I11-High Resolution Powder Diffraction
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Diamond Proposal Number(s):
[18786]
Open Access
Abstract: The crystallization of a new series of A-site substituted lanthanum ferrite materials (La1–xREx)FeO3 was explored by the hydrothermal method at 240 °C, for rare earth (RE) = Nd, Sm, Gd, Ho, Er, Yb, and Y, with 0 ≤ x ≤ 1. The effect of elemental substitution on the morphological, structural, and magnetic properties of the materials was studied using high-resolution powder X-ray diffraction, energy dispersive spectroscopy (EDS) on the scanning electron microscope, Raman spectroscopy, and SQUID magnetometry. If the radius of the La3+ and the substituent ions is similar, such as for Nd3+, Sm3+, and Gd3+, homogeneous solid solutions are formed, with the orthorhombic GdFeO3-type structure, and a continuous evolution of Raman spectra with composition and distinct magnetic behavior from the end members. When the radius difference between substituents and La3+ is large, such as for Ho3+, Er3+, Yb3+, and Y3+, then instead of forming solid solutions, crystallization in separate phases is found. However, low levels of element mixing are found and intergrowths of segregated regions give composite particles. In this case, the Raman spectra and magnetic behavior are characteristic of mixtures of phases, while EDS shows distinctive elemental segregation. A-site replacement induces an evolution in the crystallite shape with an increasing amount of substituent ions and this is most evident for RE = Y from cube-shaped crystals seen for LaFeO3 to multipodal crystals for (La1–xYx)FeO3, providing evidence for a phase-separation-driven evolution of morphology.
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Mar 2023
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B18-Core EXAFS
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Diamond Proposal Number(s):
[25120]
Open Access
Abstract: The development of multielectron redox-active cathode materials is a top priority for achieving high energy density with long cycle life in the next-generation secondary battery applications. Triggering anion redox activity is regarded as a promising strategy to enhance the energy density of polyanionic cathodes for Li/Na-ion batteries. Herein, K2Fe(C2O4)2 is shown to be a promising new cathode material that combines metal redox activity with oxalate anion (C2O42–) redox. This compound reveals specific discharge capacities of 116 and 60 mAh g–1 for sodium-ion batterie (NIB) and lithium-ion batterie (LIB) cathode applications, respectively, at a rate of 10 mA g–1, with excellent cycling stability. The experimental results are complemented by density functional theory (DFT) calculations of the average atomic charges.
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Mar 2023
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I15-1-X-ray Pair Distribution Function (XPDF)
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Diamond Proposal Number(s):
[19053]
Open Access
Abstract: A reverse Monte Carlo analysis of neutron and x-ray total scattering data from two ceria-zirconia samples of composition Ce0.75Zr0.25O2 is performed to analyze the distribution of cations and to examine the possibility of oxide-ion disorder. For the first material, heated in air under moderate conditions (800 °C), the structure is a single-phase solid-solution with the statistical distribution of cations, but a local tetragonal symmetry is found, consistent with the different coordination preferences of Ce and Zr. For the second material, heated under H2 at 1050 °C followed by reoxidation at 400 °C, the structure shows a considerable disorder, with evidence for oxygen interstitials (Frenkel-ion defects) and a non-statistical distribution of cations with significantly higher concentrations of like–like cation nearest neighbors, highlighting the existence of cation-rich nano-domains. The results highlight the dynamic nature of this solid-solution, with structural evolution upon thermal treatment, which is of relevance to understanding its stability under redox catalytic conditions in practical applications.
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Mar 2023
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I03-Macromolecular Crystallography
I04-1-Macromolecular Crystallography (fixed wavelength)
I04-Macromolecular Crystallography
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Diamond Proposal Number(s):
[18548, 25402]
Open Access
Abstract: The liver isoform of pyruvate kinase (PKL) has gained interest due to its potential capacity to regulate fatty acid synthesis involved in the progression of non-alcoholic fatty liver disease (NAFLD). Here we describe a novel series of PKL modulators that can either activate or inhibit the enzyme allosterically, from a cryptic site at the interface of two protomers in the tetrameric enzyme. Starting from urolithin D, we designed and synthesised 42 new compounds. The effect of these compounds on PKL enzymatic activity was assessed after incubation with cell lysates obtained from a liver cell line. Pronounced activation of PKL activity, up to 3.8-fold, was observed for several compounds at 10 μM, while other compounds were prominent PKL inhibitors reducing its activity to 81% at best. A structure-activity relationship identified linear-shaped sulfone-sulfonamides as activators and non-linear compounds as inhibitors. Crystal structures revealed the conformations of these modulators, which were used as a reference for designing new modulators.
