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.
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.
References
[1] W. I. F. David, Powder diffraction: least-squares and beyond. J. Res. Natl. Inst. Stand. Technol.2004, 109, 107.10.6028/jres.109.008Search in Google Scholar
[2] W. I. F. David, K. Shankland, Structure determination from powder diffraction data. Acta Crystallogr.2008, A64, 52.10.1093/acprof:oso/9780199205530.001.0001Search in Google Scholar
[3] M. U. Schmidt, M. Ermrich, R. E. Dinnebier, Determination of the structure of the violet pigment C22H12Cl2N6O4 from a non-indexed X-ray powder diagram. Acta Crystallogr.2005, B61, 37.10.1107/S010876810402693XSearch in Google Scholar
[4] E. F. Paulus, F. J. J. Leusen, M. U. Schmidt, Crystal structures of quinacridones. CrystEngComm.2007, 9, 131.10.1039/B613059CSearch in Google Scholar
[5] S. Habermehl, P. Mörschel, P. Eisenbrandt, S. M. Hammer, M. U. Schmidt, Structure determination from powder data without prior indexing, using a similarity measure based on cross-correlation functions. Acta Crystallogr.2014, B70, 347.10.1107/S2052520613033994Search in Google Scholar
[6] W. I. F. David, K. Shankland, L. B. McCusker, C. Bärlocher, Structure determination from powder diffraction data. International Union of Crystallography Monographs on Crystallography 13, Oxford Science Publications, Oxford, England, 2006.10.1093/acprof:oso/9780199205530.001.0001Search in Google Scholar
[7] K. D. M. Harris, M. Tremayne, Crystal structure determination from powder diffraction data. Chem. Mater.1996, 8, 2554.10.1021/cm960218dSearch in Google Scholar
[8] K. D. M. Harris, M. Tremayne, B. M. Kariuki, Contemporary advances in the use of powder X-ray diffraction for structure determination. Angew. Chem. Int. Ed.2001, 40, 1626.10.1002/1521-3773(20010504)40:9<1626::AID-ANIE16260>3.0.CO;2-7Search in Google Scholar
[9] R. Černý, V. Favre-Nicolin, Direct space methods of structure determination from powder diffraction: principles, guidelines and perspectives. Z. Kristallogr.2007, 222, 105.10.1524/zkri.2007.222.3-4.105Search in Google Scholar
[10] P. Fernandes, K. Shankland, A. J. Florence, N. Shankland, A. Johnston, Solving molecular crystal structures from X-ray powder diffraction data: the challenges posed by gamma-carbamazepine and chlorothiazide N,N-dimethylformamide (1/2) solvate. J. Pharm. Sci.2007, 96, 1192.10.1002/jps.20942Search in Google Scholar
[11] A. J. Florence, N. Shankland, K. Shankland, W. I. F. David, E. Pidcock, X. Xu, A. Johnston, A. R. Kennedy, P. J. Cox, J. S. O. Evans, G. Steele, S. D. Cosgrove, C. S. Frampton, Solving molecular crystal structures from laboratory X-ray powder diffraction data with DASH: the state of the art and challenges. J. Appl. Crystallogr.2005, 38, 249.10.1107/S0021889804032662Search in Google Scholar
[12] S. O. Nilsson Lill, C. M. Widdifield, A. Pettersen, A. Svensk Ankarberg, M. Lindkvist, P. Aldred, S. Gracin, N. Shankland, K. Shankland, S. Schantz, L. Emsley, Elucidating an amorphous form stabilization mechanism for tenapanor hydrochloride: crystal structure analysis using X-ray diffraction, NMR crystallography, and molecular modeling. Mol. Pharmaceutics2018, 15, 1476.10.1021/acs.molpharmaceut.7b01047Search in Google Scholar
[13] Y. Benhamou, E. Dohin, F. Lunel-Fabiani, T. Poynard, J. M. Huraux, C. Katlama, P. Opolon, M. Gentilini, Efficacy of lamivudine on replication of hepatitis B virus in HIV-infected patients. Lancet1995, 345, 396.10.1016/S0140-6736(95)90388-7Search in Google Scholar
[14] K. E. Gale, Treatment of advanced breast cancer with Aminoglutethimide: a 14-year experience. Cancer Res. (Suppl.)1982, 42, 3389s.Search in Google Scholar
