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Successful strategy for high degree of freedom crystal structure determination from powder X-ray diffraction data: a case study for selexipag form I with 38 DOF

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    0507836 - ÚMCH 2020 RIV US eng J - Journal Article
    Hušák, M. - Jegorov, A. - Czernek, Jiří - Rohlíček, J. - Žižková, S. - Vraspír, P. - Kolesa, P. - Fitch, A. - Brus, Jiří
    Successful strategy for high degree of freedom crystal structure determination from powder X-ray diffraction data: a case study for selexipag form I with 38 DOF.
    Crystal Growth & Design. Roč. 19, č. 8 (2019), s. 4625-4631. ISSN 1528-7483. E-ISSN 1528-7505
    R&D Projects: GA MŠk(CZ) LTAUSA18011
    Institutional support: RVO:61389013
    Keywords : powder X-ray diffraction * DFT methods
    Subject RIV: CF - Physical ; Theoretical Chemistry
    OECD category: Physical chemistry
    Impact factor: 4.089, year: 2019
    Method of publishing: Limited access
    https://pubs.acs.org/doi/10.1021/acs.cgd.9b00517

    The determination of crystal structures from powder X-ray diffraction (PXRD) data by using direct-space methods is significantly limited by the degrees of conformational freedom (DOF). This limit currently lies between 30 and 40 DOF. Novel strategies are thus continuously being developed to allow an increase in DOF while keeping computational time reasonable. In our contribution, we demonstrate the solution of the crystal structure of selexipag, a drug for the treatment of pulmonary arterial hypertension (PAH), from PXRD data using synchrotron radiation. With 38 DOF, this structure is one of the most complex organic molecular structures that was actually solved ab initio from powder diffraction data. As the structure solution problem was on the edge of the current methodological possibilities, we applied an advanced strategy using a combination of restraints from the Cambridge Structural Database (CSD), optimized simulated annealing (SA) parameters, and parallel code execution, all complemented by DFT-D calculations and analysis of solid-state NMR (ss-NMR) parameters. Thus, we present here a novel integrated approach that applies several techniques in conjunction to provide otherwise unavailable structural information.
    Permanent Link: http://hdl.handle.net/11104/0298863

     
     
Number of the records: 1