The title compound, [Ru(C12H14NO2)2(C12H8N2)]PF6 crystallizes in the tetra­gonal Sohnke space group P41212. The two bidentate chiral salicyloxazoline ligands and the phenanthroline co-ligand coordinate to the central RuIII atom through N,O and N,N atom pairs to form bite angles of 89.76 (15) and 79.0 (2)°, respectively. The octa­hedral coordination of the bidentate ligands leads to a propeller-like shape, which induces metal-centered chirality onto the complex, with a right-handed (Δ) absolute configuration [the Flack parameter value is −0.003 (14)]. Both the complex cation and the disordered PF6− counter-anion are located on twofold rotation axes. Apart from Coulombic forces, the crystal cohesion is ensured by non-classical C—H⋯O and C—H⋯F inter­actions.

A new triazole-based N-heterocyclic carbene IrI cationic complex with a tetra­fluorido­borate counter-anion and hemi-solvating di­chloro­methane, [Ir(C8H12)(C8H15N3)(C18H15P)]BF4·0.5CH2Cl2, has been synthesized and structurally characterized. There are two independent ion pairs in the asymmetric unit and one di­chloro­methane solvent mol­ecule per two ion pairs. The cationic complex exhibits a distorted square-planar conformation around the IrI atom, formed by a bidentate cyclo­octa-1,5,diene (COD) ligand, a tri­phenyl­phosphane ligand, and an N-heterocyclic carbene (NHC). There are several close non-standard H⋯F hydrogen-bonding inter­actions that orient the tetra­fluorido­borate anions with respect to the IrI complex mol­ecules. The complex shows promising catalytic activity in transfer hydrogenation reactions. The structure was refined as a non-merohedral twin, and one of the COD mol­ecules is statistically disordered.

The crystal structure of a new 1:1 cocrystal of carbamazepine and S-naproxen (C15H12N2O·C14H14O3) was solved from powder X-ray diffraction (PXRD). The PXRD pattern was measured at the high-resolution beamline CRISTAL at synchrotron SOLEIL (France). The structure was solved using Monte Carlo simulated annealing, then refined with Rietveld refinement. The positions of the H atoms were obtained from density functional theory (DFT) ground-state calculations. The symmetry is ortho­rhom­bic with the space group P212121 (No. 19) and the following lattice parameters: a = 33.5486 (9), b = 26.4223 (6), c = 5.3651 (10) Å and V = 4755.83 (19) Å3.

Beauveriolides, including the main beauveriolide I {systematic name: (3R,6S,9S,13S)-9-benzyl-13-[(2S)-hexan-2-yl]-6-methyl-3-(2-methyl­prop­yl)-1-oxa-4,7,10-tri­aza­cyclo­tridecane-2,5,8,11-tetrone, C27H41N3O5}, are a series of cyclo­depsipeptides that have shown promising results in the treatment of Alzheimer's disease and in the prevention of foam cell formation in atherosclerosis. Their crystal structure studies have been difficult due to their tiny crystal size and fibre-like morphology, until now. Recent developments in 3D electron diffraction methodology have made it possible to accurately study the crystal structures of submicron crystals by overcoming the problems of beam sensitivity and dynamical scattering. In this study, the absolute structure of beauveriolide I was determined by 3D electron diffraction. The cyclo­dep­si­peptide crystallizes in the space group I2 with lattice parameters a = 40.2744 (4), b = 5.0976 (5), c = 27.698 (4) Å and β = 105.729 (6)°. After dynamical refinement, its absolute structure was determined by comparing the R factors and calculating the z-scores of the two possible enanti­omorphs of beauveriolide I.

X-ray and electron diffraction methods independently identify the S-enanti­omer of Berkecoumarin [systematic name: (S)-8-hy­droxy-3-(2-hy­droxy­prop­yl)-6-meth­oxy-2H-chromen-2-one]. Isolated from Berkeley Pit Lake Penicillium sp., Berkecoumarin is a natural product with a light-atom com­position (C13H14O5) that challenges in-house absolute structure determination by anomalous scattering. This study further demonstrates the utility of dynamical refinement of electron-diffraction data for absolute structure determination.

A section in the Acta Crystallographica Section C article by Raymond & Girolami [Acta Cryst. (2023), C79, 445–455] stated that the product of the reaction of [(Cp*Rh)2(μ-OH)3]+ (Cp* is 1,2,3,4,5-penta­methyl­cyclo­penta­diene) with 1-methyl­thymine (1-MT) at pH 10 and 60 °C, to synthesize the anionic com­ponent [RhI(η1-N3-1-MT)2]−, was not an RhI com­plex, but rather an AgI com­plex, due to the use of silver triflate (AgOTf) to remove Cl− from [Cp*RhCl2]2 to synthesize [Cp*Rh(H2O)3](OTf)2, a water-soluble crystalline com­plex. We will clearly show that this premise, as stated, is invalid, while the authors have simply avoided several important facts, including that Cp*OH, a reductive elimination product, at pH 10 and 60 °C, was unequivocally identified, thus leading to the RhI anionic com­ponent [RhI(η1-N3-1-MT)2]−. More importantly, AgOH, from the reaction of NaOH at pH 10 with any potentially remaining AgOTf, after the AgCl was filtered off, would be insoluble in water. Furthermore, a control experiment with the inorganic com­plex Rh(OH)3, reacting with 1-methyl­thymine at pH 10, provided no product, and this bodes well for a similar fate with AgOTf and 1-methyl­thymine, i.e. at pH 10, AgOTf would again be converted to the water-insoluble AgOH; therefore, no reaction would occur! Finally, a 1H NMR spectroscopy experiment was carried out with synthesized and crystallized [Cp*Rh(H2O)3](OTf)2 in D2O at various pD values; at pD 8.65 no reaction took place, while at pD 13.6, and at 60 °C for 2 h, a reductive elimination reaction caused the precipitation of Cp*OH. The subsequent 1H NMR spectrum clearly demonstrated, in the absence of any AgI com­plexes, that the solution structure and the X-ray crystals in D2O were similar. A postulated mechanism for this novel anionic com­ponent structure, as published previously [Smith et al. (2014). Organometallics, 33, 2389–2404], will be presented, along with the experimental data, to insure the credibility of our results. We will also answer the comments in the response of Drs Raymond and Girolami to this rebuttal.

