I03-Macromolecular Crystallography
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Abstract: Hierarchical self-assembly of hybrid bioinorganic structures is a challenging task which requires specific and tailored interactions. Here we report a supramolecular assembly formed between the six-bladed symmetrical designer protein Pizza6-S (Pizza6) and the {K3Cu3(NO3)[A-α-PW9O34]2} (Cu3) polyoxometalate (POM). The crystal structure (1.8 Å resolution) revealed that the Cu3 dissociated and reassembled with the protein to form a novel POM-protein cage. In this hybrid assembly, six CuII ions link two Pizza6 molecules in a controlled way by binding to the six symmetrically equivalent histidine side chains. Such coordination results in the formation of a “bioinorganic cage” in which a lacunary [A-α-PW9O34]9– (PW9) anion is tightly encapsulated via coordination to CuII ions and hydrogen bonding with protein side chains. Further spectroscopic characterization of the Pizza6/Cu3 solution suggests that dissociation of Cu3 is facilitated by the synergetic effect of six histidine residues which have high affinity toward Cu(II) ions, resulting in the formation of the hierarchical supramolecular assembly.
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Mar 2022
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I11-High Resolution Powder Diffraction
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Diamond Proposal Number(s):
[27557]
Abstract: Soluble additives are widely used to control crystallization processes, modifying the morphologies, sizes, polymorphs, and physical properties of the product crystals. Here, a simple and versatile strategy is shown to significantly enhance the potency of soluble additives, ranging from ions and amino acids to large dye molecules, enabling them to be effective even at low concentrations. Addition of small amounts of miscible organic co-solvents to an aqueous crystallization solution can yield enhanced morphological changes and an order of magnitude increase of additive incorporation within single crystals─a level that cannot be achieved in pure aqueous solutions at any additive concentration. The generality of this strategy is demonstrated by application to crystals of calcium carbonate, manganese carbonate, and strontium sulfate, with a more pronounced effect observed for co-solvents with lower dielectric constants and polarities, indicating a general underlying mechanism that alters water activity. This work increases the understanding of additive/crystal interactions and may see great application in industrial-scale crystal synthesis.
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Nov 2021
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I19-Small Molecule Single Crystal Diffraction
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Jessica L.
Andrews
,
Sten O.
Nilsson Lill
,
Stefanie
Freitag-Pohl
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David C.
Apperley
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Dmitry
Yufit
,
Andrei S.
Batsanov
,
Matthew T.
Mulvee
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Katharina
Edkins
,
James F.
Mccabe
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David J.
Berry
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Michael R.
Probert
,
Jonathan W.
Steed
Diamond Proposal Number(s):
[11145]
Abstract: This work presents an updated solid-form discovery approach to the polymorphism of the antiarrhythmic drug mexiletine hydrochloride, in which experimental and computational techniques are combined to provide a rigorous characterization of the solid-form landscape of this compound. The resulting solid forms were characterized by powder and single-crystal X-ray diffraction, IR spectroscopy, differential scanning calorimetry, and 13C solid-state NMR. This approach reveals five solid-form types of mexiletine hydrochloride. Forms 1, 2, and 3 are mutually enantiotropically related anhydrous polymorphs, with Form 1 the room temperature stable form, Form 2 the high-temperature form, and Form 3 the thermodynamically stable polymorph between 148 and 167 °C. The final two forms termed Types A and B comprise two large families of isomorphous channel solvates, including a fourth nonsolvated form isostructural to the Type A solvates. We report 11 modifications of each solvate, in which a diverse range of solvents are included in the channels, without changing the fundamental structure of the drug framework. These experimental results go hand-in-hand with computational crystal structure prediction (using the AstraZeneca crystal structure prediction approach), which together suggest that it is unlikely further nonsolvated forms, at least with Z′ = 1, will be discovered under ambient conditions.
