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

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61389013%3A_____%2F19%3A00507836" target="_blank" >RIV/61389013:_____/19:00507836 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/60461373:22310/19:43918684

Výsledek na webu

<a href="https://pubs.acs.org/doi/10.1021/acs.cgd.9b00517" target="_blank" >https://pubs.acs.org/doi/10.1021/acs.cgd.9b00517</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1021/acs.cgd.9b00517" target="_blank" >10.1021/acs.cgd.9b00517</a>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10403 - Physical chemistry

Projekt

<a href="/cs/project/LTAUSA18011" target="_blank" >LTAUSA18011: Ab initio studie polymorfismu farmaceuticky aktivních látek podpořená přesnými NMR krystalografickými a kalorimetrickými experimenty</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2019

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Crystal Growth & Design

ISSN

1528-7483

e-ISSN

—

Svazek periodika

19

Číslo periodika v rámci svazku

8

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

7

Strana od-do

4625-4631

Kód UT WoS článku

000480499600047

EID výsledku v databázi Scopus

2-s2.0-85070540180