I24-Microfocus Macromolecular Crystallography
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Diamond Proposal Number(s):
[17810]
Abstract: Monoacylglycerols (MAGs) are the lipids most commonly used for crystallizing membrane proteins by the in meso method. The acyl chain and glycerol components of MAGs are ester-linked at the sn-1 hydroxyl of glycerol in 1-MAGs. 1-MAGs succumb to spontaneous transacylation where the chain migrates between the sn-1 and sn-2 hydroxyls. In the mesophase formed by 1-monoolein, the most commonly used MAG, equilibrium is reached in two weeks at 6 mol% 2-monoolein. Variability in 2-MAG content appears in synthetic MAGs produced for the purpose of host lipid screening. In the interests of reproducibility, extensive purification has been implemented to minimize the 2-MAG content of newly synthesized lipid. Here we show, with two membrane proteins, that such efforts are not needed. Specifically, the initial 2-MAG content can vary over wide limits without impacting negatively on the crystallization process or on the structures obtained with those crystals. Dispensing with rounds of purification means that MAGs can be produced using protocols that are simpler, faster, less expensive and more environmentally friendly. An added feature of having 2-monoolein in the crystallization mix is that it stabilizes mesophases with bigger aqueous channels, well suited to structure determination of proteins and complexes with large extramembrane domains.
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Jul 2020
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I11-High Resolution Powder Diffraction
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Diamond Proposal Number(s):
[12340, 88927]
Abstract: Heating of the K2ZrF6 room temperature monoclinic form-I reveals a complex polymorphism investigated by synchrotron powder temperature-dependent diffraction. The first thermal event at 240 °C corresponds to the quasi-simultaneous apparition of four different phases (noted II to V) of which only three could be indexed and two completely characterized structurally. Form-II (structure unrefined) is very probably hexagonal (a = 6.4473(1) Å, c = 3.8606(1) Å at 264 °C, Z = 1). Form-III is cubic (space group Fm3 ̅m, a = 9.0804(1) Å at 264 °C, Z = 4), related to K3ZrF7. Form-IV remains unindexed, presenting broad diffraction peaks. Form-V is present as a weak impurity at this stage, increasing in proportion after the second thermal event at 288 °C where a new form-VI is built. Form-V is tetragonal (space group P4/nmm, a = 6.3281(1) Å, c = 9.3671(2) Å at 295 °C, Z = 2) and form-VI is orthorhombic (space group Cmcm, a = 6.40840(5) Å, b = 20.7697(2) Å, c = 19.9888(2) Å, at 295 °C, Z = 16). At 317 °C, form-VI transforms into form-V. At 449 °C, a different orthorhombic form-VII is disclosed (space group Pnma, a = 10.3084(1) Å, b = 6.0291(1) Å, c = 23.8023(2) Å, at 495 °C, Z = 8), coexisting with the cubic form-III. On cooling, form VII of which an approach of the crystal structure is provided, returns to form V at 411 °C which looks stable down to 139 °C giving form I back. Isolated ZrF6 octahedra are present in forms-III, -V, -VI, -VII. Form-VI contains also dimeric entities Zr2F12 built from a ZrF7 monocapped trigonal prism sharing a corner with a ZrF6 octahedron. Form-VII structure is related to form-V by quadrupling the tetragonal a parameter, the reversible VVII transition is very probably topotactic. The coexistence of several phases at each temperature above the first transition at 240 °C was observed. Peak multi-splitting is observed at many temperatures that suggests the occurrence of coexisting micro-phases. The parallel existence of several phases was observed also by 19F MAS NMR spectroscopy measured from 250 oC → 410 oC → RT.