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Oct 2021
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Abstract: X-ray photoelectron spectroscopy (XPS) has emerged as a technique that allows for characterization and classification of hydrogen bonding and proton transfer interactions in organic crystal structures, in a way that is complementary to crystallography by X-ray or neutron diffraction. Here, we analyze the nitrogen 1s core-level binding energies (BEs) of isonicotinamide (IN) systems with proton transfer between donor and acceptor groups at short distances. We show how a careful calibration of the BE scale places these salt systems correctly on the edge of the so-called salt–cocrystal continuum. We show how performing a fitting analysis of the data that is consistent with elemental analysis, expected stoichiometry, and quantification of adventitious carbon contamination facilitates the determination of absolute BEs with accuracy and reproducibility within ±0.1 eV. The determined N 1s core-level BEs of the protonated IN acceptors suggest that the local geometric arrangements of the donor, acceptor, and proton can influence the N 1s core-level BE significantly.
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Sep 2021
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I12-JEEP: Joint Engineering, Environmental and Processing
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Diamond Proposal Number(s):
[26476]
Abstract: In this work, three new pharmaceutical salts of fenbendazole (FNB), a benzimidazole-based anthelmintic drug, with sulfonic acids have been obtained and thoroughly investigated by different analytical techniques, including thermal methods, infrared/Raman spectroscopy, and theoretical methods (periodic DFT computations and Bader analyses of the crystalline electronic density). Single-crystal and high-resolution synchrotron powder X-ray diffraction data for the first time made it possible to determine the crystal structures of mesylate and tosylate salts of the drug, which were further validated by dispersion-corrected density functional theory calculations. All the solid forms were stabilized by a robust R22(8) supramolecular motif formed by relatively strong N–H···O hydrogen bonds. In the monohydrate of FNB tosylate, a considerable gain in the stabilization energy was due to the intermolecular interactions generated by the water molecules. A careful examination of the solubility–pH profile of the FNB salts revealed that, despite being thermodynamically unstable within the physiologically relevant pH range, the new solid forms demonstrated superior dissolution performance in terms of both the apparent solubility and the release rate in comparison to the parent drug. Since FNB has also been reported to possess anticancer activity, improving the drug’s poor physicochemical properties through salt formation with the selected sulfonic acids is expected to promote further investigations toward repurposing of this potent compound.
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Jul 2021
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I11-High Resolution Powder Diffraction
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Diamond Proposal Number(s):
[17320]
Open Access
Abstract: Mechanochemical synthesis has recently emerged as a scalable “green” approach for the preparation of MOFs, but current understanding of the underlying reaction mechanisms is limited. In this work, an investigation of the reaction pathway of the mechanochemical synthesis of MOF-74 from ZnO and 2,5-dihydroxyterephthalic acid (H4HDTA), using DMF as a liquid additive, is presented. The complex reaction pathway involves the formation of four short-lived intermediate phases, prior to the crystallization of MOF-74. The crystal structures of three of these intermediates have been determined using a combination of single-crystal and powder X-ray diffraction methods and are described here. The initial stages of the reaction are very fast, with a DMF solvate of H4HDTA forming after only 2 min of milling. This is followed by crystallization, after only 4 min of milling, of a triclinic one-dimensional coordination polymer, Zn(H2DHTA)(DMF)2(H2O)2, which converts into a monoclinic polymorph on additional milling. Highly crystalline MOF-74 appears after prolonged milling, for at least 70 min.
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Apr 2021
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I19-Small Molecule Single Crystal Diffraction
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Diamond Proposal Number(s):
[22240]
Open Access
Abstract: Wide-dose-range 2D radiochromic films for radiotherapy, such as GAFchromic EBT, are based on the lithium salt of 10,12-pentacosadiynoic acid (Li-PCDA) as the photosensitive component. We show that there are two solid forms of Li-PCDA—a monohydrated form A and an anhydrous form B. The form used in commercial GAFchromic films is form A due to its short needle-shaped crystals, which provide favorable coating properties. Form B provides an enhanced photoresponse compared to that of form A, but adopts a long needle crystal morphology, which is difficult to process. The two forms were characterized by powder X-ray diffraction, Fourier transform infrared spectroscopy, CP-MAS 13C solid-state NMR spectroscopy, and thermogravimetric analysis. In sum, these data suggest a chelating bridging bidentate coordination mode for the lithium ions. The sodium salt of PCDA (Na-PCDA) is also reported, which is an ionic cocrystal with a formula of Na+PCDA–·3PCDA. The PCDA and PCDA– ligands display monodentate and bridging bidentate coordination to the sodium ion in contrast to the coordination sphere of the Li-PCDA forms. In contrast to its lithium analogues, Na-PCDA is photostable.
