature anharmonicity and symmetry breaking in the sodalite |Na8I2|[AlSiO4]6
  6. Crystal structure and in vitro antimicrobial activity studies of Robustic acid and other Alpinumisoflavones isolated from Millettia thonningii
  7. The symmetry origin of the austenite-cementite orientation relationships in steels
  8. Organic and Metalorganic Crystal Structures
  9. Structural features of uranyl acrylate complexes with s-, p-, and d-monovalent metals
  10. Challenging structure determination from powder diffraction data: two pharmaceutical salts and one cocrystal with Z′ = 2
  11. Synthesis of CdSe/ZnS@HPU-2 composites for highly sensitive and multicolor florescence response to Fe3+
  12. Letter
  13. Structure of solid chlorine at 1.45 GPa
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