B18-Core EXAFS
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Diamond Proposal Number(s):
[17052]
Abstract: Hydrogen peroxide is a co-substrate for the oxidative cleavage of saccharidic substrates by copper-containing lytic poly-saccharide monooxygenases (LPMOs). The rate of reaction of LPMOs with hydrogen peroxide is high but it is accompa-nied by rapid inactivation of the enzymes, presumably through protein oxidation. Herein, we use UV/vis, CD, XAS, EPR, VT/VH-MCD and resonance Raman spectroscopies, augmented with mass spectrometry and DFT calculations, to show that the product of reaction of an AA9 LPMO with H2O2 at higher pHs is a singlet Cu(II)-tyrosyl radical species, which is inactive for the oxidation of saccharidic substrates. The Cu(II)-tyrosyl radical center entails the formation of significant Cu(II)-(●OTyr) overlap, which in turn requires that the plane of the d(x2-y2) SOMO of the Cu(II) is orientated towards the tyrosyl radical. We propose from the Marcus cross-relation that the active site tyrosine is part of a ‘hole-hopping’ charge-transfer mechanism formed of a pathway of conserved tyrosine and tryptophan residues, which can protect the protein active site from inactivation during uncoupled turnover.
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Nov 2019
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I19-Small Molecule Single Crystal Diffraction
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Izar
Capel Berdiell
,
Tim
Hochdörffer
,
Cédric
Desplanches
,
Rafal
Kulmaczewski
,
Namrah
Shahid
,
Juliusz A.
Wolny
,
Stuart Laurence
Warriner
,
Oscar
Cespedes
,
Volker
Schünemann
,
Guillaume
Chastanet
,
Malcolm Andrew
Halcrow
Diamond Proposal Number(s):
[10334]
Abstract: Treatment of Fe[BF4]2·6H2O with 4,6-di(pyrazol-1-yl)-1H-pyrimid-2-one (HL1) or 4,6-di(4-methylpyrazol-1-yl)-1H-pyrimid-2-one (HL2) affords solvated crystals of [{FeIII(OH2)6}FeII8(μ-L)12][BF4]7 (1, HL = HL1; 2, HL = HL2). The centrosymmetric complexes contain a cubic arrangement of iron(II) centers, with bis-bidentate [L]‒ ligands bridging the edges of the cube. The encapsulated [Fe(OH2)6]3+ moiety templates the assembly through twelve O‒H…O hydrogen bonds to the [L]‒ hydroxylate groups. All four unique iron(II) ions in the cages are crystallographically high-spin at 250 K, but undergo a gradual high→low spin-crossover on cooling, which is predominantly centered on one iron(II) site and its symmetry-related congener. This was confirmed by magnetic susceptibility data, LIESST effect measurements and, for 1, Mössbauer spectroscopy and diffuse reflectance data. The clusters are stable in MeCN solution, and 1 remains high-spin above 240 K in that solvent. The cubane assembly was not obtained from re-actions using other iron(II) salts or 4,6-di(pyrazol-1-yl)pyrimidine ligands, highlighting the importance of hydrogen bonding in templating the cubane assembly.
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Nov 2019
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I11-High Resolution Powder Diffraction
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Abstract: We report the synthesis and structural characterization of the ABX3 perovskite frameworks [C(NH2)3]Mn1–x2+(Fe2x/33+,□x/3)(HCOO)3 (□ = B-site vacancy). For large x, the vacancies order, lowering the crystal symmetry. This system establishes B-site vacancies as a new type of defect in formate perovskites, with important chemical, structural, and functional implications. Monte Carlo simulations driven by nearest-neighbor vacancy repulsions show checkerboard vacancy order to emerge for x > 0.6, in accord with experiment.
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Oct 2019
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E02-JEM ARM 300CF
I15-1-X-ray Pair Distribution Function (XPDF)
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Diamond Proposal Number(s):
[20038, 20195]
Abstract: Metal-organic framework crystal-glass composites (MOF-CGCs) are materials in which a crystalline MOF is dispersed within a MOF glass. In this work, we explore the room temperature stabilization of the open-pore form of MIL-53(Al), usually observed at high-temperature, which occurs upon encapsulation within a ZIF-62(Zn) MOF glass matrix. A series of MOF-CGCs containing different loadings of MIL-53(Al) were synthesized and characterized using X-ray diffraction and nuclear magnetic resonance spectroscopy. An upper limit of MIL-53(Al) that can be stabilized in the composite was determined for the first time. The nanostructure of the composites was probed using pair distribution function analysis and scanning transmission electron microscopy. Notably, the distribution and integrity of the crystalline compo-nent in a sample series was determined, and these findings related to the MOF-CGC gas adsorption capacity in order to identify the optimal loading necessary for maximum CO2 sorption capacity.
