I11-High Resolution Powder Diffraction
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Diamond Proposal Number(s):
[36397]
Open Access
Abstract: Although it is widely accepted that the long-range (average) crystal structure plays a critical role in determining the electrochemical performance of battery materials, the relationship between local structural features and electrochemical performance is rarely studied. Disordered rock salt oxides (DRX), which have become serious contenders for next generation Li-ion electrode materials, provide an ideal platform for exploring correlations between local structure and electrochemical performance as they exhibit a simple face-centered cubic structure and combine long-range disorder and short-range order on the cation sublattice. This work examines the Li1.1Mn0.7Zr0.2−xTixO2 series of DRX cathodes and investigates the links between local structure rearrangements and capacity activation. The end-member Li1.1Mn0.7Zr0.2O2 compound exhibits a low capacity in the as-synthesized state, attributed to unfavorable short-range order that hinders Li-ion transport, yet its capacity increases seven-fold, from 20 to 140 mAh g−1, after chemical delithiation followed by a 400 °C heat treatment. Capacity activation is associated with the appearance of local spinel-like structural features that depart from the short-range order originally present in the material, without significant change to the bulk composition and average crystal structure. Investigation of a series of Li1.1Mn0.7Zr0.2−xTixO2 (x ≤ 0.2) DRX compounds reveals that the correlation length of the spinel-like ordering that emerges during the heat treatment strongly depends on the Zr[thin space (1/6-em)]:[thin space (1/6-em)]Ti ratio. Yet, dramatic capacity activation and electrochemical (pseudo-)plateaus reminiscent of Mn-based spinel cathodes are observed for all compounds irrespective of the size of the ordered domains. To explain this phenomenon, we propose that the DRX phase undergoes a complete transformation to a spinel-like domain structure, which improves bulk Li-ion transport regardless of domain size.
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Jan 2026
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I15-Extreme Conditions
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Diamond Proposal Number(s):
[29285]
Open Access
Abstract: Rutile-structured materials can exhibit negative linear compressibility (NLC) following ferroelastic phase transitions, expanding in one direction under uniform compression. We investigate this phenomenon in structural analogues—transition metal dicyanamides (dca) and tricyanomethanides (tcm) with single and double rutile-like structures, respectively. The pressure-induced structural behaviour of Cu(tcm)2 and Cu(dca)2 are studied using high-pressure diffraction. Both systems undergo anisotropic deformation upon compression, with Cu(dca)2 exhibiting NLC of −6.5(10) TPa−1 along the c-axis, while Cu(tcm)2 shows zero linear compressibility (ZLC) along the a-axis. This difference is attributed to the single rutile-like network with flexible dca− linkers in Cu(dca)2, in contrast to the more constrained doubly interpenetrating structure of Cu(tcm)2 with rigid tcm− linkers. We also study the interplay between structural features and electronic effects arising from the Jahn–Teller distortion in both materials, in controlling their compression behaviour.
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Dec 2025
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I03-Macromolecular Crystallography
I04-1-Macromolecular Crystallography (fixed wavelength)
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Diamond Proposal Number(s):
[30602]
Open Access
Abstract: Fragment-based drug design offers multiple routes to advance from fragments. One approach is to build structure-activity relationships (SAR) from analogue series in direct-to-biology workflows. Analogues can be prepared by automated chemistry and tested as crude reaction mixtures (CRMs) without purification, but assay noise often leads to hit resynthesis, potentially discarding false negatives and reducing SAR dataset size. High-throughput (HT) X-ray crystallography has the potential to address these issues by resolving hits directly from 100s–1000s of CRMs. However, no systematic analytics exist for extracting SAR models from HT crystallographic evaluation of CRMs. Here, we demonstrate that crystallographic SAR (xSAR) can be extracted from CRMs evaluated via HT X-ray crystallography. We developed a simple rule-based ligand scoring scheme that identifies conserved chemical features associated with crystallographic binding and non-binding. Applied to a crystallographic dataset of 957 fragment elaborations in CRMs targeting PHIP(2), a therapeutically relevant bromodomain, our xSAR model demonstrated effectiveness in two proof-of-concept experiments. First, it recovered 26 missed binders in the initial dataset (false negatives), doubling the hit rate and denoising the dataset. Second, it enabled a prospective virtual screen that identified novel hits with informative chemistries and measurable binding affinities. This work establishes a proof-of-concept that xSAR models can be directly extracted from large-scale crystallographic readouts of CRMs, offering a valuable methodology to build SAR models and accelerate design-make-test iterations without requiring CRM hit resynthesis and confirmation. This invites future work to utilise advanced analytics and modelling techniques to further strengthen purification-agnostic workflows.
