Electron diffraction determines molecular absolute configuration in a pharmaceutical nanocrystal

0519611 - FZÚ 2020 RIV US eng J - Článek v odborném periodiku
Brázda, Petr - Palatinus, Lukáš - Babor, M.
Electron diffraction determines molecular absolute configuration in a pharmaceutical nanocrystal.
Science. Roč. 364, č. 6441 (2019), s. 667-669. ISSN 0036-8075. E-ISSN 1095-9203
Grant CEP: GA MŠMT(CZ) LO1603; GA ČR GA16-10035S
GRANT EU: European Commission(CZ) CZ.2.16/3.1.00/24510
Institucionální podpora: RVO:68378271
Klíčová slova: organic molecules * drug development * data-collection * nanocrystalline material * electron diffraction * crystal structure
Obor OECD: Condensed matter physics (including formerly solid state physics, supercond.)
Impakt faktor: 41.846, rok: 2019
Způsob publikování: Omezený přístup
https://doi.org/10.1126/science.aaw2560

Determination of the absolute configuration of organic molecules is essential in drug development and the subsequent approval process. We show that this determination is possible through electron diffraction using nanocrystalline material. Ab initio structure determination by electron diffraction has so far been limited to compounds that maintain their crystallinity after a dose of one electron per square angstrom or more. We present a complete structure analysis of a pharmaceutical cocrystal of sofosbuvir and L-proline, which is about one order of magnitude less stable. Data collection on multip le positions of a crystal and an advanced-intensity extraction procedure enabled us to solve the structure ab initio. We further show that dynamical diffraction effects are strong enough to permit unambiguous determination of the absolute structure of material composed of light scatterers.

Trvalý link: http://hdl.handle.net/11104/0304603