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Sep 2019
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I02-Macromolecular Crystallography
I04-1-Macromolecular Crystallography (fixed wavelength)
I04-Macromolecular Crystallography
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Diamond Proposal Number(s):
[306, 7864]
Abstract: Solvent organization is a key but underexploited contributor to the thermodynamics of protein–ligand recognition, with implications for ligand discovery, drug resistance and protein engineering. Here, we explore the contribution of solvent to ligand binding in the Haemophilus influenzae virulence protein SiaP. By introducing a single mutation without direct ligand contacts, we observed a >1000-fold change in sialic acid binding affinity. Crystallographic and calorimetric data of wild-type and mutant SiaP showed that this change results from an enthalpically unfavourable perturbation of the solvent network. This disruption is reflected by changes in the normalized atomic displacement parameters of crystallographic water molecules. In SiaP’s enclosed cavity, relative differences in water-network dynamics serve as a simple predictor of changes in the free energy of binding upon changing protein, ligand or both. This suggests that solvent structure is an evolutionary con-straint on protein sequence that contributes to ligand affinity and selectivity.
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Sep 2019
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I19-Small Molecule Single Crystal Diffraction
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Diamond Proposal Number(s):
[22411]
Abstract: We report a new water-stable multivariate (MTV) Metal-Organic Framework (MOF) prepared by combining two different oxamide-based metalloligands derived from the natural amino acids L-serine and L-methionine. This unique material features hexagonal channels decorated with two types of flexible and functional “arms” (–CH2OH and –CH2CH2SCH3) capa-ble to act, synergistically, for the simultaneous and efficient removal of both inorganic (heavy metals like Hg2+, Pb2+ and Tl+) and organic (dyes such as Pyronin Y, Auramine O, Brilliant Green and Methylene Blue) contaminants and, in addi-tion, this MTV-MOF is completely reusable. Single-crystal X-ray diffraction (SCXRD) measurements allowed to solve the crystal structure of a host-guest adsorbate, containing both HgCl2 and Methylene Blue, and offered unprecedented snap-shots about this unique dual capture process. This is the very first time that a MOF can be used for the removal of all sorts of pollutants from water resources, thus opening new perspectives for this emerging type of MTV-MOFs.
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Aug 2019
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I19-Small Molecule Single Crystal Diffraction
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Diamond Proposal Number(s):
[16139]
Abstract: The solid form screening of galunisertib produced many solvates, prompting an extensive investigation into possible risks to the development of the favored monohydrate form. Inspired by crystal structure prediction, the search for neat polymorphs was expanded to an unusual range of experiments, including melt crystallization under pressure, to work around solvate formation and the thermal instability of the molecule. Ten polymorphs of galunisertib were found, however, the structure predicted to be the most stable has yet to be obtained. We present the crystal structures of all 10 unsolvated polymorphs of galunisertib, showing how state-of-the-art characterization methods can be combined with emerging computational modelling techniques to produce a complete structure landscape and assess the risk of late appearing, more stable polymorphs. The exceptional conformational polymorphism of this prolific solvate former invites further development of methods, computational and experimental, that are applicable to larger, flexible molecules with complex solid form landscapes.
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Aug 2019
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I19-Small Molecule Single Crystal Diffraction
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Diamond Proposal Number(s):
[17379]
Abstract: We report on the stereoselective synthesis of trefoil knots of single topological handedness in up to 90 % yield (over two steps), through the formation of trimeric circular helicates from ligand strands containing either imine or, unexpectedly, amide chelating units and metal ion templates of the appropriate coordination character (zinc(II) for imines; cobalt(III) for amides). The coordination stereochemistry of the octahedral metal complexes is determined by asymmetric carbon centers in the strands, ulti-mately translating into trefoil knots that are a single enantiomer, both physically and in terms of their fundamental topology. Both the imine-zinc and amide-cobalt systems display self-sorting behavior, with racemic ligands forming knots that individually contain only building blocks of the same chirality. The knots and the corresponding trimeric circular helicate intermediates (Zn(II)3 com-plex for the imine ligands; Co(III)3 complex for the amide ligands) were characterized by NMR spectroscopy, mass spectrometry and X-ray crystallography. The latter confirms the trefoil knots as 84-membered macrocycles with each of the metal ions sited at crossing points for three parts of the strand. The stereochemistry of the octahedral coordination centers impart alternating crossings of the same handedness. The expression of chirality of the knotted molecules was probed by circular dichroism: the topological handedness of the demetallated knots was found to have a greater effect on the CD response than the Euclidean chirality of individual chiral centers.