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Dec 2025
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I19-Small Molecule Single Crystal Diffraction
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Diamond Proposal Number(s):
[34390, 34452, 26668]
Open Access
Abstract: A series of new isostructural Ti-oxo clusters containing bridging bidentate 1,n-alkane diolate ligands with the formula [Ti4O4(O2PR2)4{O(CH2)nO}2] (R = Ph, n = 2–5; R = Cy, n = 2–4) were prepared by an alkoxide exchange strategy. The cluster with the 1,5-pentane diolate ligand undergoes productive photoredox chemistry in solution under UV light, resulting in the oxidation of one end of the alkane diolate, and subsequent cyclisation into the lactone tetrahydro-2H-pyran-2-ol, along with formation of a two-electron reduced Ti-oxo cluster stabilised by pyridine. Clusters with smaller bridging alkane diolates show no productive photoredox reactivity, except for R = Cy, n = 3, in which the photoredox products are unstable to further redox processes. Ultrafast electronic absorption spectroscopy studies reveal that all clusters undergo a similar initial photoexcitation step, therefore, productive redox pathways are controlled by the availability of a suitable transition state for rapid proton-coupled electron transfer from the initially generated pendant alkane diolate radicals {Ti–O(CH2)nO˙}. This is dependent on the flexibility (i.e. size) of the 1,n-alkane diolate ligand backbone. Interestingly, the productive photoredox pathway of the 1,5-pentane diolate cluster is turned off when the flexibility of the cluster is restricted in the single crystal phase.
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Nov 2025
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B21-High Throughput SAXS
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Marta
Tiemblo Martín
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Marcello
Mercogliano
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Kaisa
Hiippala
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Luca
De Simone Carone
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María
Asunción Campanero-Rhodes
,
Maria
Masiello
,
Alessandro
Cangiano
,
Antonio
Molinaro
,
Luigi
Paduano
,
Dolores
Solís
,
Reetta
Satokari
,
Flaviana
Di Lorenzo
,
Alba
Silipo
Diamond Proposal Number(s):
[34244]
Open Access
Abstract: Odoribacter splanchnicus, a prominent member of the human gut microbiota, has emerged as a promising next-generation probiotic due to its anti-inflammatory properties and association with intestinal health. While previous studies have demonstrated its ability to attenuate inflammation and protect epithelial integrity, the molecular basis underlying these effects remained elusive. In this study, we provide the first comprehensive structural and functional characterization of the O. splanchnicus lipooligosaccharide (LOS), a major immunomodulatory surface component. NMR spectroscopy and Mass spectrometry revealed a heterogeneous LOS structure composed of a mono-phosphorylated tetra-and penta-acylated lipid A backbone and a highly branched, short core oligosaccharide featuring unique residues such as 4-lactylmannose and galactosaminuronic acid. Small-angle X-ray scattering demonstrated that the LOS self-assembles into core-shell spherical micelles, with a large oligosaccharide corona shielding the lipid A, thereby limiting its accessibility to the innate immunity TLR4/MD-2 receptor complex. Accordingly, O. splanchnicus LOS exhibited minimal TLR4 activation and failed to induce IL-8 secretion in enterocyte cell lines, in stark contrast to proinflammatory Escherichia coli LPS; in addition, it potently antagonized E. coli LPS-induced inflammation. These findings identify the LOS as a key effector of O. splanchnicus antiinflammatory phenotype and support its further development as a live biotherapeutic agent.