We stand fully behind our earlier suggestion [Raymond & Girolami (2023). Acta Cryst. C79, 445–455] that the claim by Fish and co-workers [Chen et al. (1995). J. Am. Chem. Soc. 117, 9097–9098; Smith et al. (2014). Organometallics, 33, 2389–2404] of a linear two-coordinate rhodium(I) species is incorrect, and that the putative rhodium atom is in fact silver.

Using a 1:1 cocrystal of (E)-N-(3,4-di­fluoro­phen­yl)-1-(pyridin-4-yl)methanimine with acetic acid, C12H8F2N2·C2H4O2, we investigate the influence of F atoms introduced to the aromatic ring on promoting π–π inter­actions. The cocrystal crystallizes in the triclinic space group P1. Through crystallographic analysis and com­putational studies, we reveal the mol­ecular arrangement within this co­crystal, demonstrating the presence of hydrogen bonding between the acetic acid mol­ecule and the pyridyl group, along with π–π inter­actions between the aromatic rings. Our findings highlight the importance of F atoms in promoting π–π inter­actions without necessitating full halogenation of the aromatic ring.

3D electron diffraction (3D ED), or microcrystal electron diffraction (MicroED), has become an alternative technique for determining the high-resolution crystal structures of compounds from sub-micron-sized crystals. Here, we considered l-alanine, α-glycine and urea, which are known to form good-quality crystals, and collected high-resolution 3D ED data on our in-house TEM instrument. In this study, we present a comparison of independent atom model (IAM) and transferable aspherical atom model (TAAM) kinematical refinement against experimental and simulated data. TAAM refinement on both experimental and simulated data clearly improves the model fitting statistics (R factors and residual electrostatic potential) compared to IAM refinement. This shows that TAAM better represents the experimental electrostatic potential of organic crystals than IAM. Furthermore, we compared the geometrical parameters and atomic displacement parameters (ADPs) resulting from the experimental refinements with the simulated refinements, with the periodic density functional theory (DFT) calculations and with published X-ray and neutron crystal structures. The TAAM refinements on the 3D ED data did not improve the accuracy of the bond lengths between the non-H atoms. The experimental 3D ED data provided more accurate H-atom positions than the IAM refinements on the X-ray diffraction data. The IAM refinements against 3D ED data had a tendency to lead to slightly longer X—H bond lengths than TAAM, but the difference was statistically insignificant. Atomic displacement parameters were too large by tens of percent for l-alanine and α-glycine. Most probably, other unmodelled effects were causing this behaviour, such as radiation damage or dynamical scattering.

The title compound, 3-[(benzo-1,3-dioxol-5-yl)amino]-4-meth­oxy­cyclo­but-3-ene-1,2-dione, C12H9NO5 (3), is a precursor to an anti­mycobacterial squaramide. Block-shaped crystals of a monoclinic form (3-I, space group P21/c, Z = 8, Z' = 2) and needle-shaped crystals of a triclinic form (3-II, space group P-1, Z = 4, Z' = 2) were found to crystallize concomitantly. In both crystal forms, R22(10) dimers assemble through N—H⋯O=C hydrogen bonds. These dimers are formed from crystallographically unique mol­ecules in 3-I, but exhibit crystallographic Ci symmetry in 3-II. Twinning by pseudomerohedry was encountered in the crystals of 3-II. The conformations of 3 in the solid forms 3-I and 3-II are different from one another but are similar for the unique mol­ecules in each polymorph. Density functional theory (DFT) calculations on the free mol­ecule of 3 indicate that a nearly planar conformation is preferred.

Chalcopyrite, the world's primary copper ore mineral, is abundant in Latin America. Copper extraction offers significant economic and social benefits due to its strategic importance across various industries. However, the hydro­metallurgical route, considered more environmentally friendly for processing low-grade chal­co­py­rite ores, remains challenging, as does its concentration by froth flotation. This limited understanding stems from the poorly understood structure and reactivity of chal­co­py­rite surfaces. This study reviews recent contributions using density functional theory (DFT) calculations with periodic boundary conditions and slab models to elucidate chal­co­py­rite surface properties. Our analysis reveals that reconstructed surfaces preferentially expose S atoms at the topmost layer. Furthermore, some studies report the formation of di­sulfide groups (S22−) on pristine sulfur-terminated surfaces, accom­panied by the reduction of Fe3+ to Fe2+, likely due to surface oxidation. Additionally, Fe sites are consistently identified as favourable adsorption locations for both oxygen (O2) and water (H2O) mol­ecules. Finally, the potential of com­puter modelling for investigating collector–chal­co­py­rite surface inter­actions in the context of selective froth flotation is discussed, highlighting the need for further research in this area.