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Mar 2023
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I04-Macromolecular Crystallography
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Martina
Durcik
,
Andrej Emanuel
Cotman
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Žan
Toplak
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Štefan
Možina
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Žiga
Skok
,
Petra Eva
Szili
,
Márton
Czikkely
,
Elvin
Maharramov
,
Thu Hien
Vu
,
Maria Vittoria
Piras
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Nace
Zidar
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Janez
Ilaš
,
Anamarija
Zega
,
Jurij
Trontelj
,
Luis A.
Pardo
,
Diarmaid
Hughes
,
Douglas
Huseby
,
Tália
Berruga-Fernández
,
Sha
Cao
,
Ivailo
Simoff
,
Richard
Svensson
,
Sergiy V.
Korol
,
Zhe
Jin
,
Francisca
Vicente
,
Maria C.
Ramos
,
Julia E. A.
Mundy
,
Anthony
Maxwell
,
Clare E. M.
Stevenson
,
David M.
Lawson
,
Björn
Glinghammar
,
Eva
Sjöström
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Martin
Bohlin
,
Joanna
Oreskär
,
Sofie
Alvér
,
Guido V.
Janssen
,
Geert Jan
Sterk
,
Danijel
Kikelj
,
Csaba
Pal
,
Tihomir
Tomašič
,
Lucija
Peterlin Mašič
Diamond Proposal Number(s):
[25108]
Open Access
Abstract: A new series of dual low nanomolar benzothiazole inhibitors of bacterial DNA gyrase and topoisomerase IV were developed. The resulting compounds show excellent broad-spectrum antibacterial activities against Gram-positive Enterococcus faecalis, Enterococcus faecium and multidrug resistant (MDR) Staphylococcus aureus strains [best compound minimal inhibitory concentrations (MICs): range, <0.03125–0.25 μg/mL] and against the Gram-negatives Acinetobacter baumannii and Klebsiella pneumoniae (best compound MICs: range, 1–4 μg/mL). Lead compound 7a was identified with favorable solubility and plasma protein binding, good metabolic stability, selectivity for bacterial topoisomerases, and no toxicity issues. The crystal structure of 7a in complex with Pseudomonas aeruginosa GyrB24 revealed its binding mode at the ATP-binding site. Expanded profiling of 7a and 7h showed potent antibacterial activity against over 100 MDR and non-MDR strains of A. baumannii and several other Gram-positive and Gram-negative strains. Ultimately, in vivo efficacy of 7a in a mouse model of vancomycin-intermediate S. aureus thigh infection was also demonstrated.
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Mar 2023
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I03-Macromolecular Crystallography
I04-1-Macromolecular Crystallography (fixed wavelength)
I04-Macromolecular Crystallography
I24-Microfocus Macromolecular Crystallography
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Mona M.
Katariya
,
Matthew
Snee
,
Richard B.
Tunnicliffe
,
Madeline E.
Kavanagh
,
Helena I. M.
Boshoff
,
Cecilia N.
Amadi
,
Colin W.
Levy
,
Andrew W.
Munro
,
Chris
Abell
,
David
Leys
,
Anthony G.
Coyne
,
Kirsty J.
Mclean
Diamond Proposal Number(s):
[17773, 24447]
Open Access
Abstract: Mycobacterium tuberculosis (Mtb) was responsible for approximately 1.6 million deaths in 2021. With the emergence of extensive drug resistance, novel therapeutic agents are urgently needed, and continued drug discovery efforts required. Host-derived lipids such as cholesterol support Mtb growth, and are also suspected to function in immunomodulation, with links to persistence and immune evasion. Mtb cytochrome P450 (CYP) enzymes facilitate key steps in lipid catabolism and thus present potential targets for inhibition. Here we present a series of compounds based on an ethyl 5-(pyridin-4-yl)-1H-indole-2-carboxylate pharmacophore which bind strongly to both Mtb cholesterol oxidases CYP125 and CYP142. Using a structure-guided approach, combined with biophysical characterization, compounds with micromolar range in-cell activity against clinically relevant drug-resistant isolates were obtained. These will support further development of much-needed additional treatment options and provide routes to probe the role of CYP125 and CYP142 in Mtb pathogenesis.
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Mar 2023
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I22-Small angle scattering & Diffraction
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Diamond Proposal Number(s):
[28511]
Open Access
Abstract: The contents of biological cells are retained within compartments formed of phospholipid membranes. The movement of material within and between cells is often mediated by the fusion of phospholipid membranes, which allows mixing of contents or excretion of material into the surrounding environment. Biological membrane fusion is a highly regulated process that is catalyzed by proteins and often triggered by cellular signaling. In contrast, the controlled fusion of polymer-based membranes is largely unexplored, despite the potential application of this process in nanomedicine, smart materials, and reagent trafficking. Here, we demonstrate triggered polymersome fusion. Out-of-equilibrium polymersomes were formed by ring-opening metathesis polymerization-induced self-assembly and persist until a specific chemical signal (pH change) triggers their fusion. Characterization of polymersomes was performed by a variety of techniques, including dynamic light scattering, dry-state/cryogenic-transmission electron microscopy, and small-angle X-ray scattering (SAXS). The fusion process was followed by time-resolved SAXS analysis. Developing elementary methods of communication between polymersomes, such as fusion, will prove essential for emulating life-like behaviors in synthetic nanotechnology.
