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 originale | Anglais |
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Pages (de - à) | 2880-2892 |
Nombre de pages | 13 |
journal | Crystal Growth and Design |
Volume | 14 |
Numéro de publication | 6 |
Les DOIs | |
Etat de la publication | Publié - 4 juin 2014 |
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Examiner les sujets de recherche de « Does chirality influence the tendency toward cocrystal formation? ». Ensemble, ils forment une empreinte digitale unique.Ensembles de données
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CCDC 984565: Experimental Crystal Structure Determination
Filinchuk, Y. (Contributeur), George, F. (Contributeur), Leyssens, T. (Contributeur), Norberg, B. (Contributeur), Robeyns, K. (Contributeur), Tumanov, N. (Contributeur) & Wouters, J. (Contributeur), Cambridge Crystallographic Data Centre, 1 janv. 2014
DOI: 10.5517/cc121j5t, http://www.ccdc.cam.ac.uk/services/structure_request?id=doi:10.5517/cc121j5t&sid=DataCite
Ensemble de données
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CCDC 984573: Experimental Crystal Structure Determination
Filinchuk, Y. (Contributeur), George, F. (Contributeur), Leyssens, T. (Contributeur), Norberg, B. (Contributeur), Robeyns, K. (Contributeur), Tumanov, N. (Contributeur) & Wouters, J. (Contributeur), Cambridge Crystallographic Data Centre, 1 janv. 2014
DOI: 10.5517/cc121jf2, http://www.ccdc.cam.ac.uk/services/structure_request?id=doi:10.5517/cc121jf2&sid=DataCite
Ensemble de données
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CCDC 984574: Experimental Crystal Structure Determination
Filinchuk, Y. (Contributeur), George, F. (Contributeur), Leyssens, T. (Contributeur), Norberg, B. (Contributeur), Robeyns, K. (Contributeur), Tumanov, N. (Contributeur) & Wouters, J. (Contributeur), Cambridge Crystallographic Data Centre, 1 janv. 2014
DOI: 10.5517/cc121jg3, http://www.ccdc.cam.ac.uk/services/structure_request?id=doi:10.5517/cc121jg3&sid=DataCite
Ensemble de données