The incommensurately modulated structure of (2S,3S)-2-amino-3-hy­droxy-3-methyl-4-phen­oxy­butanoic acid dihydrate (C11H15NO4·2H2O or I·2H2O) is described in the (3+1)-dimensional superspace group P212121(0β0)000 (β = 0.357). The loss of the three-dimensional periodicity is ascribed to the occupational modulation of one positionally disordered solvent water mol­ecule, where the two positions are related by a small translation [ca 0.666 (9) Å] and ∼168 (5)° rotation about one of its O—H bonds, with an average 0.624 (3):0.376 (3) occupancy ratio. The occupational modulation of this mol­ecule arises due to the com­petition between the different hy­dro­gen-bonding motifs associated with each position. The structure can be very well refined in the average approximation (all satellite reflections disregarded) in the space group P212121, with the water mol­ecule refined as disordered over two positions in a 0.625 (16):0.375 (16) ratio. The refinement in the commensurate threefold supercell approximation in the space group P1121 is also of high quality, with the six corresponding water mol­ecules exhibiting three different occupancy ratios averaging 0.635:0.365.

The activation of C—C bonds by transition-metal com­plexes is of continuing inter­est and aceto­nitrile (MeCN) has attracted attention as a cyanide source with com­paratively low toxicity for organic cyanation reactions. A di­iron end-on μ-η1:η1-CN-bridged com­plex was obtained from a crystallization experiment of an open-chain iron–NHC com­plex, namely, μ-cyanido-κ2C:N-bis­{[(aceto­nitrile-κN)[3,3'-bis­(pyridin-2-yl)-1,1'-(methyl­idene)bis­(benzimidazol-2-yl­idene)]iron(II)} tris­(hexa­fluoro­phos­phate), [Fe2(CN)(C2H3N)2(C25H18N6)2](PF6)3. The cyanide appears to originate from the MeCN solvent by C—C bond cleavage or through carbon–hy­dro­gen oxidation.

Over the last decade, the development of time-resolved serial crystallography (TR-SX) at X-ray free-electron lasers (XFELs) and synchrotrons has allowed researchers to study phenomena occurring in proteins on the femtosecond-to-minute timescale, taking advantage of many technical and methodological breakthroughs. Protein crystals of various sizes are presented to the X-ray beam in either a static or a moving medium. Photoactive proteins were naturally the initial systems to be studied in TR-SX experiments using pump–probe schemes, where the pump is a pulse of visible light. Other reaction initiations through small-molecule diffusion are gaining momentum. Here, selected examples of XFEL and synchrotron time-resolved crystallography studies will be used to highlight the specificities of the various instruments and methods with respect to time resolution, and are compared with cryo-trapping studies.

The validation of structural models obtained by macromolecular X-ray crystallography against experimental diffraction data, whether before deposition into the PDB or after, is typically carried out exclusively against the merged data that are eventually archived along with the atomic coordinates. It is shown here that the availability of unmerged reflection data enables valuable additional analyses to be performed that yield improvements in the final models, and tools are presented to implement them, together with examples of the results to which they give access. The first example is the automatic identification and removal of image ranges affected by loss of crystal centering or by excessive decay of the diffraction pattern as a result of radiation damage. The second example is the `reflection-auditing' process, whereby individual merged data items showing especially poor agreement with model predictions during refinement are investigated thanks to the specific metadata (such as image number and detector position) that are available for the corresponding unmerged data, potentially revealing previously undiagnosed instrumental, experimental or processing problems. The third example is the calculation of so-called F(early) − F(late) maps from carefully selected subsets of unmerged amplitude data, which can not only highlight the location and extent of radiation damage but can also provide guidance towards suitable fine-grained parametrizations to model the localized effects of such damage.

The widespread adoption of cryoEM technologies for structural biology has pushed the discipline to new frontiers. A significant worldwide effort has refined the single-particle analysis (SPA) workflow into a reasonably standardized procedure. Significant investments of development time have been made, particularly in sample preparation, microscope data-collection efficiency, pipeline analyses and data archiving. The widespread adoption of specific commercial microscopes, software for controlling them and best practices developed at facilities worldwide has also begun to establish a degree of standardization to data structures coming from the SPA workflow. There is opportunity to capitalize on this moment in the maturation of the field, to capture metadata from SPA experiments and correlate the metadata with experimental outcomes, which is presented here in a set of programs called EMinsight. This tool aims to prototype the framework and types of analyses that could lead to new insights into optimal microscope configurations as well as to define methods for metadata capture to assist with the archiving of cryoEM SPA data. It is also envisaged that this tool will be useful to microscope operators and facilities looking to rapidly generate reports on SPA data-collection and screening sessions.

The Swiss Light Source facilitates fragment-based drug-discovery campaigns for academic and industrial users through the Fast Fragment and Compound Screening (FFCS) software suite. This framework is further enriched by the option to utilize the Smart Digital User (SDU) software for automated data collection across the PXI, PXII and PXIII beamlines. In this work, the newly developed HEIDI webpage (https://heidi.psi.ch) is introduced: a platform crafted using state-of-the-art software architecture and web technologies for sample management of rotational data experiments. The HEIDI webpage features a data-review tab for enhanced result visualization and provides programmatic access through a representational state transfer application programming interface (REST API). The migration of the local FFCS MongoDB instance to the cloud is highlighted and detailed. This transition ensures secure, encrypted and consistently accessible data through a robust and reliable REST API tailored for the FFCS software suite. Collectively, these advancements not only significantly elevate the user experience, but also pave the way for future expansions and improvements in the capabilities of the system.

The determination of the atomic resolution structure of biomacromolecules is essential for understanding details of their function. Traditionally, such a structure determination has been performed with crystallographic or nuclear resonance methods, but during the last decade, cryogenic transmission electron microscopy (cryo-TEM) has become an equally important tool. As the blotting and flash-freezing of the samples can induce conformational changes, external validation tools are required to ensure that the vitrified samples are representative of the solution. Although many validation tools have already been developed, most of them rely on fully resolved atomic models, which prevents early screening of the cryo-TEM maps. Here, a novel and automated method for performing such a validation utilizing small-angle X-ray scattering measurements, publicly available through the new software package AUSAXS, is introduced and implemented. The method has been tested on both simulated and experimental data, where it was shown to work remarkably well as a validation tool. The method provides a dummy atomic model derived from the EM map which best represents the solution structure.

