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Discusses changes in the crystal structure of iron and steel when these materials are heated. Focuses on observations related to an experiment in which a 60-inch length of piano wire (No. 29 steel wire) is heated and then cooled. (JN)

Presents an exercise to get students more intimately involved in the three dimensional nature of basic units by constructing models. Uses balsa wood, glue, sandpaper, and a square. Studies seven crystals: cubic, hexagonal, monoclinic, orthorhombic, rhombohedral, tetragonal, and triclinic. Plans are available for a Macintosh computer. (MVL)

Discusses the physics of liquid crystal displays (LCD) which is based on polarizing properties of crystals controlled by electric command. Production of alphanumerics, display control, and input are considered. (JM)

Thermal properties of materials are essential to many applications of thermal electronic devices. Density functional theory (DFT) has shown capability in obtaining an accurate calculation. However, the expensive computational cost limits the application of the DFT method for high-throughput screening of materials. Recently, machine learning models, especially graph neural networks (GNNs), have demonstrated high accuracy in many material properties' prediction, such as bandgap and formation energy, but fail to accurately predict heat capacity(C V) due to the limitation in capturing crystallographic features. In our study, we have implemented the material informatics transformer (MatInFormer) framework, which has been pretrained on lattice reconstruction tasks. This approach has shown proficiency in capturing essential crystallographic features. By concatenating these features with human-designed descriptors, we achieved a mean absolute error of 4.893 and 4.505 J/(mol K) in our predictions. Our findings underscore the efficacy of the MatInFormer framework in leveraging crystallography, augmented with additional information processing capabilities. [ABSTRACT FROM AUTHOR]

K-Ras is the most commonly mutated oncogene in human cancer. The recently approved non-small cell lung cancer drugs sotorasib and adagrasib covalently capture an acquired cysteine in K-Ras-G12C mutation and lock it in a signaling-incompetent state. However, covalent inhibition of G12D, the most frequent K-Ras mutation particularly prevalent in pancreatic ductal adenocarcinoma, has remained elusive due to the lack of aspartate-targeting chemistry. Here we present a set of malolactone-based electrophiles that exploit ring strain to crosslink K-Ras-G12D at the mutant aspartate to form stable covalent complexes. Structural insights from X-ray crystallography and exploitation of the stereoelectronic requirements for attack of the electrophile allowed development of a substituted malolactone that resisted attack by aqueous buffer but rapidly crosslinked with the aspartate-12 of K-Ras in both GDP and GTP state. The GTP-state targeting allowed effective suppression of downstream signaling, and selective inhibition of K-Ras-G12D-driven cancer cell proliferation in vitro and xenograft growth in mice.

KAI2 receptors, classified as plant α/β hydrolase enzymes, are capable of perceiving smoke-derived butenolide signals and endogenous yet unidentified KAI2-ligands (KLs). While the number of functional KAI2 receptors varies among land plant species, rice has only one KAI2 gene. Rice, a significant crop and representative of grasses, relies on KAI2-mediated Arbuscular mycorrhiza (AM) symbioses to flourish in traditionally arid and nutrient-poor environments. This study presents the first crystal structure of an active rice (Oryza sativa, Os) KAI2 hydrolase receptor. Our structural and biochemical analyses uncover grass-unique pocket residues influencing ligand sensitivity and hydrolytic activity. Through structure-guided analysis, we identify a specific residue whose mutation enables the increase or decrease of ligand perception, catalytic activity, and signal transduction. Furthermore, we investigate OsKAI2-mediated signaling by examining its ability to form a complex with its binding partner, the F-box protein DWARF3 (D3) ubiquitin ligase and subsequent degradation of the target substrate OsSMAX1, demonstrating the significant role of hydrophobic interactions in the OsKAI2-D3 interface. This study provides new insights into the diverse and pivotal roles of the OsKAI2 signaling pathway in the plant kingdom, particularly in grasses.

Engineered reverse hairpin constructs containing a partial C-heptad repeat (CHR) sequence followed by a short loop and full-length N-heptad repeat (NHR) were previously shown to form trimers in solution and to be nanomolar inhibitors of HIV-1 Env mediated fusion. Their target is the in situ gp41 fusion intermediate, and they have similar potency to other previously reported NHR trimers. However, their design implies that the NHR is partially covered by CHR, which would be expected to limit potency. An exposed hydrophobic pocket in the folded structure may be sufficient to confer the observed potency, or they may exist in a partially unfolded state exposing full length NHR. Here we examined their structure by crystallography, CD and fluorescence, establishing that the proteins are folded hairpins both in crystal form and in solution. We examined unfolding in the milieu of the fusion reaction by conducting experiments in the presence of a membrane mimetic solvent and by engineering a disulfide bond into the structure to prevent partial unfolding. We further examined the role of the hydrophobic pocket, using a hairpin-small molecule adduct that occluded the pocket, as confirmed by X-ray footprinting. The results demonstrated that the NHR region nominally covered by CHR in the engineered constructs and the hydrophobic pocket region that is exposed by design were both essential for nanomolar potency and that interaction with membrane is likely to play a role in promoting the required inhibitor structure. The design concepts can be applied to other Class 1 viral fusion proteins.