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Apr 2020
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I11-High Resolution Powder Diffraction
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Diamond Proposal Number(s):
[20626]
Abstract: Variable-temperature single-crystal and powder X-ray diffraction techniques have been used to study the thermal and mechanical decomposition of the acetonitrile solvate of the co-crystal formed between piroxicam and succinic acid (PRXSA-ACN). The results show that the thermal expansion behavior of PRXSA-ACN is highly anisotropic and can be correlated with structural features of the crystal lattice. Thermally-induced desolvation of PRXSA-ACN led initially to the formation of the α-form of piroxicam and the 1:1 piroxicam:succinic acid co-crystal (PRXSA), and this can be rationalized on the basis of the crystal structure of PRXSA-ACN and its thermal expansion behavior. Subsequent decomposition of PRXSA produced amorphous succinic acid and the thermodynamically more stable β-form of piroxicam. The α- and β-forms co-existed up until the melting point of the α-form, at which point the sample recrystallized to give the β-form of piroxicam. Mechanical treatment (light grinding) of PRXSA-ACN resulted in mild structural damage to the crystal structure and this led to subsequent desolvation.
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Nov 2019
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I11-High Resolution Powder Diffraction
I19-Small Molecule Single Crystal Diffraction
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Abstract: A new porous and flexible metal-organic framework (MOF) has been synthesised from the flexible asymmetric linker N-(4-Carboxyphenyl)succinamate (CSA) and heptanuclear zinc oxo-clusters of formula [Zn7O2(Carboxylate)10DMF2] involving two coordinated terminal DMF ligands. The structural response of this MOF to the removal or exchange of its guest molecules has been probed using a combination of experimental and computational approaches. The topology of the material, involving double linker connections in the a and b directions and single linker connections along the c axis, is shown to be key in the materials anisotropic response. The a and b directions remain locked during guest removal, while the c axis linker undergoes large changes significantly reducing the material’s void space. The changes to the c axis linker involve a combination of a hinge motion on the linker’s rigid side and conformational rearrangements on its flexible end, which were probed in detail during this process despite the presence of crystallographic disorder along this axis which prevented accurate characterisation by experimental methods alone. While inactive during guest removal, the flexible ends of the a and b axis linkers are observed to play a prominent role during DMF to DMSO solvent exchange, facilitating the exchange reaction arising in the cluster.
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Aug 2019
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I12-JEEP: Joint Engineering, Environmental and Processing
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Abstract: In this work, three new cocrystals of the nonsteroidal anti-inflammatory drug flurbiprofen with salicylamide, benzamide and picolinamide have been discovered using thermodynamic analysis of solid-liquid binary phase diagrams, and their crystal structures have been determined from the high-resolution synchrotron powder diffraction data. Solid state DFT calculations have been carried out to gain additional insight into energy differences between the cocrystal structures. The pH-solubility behavior and solubility advantage of the cocrystals have been examined via eutectic concentrations of the components, and the thermodynamic stability relationships between different solid phases have been rationalized in terms of Gibbs energies of the formation reactions. In addition, a new model has been proposed for estimating the solubility product (Ksp) of a cocrystal, based on the experimental intrinsic solubility of the drug and coformer complemented by calculated physicochemical HYBOT descriptors. The applicability of the molecular volume of cocrystal formation as a reliable parameter for clarifying the relationship between the driving force of the cocrystallization process and the structural features of participating solids has been also discussed.
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Aug 2019
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I19-Small Molecule Single Crystal Diffraction
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Diamond Proposal Number(s):
[15777]
Abstract: Porous organic cages have emerged over the last 10 years as a subclass of functional microporous materials. However, among all of the organic cages published, large multicomponent organic cages with 20 components or more are still rare. Here, we present an [8+12] porous organic imine cage, CC20, which has an apparent surface area up to 1752 m2 g-1, depending on the crystallization and activation conditions. The cage is solvatomorphic and displays distinct geometrical cage structures, caused by crystal packing ef-fects, in its crystal structures. This indicates that larger cages can display a certain range of shape flexibility in the solid state, while remaining shape persistent and porous.