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Nov 2025
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I19-Small Molecule Single Crystal Diffraction
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Diamond Proposal Number(s):
[30280]
Open Access
Abstract: A new metal–organic framework (MOF) comprising copper and 2,3-dihydroxyterephthalate (2,3-dhtp) has been prepared using solvothermal synthesis. The solid (chemical formula of the as-made material): Cu12(dhtp)4(H2dhtp)3(CH3CO2)2 2DMF·10H2O is flexible in that its pore size adapts to match the size of guest molecules that are adsorbed. Carboxylate-containing molecules of different sizes (acetate, benzoic acid and ibuprofen) can be accommodated within the pores of the material and are coordinated to a dimeric copper unit. The localisation of the adsorbate guest molecule, the mode of binding and relatively low symmetry of the MOF allows the system to be used as a crystalline sponge. The crystal structure determination of the as-synthesised acetate-bound MOF was accomplished using single-crystal X-ray diffraction using a synchrotron source, while the benzoate- and ibuprofen-bound structures were solved using electron diffraction. A more practical adsorbent can be formulated by growing the MOF on a cotton fabric substrate, and this is shown to adsorb ibuprofen in a similar manner to the powdered MOF.
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Nov 2025
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I20-Scanning-X-ray spectroscopy (XAS/XES)
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Diamond Proposal Number(s):
[31504, 31559]
Open Access
Abstract: Lytic polysaccharide monooxygenases (LPMOs) play a critical role in the depolymerization of recalcitrant polysaccharides, such as chitin, making them of interest in biotechnological applications. These interfacial enzymes are also of great chemical interest because of their unique monocopper catalytic center and their ability to activate high energy C–H bonds. This report investigates the structural and electronic changes at the copper (Cu) site of an LPMO, SmAA10A, upon binding of its chitin substrate, utilizing a suite of spectroscopic and computational methods. Herein, we present the first reported X-ray Absorption (XAS) and Emission (XES) spectroscopic data on substrate-bound LPMO. By comparing the Cu(II) and Cu(I) states of SmAA10A in both the chitin-bound and unbound states, we provide insights into the structural adjustments facilitating substrate specificity and productive catalytic turnover. Our results indicate a substrate binding-induced conformational change in Cu(I) site geometry and concurrent modulations to the electronic structure, which prime the enzyme for targeted C–H activation with an H2O2 co-substrate. This work offers an atomistic understanding of interaction dynamics between the LPMO Cu site and the chitin substrate, advancing our knowledge of LPMO functionality and substrate specificity.
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Nov 2025
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B18-Core EXAFS
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Yinghao
Xu
,
Yi-Hsuan
Wu
,
Paula M.
Abdala
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Connor
Sherwin
,
Veronica
Celorrio
,
Diana
Piankova
,
Payal
Chaudhary
,
Vitaly
Alexandrov
,
Agnieszka
Kierzkowska
,
Denis A.
Kuznetsov
,
Christoph R.
Müller
Diamond Proposal Number(s):
[36625]
Open Access
Abstract: Iridium-based oxides are among the most promising catalysts for the acidic oxygen evolution reaction (OER) owing to their high catalytic activity and stability. Substituting iridium with earth-abundant elements could lower costs and potentially boost its intrinsic activity even further; however, no unambiguous structure–activity relationships describing the physical origins of the effect of the substituent for this class of electrocatalysts have been established. In this work, we utilized a series of IrOx(:M) nanoparticle catalysts to correlate their in situ structural changes with intrinsic OER activity. We observe that IrOx(:M) with M = W and In feature a significantly higher Ir-mass-normalized OER activity than IrOx, however the activity enhancements have a different origin. While the increased activity of IrOx[thin space (1/6-em)]:[thin space (1/6-em)]In stems from a higher number of electrochemically active iridium centers (due to the leaching of indium), IrOx[thin space (1/6-em)]:[thin space (1/6-em)]W features a higher intrinsic OER activity compared to IrOx, due to electronic effects of W on neighboring Ir/O sites. Furthermore, operando electrochemical mass spectrometry experiments and density functional theory (DFT) calculations revealed that the enhanced OER activity of IrOx(:M) does not originate from a promotion of the lattice oxygen coupling mechanism, but is instead associated with a facilitated conventional adsorbate evolution mechanism.
