New insights into an Old Molecule: Interaction Energies of Theophylline Crystal Forms

Fucke, K.; McIntyre, G.J.; Wilkinson, C.; Henry, M.; Howard, J.A.K.; Steed, J.W.

doi:10.1021/cg201499s

New insights into an Old Molecule: Interaction Energies of Theophylline Crystal Forms

Fucke, K.; McIntyre, G.J.; Wilkinson, C.; Henry, M.; Howard, J.A.K.; Steed, J.W.

Authors

K. Fucke

G.J. McIntyre

C. Wilkinson

M. Henry

J.A.K. Howard

Professor Jonathan Steed jon.steed@durham.ac.uk
Professor

Abstract

The asthma therapeutic theophylline exists in at least three anhydrous polymorphs and a monohydrate. The single-crystal X-ray structure of the high-temperature polymorph form I is presented for the first time, and the energetic relationship between forms I and II is investigated using the partial charges and chemical hardness analysis (PACHA) algorithm. It is shown that the interactions in the form I crystal network are stronger, especially the hydrogen bond. The single-crystal neutron structure of the monohydrate demonstrates static disorder of the water molecule as well as dynamic disorder of the methyl groups. PACHA investigations based on the neutron coordinates reveal that the homomeric interactions in this form are stronger than the interaction of the water with the host molecules. The dehydration of the hydrate should thus leave the theophylline network intact, explaining the isomorphic powder X-ray diffractograms of the monohydrate and its dehydrated form III.

Citation

Fucke, K., McIntyre, G., Wilkinson, C., Henry, M., Howard, J., & Steed, J. (2012). New insights into an Old Molecule: Interaction Energies of Theophylline Crystal Forms. Crystal Growth and Design, 12(3), 1395-1401. https://doi.org/10.1021/cg201499s

Journal Article Type	Article
Publication Date	Mar 1, 2012
Deposit Date	Mar 27, 2013
Publicly Available Date	Mar 27, 2013
Journal	Crystal Growth and Design
Print ISSN	1528-7483
Electronic ISSN	1528-7505
Publisher	American Chemical Society
Peer Reviewed	Peer Reviewed
Volume	12
Issue	3
Pages	1395-1401
DOI	https://doi.org/10.1021/cg201499s

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Copyright Statement
This document is the Accepted Manuscript version of a Published Work that appeared in final form in Crystal growth & design, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://dx.doi.org/10.1021/cg201499s