In the folded state, biomolecules exchange between multiple conformational states crucial for their function. However, most structural models derived from experiments and computational predictions only encode a single state. To represent biomolecules accurately, we must move towards modeling and predicting structural ensembles. Information about structural ensembles exists within experimental data from X-ray crystallography and cryo-electron microscopy. Although new tools are available to detect conformational and compositional heterogeneity within these ensembles, the legacy PDB data structure does not robustly encapsulate this complexity. We propose modifications to the macromolecular crystallographic information file (mmCIF) to improve the representation and interrelation of conformational and compositional heterogeneity. These modifications will enable the capture of macromolecular ensembles in a human and machine-interpretable way, potentially catalyzing breakthroughs for ensemble-function predictions, analogous to the achievements of AlphaFold with single-structure prediction.

Natural photosystems couple light harvesting to charge separation using a 'special pair' of chlorophyll molecules that accepts excitation energy from the antenna and initiates an electron-transfer cascade. To investigate the photophysics of special pairs independently of the complexities of native photosynthetic proteins, and as a first step toward creating synthetic photosystems for new energy conversion technologies, we designed C2-symmetric proteins that hold two chlorophyll molecules in closely juxtaposed arrangements. X-ray crystallography confirmed that one designed protein binds two chlorophylls in the same orientation as native special pairs, whereas a second designed protein positions them in a previously unseen geometry. Spectroscopy revealed that the chlorophylls are excitonically coupled, and fluorescence lifetime imaging demonstrated energy transfer. The cryo-electron microscopy structure of a designed 24-chlorophyll octahedral nanocage with a special pair on each edge closely matched the design model. The results suggest that the de novo design of artificial photosynthetic systems is within reach of current computational methods.

Attempts to understand the molecular structure of water were first made well over a century ago. Looking back at the various attempts, it is illuminating to see how these were conditioned by the state of knowledge of chemistry and physics at the time and the experimental and theoretical tools then available. Progress in the intervening years has been facilitated by not only conceptual and theoretical advances in physics and chemistry but also the development of experimental techniques and instrumentation. Exploitation of powerful computational methods in interpreting what at first sight may seem impenetrable experimental data has led us to the consistent and detailed picture we have today of not only the structure of liquid water itself and how it changes with temperature and pressure but also its interactions with other molecules, in particular those relevant to water's role in important chemical and biological processes. Much remains to be done in the latter areas, but the experimental and computational techniques that now enable us to do what might reasonably be termed "liquid state crystallography" have opened the door to make possible further advances. Consequently, we now have the tools to explore further the role of water in those processes that underpin life itself—the very prospect that inspired Bernal to develop his ideas on the structure of liquids in general and of water in particular. [ABSTRACT FROM AUTHOR]

Schistosomiasis, caused by a parasitic blood fluke of the genus Schistosoma, is a global health problem for which new chemotherapeutic options are needed. We explored the scaffold of gallinamide A, a natural peptidic metabolite of marine cyanobacteria that has previously been shown to inhibit cathepsin L-type proteases. We screened a library of 19 synthetic gallinamide A analogs and identified nanomolar inhibitors of the cathepsin B-type protease SmCB1, which is a drug target for the treatment of schistosomiasis mansoni. Against cultured S. mansoni schistosomula and adult worms, many of the gallinamides generated a range of deleterious phenotypic responses. Imaging with a fluorescent-activity-based probe derived from gallinamide A demonstrated that SmCB1 is the primary target for gallinamides in the parasite. Furthermore, we solved the high-resolution crystal structures of SmCB1 in complex with gallinamide A and its two analogs and describe the acrylamide covalent warhead and binding mode in the active site. Quantum chemical calculations evaluated the contribution of individual positions in the peptidomimetic scaffold to the inhibition of the target and demonstrated the importance of the P1 and P2 positions. Our study introduces gallinamides as a powerful chemotype that can be exploited for the development of novel antischistosomal chemotherapeutics.