Advances in structural biology have relied heavily on synchrotron cryo-crystallography and cryogenic electron microscopy to elucidate biological processes and for drug discovery. However, disparities between cryogenic and room-temperature (RT) crystal structures pose challenges. Here, Cryo2RT, a high-throughput RT data-collection method from cryo-cooled crystals that leverages the cryo-crystallography workflow, is introduced. Tested on endothiapepsin crystals with four soaked fragments, thaumatin and SARS-CoV-2 3CLpro, Cryo2RT reveals unique ligand-binding poses, offers a comparable throughput to cryo-crystallography and eases the exploration of structural dynamics at various temperatures.

A key prerequisite for the successful application of protein crystallography in drug discovery is to establish a robust crystallization system for a new drug-target protein fast enough to deliver crystal structures when the first inhibitors have been identified in the hit-finding campaign or, at the latest, in the subsequent hit-to-lead process. The first crucial step towards generating well folded proteins with a high likelihood of crystallizing is the identification of suitable truncation variants of the target protein. In some cases an optimal length variant alone is not sufficient to support crystallization and additional surface mutations need to be introduced to obtain suitable crystals. In this contribution, four case studies are presented in which rationally designed surface modifications were key to establishing crystallization conditions for the target proteins (the protein kinases Aurora-C, IRAK4 and BUB1, and the KRAS–SOS1 complex). The design process which led to well diffracting crystals is described and the crystal packing is analysed to understand retrospectively how the specific surface mutations promoted successful crystallization. The presented design approaches are routinely used in our team to support the establishment of robust crystallization systems which enable structure-guided inhibitor optimization for hit-to-lead and lead-optimization projects in pharmaceutical research.

During the automatic processing of crystallographic diffraction experiments, beamstop shadows are often unaccounted for or only partially masked. As a result of this, outlier reflection intensities are integrated, which is a known issue. Traditional statistical diagnostics have only limited effectiveness in identifying these outliers, here termed Not-Excluded-unMasked-Outliers (NEMOs). The diagnostic tool AUSPEX allows visual inspection of NEMOs, where they form a typical pattern: clusters at the low-resolution end of the AUSPEX plots of intensities or amplitudes versus resolution. To automate NEMO detection, a new algorithm was developed by combining data statistics with a density-based clustering method. This approach demonstrates a promising performance in detecting NEMOs in merged data sets without disrupting existing data-reduction pipelines. Re-refinement results indicate that excluding the identified NEMOs can effectively enhance the quality of subsequent structure-determination steps. This method offers a prospective automated means to assess the efficacy of a beamstop mask, as well as highlighting the potential of modern pattern-recognition techniques for automating outlier exclusion during data processing, facilitating future adaptation to evolving experimental strategies.

AlphaFold2 has revolutionized structural biology by offering unparalleled accuracy in predicting protein structures. Traditional methods for determining protein structures, such as X-ray crystallography and cryo-electron microscopy, are often time-consuming and resource-intensive. AlphaFold2 provides models that are valuable for molecular replacement, aiding in model building and docking into electron density or potential maps. However, despite its capabilities, models from AlphaFold2 do not consistently match the accuracy of experimentally determined structures, need to be validated experimentally and currently miss some crucial information, such as post-translational modifications, ligands and bound ions. In this paper, the advantages are explored of collecting X-ray anomalous data to identify chemical elements, such as metal ions, which are key to understanding certain structures and functions of proteins. This is achieved through methods such as calculating anomalous difference Fourier maps or refining the imaginary component of the anomalous scattering factor f''. Anomalous data can serve as a valuable complement to the information provided by AlphaFold2 models and this is particularly significant in elucidating the roles of metal ions.

A group of three deep-learning tools, referred to collectively as CHiMP (Crystal Hits in My Plate), were created for analysis of micrographs of protein crystallization experiments at the Diamond Light Source (DLS) synchrotron, UK. The first tool, a classification network, assigns images into categories relating to experimental outcomes. The other two tools are networks that perform both object detection and instance segmentation, resulting in masks of individual crystals in the first case and masks of crystallization droplets in addition to crystals in the second case, allowing the positions and sizes of these entities to be recorded. The creation of these tools used transfer learning, where weights from a pre-trained deep-learning network were used as a starting point and repurposed by further training on a relatively small set of data. Two of the tools are now integrated at the VMXi macromolecular crystallography beamline at DLS, where they have the potential to absolve the need for any user input, both for monitoring crystallization experiments and for triggering in situ data collections. The third is being integrated into the XChem fragment-based drug-discovery screening platform, also at DLS, to allow the automatic targeting of acoustic compound dispensing into crystallization droplets.

Pollution from plastics is a global problem that threatens the biosphere for a host of reasons, including the time scale that it takes for most plastics to degrade. Biodegradation is an ideal solution for remediating bioplastic waste as it does not require the high temperatures necessary for thermal degradation and does not introduce additional pollutants into the environment. Numerous organisms can scavenge for bioplastics, such as polylactic acid (PLA) or poly-(R)-hydroxybutyrate (PHB), which they can use as an energy source. Recently, a promiscuous PHBase from the thermophilic soil bacterium Lihuaxuella thermophila (LtPHBase) was identified. LtPHBase can accommodate many substrates, including PHB granules and films and PHB block copolymers, as well as the unrelated polymers polylactic acid (PLA) and polycaprolactone (PCL). LtPHBase uses the expected Ser–His–Asp catalytic triad for hydrolysis at an optimal enzyme activity near 70°C. Here, the 1.75 Å resolution crystal structure of apo LtPHBase is presented and its chemical stability is profiled. Knowledge of its substrate preferences was extended to different-sized PHB granules. It is shown that LtPHBase is highly resistant to unfolding, with barriers typical for thermophilic enzymes, and shows a preference for low-molecular-mass PHB granules. These insights have implications for the long-term potential of LtPHBase as an industrial PHB hydrolase and shed light on the evolutionary role that this enzyme plays in bacterial metabolism.