[15] C. Schlesinger, L. Tapmeyer, S. D. Gumbert, D. Prill, M. Bolte, M. U. Schmidt, C. Saal, Absolute configuration of pharmaceutical research compounds determined by X-ray powder diffraction. Angew. Chem.2018, 130, 9289; Angew. Chem. Int. Ed.2018, 57, 9150.10.1002/anie.201713168Search in Google Scholar PubMed
[16] L. Hendeles, M. Weinberger, Theophylline. A “state of the art” review. Pharmacotherapy1983, 3, 2.10.1002/j.1875-9114.1983.tb04531.xSearch in Google Scholar PubMed
[17] F. Fischer, M. U. Schmidt, S. Greisera, F. Emmerling, The challenging case of the theophylline-benzamide cocrystal. Acta Crystallogr.2016, C72, 217.10.1107/S2053229616002643Search in Google Scholar PubMed
[18] Stoe & Cie: WinXPow (Computer Software), Darmstadt, 2005.Search in Google Scholar
[19] A. Boultif, D. Louër, Indexing of powder diffraction patterns for low-symmetry lattices by the successive dichotomy method. J. Appl. Crystallogr.1991, 24, 987.10.1107/S0021889891006441Search in Google Scholar
[20] W. I. F. David, K. Shankland, J. van de Streek, E. Pidcock, W. D. S. Motherwell, J. C. Cole, DASH: a program for crystal structure determination from powder diffraction data. J. Appl. Crystallogr.2006, 39, 910.10.1107/S0021889806042117Search in Google Scholar
[21] E. A. Kabova, J. C. Cole, O. Korb, M. López-Ibánez, A. C. Williams, K. Shankland, Improved performance of crystal structure solution from powder diffraction data through parameter tuning of a simulated annealing algorithm. J. Appl. Crystallogr.2017, 50, 1411.10.1107/S1600576717012602Search in Google Scholar
[22] C. R. Groom, I. J. Bruno, M. P. Lightfood, S. C. Ward, The Cambridge structural database. Acta Crystallogr.2016, B72, 171.10.1016/B978-0-12-409547-2.02529-4Search in Google Scholar
[23] H. M. Rietveld, A profile refinement method for nuclear and magnetic structures. J. Appl. Crystallogr.1969, 2, 65.10.1107/S0021889869006558Search in Google Scholar
[24] R. A. Young, The Rietveld Method, International Union of Crystallography and Oxford Science Publications,Oxford Science Publication, Oxford, England, 1995.Search in Google Scholar
[25] A. A. Coelho, TOPAS and TOPAS-Academic: an optimization program integrating computer algebra and crystallographic objects written in C++. J. Appl. Crystallogr.2018, 51, 210.10.1107/S1600576718000183Search in Google Scholar
[26] G. S. Pawley, Unit-cell refinement from powder diffraction scan. J. Appl. Crystallogr.1981, 14, 357.10.1107/S0021889881009618Search in Google Scholar
[27] Stoe & Cie, X-AREA. Diffractometer control program system. Stoe & Cie, Darmstadt, Germany, 2002.Search in Google Scholar
[28] G. M. Sheldrick, Crystal structure refinement with SHELXL. Acta Crystallogr.2008, A64, 112.10.1107/S0108767307043930Search in Google Scholar PubMed
[29] S. Parsons, H. D. Flack, T. Wagner, Absolute structure determination using CRYSTALS. Acta Crystallogr.2013, B69, 249.10.1107/S2052519213010014Search in Google Scholar
[30] D. W. M. Hofmann, Fast estimation of crystal densities. Acta Crystallogr.2002, B58, 489.10.1107/S0108768101021814Search in Google Scholar
[31] A. D. Bond, Automated derivation of structural class symbols and extended Z’ descriptors for molecular crystal structures in the Cambridge Structural Database. CrystEngComm.2008, 10, 411.10.1039/b800642cSearch in Google Scholar
[32] V. K. Belsky, O. N. Zorkaya, P. M. Zorky, Structural classes and space groups of organic homomolecular crystals: new statistical data. Acta Crystallogr.1995, A51, 473.10.1107/S0108767394013140Search in Google Scholar
[33] I. J. Bruno, J. C. Cole, M. Kessler, J. Luo, W. D. S. Motherwell, L. H. Purkis, B. R. Smith, R. Taylor, R. I. Cooper, S. E. Harris, A. G. Orpen, Retrieval of crystallographically-derived molecular geometry information. J. Chem. Inf. Comput. Sci.2004, 44, 2133.10.1021/ci049780bSearch in Google Scholar PubMed