Imaging scaffolds composed of designed protein cages fused to designed ankyrin repeat proteins (DARPins) have enabled the structure determination of small proteins by cryogenic electron microscopy (cryo-EM). One particularly well characterized scaffold type is a symmetric tetrahedral assembly composed of 24 subunits, 12 A and 12 B, which has three cargo-binding DARPins positioned on each vertex. Here, the X-ray crystal structure of a representative tetrahedral scaffold in the apo state is reported at 3.8 Å resolution. The X-ray crystal structure complements recent cryo-EM findings on a closely related scaffold, while also suggesting potential utility for crystallographic investigations. As observed in this crystal structure, one of the three DARPins, which serve as modular adaptors for binding diverse `cargo proteins, present on each of the vertices is oriented towards a large solvent channel. The crystal lattice is unusually porous, suggesting that it may be possible to soak crystals of the scaffold with small (≤30 kDa) protein cargo ligands and subsequently determine cage-cargo structures via X-ray crystallography. The results suggest the possibility that cryo-EM scaffolds may be repurposed for structure determination by X-ray crystallography, thus extending the utility of electron-microscopy scaffold designs for alternative structural biology applications.

Macromolecular crystallography generally requires the recovery of missing phase information from diffraction data to reconstruct an electron-density map of the crystallized molecule. Most recent structures have been solved using molecular replacement as a phasing method, requiring an a priori structure that is closely related to the target protein to serve as a search model; when no such search model exists, molecular replacement is not possible. New advances in computational machine-learning methods, however, have resulted in major advances in protein structure predictions from sequence information. Methods that generate predicted structural models of sufficient accuracy provide a powerful approach to molecular replacement. Taking advantage of these advances, AlphaFold predictions were applied to enable structure determination of a bacterial protein of unknown function (UniProtKB Q63NT7, NCBI locus BPSS0212) based on diffraction data that had evaded phasing attempts using MIR and anomalous scattering methods. Using both X-ray and micro-electron (microED) diffraction data, it was possible to solve the structure of the main fragment of the protein using a predicted model of that domain as a starting point. The use of predicted structural models importantly expands the promise of electron diffraction, where structure determination relies critically on molecular replacement.

Enzymes populate ensembles of structures necessary for catalysis that are difficult to experimentally characterize. We use time-resolved mix-and-inject serial crystallography at an x-ray free electron laser to observe catalysis in a designed mutant isocyanide hydratase (ICH) enzyme that enhances sampling of important minor conformations. The active site exists in a mixture of conformations, and formation of the thioimidate intermediate selects for catalytically competent substates. The influence of cysteine ionization on the ICH ensemble is validated by determining structures of the enzyme at multiple pH values. Large molecular dynamics simulations in crystallo and time-resolved electron density maps show that Asp17 ionizes during catalysis and causes conformational changes that propagate across the dimer, permitting water to enter the active site for intermediate hydrolysis. ICH exhibits a tight coupling between ionization of active site residues and catalysis-activated protein motions, exemplifying a mechanism of electrostatic control of enzyme dynamics.

A wooden house frame consists of many different lumber pieces, but because of the regularity of these building blocks, the structure can be designed using straightforward geometrical principles. The design of multicomponent protein assemblies, in comparison, has been much more complex, largely owing to the irregular shapes of protein structures1. Here we describe extendable linear, curved and angled protein building blocks, as well as inter-block interactions, that conform to specified geometric standards; assemblies designed using these blocks inherit their extendability and regular interaction surfaces, enabling them to be expanded or contracted by varying the number of modules, and reinforced with secondary struts. Using X-ray crystallography and electron microscopy, we validate nanomaterial designs ranging from simple polygonal and circular oligomers that can be concentrically nested, up to large polyhedral nanocages and unbounded straight 'train track' assemblies with reconfigurable sizes and geometries that can be readily blueprinted. Because of the complexity of protein structures and sequence-structure relationships, it has not previously been possible to build up large protein assemblies by deliberate placement of protein backbones onto a blank three-dimensional canvas; the simplicity and geometric regularity of our design platform now enables construction of protein nanomaterials according to 'back of an envelope' architectural blueprints.