Fatty acid-derivative prodrugs have been utilized extensively to improve the physicochemical, biopharmaceutical and pharmacokinetic properties of active pharmaceutical ingredients. However, to our knowledge, the crystallization behavior of prodrugs modified with different fatty acids has not been explored. In the present work, a series of paliperidone aliphatic prodrugs with alkyl chain lengths ranging from C4 to C16 was investigated with respect to crystal structure, crystal morphology and crystallization kinetics. The paliperidone derivatives exhibited isostructural crystal packing, despite the different alkyl chain lengths, and crystallized with the dominant (100) face in both melt and solution. The rate of crystallization for paliperidone derivatives in the melt increases with alkyl chain length owing to greater molecular mobility. In contrast, the longer chains prolong the nucleation induction time and reduce the crystal growth kinetics in solution. The results show a correlation between difficulty of nucleation in solution and the interfacial energy. This work provides insight into the crystallization behavior of paliperidone aliphatic prodrugs and reveals that the role of alkyl chain length in the crystallization behavior has a strong dependence on the crystallization method.

Serial electron diffraction (SerialED), which applies a snapshot data acquisition strategy for each crystal, was introduced to tackle the problem of radiation damage in the structure determination of beam-sensitive materials by three-dimensional electron diffraction (3DED). The snapshot data acquisition in SerialED can be realized using both transmission and scanning transmission electron microscopes (TEM/STEM). However, the current SerialED workflow based on STEM setups requires special external devices and software, which limits broader adoption. Here, we present a simplified experimental implementation of STEM-based SerialED on Thermo Fisher Scientific STEMs using common proprietary software interfaced through Python scripts to automate data collection. Specifically, we utilize TEM Imaging and Analysis (TIA) scripting and TEM scripting to access the STEM functionalities of the microscope, and DigitalMicrograph scripting to control the camera for snapshot data acquisition. Data analysis adapts the existing workflow using the software CrystFEL, which was developed for serial X-ray crystallography. Our workflow for STEM SerialED can be used on any Gatan or Thermo Fisher Scientific camera. We apply this workflow to collect high-resolution STEM SerialED data from two aluminosilicate zeolites, zeolite Y and ZSM-25. We demonstrate, for the first time, ab initio structure determination through direct methods using STEM SerialED data. Zeolite Y is relatively stable under the electron beam, and STEM SerialED data extend to 0.60 Å. We show that the structural model obtained using STEM SerialED data merged from 358 crystals is nearly identical to that using continuous rotation electron diffraction data from one crystal. This demonstrates that accurate structures can be obtained from STEM SerialED. Zeolite ZSM-25 is very beam-sensitive and has a complex structure. We show that STEM SerialED greatly improves the data resolution of ZSM-25, compared with serial rotation electron diffraction (SerialRED), from 1.50 to 0.90 Å. This allows, for the first time, the use of standard phasing methods, such as direct methods, for the ab initio structure determination of ZSM-25.

As an important characterization method, pair distribution function (PDF) has been extensively used in structural analysis of nanomaterials, providing key insights into the degree of crystallinity, atomic structure, local disorder etc. The collection of scattering signals with good statistics is necessary for a reliable structural analysis. However, current conventional electron diffraction experiments using PDF (ePDF) are limited in their ability to acquire continuous diffraction rings for large nanoparticles. Herein, a new method – tilt-ePDF – is proposed to improve the data quality and compatibility of ePDF by a combination of electron diffraction and specimen tilting. In the present work, a tilt-series of electron diffraction patterns was collected from gold nanoparticles with three different sizes and a standard sample polycrystalline aluminium film for ePDF analysis. The results show that tilt-ePDF can not only enhance the continuity of diffraction rings, but can also improve the signal-to-noise ratio in the high scattering angle range. As a result, compared with conventional ePDF data, tilt-ePDF data provide structure parameters with a better accuracy and lower residual factors in the refinement against the crystal structure. This method provides a new way of utilizing ePDF to obtain accurate local structure information from nanoparticles.

The Protein Data Bank (PDB) was established as the first open-access digital data resource in biology and medicine in 1971 with seven X-ray crystal structures of proteins. Today, the PDB houses >210 000 experimentally determined, atomic level, 3D structures of proteins and nucleic acids as well as their complexes with one another and small molecules (e.g. approved drugs, enzyme cofactors). These data provide insights into fundamental biology, biomedicine, bioenergy and biotechnology. They proved particularly important for understanding the SARS-CoV-2 global pandemic. The US-funded Research Collaboratory for Structural Bioinformatics Protein Data Bank (RCSB PDB) and other members of the Worldwide Protein Data Bank (wwPDB) partnership jointly manage the PDB archive and support >60 000 `data depositors' (structural biologists) around the world. wwPDB ensures the quality and integrity of the data in the ever-expanding PDB archive and supports global open access without limitations on data usage. The RCSB PDB research-focused web portal at https://www.rcsb.org/ (RCSB.org) supports millions of users worldwide, representing a broad range of expertise and interests. In addition to retrieving 3D structure data, PDB `data consumers' access comparative data and external annotations, such as information about disease-causing point mutations and genetic variations. RCSB.org also provides access to >1 000 000 computed structure models (CSMs) generated using artificial intelligence/machine-learning methods. To avoid doubt, the provenance and reliability of experimentally determined PDB structures and CSMs are identified. Related training materials are available to support users in their RCSB.org explorations.

