Browsing by Author "Howard, JAK"

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    Insights into the crystallisation process from anhydrous, hydrated and solvated crystal forms of diatrizoic acid
    (Wiley, 2014-11-04) Fucke, K; McIntyre, GJ; Lemée-Cailleau, MH; Wilkinson, C; Edwards, AJ; Howard, JAK; Steed, JW
    Diatrizoic acid (DTA), a clinically used X-ray contrast agent, crystallises in two hydrated, three anhydrous and nine solvated solid forms, all of which have been characterised by X-ray crystallography. Single-crystal neutron structures of DTA dihydrate and monosodium DTA tetrahydrate have been determined. All of the solid-state structures have been analysed using partial atomic charges and hardness algorithm (PACHA) calculations. Even though in general all DTA crystal forms reveal similar intermolecular interactions, the overall crystal packing differs considerably from form to form. The water of the dihydrate is encapsulated between a pair of host molecules, which calculations reveal to be an extraordinarily stable motif. DTA presents functionalities that enable hydrogen and halogen bonding, and whilst an extended hydrogen-bonding network is realised in all crystal forms, halogen bonding is not present in the hydrated crystal forms. This is due to the formation of a hydrogen-bonding network based on individual enclosed water squares, which is not amenable to the concomitant formation of halogen bonds. The main interaction in the solvates involves the carboxylic acid, which corroborates the hypothesis that this strong interaction is the last one to be broken during the crystal desolvation and nucleation process.© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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    New insights into an old molecule: Interaction energies of theophylline crystal forms
    (American Chemical Society, 2012-01-06) Fucke, K; McIntyre, GJ; Wilkinson, C; Henry, M; Howard, JAK; Steed, JW
    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. © 2012 American Chemical Society
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    Unexpected low-temperature behaviour of piroxicam monohydrate
    (Wiley-VCH Verlag, 2013-03-18) Fucke, K; Edwards, AJ; Probert, MR; Tallentire, SE; Howard, JAK; Steed, JW
    Upon cooling the monohydrate of the anti-inflammatory drug piroxicam shows reversible splitting. The cell also shows an irregular contraction over temperature and has a memory effect of its thermal history. This is due to strongly hydrogen bonded chains present in the monohydrate, which allow the crystal domains to contract separately from each other. © 2013, Wiley-VCH Verlag.