In our efforts to develop inhibitors selective for neuronal nitric oxide synthase (nNOS) over endothelial nitric oxide synthase (eNOS), we found that nNOS can undergo conformational changes in response to inhibitor binding that does not readily occur in eNOS. One change involves movement of a conserved tyrosine, which hydrogen bonds to one of the heme propionates, but in the presence of an inhibitor, changes conformation, enabling part of the inhibitor to hydrogen bond with the heme propionate. This movement does not occur as readily in eNOS and may account for the reason why these inhibitors bind more tightly to nNOS. A second structural change occurs upon the binding of a second inhibitor molecule to nNOS, displacing the pterin cofactor. Binding of this second site inhibitor requires structural changes at the dimer interface, which also occurs more readily in nNOS than in eNOS. Here, we used a combination of crystallography, mutagenesis, and computational methods to better understand the structural basis for these differences in NOS inhibitor binding. Computational results show that a conserved tyrosine near the primary inhibitor binding site is anchored more tightly in eNOS than in nNOS, allowing for less flexibility of this residue. We also find that the inefficiency of eNOS to bind a second inhibitor molecule is likely due to the tighter dimer interface in eNOS compared with nNOS. This study provides a better understanding of how subtle structural differences in NOS isoforms can result in substantial dynamic differences that can be exploited in the development of isoform-selective inhibitors.

Amyloid-β (Aβ) forms heterogeneous oligomers, which are implicated in the pathogenesis of Alzheimers disease (AD). Many Aβ oligomers consist of β-hairpin building blocks─Aβ peptides in β-hairpin conformations. β-Hairpins of Aβ can adopt a variety of alignments, but the role that β-hairpin alignment plays in the formation and heterogeneity of Aβ oligomers is poorly understood. To explore the effect of β-hairpin alignment on the oligomerization of Aβ peptides, we designed and studied two model peptides with two different β-hairpin alignments. Peptides Aβm17-36 and Aβm17-35 mimic two different β-hairpins that Aβ can form, the Aβ17-36 and Aβ17-35 β-hairpins, respectively. These hairpins are similar in composition but differ in hairpin alignment, altering the facial arrangements of the side chains of the residues that they contain. X-ray crystallography and SDS-PAGE demonstrate that the difference in facial arrangement between these peptides leads to distinct oligomer formation. In the crystal state, Aβm17-36 forms triangular trimers that further assemble to form hexamers, while Aβm17-35 forms tetrameric β-barrels. In SDS-PAGE, Aβm17-36 assembles to form a ladder of oligomers, while Aβm17-35 either assembles to form a dimer or does not assemble at all. The differences in the behavior of Aβm17-36 and Aβm17-35 suggest β-hairpin alignment as a source of the observed heterogeneity of Aβ oligomers.

Phytohormone levels are regulated through specialized enzymes, participating not only in their biosynthesis but also in post-signaling processes for signal inactivation and cue depletion. Arabidopsis thaliana (At) carboxylesterase 15 (CXE15) and carboxylesterase 20 (CXE20) have been shown to deplete strigolactones (SLs) that coordinate various growth and developmental processes and function as signaling molecules in the rhizosphere. Here, we elucidate the X-ray crystal structures of AtCXE15 (both apo and SL intermediate bound) and AtCXE20, revealing insights into the mechanisms of SL binding and catabolism. The N-terminal regions of CXE15 and CXE20 exhibit distinct secondary structures, with CXE15 characterized by an alpha helix and CXE20 by an alpha/beta fold. These structural differences play pivotal roles in regulating variable SL hydrolysis rates. Our findings, both in vitro and in planta, indicate that a transition of the N-terminal helix domain of CXE15 between open and closed forms facilitates robust SL hydrolysis. The results not only illuminate the distinctive process of phytohormone breakdown but also uncover a molecular architecture and mode of plasticity within a specific class of carboxylesterases.

Chitin is an abundant biopolymer and pathogen-associated molecular pattern that stimulates a host innate immune response. Mammals express chitin-binding and chitin-degrading proteins to remove chitin from the body. One of these proteins, Acidic Mammalian Chitinase (AMCase), is an enzyme known for its ability to function under acidic conditions in the stomach but is also active in tissues with more neutral pHs, such as the lung. Here, we used a combination of biochemical, structural, and computational modeling approaches to examine how the mouse homolog (mAMCase) can act in both acidic and neutral environments. We measured kinetic properties of mAMCase activity across a broad pH range, quantifying its unusual dual activity optima at pH 2 and 7. We also solved high-resolution crystal structures of mAMCase in complex with oligomeric GlcNAcn, the building block of chitin, where we identified extensive conformational ligand heterogeneity. Leveraging these data, we conducted molecular dynamics simulations that suggest how a key catalytic residue could be protonated via distinct mechanisms in each of the two environmental pH ranges. These results integrate structural, biochemical, and computational approaches to deliver a more complete understanding of the catalytic mechanism governing mAMCase activity at different pH. Engineering proteins with tunable pH optima may provide new opportunities to develop improved enzyme variants, including AMCase, for therapeutic purposes in chitin degradation.

