Journal article
Synthon Hierarchies in Crystal Forms Composed of Theophylline and Hydroxybenzoic Acids: Cocrystal Screening via Solution-Mediated Phase Transformation
Crystal growth & design, Vol.14(10), pp.5318-5328
2014
DOI: 10.1021/cg501204k
Abstract
Theophylline, a pharmaceutical model compound, was screened for cocrystal formation using nine (di)hydroxybenzoic acids as cocrystal formers, namely, 2-, 3-, 4-hydroxybenzoic- and 2,3-, 2,4-, 2,5-, 2,6-, 3,4-, and 3,5-dihydroxybenzoic acids. The experiments were conducted using an efficient, reliable, and fast screening method based on thermodynamically driven solution-mediated phase transformation and revealed the formation of eight cocrystals and one salt. The theophylline-based solids were identified using powder and structurally characterized via single-crystal X-ray diffraction. The obtained solids are sustained by theopylline-carboxylic acid heterosynthons, in addition to both theophylline and carboxylic acid homosynthons. The results are a part of a systematic study of xanthine-alkaloid cocrystals that aims to establish synthon hierarchies in cocrystals comprised of molecules with multiple hydrogen-bonding functional groups. Structural features and synthon hierachies are discussed and compared to those in a series of published caffeine cocrystals.
Details
- Title: Subtitle
- Synthon Hierarchies in Crystal Forms Composed of Theophylline and Hydroxybenzoic Acids: Cocrystal Screening via Solution-Mediated Phase Transformation
- Creators
- Dejan-Krešimir Bucar - Department of Chemistry, University of Iowa, Iowa City, Iowa 52242, United StatesRodger F Henry - Drug Product Development, Research and Development, AbbVie Inc., North Chicago, Illinois 60064, United StatesGeoff G. Z Zhang - Department of Chemistry, University of Iowa, Iowa City, Iowa 52242, United StatesLeonard R Macgillivray - Department of Chemistry, University of Iowa, Iowa City, Iowa 52242, United States
- Resource Type
- Journal article
- Publication Details
- Crystal growth & design, Vol.14(10), pp.5318-5328
- Publisher
- American Chemical Society
- DOI
- 10.1021/cg501204k
- ISSN
- 1528-7483
- eISSN
- 1528-7505
- Language
- English
- Date published
- 2014
- Academic Unit
- Chemistry; Pharmaceutical Sciences and Experimental Therapeutics
- Record Identifier
- 9984216708102771
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