[34] E. A. Kabova, J. C. Cole, O. Korb, A. C. Williams, K. Shankland, Improved crystal structure solution from powder diffraction data by the use of conformational information. J. Appl. Crystallogr.2017, 50, 1421.10.1107/S1600576717012596Search in Google Scholar
[35] S. L. Bekö, S. D. Thoms, J. Brüning, E. Alig, J. van de Streek, A. Lakatos, C. Glaubitz, M. U. Schmidt, X-ray powder diffraction, solid-state NMR and dispersion-corrected DFT calculations to investigate the solid state structure of 2-ammonio-5-chloro-4-methylbenzenesulfonate. Z. Kristallogr.2010, 225, 382.10.1524/zkri.2010.1259Search in Google Scholar
[36] S. L. Bekö, C. Czech, M. A. Neumann, M. U. Schmidt, Determination of crystal structures and tautomeric states of 2-ammoniobenzenesulfonates by laboratory X-ray powder diffraction. Z. Kristallogr.2015, 230, 611.10.1515/zkri-2015-1845Search in Google Scholar
[37] M. Tremayne, Presentation, 27th European Crystallographic Meeting2012, Bergen.Search in Google Scholar
[38] A. J. Markvardsen, W. I. F. David, J. C. Johnson, K. Shankland, A probabilistic approach to space-group determination from powder diffraction data. Acta Crystallogr.2001, A57, 47.10.1107/S0108767300012174Search in Google Scholar PubMed
[39] S. N. Ivashevskaya, J. van de Streek, J. E. DJanhan, J. Brüning, E. Alig, M. Bolte, M. U. Schmidt, P. Blaschka, H. W. Höffken, P. Erk, Structure determination of seven phases and solvates of Pigment Yellow 183 and Pigment Yellow 191 from X-ray powder and single-crystal data. Acta Crystallogr.2009, B65, 212.10.1107/S0108768109001827Search in Google Scholar PubMed
[40] M. U. Schmidt, S. Brühne, A. K. Wolf, A. Rech, J. Brüning, J. Glinemann, J. van de Streek, F. Gozzo, M. Brunelli, F. Stowasser, T. Gorelik, E. Mugnaioli, U. Kolb, Electron diffraction, X-ray powder diffraction and pair-distribution-function analyses to determine the crystal structures of Pigment Yellow 213, C23H21N5O9. Acta Crystallogr.2009, B65, 189.10.1107/S0108768109003759Search in Google Scholar PubMed
[41] W. I. F. David, On the equivalence of Rietveld method and the correlated integrated intensities method in powder diffraction. J. Appl. Crystallogr.2004, 37, 621.10.1107/S0021889804013184Search in Google Scholar
[42] C. F. Macrae, P. R. Edgington, P. McCabe, E. Pidcock, G. P. Shields, R. Taylor, M. Towler, J. van de Streek, Mercury: visualization and analysis of crystal structures. J. Appl. Crystallogr.2006, 39, 453.10.1107/S002188980600731XSearch in Google Scholar
Supplementary Material
The online version of this article offers supplementary material (https://doi.org/10.1515/zkri-2018-2093).
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Articles in the same Issue
- Frontmatter
- Graphical Synopsis
- Inorganic Crystal Structures
- Density functional theory calculations of merohedric twinning in KLiSO4
- Low-temperature anharmonicity and symmetry breaking in the sodalite |Na8I2|[AlSiO4]6
- Crystal structure and in vitro antimicrobial activity studies of Robustic acid and other Alpinumisoflavones isolated from Millettia thonningii
- The symmetry origin of the austenite-cementite orientation relationships in steels
- Organic and Metalorganic Crystal Structures
- Structural features of uranyl acrylate complexes with s-, p-, and d-monovalent metals
- Challenging structure determination from powder diffraction data: two pharmaceutical salts and one cocrystal with Z′ = 2
- Synthesis of CdSe/ZnS@HPU-2 composites for highly sensitive and multicolor florescence response to Fe3+
- Letter
- Structure of solid chlorine at 1.45 GPa