I19-Small Molecule Single Crystal Diffraction
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Diamond Proposal Number(s):
[33014, 35357]
Open Access
Abstract: The increasing availability of ultrabright Light Sources is facilitating the study of smaller crystals at faster timescales but with an increased risk of severe X-ray damage, leading to developments in multi-crystal methods such as serial crystallography (SX). SX studies on crystals with small unit cells are challenging as very few reflections are recorded in a single data image, making it difficult to determine the orientation matrix for each crystal and thus preventing the combination of the data from all crystals for structure solution. We herein present a Small-Rotative Fixed-Target Serial Synchrotron Crystallography (SR-FT-SSX) methodology, in which rotation of the serial target through a small diffraction angle at each crystal delivers high-quality data, facilitating ab initio unit cell determination and atomic-scale structure solution. The method is benchmarked using microcrystals of the small-molecule photoswitch sodium nitroprusside dihydrate, obtaining complete data to dmin = 0.6 Å by combining just 66 partial datasets selected against rigorous quality criteria.
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Nov 2024
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I18-Microfocus Spectroscopy
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Diamond Proposal Number(s):
[31385]
Open Access
Abstract: A free-standing and compact reaction cell for combined in situ/operando x-ray spectroscopy, scattering, and imaging measurements at high pressures and high temperatures is described. The cell permits measurements under realistic operating conditions (up to 50 bar and 1000 °C), under static and flow conditions (up to 100 ml/min), over a wide range of hard x-ray energies, variable detection modes (transmission, fluorescence, and scattering), and at all angles of rotation. An operando XAS, x-ray fluorescence, x-ray computed tomography, and x-ray diffraction computed tomography case study on the reduction of a heterogeneous catalyst is presented to illustrate the performance of the reaction cell.
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Oct 2024
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I20-Scanning-X-ray spectroscopy (XAS/XES)
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Diamond Proposal Number(s):
[28859, 30113]
Open Access
Abstract: Here, the novel technique of extended-range high-energy-resolution fluorescence detection (XR-HERFD) has successfully observed the n = 2 satellite in manganese to a high accuracy. The significance of the satellite signature presented is many hundreds of standard errors and well beyond typical discovery levels of three to six standard errors. This satellite is a sensitive indicator for all manganese-containing materials in condensed matter. The uncertainty in the measurements has been defined, which clearly observes multiple peaks and structure indicative of complex physical quantum-mechanical processes. Theoretical calculations of energy eigenvalues, shake-off probability and Auger rates are also presented, which explain the origin of the satellite from physical n = 2 shake-off processes. The evolution in the intensity of this satellite is measured relative to the full Kα spectrum of manganese to investigate satellite structure, and therefore many-body processes, as a function of incident energy. Results demonstrate that the many-body reduction factor S02 should not be modelled with a constant value as is currently done. This work makes a significant contribution to the challenge of understanding many-body processes and interpreting HERFD or resonant inelastic X-ray scattering spectra in a quantitative manner.
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Jul 2024
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I23-Long wavelength MX
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Yishun
Lu
,
Ramona
Duman
,
James
Beilsten-Edmands
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Graeme
Winter
,
Mark
Basham
,
Gwyndaf
Evans
,
Jos J. A. G.
Kamps
,
Allen M.
Orville
,
Hok-Sau
Kwong
,
Konstantinos
Beis
,
Wesley
Armour
,
Armin
Wagner
Open Access
Abstract: rocessing of single-crystal X-ray diffraction data from area detectors can be separated into two steps. First, raw intensities are obtained by integration of the diffraction images, and then data correction and reduction are performed to determine structure-factor amplitudes and their uncertainties. The second step considers the diffraction geometry, sample illumination, decay, absorption and other effects. While absorption is only a minor effect in standard macromolecular crystallography (MX), it can become the largest source of uncertainty for experiments performed at long wavelengths. Current software packages for MX typically employ empirical models to correct for the effects of absorption, with the corrections determined through the procedure of minimizing the differences in intensities between symmetry-equivalent reflections; these models are well suited to capturing smoothly varying experimental effects. However, for very long wavelengths, empirical methods become an unreliable approach to model strong absorption effects with high fidelity. This problem is particularly acute when data multiplicity is low. This paper presents an analytical absorption correction strategy (implemented in new software AnACor) based on a volumetric model of the sample derived from X-ray tomography. Individual path lengths through the different sample materials for all reflections are determined by a ray-tracing method. Several approaches for absorption corrections (spherical harmonics correction, analytical absorption correction and a combination of the two) are compared for two samples, the membrane protein OmpK36 GD, measured at a wavelength of λ = 3.54 Å, and chlorite dismutase, measured at λ = 4.13 Å. Data set statistics, the peak heights in the anomalous difference Fourier maps and the success of experimental phasing are used to compare the results from the different absorption correction approaches. The strategies using the new analytical absorption correction are shown to be superior to the standard spherical harmonics corrections. While the improvements are modest in the 3.54 Å data, the analytical absorption correction outperforms spherical harmonics in the longer-wavelength data (λ = 4.13 Å), which is also reflected in the reduced amount of data being required for successful experimental phasing.
