Indomethacin Polymorph δ Revealed To Be Two Plastically Bendable Crystal Forms by 3D Electron Diffraction: Correcting a 47-Year-Old Misunderstanding.
Electron Diffraction
Indomethacin
Melt Crystallization
Plasticity
Polymorphism
Structure Elucidation
Journal
Angewandte Chemie (International ed. in English)
ISSN: 1521-3773
Titre abrégé: Angew Chem Int Ed Engl
Pays: Germany
ID NLM: 0370543
Informations de publication
Date de publication:
07 02 2022
07 02 2022
Historique:
received:
04
11
2021
pubmed:
14
12
2021
medline:
22
2
2022
entrez:
13
12
2021
Statut:
ppublish
Résumé
Indomethacin is a clinically classical non-steroidal anti-inflammatory drug that has been marketed since 1965. The third polymorph, Form δ, was discovered by both melt and solution crystallization in 1974. δ-indomethacin cannot be cultivated as large single crystals suitable for X-ray crystallography and, therefore, its crystal structure has not yet been determined. Here, we report the structure elucidation of δ-indomethacin by 3D electron diffraction and reveal the truth that melt-crystallized and solution-crystallized δ-indomethacin are in fact two polymorphs with different crystal structures. We propose to keep the solution-crystallized polymorph as Form δ and name the melt-crystallized polymorph as Form θ. Intriguingly, both structures display plastic flexibility based on a slippage mechanism, making indomethacin the first drug to have two plastic polymorphs. This discovery and correction of a 47-year-old misunderstanding signify that 3D electron diffraction has become a powerful tool for polymorphic structural studies.
Identifiants
pubmed: 34902212
doi: 10.1002/anie.202114985
pmc: PMC9306882
doi:
Substances chimiques
Anti-Inflammatory Agents, Non-Steroidal
0
Indomethacin
XXE1CET956
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e202114985Subventions
Organisme : Vetenskapsrådet
ID : 2017-05333
Organisme : Vetenskapsrådet
ID : 2019-00815
Organisme : Knut och Alice Wallenbergs Stiftelse
ID : 2019.0124
Organisme : Science for Life Laboratory
ID : MicroED@SciLifeLab
Organisme : Guangdong Basic and Applied Basic Research Foundation
ID : 2020A1515010782
Informations de copyright
© 2021 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.
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