Does chirality influence the tendency toward cocrystal formation?

Fanny George, Nikolay Tumanov, Bernadette Norberg, Koen Robeyns, Yaroslav Filinchuk, Johan Wouters, Tom Leyssens

Résultats de recherche: Contribution à un journal/une revueArticle

Résumé

We performed a systematic cocrystal search for the enantiopure and racemic version of a selected active pharmaceutical ingredient, expecting that a coformer giving a cocrystal with a single enantiomer will also interact with the racemic mixture since they present identical functional groups prone to cocrystallization. We identified several novel cocrystals of levetiracetam and its racemic equivalent, etiracetam, using a wide variety of nonchiral coformers. Fourteen novel cocrystals of the enantiopure compound were obtained, whereas 18 of the racemic compound were identified. Out of these, 13 share a common coformer. A structural analysis indicates that in most cases the strongest hydrogen bonding interactions occur both in the enantiopure, as well as the racemic cocrystal, whereas van der Waals interactions, or less strong secondary hydrogen bonding interactions, lead to a differentiation of the final structure. On the basis of our work, we suggest an approach that could lead to a more optimal cocrystal screening of an enantiopure compound, especially when a limited amount of this compound is available. Starting with a screen of the racemic compound, the set of possible coformers for the enantiopure screen can be limited to those yielding a positive hit in the former screen. Doing so, our example shows an increase in efficiency from 10% to 72%.

langue originaleAnglais
Pages (de - à)2880-2892
Nombre de pages13
journalCrystal Growth and Design
Volume14
Numéro de publication6
Les DOIs
étatPublié - 4 juin 2014

Empreinte digitale

etiracetam
Chirality
chirality
Hydrogen bonds
tendencies
Enantiomers
Structural analysis
Drug products
Functional groups
Screening
enantiomers
interactions
hydrogen
structural analysis
ingredients
screening
Pharmaceutical Preparations

Citer ceci

George, Fanny ; Tumanov, Nikolay ; Norberg, Bernadette ; Robeyns, Koen ; Filinchuk, Yaroslav ; Wouters, Johan ; Leyssens, Tom. / Does chirality influence the tendency toward cocrystal formation?. Dans: Crystal Growth and Design. 2014 ; Vol 14, Numéro 6. p. 2880-2892.
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Does chirality influence the tendency toward cocrystal formation? / George, Fanny; Tumanov, Nikolay; Norberg, Bernadette; Robeyns, Koen; Filinchuk, Yaroslav; Wouters, Johan; Leyssens, Tom.

Dans: Crystal Growth and Design, Vol 14, Numéro 6, 04.06.2014, p. 2880-2892.

Résultats de recherche: Contribution à un journal/une revueArticle

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AU - Wouters, Johan

AU - Leyssens, Tom

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