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New insights into an old molecule : interaction energies of theophylline crystal forms.

Fucke, K. and McIntyre, G. J. and Wilkinson, C. and Henry, M. and Howard, J. A. K. and Steed, J. W. (2012) 'New insights into an old molecule : interaction energies of theophylline crystal forms.', Crystal growth & design., 12 (3). pp. 1395-1401.


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.

Item Type:Article
Full text:(AM) Accepted Manuscript
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Publisher 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
Date accepted:No date available
Date deposited:27 March 2013
Date of first online publication:March 2012
Date first made open access:No date available

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