Appreciating that the role of the solute–solvent and other outer-sphere interactions is essential for understanding chemistry and chemical dynamics in solution, experimental approaches are needed to address the structural consequences of these interactions, complementing condensed-matter simulations and coarse-grained theories. High-energy X-ray scattering (HEXS) combined with pair distribution function analysis presents the opportunity to probe these structures directly and to develop quantitative, atomistic models of molecular systems in situ in the solution phase. However, at concentrations relevant to solution-phase chemistry, the total scattering signal is dominated by the bulk solvent, prompting researchers to adopt a differential approach to eliminate this unwanted background. Though similar approaches are well established in quantitative structural studies of macromolecules in solution by small- and wide-angle X-ray scattering (SAXS/WAXS), analogous studies in the HEXS regime—where sub-ångström spatial resolution is achieved—remain underdeveloped, in part due to the lack of a rigorous theoretical description of the experiment. To address this, herein we develop a framework for differential solution scattering experiments conducted at high energies, which includes concepts of the solvent-excluded volume introduced to describe SAXS/WAXS data, as well as concepts from the time-resolved X-ray scattering community. Our theory is supported by numerical simulations and experiment and paves the way for establishing quantitative methods to determine the atomic structures of small molecules in solution with resolution approaching that of crystallography.

A new polymorph of 1,3-diacetylpyrene has been obtained from its melt and thoroughly characterized using single-crystal X-ray diffraction, steady-state UV–Vis spectroscopy and periodic density functional theory calculations. Experimental studies covered the temperature range from 90 to 390 K and the pressure range from atmospheric to 4.08 GPa. Optimal sample placement in a diamond anvil cell according to our previously presented methodology ensured over 80% data coverage up to 0.8 Å for a monoclinic sample. Unrestrained Hirshfeld atom refinement of the high-pressure crystal structures was successful and anharmonic behavior of carbonyl oxygen atoms was observed. Unlike the previously characterized polymorph, the structure of 2°AP-β is based on infinite π-stacks of antiparallel 2°AP molecules. 2°AP-β displays piezochromism and piezofluorochromism which are directly related to the variation in interplanar distances within the π-stacking. The importance of weak intermolecular interactions is reflected in the substantial negative thermal expansion coefficient of −55.8 (57) MK−1 in the direction of C—H⋯O interactions.

In this work, regenerated cellulose textile fibers, Ioncell-F, dry-wet spun with different draw ratios, have been investigated by scanning wide-angle X-ray scattering (WAXS) using a mesoscopic X-ray beam. The fibers were found to be homogeneous on the 500 nm length scale. Analysis of the azimuthal angular dependence of a crystalline Bragg spot intensity revealed a radial dependence of the degree of orientation of crystallites that was found to increase with the distance from the center of the fiber. We attribute this to radial velocity gradients during the extrusion of the spin dope and the early stage of drawing. On the other hand, the fiber crystallinity was found to be essentially homogeneous over the fiber cross section.

The hardware for data archiving has expanded capacities for digital storage enormously in the past decade or more. The IUCr evaluated the costs and benefits of this within an official working group which advised that raw data archiving would allow ground truth reproducibility in published studies. Consultations of the IUCr's Commissions ensued via a newly constituted standing advisory committee, the Committee on Data. At all stages, the IUCr financed workshops to facilitate community discussions and possible methods of raw data archiving implementation. The recent launch of the IUCrData journal's Raw Data Letters is a milestone in the implementation of raw data archiving beyond the currently published studies: it includes diffraction patterns that have not been fully interpreted, if at all. The IUCr 75th Congress in Melbourne included a workshop on raw data reuse, discussing the successes and ongoing challenges of raw data reuse. This article charts the efforts of the IUCr to facilitate discussions and plans relating to raw data archiving and reuse within the various communities of crystallography, diffraction and scattering.

Investigation of the analyte soaking conditions on the crystalline sponge {[(ZnI2)3(tpt)2·x(solvent)]n} method using a statistical design of experiments model has provided fundamental insights into the influence of experimental variables. This approach focuses on a single analyte tested via 60 experiments (20 unique conditions) to identify the main effects for success and overall guest structure quality. This is employed as a basis for the development of a novel molecular structure grading system that enables the quantification of guest exchange quality.

The success of experimental phasing in macromolecular crystallography relies primarily on the accurate locations of heavy atoms bound to the target crystal. To improve the process of substructure determination, a modified phase-retrieval algorithm built on the framework of the relaxed alternating averaged reflection (RAAR) algorithm has been developed. Importantly, the proposed algorithm features a combination of the π-half phase perturbation for weak reflections and enforces the direct-method-based tangent formula for strong reflections in reciprocal space. The proposed algorithm is extensively demonstrated on a total of 100 single-wavelength anomalous diffraction (SAD) experimental datasets, comprising both protein and nucleic acid structures of different qualities. Compared with the standard RAAR algorithm, the modified phase-retrieval algorithm exhibits significantly improved effectiveness and accuracy in SAD substructure determination, highlighting the importance of additional constraints for algorithmic performance. Furthermore, the proposed algorithm can be performed without human intervention under most conditions owing to the self-adaptive property of the input parameters, thus making it convenient to be integrated into the structural determination pipeline. In conjunction with the IPCAS software suite, we demonstrated experimentally that automatic de novo structure determination is possible on the basis of our proposed algorithm.

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.