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Mar 2023
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I03-Macromolecular Crystallography
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Rob
Barringer
,
Alice E.
Parnell
,
Aleix
Lafita
,
Vivian
Monzon
,
Catherine R.
Back
,
Mariusz
Madej
,
Jan
Potempa
,
Angela H.
Nobbs
,
Steven G.
Burston
,
Alex
Bateman
,
Paul R.
Race
Diamond Proposal Number(s):
[23269]
Abstract: Bacterial fibrillar adhesins are specialised extracellular polypeptides that promote the attachment of bacteria to the surfaces of other cells or materials. Adhesin-mediated interactions are critical for the establishment and persistence of stable bacterial populations within diverse environmental niches and are important determinants of virulence. The fibronectin (Fn) binding fibrillar adhesin CshA, and its paralogue CshB, play important roles in host colonisation by the oral commensal and opportunistic pathogen Streptococcus gordonii. As paralogues are often catalysts for functional diversification, we have probed the early stages of structural and functional divergence in Csh proteins by determining the X-ray crystal structure of the CshB adhesive domain NR2 and characterising its Fn binding properties in vitro. Despite sharing a common fold, CshB_NR2 displays an ~1.7-fold reduction in Fn binding affinity relative to CshA_NR2. This correlates with reduced electrostatic charge in the Fn binding cleft. Complementary bioinformatic studies reveal that homologues of CshA/B_NR2 domains are widely distributed in both Gram-positive and Gram-negative bacteria, where they are found housed within functionally cryptic multi-domain polypeptides. Our findings are consistent with the classification of Csh adhesins and their relatives as members of the recently defined Polymer Adhesin Domain (PAD) family of bacterial proteins.
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Mar 2023
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I19-Small Molecule Single Crystal Diffraction
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Diamond Proposal Number(s):
[22240]
Open Access
Abstract: Hole transport materials (HTMs) based on truxene cores have emerged as promising candidates in recent years. They are noted by properties such as higher hole mobility and higher glass transition temperature than the 2,2′,7,7′-tetrakis (N,N-di-p-methoxyphenamine)-9,9′-spirobiflourene (spiro-MeOTAD), as well as good hydrophobicity and energy alignment. Truxene derivatives have been studied for application in transistors, OLEDs, lasers, supercapacitors, etc., however, there are only a few studies on their use as HTMs in perovskite solar cells (PSCs). In this study, we synthesised a novel small organic molecule HTM with a monothiatruxene (TrxS) core, namely TrxS-2MeOTAD, and characterised its basic properties and ability as an HTM in n–i–p planar PSCs. The TrxS-2MeOTAD showed suitable electrochemical, optical, structural and thermal properties for an HTM, such as a relatively high glass transition temperature (145 °C) and stable amorphous nature when deposited as films. The PSCs using TrxS-2MeOTAD achieved 18.9% power conversion efficiency (PCE) compared to the reference spiro-MeOTAD at 19.3% PCE. The unencapsulated TrxS-2MeOTAD devices showed better operational stability than spiro-MeOTAD, with a 1.5 times longer lifetime under constant AM1.5G illumination. Our results suggest that small molecules based on the TrxS core can be a promising direction for the development of alternative HTMs.
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Mar 2023
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B23-Circular Dichroism
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Diamond Proposal Number(s):
[31552]
Open Access
Abstract: A non-chiral ferroelectric nematic compound with a 1,3-dioxane unit in the mesogenic core called 2,3',4',5'-tetrafluoro-[1,1'-biphenyl]-4-yl 2,6-difluoro-4-(5-propyl-1,3-dioxan-2-yl) benzoate (DIO) was studied by dielectric spectroscopy in the frequency range 0.1 Hz to 10 MHz over a wide range of temperatures. The compound exhibits three nematic phases on cooling from the isotropic phase, i.e., the ordinary paraelectric nematic N; the intermediate nematic NX and the ferroelectric NF phases. The least frequency process is due to the dynamics of ions. The middle frequency relaxation process P1 is like as observed in other ferronematic compounds and this mode is a continuation of the molecular flip-flop motion in the isotropic phase to the collective dynamics of dipoles which are strongly coupled with the splay fluctuations in nematic phases. In addition to this process, DIO shows an additional collective relaxation process P2 at higher frequencies both in the N and the NX phases. This mode originates from the polar/chiral molecules of the opposite chirality, these arise from the spontaneous symmetry breaking of achiral mesogens in the N phase. Both collective processes, P1 and P2, show soft mode-like characteristic behavior on cooling from the N to the NX-NF phase transition temperature and are shown to contribute independently to the formation of the ferronematic NF phase.
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Mar 2023
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