B21-High Throughput SAXS
B23-Circular Dichroism
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Alessandro
Paciaroni
,
Valeria
Libera
,
Francesca
Ripanti
,
Andrea
Orecchini
,
Caterina
Petrillo
,
Daniela
Francisci
,
Elisabetta
Schiaroli
,
Samuele
Sabbatini
,
Anna
Gidari
,
Elisa
Bianconi
,
Antonio
Macchiarulo
,
Rohanah
Hussain
,
Lucia
Silvestrini
,
Paolo
Moretti
,
Norhan
Belhaj
,
Matteo
Vercelli
,
Yessica
Roque
,
Paolo
Mariani
,
Lucia
Comez
,
Francesco
Spinozzi
Diamond Proposal Number(s):
[29982, 32331]
Open Access
Abstract: The main protease (Mpro or 3CLpro) is an enzyme that is evolutionarily conserved among different genera of coronaviruses. As it is essential for processing and maturing viral polyproteins, Mpro has been identified as a promising target for the development of broad-spectrum drugs against coronaviruses. Like SARS-CoV and MERS-CoV, the mature and active form of SARS-CoV-2 Mpro is a dimer composed of identical subunits, each with a single active site. Individual monomers, however, have very low or no catalytic activity. As such, inhibition of Mpro can be achieved by molecules that target the substrate binding pocket to block catalytic activity or target the dimerization process. In this study, we investigated GC376, a transition-state analog inhibitor of the main protease of feline infectious peritonitis coronavirus, and Nirmatrelvir (NMV), an oral, bioavailable SARS-CoV-2 Mpro inhibitor with pan-human coronavirus antiviral activity. Our results show that both GC376 and NMV are capable of strongly binding to SARS-CoV-2 Mpro and altering the monomer-dimer equilibrium by stabilizing the dimeric state. This behavior is proposed to be related to a structured hydrogen-bond network established at the Mpro active site, where hydrogen bonds between Ser1’ and Glu166/Phe140 are formed in addition to those achieved by the latter residues with GC376 or NMV.
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Mar 2023
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William
Mccorkindale
,
Kadi L.
Saar
,
Daren
Fearon
,
Melissa
Boby
,
Haim
Barr
,
Amir
Ben-Shmuel
,
Nir
London
,
Frank
Von Delft
,
John D.
Chodera
,
Alpha. A.
Lee
,
The
Covid Moonshot Consortium
Open Access
Abstract: A common challenge in drug design pertains to finding chemical modifications to a ligand that increases its affinity to the target protein. An underutilized advance is the increase in structural biology throughput, which has progressed from an artisanal endeavor to a monthly throughput of hundreds of different ligands against a protein in modern synchrotrons. However, the missing piece is a framework that turns high-throughput crystallography data into predictive models for ligand design. Here, we designed a simple machine learning approach that predicts protein–ligand affinity from experimental structures of diverse ligands against a single protein paired with biochemical measurements. Our key insight is using physics-based energy descriptors to represent protein–ligand complexes and a learning-to-rank approach that infers the relevant differences between binding modes. We ran a high-throughput crystallography campaign against the SARS-CoV-2 main protease (MPro), obtaining parallel measurements of over 200 protein–ligand complexes and their binding activities. This allows us to design one-step library syntheses which improved the potency of two distinct micromolar hits by over 10-fold, arriving at a noncovalent and nonpeptidomimetic inhibitor with 120 nM antiviral efficacy. Crucially, our approach successfully extends ligands to unexplored regions of the binding pocket, executing large and fruitful moves in chemical space with simple chemistry.
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Mar 2023
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I19-Small Molecule Single Crystal Diffraction
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Diamond Proposal Number(s):
[29217]
Open Access
Abstract: Metal-organic frameworks (MOFs) are well known for their ability to adsorb various gases. The use of MOFs for the storage and release of biologically active gases, particularly nitric oxide (NO) and carbon monoxide (CO), has been a subject of interest. To elucidate the binding mechanisms and geometry of these gases, an in situ single crystal X-ray diffraction (scXRD) study using synchrotron radiation at Diamond Light Source has been performed on a set of MOFs that display promising gas adsorption properties. NO and CO, were introduced into activated Ni-CPO-27 and the related Co-4,6-dihydroxyisophthalate (Co-4,6-dhip). Both MOFs show strong binding affinity towards CO and NO, however CO suffers more from competitive co-adsorption of water. Additionally, we show that morphology can play an important role in the ease of dehydration for these two systems.