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Oct 2025
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I03-Macromolecular Crystallography
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Diamond Proposal Number(s):
[18812]
Open Access
Abstract: Here, we have linked one of the most common protein-protein interaction events, homodimerisation, to an essential trace metal, copper, through engineering green fluorescent protein. Mutation of H148 to cysteine promotes the neutral phenolic chromophore in the monomer that excites predominantly at ~400 nm. Homodimerisation via a copper-dependent disulphide bridge, switches the chromophore to the charged phenolate that excites at ~490 nm. The result is ~30 fold increase in the fluorescence emission ratio. Homo-dimerisation kinetics are further improved by optimising the sfGFP homodimer interface, generating the variant termed GFP-diS2. Structures of the monomeric and dimeric GFP-diS2 suggests charge switching is through peptide bond flipping and the formation of a buried organised water network around the chromophore that span the interface region. Fusion to a leucine zipper protein dimerisation element greatly increased GFP-diS2 association rate making it a more effective copper sensor in vitro and in vivo with Cu(I) instigating the signal change quicker and at lower ion concentrations than Cu(II). Thus, GFP-diS2 provides the framework for generating a sensitive genetically encoded copper sensor and will eventually be adapted to monitor one of the most important protein-protein interactions in biology, homo-oligomerisation.
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Oct 2025
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I04-Macromolecular Crystallography
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Thomas D.
Downes
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S. Paul
Jones
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James D.
Firth
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John F.
Darby
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Amelia K.
Gilio
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Hanna F.
Klein
,
Xinyu
Wang
,
David C
Blakemore
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Claudia
De Fusco
,
Stephen D.
Roughley
,
Lewis R.
Vidler
,
Maria A.
Whatton
,
Alison Jo-Anne
Woolford
,
Gail L.
Wrigley
,
Roderick E.
Hubbard
,
Gideon
Davies
,
Peter
O'Brien
,
Liang
Wu
Diamond Proposal Number(s):
[18598]
Open Access
Abstract: Fragment-based drug discovery is widely used in both academia and industry during the early stages of drug discovery. There is a growing interest in the design of 3-D fragments for inclusion in fragment libraries in order to increase chemical space coverage. We present herein the design and synthesis of 58 shape-diverse 3-D fragments that are prepared using just three modular synthetic methodologies. The 3-D fragments comprise a cyclic scaffold (cyclopentane, pyrrolidine, piperidine, tetrahydrofuran or tetrahydropyran) with one aromatic or heteroaromatic ring and possess properties within 'rule-of-three' fragment space. 3-D shape is assessed using principal moments of inertia analysis and conformational diversity is achieved by considering all conformations up to 1.5 kcal mol -1 above the energy of the global minimum energy conformer. Due to the modular nature of the fragment syntheses, these 3-D fragments are synthetically-enabled for fragment elaboration followon work, a key design feature. This modular, shape-diverse 3-D fragment collection has delivered privileged starting points across a spectrum of targets. Fragments from the set have been crystallographically validated in the SARS-CoV-2 main protease (M pro ) and the nonstructural protein 3 (Nsp3) (Mac1) as well as human glycosyltransferase MGATV, a major enzyme in the mammalian N-glycosylation pathway and a promoter of aggressive metastatic cancers, underscoring the breadth of biological space that can be explored.
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Sep 2025
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