Browsing by Author "Steed, JW"

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    Extensive sequential polymorphic interconversion in the solid state: two hydrates and ten anhydrous phases of hexamidine diisethionate
    (American Chemical Society, 2019-10-22) Edkins, K; McIntyre, GJ; Wilkinson, C; Kahlenberg, V; Többens, D; Griesser, UJ; Brüning, J; Schmidt, MU; Steed, JW
    Crystal polymorphism and solvent inclusion are a dominant research area in the pharmaceutical industry and continue to unveil complex systems. Here, we present the solid-state system of hexamidine diisethionate (HDI), an antiseptic drug compound forming a dimorphic dihydrate as well as 10 anhydrous polymorphs. The X-ray and neutron crystal structures of the hydrated crystal forms and related interaction energies show no direct interaction between the cation and water but very strong interactions between cation and anion, and anion and water. This is observed macroscopically as high stability of the hydrate against dehydration by temperature and humidity. The anhydrous polymorphs reveal a rare case of sequential and reversible polymorphic transformations, which are characterized by thermal analysis and variable-temperature powder X-ray diffraction. While most transitions are accompanied by significant structural changes, the low-energy transitions can only be detected as slight changes in the reflection positions with temperature. HDI thus represents a model compound to investigate polymorphic transitions with small structural changes. © 2019 American Chemical Society
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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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    Reduction of a chelating bis(NHC) palladium(II) complex to [{μbis( NHC)}2Pd2H]+: a terminal hydride in a binuclear palladium(I) species formed under catalytically relevant conditions
    (Wiley-VCH Verlag Berlin, 2010-08-23) Boyd, PDW; Edwards, AJ; Gardiner, MG; Ho, CC; Lemée-Cailleau, MH; McGuinness, DS; Riapanitra, A; Steed, JW; Stringer, DN; Yates, BF
    The first palladium(I) N-heterocyclic carbene complex has been isolated in high yield by the base-assisted reduction of a palladium(II) precursor. The location of the unique terminal hydride (see picture; PdI cyan, H white, N blue) was established by neutron crystal structure determination, and the solution fluxional behavior of the complex was explored. © 2010, Wiley-VCH Verlag Berlin
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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.