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

0507836 - ÚMCH 2020 RIV US eng J - Článek v odborném periodiku
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
Grant CEP: GA MŠMT(CZ) LTAUSA18011
Institucionální podpora: RVO:61389013
Klíčová slova: powder X-ray diffraction * DFT methods
Obor OECD: Physical chemistry
Impakt faktor: 4.089, rok: 2019
Způsob publikování: Omezený přístup
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.
Trvalý link: http://hdl.handle.net/11104/0298863