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Aug 2019
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Kealan J.
Fallon
,
Peter
Budden
,
Enrico
Salvadori
,
Alex M.
Ganose
,
Christopher N.
Savory
,
Lissa
Eyre
,
Simon
Dowland
,
Qianxiang
Ai
,
Stephen
Goodlett
,
Chad
Risko
,
David O.
Scanlon
,
Christopher W. M.
Kay
,
Akshay
Rao
,
Richard H.
Friend
,
Andrew J.
Musser
,
Hugo
Bronstein
Abstract: Singlet fission, the process of forming two triplet excitons from one photon, is a characteristic reserved for only a handful of organic molecules due to the atypical energetic requirement for low energy excited triplet states. The predominant strategy for achieving such trait is by increasing ground state diradical character, however this greatly reduces ambient stability. Herein, we exploit Baird’s rule of excited state aromaticity to manipulate the singlet-triplet energy gap and create novel singlet fission candidates. We achieve this through the inclusion of a [4n] 5-membered heterocycle, whose electronic resonance promotes aromaticity in the triplet state, stabilizing its energy relative to the singlet excited state. Using this theory, we design a family of derivatives of indolonaphthyridine thiophene (INDT) with highly tunable excited state energies. Not only do we access novel singlet fission materials, they also exhibit excellent ambient stability, imparted due to the delocalized nature of the triplet excited state. Spin-coated films retained up to 85% activity after several weeks of exposure to oxygen and light, whilst analo-gous films of TIPS-pentacene showed full degradation after four days, showcasing the excellent stability of this class of singlet fission scaffold. Extension of our theoretical analysis to almost ten thousand candidates reveals an unprecedented degree of tuneability and several thousand potential fission-capable candidates, whilst clearly demonstrating the relationship between triplet aromaticity and singlet-triplet energy gap, confirming this novel strategy for manipulating the exchange energy in organic materials.
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Aug 2019
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I19-Small Molecule Single Crystal Diffraction
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Diamond Proposal Number(s):
[17379]
Abstract: We report a family of hybrid [2]rotaxanes based on inorganic [Cr7NiF8(O2CtBu)16]- (“{Cr7Ni}”) rings templated about organic threads that are terminated at one end with pyridyl groups. These rotaxanes can be coordinated to [Cu(hfac)2] (where hfac = 1,1,1,5,5,5-hexafluoroacetylacetone), to give 1:1 or 1:2 Cu:{Cr7Ni} adducts: {[Cu(hfac)2](py-CH2NH2CH2CH2Ph)[Cr7NiF8(O2CtBu)16]}, {[Cu(hfac)2][py-CH2NH2CH2CH3][Cr7NiF8(O2CtBu)16]}, {[Cu(hfac)2]([py-CH2CH2NH2CH2C6H4SCH3][Cr7NiF8(O2CtBu)16])2}, {[Cu(hfac)2]([py-C6H4-CH2NH2(CH2)4Ph][Cr7NiF8(O2CtBu)16])2}, and {[Cu(hfac)2]([3-py-CH2CH2NH2(CH2)3SCH3][Cr7NiF8(O2CtBu)16])2}, the structures of which have been determined by X-ray diffraction. The {Cr7Ni} rings and CuII ions both have electronic spin S = ½, but with very different g-values. Continuous-wave EPR spectroscopy reveals the exchange interactions between these dissimilar spins, and hence the communication between the different molecular components that comprise these supramolecular systems. The interactions are weak such that we observe AX or AX2 type spectra. The connectivity between the {Cr7Ni} ring and thread terminus is varied such that the magnitude of the exchange interaction J can be tuned. The coupling is shown to be dominated by through-bond rather than through-space mechanisms.
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Aug 2019
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