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Mar 2023
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B18-Core EXAFS
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Abstract: During my PhD research activity, I was involved in the development of smart materials with self-healing functionalities, the possibility to repair the "tissue" that constitutes the electrode, and the electrode/electrolyte interface is the first step towards improve batteries reliability. Concerning the anodic compartment, the active materials subjected to research were black phosphorus-based nanocomposite with carbon and advanced high entropy oxides with rock-salt structure. Subsequently, innovative functional cathode materials were developed for application in lithium-ion batteries that exhibits excellent cycling stability in a wide voltage range and high specific capacities. During the last year I focused on improving lithium metal battery technology, by realizing an enhanced polymer gel electrolyte by means of a Janus separator that showed excellent electrochemical performance, reduced capacity loss and the ability to intercept dendrite growth. A further improvement were Cu-based 3D current collectors as advanced anodes. They showed good capacity, life cycle of more than 300 hours and enhanced safety due to the greater surface area as well as the decrease in local current densities.
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Mar 2023
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I20-EDE-Energy Dispersive EXAFS (EDE)
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Diamond Proposal Number(s):
[29667]
Abstract: Single-atoms on carbon-nitrogen supports are considered catalysts for a multitude of reactions. However, doubts remain whether really these species or subnanometer clusters formed under reaction conditions are the active species. In this work, we investigate the dynamics of palladium single-atoms on graphitic carbon nitride during ethylene hydrogenation and H2-D2 exchange. By employing aberration-corrected scanning transmission electron microscopy, x-ray photoelectron spectroscopy and x-ray absorption spectroscopy, we will show that palladium, originally present as single-atoms, agglomerates to clusters at 100 °C in a gas atmosphere that contains both ethylene and hydrogen. This agglomeration goes in hand with the emergence of catalytic activity in both ethylene hydrogenation and H2-D2 exchange, suggesting that clusters, rather than single-atoms, are the active species. The results presented herein highlight the potential of analytics over the course of reaction to identify the active species and provide new insights into the influence of gas atmosphere on metal speciation.
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Mar 2023
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B07-C-Versatile Soft X-ray beamline: Ambient Pressure XPS and NEXAFS
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Diamond Proposal Number(s):
[22687]
Abstract: Designing CO2 methanation catalysts that meet industrial requirements is still challenging. We report Ni-Fe hydrotalcite-derived catalysts with a wide range of Ni and Mg loadings showing that an optimised composition with Ni0.4 gives a very high CO2 conversion rate of 0.37 mmol/gcat/s at 300°C. This catalyst is studied by in-situ APXPS and NEXAFS spectroscopies and compared with the other synthesised samples to obtain new mechanistic insights on methanation catalysts active for low-temperature (300°C) methanation, which is an industrial requirement. Under methanation conditions, in-situ investigations revealed the presence of metallic Ni sites and low nuclearity Ni-Fe species at
(Ni loading) = 21.2 mol%. These sites are oxidised on the low Ni-loaded catalyst (
= 9.2 mol%). The best CO2 conversion rate and CH4 selectivity are shown at intermediate
(21.2 mol%), in the presence of Mg. These superior performances are related to the high metallic surface area, dispersion, and optimal density of basic sites. The
(turnover frequency of CO2 conversion) increases exponentially with the fractional density of basic to metallic sites (
) from 1.1 s-1 (
= 29.2 mol%) to 9.1 s-1 (
= 7.6 mol%). It follows the opposite trend of the CO2 conversion rate. In-situ DRIFTS data under methanation conditions evidence that the
at high
is related to the presence of a formate route which is not predominant at low
(high
). A synergistic interplay of basic and metallic sites is present. This contribution provides a rationale for designing industrially competitive CO2 methanation catalysts with high catalytic activity while maintaining low Ni loading.
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Mar 2023
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I12-JEEP: Joint Engineering, Environmental and Processing
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Diamond Proposal Number(s):
[25682]
Open Access
Abstract: The crystallographic texture development during processing of dual-phase Ti alloys like Ti-6Al-4 V is of fundamental technological importance. However, measuring texture in both phases in these materials is a significant challenge because of the spatial inhomogeneity of the texture and low volume fraction of the minority β-phase at room temperature. Here we demonstrate how synchrotron X-ray diffraction can be used to overcome these difficulties and measure texture and texture variation in hot-rolled samples in a reproducible manner. The texture in hot-rolled Ti-64 was calculated from 2D synchrotron diffraction patterns obtained along different directions. The data was analysed using MAUD, which is based on Rietveld refinement of the diffracted intensities, and using a Fourier series based analysis method, that extracts intensities directly from the 2D diffraction patterns, and then uses the open-source software MTEX to fit an orientation distribution function (ODF). By comparing the results with faithful EBSD measurements, we show that the Fourier series method produces much more accurate texture measurements, especially for the minority β-phase. We also show that a minimum of 2, and preferably 3, different measurement orientations are needed to fully represent the texture. This implies that measurements of texture which rely on diffraction data from a single sample orientation, like in fast in-situ studies or spatially resolved measurements, can only provide qualitative information and must be interpreted with care.
