Journal article
Cocrystals of Caffeine and Hydroxybenzoic Acids Composed of Multiple Supramolecular Heterosynthons : Screening via Solution-Mediated Phase Transformation and Structural Characterization
Crystal growth & design, Vol.9(4), pp.1932-1943
2009
DOI: 10.1021/cg801178m
Abstract
Caffeine, a pharmaceutical model compound, generally forms cocrystals with carboxylic acids that involve an O-H ⋯ N hydrogen bond between the carboxylic acid group of the acid and the caffeine imidazole moiety. Such solids are typically based on a single heterosynthon. To examine the facility of introducing additional supramolecular heterosynthons to the caffeine-carboxylic- acid cocrystal system, structural isomers of aromatic carboxylic acids (i.e., hydroxy- and dihydroxybenzoic acids) with additional hydrogen-bonding functional groups (i.e., hydroxy group) were screened for cocrystal formation. For this purpose, a highly efficient screening method based on thermodynamically driven solution-mediated phase transformation was utilized. This method enabled the rapid discovery of nine new solid phases involving caffeine. These caffeine phases were identified using single-crystal X-ray diffraction and FT-IR spectroscopy as cocrystals based on 2-, 3-, 4-hydroxybenzoic- and 2,3-, 2,4-, 2,5-, 3,4-, and 3,5-dihydroxybenzoic acids. Structural analyses of the cocrystals revealed solids composed of up to three caffeine-carboxylic acid heterosynthons. © 2009 American Chemical Society.
Details
- Title: Subtitle
- Cocrystals of Caffeine and Hydroxybenzoic Acids Composed of Multiple Supramolecular Heterosynthons : Screening via Solution-Mediated Phase Transformation and Structural Characterization
- Creators
- Dejan-Kresimir Bucar - Solid State Sciences, Global Pharmaceutical R & D, Abbott Laboratories, North Chicago, Illinois 60064, United StatesRodger F Henry - Structural Chemistry, Global Pharmaceutical R & D, Abbott Laboratories, North Chicago, Illinois 60064, United StatesXIAOCHUN Lou - Solid State Sciences, Global Pharmaceutical R & D, Abbott Laboratories, North Chicago, Illinois 60064, United StatesRichard W Duerst - Microscopy Group, Global Pharmaceutical R & D, Abbott Laboratories, North Chicago, Illinois 60064, United StatesLeonard R Macgillivray - Department of Chemistry, University of Iowa, Iowa City, Iowa 52242, United StatesGeoff G. Z Zhang - Solid State Sciences, Global Pharmaceutical R & D, Abbott Laboratories, North Chicago, Illinois 60064, United States
- Resource Type
- Journal article
- Publication Details
- Crystal growth & design, Vol.9(4), pp.1932-1943
- Publisher
- American Chemical Society
- DOI
- 10.1021/cg801178m
- ISSN
- 1528-7483
- eISSN
- 1528-7505
- Language
- English
- Date published
- 2009
- Academic Unit
- Chemistry; Pharmaceutical Sciences and Experimental Therapeutics
- Record Identifier
- 9984216687902771
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