Cocrystals of Caffeine and Hydroxybenzoic Acids Composed of Multiple Supramolecular Heterosynthons: Screening via Solution-Mediated Phase Transformation and Structural Characterization

详细信息    查看全文

• 作者：Dejan-Kreimir Buar^† ; ^‡ ; ; Rodger F. Henry^§ ; ; Xiaochun Lou^† ; ; Richard W. Duerst ; Leonard R. MacGillivray^‡ ; * ; Geoff
• 刊名：Crystal Growth & Design
• 出版年：2009
• 出版时间：April 1, 2009
• 年：2009
• 卷：9
• 期：4
• 页码：1932-1943
• 全文大小：701K
• 年卷期：v.9,no.4(April 1, 2009)
• ISSN：1528-7505

文摘

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.