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Mar 2023
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I10-Beamline for Advanced Dichroism
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Diamond Proposal Number(s):
[16141]
Open Access
Abstract: Owing to the unique chemical and electronic properties arising from 3d-electrons, substitution with transition metal ions is one of the key routes for engineering new functionalities into materials. While this approach has been used extensively in complex metal oxide perovskites, metal halide perovskites have largely resisted facile isovalent substitution. In this work, it is demonstrated that the substitution of Co2+ into the lattice of methylammonium lead triiodide imparts magnetic behavior to the material while maintaining photovoltaic performance at low concentrations. In addition to comprehensively characterizing its magnetic properties, the Co2+ ions themselves are utilized as probes to sense the local electronic environment of Pb in the perovskite, thereby revealing the nature of their incorporation into the material. A comprehensive understanding of the effect of transition metal incorporation is provided, thereby opening the substitution gateway for developing novel functional perovskite materials and devices for future technologies.
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Mar 2023
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I22-Small angle scattering & Diffraction
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Abstract: Quasicrystals are intriguing structures that have long-range positional correlations but no periodicity in real space, and typically with rotational symmetries that are ‘forbidden’ in conventional periodic crystals. Here, we present a two-dimensional columnar liquid quasicrystal with dodecagonal symmetry. Unlike previous dodecagonal quasicrystals based on random tiling, a honeycomb structure based on a strictly quasiperiodic tessellation of tiles is observed. The structure consists of dodecagonal clusters made up of triangular, square and trapezoidal cells that are optimal for local packing. To maximize the presence of such dodecagonal clusters, the system abandons periodicity but adopts a quasiperiodic structure that follows strict packing rules. The stability of random-tiling dodecagonal quasicrystals is often attributed to the entropy of disordering when strict tiling rules are broken, at the sacrifice of the long-range positional order. However, our results demonstrate that quasicrystal stability may rest on energy minimization alone, or with only minimal entropic intervention.
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Mar 2023
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I07-Surface & interface diffraction
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Yuqi
Sun
,
Lishuang
Ge
,
Linjie
Dai
,
Changsoon
Cho
,
Jordi
Ferrer Orri
,
Kangyu
Ji
,
Szymon J.
Zelewski
,
Yun
Liu
,
Alessandro J.
Mirabelli
,
Youcheng
Zhang
,
Jun-Yu
Huang
,
Yusong
Wang
,
Ke
Gong
,
May Ching
Lai
,
Lu
Zhang
,
Dan
Yang
,
Jiudong
Lin
,
Elizabeth M.
Tennyson
,
Caterina
Ducati
,
Samuel D.
Stranks
,
Lin-Song
Cui
,
Neil C.
Greenham
Diamond Proposal Number(s):
[30575]
Abstract: Perovskite light-emitting diodes (LEDs) have attracted broad attention due to their rapidly increasing external quantum efficiencies (EQEs)1,2,3,4,5,6,7,8,9,10,11,12,13,14,15. However, most high EQEs of perovskite LEDs are reported at low current densities (<1 mA cm−2) and low brightness. Decrease in efficiency and rapid degradation at high brightness inhibit their practical applications. Here, we demonstrate perovskite LEDs with exceptional performance at high brightness, achieved by the introduction of a multifunctional molecule that simultaneously removes non-radiative regions in the perovskite films and suppresses luminescence quenching of perovskites at the interface with charge-transport layers. The resulting LEDs emit near-infrared light at 800 nm, show a peak EQE of 23.8% at 33 mA cm−2 and retain EQEs more than 10% at high current densities of up to 1,000 mA cm−2. In pulsed operation, they retain EQE of 16% at an ultrahigh current density of 4,000 mA cm−2, along with a high radiance of more than 3,200 W s−1 m−2. Notably, an operational half-lifetime of 32 h at an initial radiance of 107 W s−1 m−2 has been achieved, representing the best stability for perovskite LEDs having EQEs exceeding 20% at high brightness levels. The demonstration of efficient and stable perovskite LEDs at high brightness is an important step towards commercialization and opens up new opportunities beyond conventional LED technologies, such as perovskite electrically pumped lasers.
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Mar 2023
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