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Mar 2021
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I11-High Resolution Powder Diffraction
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Diamond Proposal Number(s):
[23985]
Abstract: A study on the hydration behavior of fluconazole demonstrates that both sample age and polymorphic form impact the drug’s kinetic stability to hydration. For two of the polymorphs, aged samples were found to hydrate more readily than fresh samples. The aging effect was attributed to the formation of monohydrate (MH) crystals over time. The MH, despite being initially undetectable, had a seeding effect, thus impacting the hydration kinetics.
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Mar 2021
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I11-High Resolution Powder Diffraction
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Diamond Proposal Number(s):
[19360, 26269]
Abstract: Two multicomponent crystalline phases of (S)-ibuprofen and l-proline with 1:1 stoichiometry are reported, specifically a nonsolvate phase (Ibu-Pro) and a quarter-hydrate phase (Ibu-Pro-QH). Ibu-Pro was prepared only by solid-state mechanochemical synthesis, while Ibu-Pro-QH was obtained both by solution-state crystallization and by solid-state mechanochemistry. The crystal structures of Ibu-Pro and Ibu-Pro-QH were determined directly from powder X-ray diffraction (XRD) data, with structure solution carried out using the direct-space strategy (implemented with a genetic algorithm search procedure) and structure refinement carried out using the Rietveld method. The process of structure determination from powder XRD data was augmented by information from other complementary techniques, specifically solid-state NMR spectroscopy, thermal analysis methods, and periodic DFT-D calculations. A preliminary powder XRD study of the dehydration behavior of Ibu-Pro-QH at elevated temperature is also reported.
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Mar 2021
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I22-Small angle scattering & Diffraction
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Diamond Proposal Number(s):
[24530, 22659, 20481]
Abstract: Edible air-in-oil systems, also referred to as oleofoams, constitute a novel promising material for healthier, low-calorie fat replacers in confectionary products. Oleofoams can be formed by whipping oleogels, which are dispersions of fat crystals in an oil phase. Understanding how the properties of the fat crystals (i.e., size, shape, and polymorphism) contained in oleogels affect the microstructure and stability of oleofoams is essential for both the efficient design and manufacture of novel food products. In this work, cocoa butter, one of the main fat phases present in confectionary productions, which is responsible for pleasant texture and mouthfeel properties, was mixed with high oleic sunflower oil and crystallized to obtain an oleogel. This was subsequently whipped to yield a stable, highly aerated oleofoam. The effect of the crystallization conditions (oleogel composition and cooling rate) on the properties of the oleogels and related oleofoams was investigated with a multitechnique characterization approach, featuring polarized light microscopy, cryogenic scanning electron microscopy, X-ray diffraction, differential scanning calorimetry, and oscillatory rheology. Oleogel crystallization was performed in a lab-scale vessel and was monitored using light turbidimetry as an in situ technique. Results showed that the concentration of cocoa butter in sunflower oil was the parameter that affected most strongly the foamability and rheology of oleofoam samples. The size and shape of cocoa butter crystals within the oleogel was found to have a less significant effect since crystals were broken or partially melted during the aeration process. Oleofoams whipped from oleogels containing 15 and 22% w/w cocoa butter displayed an overrun of 200%, corresponding to a calorific density reduction to one-third, and an increase in both the elastic and viscous moduli compared to their oleogel precursor. This was explained by a structuring effect caused by the aeration process, where cocoa butter β(V) crystal nanoplatelets (CNPs) in the oleogel rearranged to stabilize the air bubbles via a Pickering mechanism. Oleofoams prepared from 30% w/w cocoa butter oleogels, on the other hand, incorporated less air (overrun between 150 and 180%) and displayed a similar viscoelastic profile to their unwhipped precursors potentially due to air incorporation being limited by the relatively high elastic modulus of the parent oleogels. Nevertheless, the calorific density of these samples was reduced by a factor of 1.6–2.5 compared to their full-fat analogues.
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Feb 2021
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