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Jun 2024
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I08-Scanning X-ray Microscopy beamline (SXM)
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James
Everett
,
Jake
Brooks
,
Vindy Tjendana
Tjhin
,
Frederik
Lermyte
,
Ian
Hands-Portman
,
Germán
Plascencia-Villa
,
George
Perry
,
Peter J.
Sadler
,
Peter B.
O’connor
,
Joanna F.
Collingwood
,
Neil D.
Telling
Open Access
Abstract: The accumulation of amyloid plaques and increased brain redox burdens are neuropathological hallmarks of Alzheimer’s disease. Altered metabolism of essential biometals is another feature of Alzheimer’s, with amyloid plaques representing sites of disturbed metal homeostasis. Despite these observations, metal-targeting disease treatments have not been therapeutically effective to date. A better understanding of amyloid plaque composition and the role of the metals associated with them is critical. To establish this knowledge, the ability to resolve chemical variations at nanometer length scales relevant to biology is essential. Here, we present a methodology for the label-free, nanoscale chemical characterization of amyloid plaques within human Alzheimer’s disease tissue using synchrotron X-ray spectromicroscopy. Our approach exploits a C–H carbon absorption feature, consistent with the presence of lipids, to visualize amyloid plaques selectively against the tissue background, allowing chemical analysis to be performed without the addition of amyloid dyes that alter the native sample chemistry. Using this approach, we show that amyloid plaques contain elevated levels of calcium, carbonates, and iron compared to the surrounding brain tissue. Chemical analysis of iron within plaques revealed the presence of chemically reduced, low-oxidation-state phases, including ferromagnetic metallic iron. The zero-oxidation state of ferromagnetic iron determines its high chemical reactivity and so may contribute to the redox burden in the Alzheimer’s brain and thus drive neurodegeneration. Ferromagnetic metallic iron has no established physiological function in the brain and may represent a target for therapies designed to lower redox burdens in Alzheimer’s disease. Additionally, ferromagnetic metallic iron has magnetic properties that are distinct from the iron oxide forms predominant in tissue, which might be exploitable for the in vivo detection of amyloid pathologies using magnetically sensitive imaging. We anticipate that this label-free X-ray imaging approach will provide further insights into the chemical composition of amyloid plaques, facilitating better understanding of how plaques influence the course of Alzheimer’s disease.
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Mar 2024
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B18-Core EXAFS
I14-Hard X-ray Nanoprobe
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Diamond Proposal Number(s):
[25824]
Open Access
Abstract: The application of X-ray spectro-microscopy to image changes in the chemical state in application areas such as catalysis, environmental science, or biological samples can be limited by factors such as the speed of measurement, the presence of dilute concentrations, radiation damage, and thermal drift during the measurement. We have adapted a reduced-order model approach, known as the discrete empirical interpolation method, which identifies how to optimally subsample the spectroscopic information, accounting for background variations in the signal, to provide an accurate approximation of an equivalent full spectroscopic measurement from the sampled material. This approach uses readily available prior information to guide and significantly reduce the sampling requirements impacting both the total X-ray dose and the acquisition time. The reduced-order model approach can be adapted more broadly to any spectral or spectro-microscopy measurement where a low-rank approximation can be made from prior information on the possible states of a system, and examples of the approach are presented.
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Mar 2024
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I19-Small Molecule Single Crystal Diffraction
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Diamond Proposal Number(s):
[22240]
Open Access
Abstract: Single-crystal X-ray diffraction analysis of small molecule active pharmaceutical ingredients is a key technique in the confirmation of molecular connectivity, including absolute stereochemistry, as well as the solid-state form. However, accessing single crystals suitable for X-ray diffraction analysis of an active pharmaceutical ingredient can be experimentally laborious, especially considering the potential for multiple solid-state forms (solvates, hydrates and polymorphs). In recent years, methods for the exploration of experimental crystallization space of small molecules have undergone a `step-change', resulting in new high-throughput techniques becoming available. Here, the application of high-throughput encapsulated nanodroplet crystallization to a series of six dihydropyridines, calcium channel blockers used in the treatment of hypertension related diseases, is described. This approach allowed 288 individual crystallization experiments to be performed in parallel on each molecule, resulting in rapid access to crystals and subsequent crystal structures for all six dihydropyridines, as well as revealing a new solvate polymorph of nifedipine (1,4-dioxane solvate) and the first known solvate of nimodipine (DMSO solvate). This work further demonstrates the power of modern high-throughput crystallization methods in the exploration of the solid-state landscape of active pharmaceutical ingredients to facilitate crystal form discovery and structural analysis by single-crystal X-ray diffraction.