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May 2019
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Abstract: We report the solid-state structural properties and phase transition behaviour of 1,4-dibromo-2,3,5,6-tetramethylbenzene, demonstrating that this material undergoes an order-disorder phase transition below ambient temperature (at ca. 156 K on cooling and ca. 159 K on heating). In both the high-temperature and low-temperature phases, the crystal structure is based on π-stacking of the molecules. In the high-temperature phase, the bromine and methyl groups are located with essentially equal probability in each of the six substituent positions, and it is shown by natural-abundance solid-state 2H NMR spectroscopy that, at ambient temperature, this disorder is dynamic via rapid molecular reorientation about an axis perpendicular to the aromatic ring. In the low-temperature phase, the bromine and methyl substituents occupy preferred sites within the crystal structure, with the distribution of site occupancies becoming progressively more ordered on decreasing temperature.
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Mar 2019
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I12-JEEP: Joint Engineering, Environmental and Processing
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Diamond Proposal Number(s):
[17450]
Abstract: Olanzapine is a polymorphic drug molecule that has been extensively studied, with over 60 structures reported in the Cambridge Structural Database. All anhydrous and solvated forms of olanzapine known to date contain the SC0 dimer packing motif. In this study, a new screening approach was adopted involving heat-induced forced crystallization from a polymer-based molecular dispersion of olanzapine. Simultaneous differential scanning calorimetry-powder X-ray diffraction (DSC-PXRD) was used to heat the amorphous dispersion and to identify a novel physical form from diffraction and heat flow data. Comparison of the diffraction data with those from a computed crystal energy landscape allowed the crystal structure to be determined. The result was the discovery of a new polymorph, form IV, which does not use the SC0 motif. Hence, while dimer formation is the dominant process that defines crystal packing for olanzapine formed from solution, it seems that molecularly dispersing the drug in a polymeric ma-trix permits crystallization of alternative motifs. Having identified form IV, it proved possible to scale up the synthesis and demonstrate its enhanced dissolution properties over form I.
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Mar 2019
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I19-Small Molecule Single Crystal Diffraction
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Diamond Proposal Number(s):
[2871]
Abstract: A series of “light metal” metal–organic frameworks containing secondary building units (SBUs) based on Li+ and Na+ cations have been prepared using the silicon-centered linkers MexSi(p-C6H4CO2H)4-x (x = 2, 1, 0). The unipositive charge, small size, and oxophilic nature of the metal cations give rise to some unusual and unique SBUs, including a three-dimensional nodal structure built from sodium and oxygen ions when using the triacid linker (x = 1). The same linker with Li+ cations generated a chiral, helical SBU, formed from achiral starting materials. One-dimensional rod SBUs are observed for the diacid (x = 2) and tetra-acid (x = 0) linkers with both Li+ and Na+ cations, where the larger size of Na+ compared to Li+ leads to subtle differences in the constitution of the metal nodes.
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Nov 2018
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I22-Small angle scattering & Diffraction
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Diamond Proposal Number(s):
[8973]
Abstract: Iron sufides are important mineral phases in natural environments where they control global elemental cycles. Fe-S phases have been suggested to form through transformation of several possible precursors to finally reach stable crystalline structures. Mackinawite is a metastable intermediate, of which a full chemical and structural characteristisation of various possible intermediate stages in its formation pathways, or the chemical conditions that affect the transformations to the metastable mackinawite are well understood. Here we report, the various steps of mackinawite formation via oriented aggregation (OA) from a nanoparticulate precursor. During OA, the formation of aggregates is a crucial stage for self-assembly of primary particles to reach stable structures. The formation occurs in five steps: (1) homogeneous nucleation of primary FeSnano particles, (2 and 3) formation of mass fractal-like aggregates from the FeSnano as precursor towards the transformation to mackinawite; (4) oriented alignment and self-assembly of these mackinawite-like aggregates, and (5) transformation to a still metastable but typical layered mackinawite structure.
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Sep 2018
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