Spectroscopic data, particularly diffraction data, are essential for materials characterization due to their comprehensive crystallographic information. The current crystallographic phase identification, however, is very time consuming. To address this challenge, we have developed a real-time crystallographic phase identifier based on a convolutional self-attention neural network (CPICANN). Trained on 692 190 simulated powder X-ray diffraction (XRD) patterns from 23 073 distinct inorganic crystallographic information files, CPICANN demonstrates superior phase-identification power. Single-phase identification on simulated XRD patterns yields 98.5 and 87.5% accuracies with and without elemental information, respectively, outperforming JADE software (68.2 and 38.7%, respectively). Bi-phase identification on simulated XRD patterns achieves 84.2 and 51.5% accuracies, respectively. In experimental settings, CPICANN achieves an 80% identification accuracy, surpassing JADE software (61%). Integration of CPICANN into XRD refinement software will significantly advance the cutting-edge technology in XRD materials characterization.

Single-particle cryo-electron microscopy (cryo-EM) has become an essential structural determination technique with recent hardware developments making it possible to reach atomic resolution, at which individual atoms, including hydrogen atoms, can be resolved. In this study, we used the enzyme involved in the penultimate step of riboflavin biosynthesis as a test specimen to benchmark a recently installed microscope and determine if other protein complexes could reach a resolution of 1.5 Å or better, which so far has only been achieved for the iron carrier ferritin. Using state-of-the-art microscope and detector hardware as well as the latest software techniques to overcome microscope and sample limitations, a 1.42 Å map of Aquifex aeolicus lumazine synthase (AaLS) was obtained from a 48 h microscope session. In addition to water molecules and ligands involved in the function of AaLS, we can observe positive density for ∼50% of the hydrogen atoms. A small improvement in the resolution was achieved by Ewald sphere correction which was expected to limit the resolution to ∼1.5 Å for a molecule of this diameter. Our study confirms that other protein complexes can be solved to near-atomic resolution. Future improvements in specimen preparation and protein complex stabilization may allow more flexible macromolecules to reach this level of resolution and should become a priority of study in the field.

Ultrahigh-resolution structures provide unprecedented details about protein dynamics, hydrogen bonding and solvent networks. The reported 0.70 Å, room-temperature crystal structure of crambin is the highest-resolution ambient-temperature structure of a protein achieved to date. Sufficient data were collected to enable unrestrained refinement of the protein and associated solvent networks using SHELXL. Dynamic solvent networks resulting from alternative side-chain conformations and shifts in water positions are revealed, demonstrating that polypeptide flexibility and formation of clathrate-type structures at hydro­phobic surfaces are the key features endowing crambin crystals with extraordinary diffraction power.

3D electron diffraction (3DED) is increasingly employed to determine molec­ular and crystal structures from micro-crystals. Indomethacin is a well known, marketed, small-molecule non-steroidal anti-inflammatory drug with eight known polymorphic forms, of which four structures have been elucidated to date. Using 3DED, we determined the structure of a new ninth polymorph, σ, found within an amorphous solid dispersion, a product formulation sometimes used for active pharmaceutical ingredients with poor aqueous solubility. Subsequently, we found that σ indomethacin can be produced from direct solvent evaporation using di­chloro­methane. These results demonstrate the relevance of 3DED within drug development to directly probe product formulations.

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.

The NaZr2P3O12 family of materials have shown low and tailorable thermal expansion properties. In this study, SrZr4P6O24 (SrO·4ZrO2·3P2O5), CaZr4P6O24 (CaO·4ZrO2·3P2O5), MgZr4P6O24 (MgO·4ZrO2·3P2O5), NaTi2P3O12 [½(Na2O·4TiO2·3P2O5)], NaZr2P3O12 [½(Na2O·4ZrO2·3P2O5)], and related solid solutions were synthesized using the organic–inorganic steric entrapment method. The samples were characterized by in-situ high-temperature X-ray diffraction from 25 to 1500°C at the Advanced Photon Source and National Synchrotron Light Source II. The average linear thermal expansion of SrZr4P6O24 and CaZr4P6O24 was between −1 × 10−6 per °C and 6 × 10−6 per °C from 25 to 1500°C. The crystal structures of the high-temperature polymorphs of CaZr4P6O24 and SrZr4P6O24 with R3c symmetry were solved by Fourier difference mapping and Rietveld refinement. This polymorph is present above ∼1250°C. This work measured thermal expansion coefficients to 1500°C for all samples and investigated the differences in thermal expansion mechanisms between polymorphs and between compositions.

In the title compound, C15H14N2O2·H2O, the 1H-pyrrole ring makes a dihedral angle of 59.95 (13)° with the phenyl ring. In the crystal, the mol­ecules are connected by C—H⋯O hydrogen bonds into layers parallel to the (020) plane, while two mol­ecules are connected to the water mol­ecule by two N—H⋯O hydrogen bonds and one mol­ecule by an O—H⋯O hydrogen bond. C—H⋯π and π–π inter­actions further link the mol­ecules into chains extending in the [overline{1}01] direction and stabilize the mol­ecular packing. According to a Hirshfeld surface study, H⋯H (49.4%), C⋯H/H⋯C (23.2%) and O⋯H/H⋯O (20.0%) inter­actions are the most significant contributors to the crystal packing.

We report the synthesis and structures of two transition-metal complexes involving 2-(2-hy­droxy­phen­yl)benzimidazole (2hpbi – a ligand of inter­est for its photoluminescent applications), with cobalt, namely, bis­[μ-2-(1H-1,3-benzo­diazol-2-yl)phenolato]bis­[ethanol(thio­cyanato)­cobalt(II)], [Co2(C13H9N2O)2(NCS)2(C2H6O)2], (1), and manganese, namely, bis­[μ-2-(1H-1,3-benzo­diazol-2-yl)phenolato]bis­{[2-(1H-1,3-benzo­diazol-2-yl)phenolato](thio­cyanato)­mang­an­ese(III)} dihydrate, [Mn2(C13H9N2O)4(NCS)2]·2H2O, (2). These structures are two recent examples of a fruitful collaboration between researchers at the Laboratoire de Chimie de Coordination Organique/Organic Coordination Chemistry Laboratory (LCCO), University of Dakar, Senegal and the National Crystallography Service (NCS), School of Chemistry, University Southampton, UK. This productive partnership was forged through meeting at Pan-African Conferences on Crystallography and quickly grew as the plans for the AfCA (African Crystallographic Association) developed. This article therefore also showcases this productive partnership, in celebration of the IUCr's 75 year anniversary and the recent inclusion of AfCA as a Regional Associate of the IUCr.