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Dec 2023
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Brian R.
Pauw
,
Glen J.
Smales
,
Andy
Anker
,
Venkatasamy
Annadurai
,
Daniel M.
Balazs
,
Ralf
Bienert
,
Wim G.
Bouwman
,
Ingo
Breßler
,
Joachim
Breternitz
,
Erik S.
Brok
,
Gary
Bryant
,
Andrew
Clulow
,
Erin R.
Crater
,
Frédéric
De Geuser
,
Alessandra
Del Giudice
,
Jérôme
Deumer
,
Sabrina
Disch
,
Shankar
Dutt
,
Kilian
Frank
,
Emiliano
Fratini
,
Paulo R. A. F.
Garcia
,
Elliot P.
Gilbert
,
Marc B.
Hahn
,
James
Hallett
,
Max
Hohenschutz
,
Martin J.
Hollamby
,
Steven
Huband
,
Jan
Ilavsky
,
Johanna K.
Jochum
,
Mikkel
Juelsholt
,
Bradley W.
Mansel
,
Paavo
Penttilä
,
Rebecca K.
Pittkowski
,
Giuseppe
Portale
,
Lilo D.
Pozzo
,
Leonhard
Rochels
,
Julian M.
Rosalie
,
Patrick E. J.
Saloga
,
Susanne
Seibt
,
Andrew J.
Smith
,
Gregory N.
Smith
,
Glenn A.
Spiering
,
Tomasz M.
Stawski
,
Olivier
Taché
,
Andreas F.
Thünemann
,
Kristof
Toth
,
Andrew E.
Whitten
,
Joachim
Wuttke
Open Access
Abstract: A round-robin study has been carried out to estimate the impact of the human element in small-angle scattering data analysis. Four corrected datasets were provided to participants ready for analysis. All datasets were measured on samples containing spherical scatterers, with two datasets in dilute dispersions and two from powders. Most of the 46 participants correctly identified the number of populations in the dilute dispersions, with half of the population mean entries within 1.5% and half of the population width entries within 40%. Due to the added complexity of the structure factor, far fewer people submitted answers on the powder datasets. For those that did, half of the entries for the means and widths were within 44 and 86%, respectively. This round-robin experiment highlights several causes for the discrepancies, for which solutions are proposed.
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Dec 2023
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I11-High Resolution Powder Diffraction
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Tian
Luo
,
Zi
Wang
,
Yinlin
Chen
,
Hengzhao
Li
,
Mengqi
Peng
,
Floriana
Tuna
,
Eric J. L.
Mcinnes
,
Sarah J.
Day
,
Jie
An
,
Martin
Schroeder
,
Sihai
Yang
Diamond Proposal Number(s):
[31365]
Open Access
Abstract: Deuterium labelling of organic compounds is an important process in chemistry. We report the first example of photocatalytic dehalogenative deuteration of both arylhalides and alkylhalides (40 substrates) over a metal-organic framework, MFM-300(Cr), using CD3CN as the deuterium source at room temperature. MFM-300(Cr) catalyses high deuterium incorporation and shows excellent tolerance to various functional groups. Synchrotron X-ray powder diffraction reveals the activation of halogenated substrates via confined binding within MFM-300(Cr). In situ electron paramagnetic resonance spectroscopy confirms the formation of carbon-based radicals as intermediates and reveals the reaction pathway. This protocol removes the use of precious-metal catalysts from state-of-the-art processes based upon direct hydrogen isotope exchange and shows high photocatalytic stability, thus enabling multiple catalytic cycles.
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Oct 2023
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B18-Core EXAFS
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Diamond Proposal Number(s):
[14673]
Open Access
Abstract: Process analytical technologies are widely used to inform process control by identifying relationships between reagents and products. Here, we present a novel process analytical technology system for operando XAS on multiphase multicomponent synthesis processes based on the combination of a conventional lab-scale agitated reactor with a liquid-jet cell. The preparation of sulfonate-stabilized CaCO3 particles from polyphasic Ca(OH)2 dispersions was monitored in real time by Ca K-edge XAS to identify changes in Ca speciation in the bulk solution/dispersion as a function of time and process conditions. Linear combination fitting of the spectra quantitatively resolved composition changes from the initial conversion of Ca(OH)2 to the Ca(R–SO3)2 surfactant to the ultimate formation of nCaCO3·mCa(R− SO3)2 particles. The system provides a novel tool with strong chemical specificity for probing multiphase synthesis processes at a molecular level, providing an avenue to establishing the relationships between critical quality attributes of a process and the quality and performance of the product.
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Oct 2023
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