In the title compound, C19H20Cl2N2O, the seven-membered 1,4-diazepane ring adopts a chair conformation while the 4-chloro­phenyl substituents adopt equatorial orientations. The chloro­phenyl ring at position 7 is disordered over two positions [site occupancies 0.480 (16):0.520 (16)]. The dihedral angle between the two benzene rings is 63.0 (4)°. The methyl groups at position 3 have an axial and an equatorial orientation. The compound exists as a dimer exhibiting inter­molecular N—H⋯O hydrogen bonding with R22(8) graph-set motifs. The crystal structure is further stabilized by C—H⋯O hydrogen bonds together with two C—Cl⋯π (ring) inter­actions. The geometry was optimized by DFT using the B3LYP/6–31 G(d,p) level basis set. In addition, the HOMO and LUMO energies, chemical reactivity parameters and mol­ecular electrostatic potential were calculated at the same level of theory. Hirshfeld surface analysis indicated that the most important contributions to the crystal packing are from H⋯H (45.6%), Cl⋯H/H⋯Cl (23.8%), H⋯C/C⋯H (12.6%), H⋯O/O⋯H (8.7%) and C⋯Cl/Cl⋯C (7.1%) inter­actions. Analysis of the inter­action energies showed that the dispersion energy is greater than the electrostatic energy. A crystal void volume of 237.16 Å3 is observed. A mol­ecular docking study with the human oestrogen receptor 3ERT protein revealed good docking with a score of −8.9 kcal mol−1.

The title compound, [RuCl2(C33H43N3O)], is an example of a new generation of N,N-dialkyl ruthenium catalysts with an N—Ru coordination bond as part of a six-membered chelate ring. The Ru atom has an Addison τ parameter of 0.244, which indicates a geometry inter­mediate between square-based pyramidal and trigonal–bipyramidal. The complex shows the usual trans arrangement of the two chlorides, with Ru—Cl bond lengths of 2.3515 (8) and 2.379 (7) Å, and a Cl—Ru—Cl angle of 158.02 (3)°. One of the chlorine atoms and the atoms of the 2-meth­oxy-N-methyl-N-[(2-methyl­phen­yl)meth­yl]ethane-1-amine group of the title complex display disorder over two positions in a 0.889 (2): 0.111 (2) ratio.

JUAMI, the joint undertaking for an African materials institute, is a project to build collaborations and materials research capabilities between PhD researchers in Africa, the United States, and the world. Focusing on research-active universities in the East African countries of Kenya, Ethiopia, Tanzania and Uganda, the effort has run a series of schools focused on materials for sustainable energy and materials for sustainable development. These bring together early-career researchers from Africa, the US, and beyond, for two weeks in a close-knit environment. The program includes lectures on cutting-edge research from internationally renowned speakers, highly interactive tutorial lectures on the science behind the research, also from internationally known researchers, and hands-on practicals and team-building exercises that culminate in group proposals from self-formed student teams. The schools have benefited more than 300 early-career students and led to proposals that have received funding and have led to research collaborations and educational non-profits. JUAMI continues and has an ongoing community of alumni who share resources and expertise, and is open to like-minded people who want to join and develop contacts and collaborations internationally.

In the title compound, C20H18O4, the dihedral angle between the 2H-chromen-2-one ring system and the phenyl ring is 89.12 (5)°. In the crystal, the mol­ecules are connected through C—H⋯O hydrogen bonds to generate [010] double chains that are reinforced by weak aromatic π–π stacking inter­actions. The unit-cell packing can be described as a tilted herringbone motif. The H⋯H, H⋯O/O⋯H, H⋯C/C⋯H and C⋯C contacts contribute 46.7, 24.2, 16.7 and 7.6%, respectively, to its Hirshfeld surface.

The title compound, C10H11N5O2S2, consists of an unexpected tautomer with a protonated nitro­gen atom in the triazine ring and a formal exocyclic double bond C=N to the sulfonamide moiety. The ring angles at the unsubstituted nitro­gen atoms are narrow, at 115.57 (12) and 115.19 (12)°, respectively, whereas the angle at the carbon atom between these N atoms is very wide, 127.97 (13)°. The inter­planar angle between the two rings is 79.56 (5)°. The mol­ecules are linked by three classical hydrogen bonds, forming a ribbon structure. There are also unusual linkages involving three short contacts (< 3 Å) from a sulfonamide oxygen atom to the C—NH—C part of a triazine ring.

The reaction between 2-pyridyl­selenenyl chloride and isobutyro­nitrile results in the formation of the corresponding cationic pyridinium-fused 1,2,4-seleno­diazole, namely, 3-(propan-2-yl)-1,2,4-[1,2,4]selena­diazolo[4,5-a]pyridin-4-ylium chloride, C9H11N2Se+·Cl−, in high yield (89%). The structure of the compound, established by means of single-crystal X-ray analysis at 100 K, has monoclinic (P21/c) symmetry and revealed the presence of bifurcated chalcogen-hydrogen bonding Se⋯Cl−⋯H—Cl, and these non-covalent contacts were analysed by DFT calculations followed by a topological analysis of the electron-density distribution (ωB97XD/6-311++G** level of theory).