In their folded state, biomolecules exchange between multiple conformational states that are crucial for their function. Traditional structural biology methods, such as X-ray crystallography and cryogenic electron microscopy (cryo-EM), produce density maps that are ensemble averages, reflecting molecules in various conformations. Yet, most models derived from these maps explicitly represent only a single conformation, overlooking the complexity of biomolecular structures. To accurately reflect the diversity of biomolecular forms, there is a pressing need to shift toward modeling structural ensembles that mirror the experimental data. However, the challenge of distinguishing signal from noise complicates manual efforts to create these models. In response, we introduce the latest enhancements to qFit, an automated computational strategy designed to incorporate protein conformational heterogeneity into models built into density maps. These algorithmic improvements in qFit are substantiated by superior Rfree and geometry metrics across a wide range of proteins. Importantly, unlike more complex multicopy ensemble models, the multiconformer models produced by qFit can be manually modified in most major model building software (e.g., Coot) and fit can be further improved by refinement using standard pipelines (e.g., Phenix, Refmac, Buster). By reducing the barrier of creating multiconformer models, qFit can foster the development of new hypotheses about the relationship between macromolecular conformational dynamics and function.

The receptor tyrosine kinase ROR2 mediates noncanonical WNT5A signaling to orchestrate tissue morphogenetic processes, and dysfunction of the pathway causes Robinow syndrome, brachydactyly B, and metastatic diseases. The domain(s) and mechanisms required for ROR2 function, however, remain unclear. We solved the crystal structure of the extracellular cysteine-rich (CRD) and Kringle (Kr) domains of ROR2 and found that, unlike other CRDs, the ROR2 CRD lacks the signature hydrophobic pocket that binds lipids/lipid-modified proteins, such as WNTs, suggesting a novel mechanism of ligand reception. Functionally, we showed that the ROR2 CRD, but not other domains, is required and minimally sufficient to promote WNT5A signaling, and Robinow mutations in the CRD and the adjacent Kr impair ROR2 secretion and function. Moreover, using function-activating and -perturbing antibodies against the Frizzled (FZ) family of WNT receptors, we demonstrate the involvement of FZ in WNT5A-ROR signaling. Thus, ROR2 acts via its CRD to potentiate the function of a receptor super-complex that includes FZ to transduce WNT5A signals.

Artificial intelligence-based protein structure prediction methods such as AlphaFold have revolutionized structural biology. The accuracies of these predictions vary, however, and they do not take into account ligands, covalent modifications or other environmental factors. Here, we evaluate how well AlphaFold predictions can be expected to describe the structure of a protein by comparing predictions directly with experimental crystallographic maps. In many cases, AlphaFold predictions matched experimental maps remarkably closely. In other cases, even very high-confidence predictions differed from experimental maps on a global scale through distortion and domain orientation, and on a local scale in backbone and side-chain conformation. We suggest considering AlphaFold predictions as exceptionally useful hypotheses. We further suggest that it is important to consider the confidence in prediction when interpreting AlphaFold predictions and to carry out experimental structure determination to verify structural details, particularly those that involve interactions not included in the prediction.

Time-resolved serial femtosecond crystallography (TR-SFX) has emerged as a crucial tool for studying the structural dynamics of proteins. In principle, TR-SFX has the potential to be a powerful tool not only for studying proteins but also for investigating chemical reactions. However, non-protein systems generally face challenges in indexing due to sparse Bragg spots and encounter difficulties in effectively exciting target molecules. Nevertheless, successful TR-SFX studies on chemical systems have been recently reported in a few instances, boding well for the application of TR-SFX to study chemical reactions in the future. In this context, we review the static SFX and TR-SFX studies conducted on chemical systems reported to date and suggest prospects for future research directions. [ABSTRACT FROM AUTHOR]

exo‐6b2‐Methyl‐substituted pentabenzocorannulene (exo‐PBC‐Me) was synthesized by the palladium‐catalyzed cyclization of 1,2,3‐triaryl‐1H‐cyclopenta[l]phenanthrene. Its bowl‐shaped geometry with an sp3 carbon atom in the backbone and a methyl group located at the convex (exo) face was verified by X‐ray crystallography. According to DFT calculations, the observed conformer is energetically more favorable than the endo one by 39.9 kcal/mol. Compared to the nitrogen‐doped analogs with intact π‐conjugated backbones (see the main text), exo‐PBC‐Me displayed a deeper bowl depth (avg. 1.93 Å), redshifted and broader absorption (250–620 nm) and emission (from 585 to more than 850 nm) bands and a smaller optical HOMO–LUMO gap (2.01 eV). exo‐PBC‐Me formed polar crystals where all bowl‐in‐bowl stacking with close π ⋅ ⋅ ⋅ π contacts is arranged unidirectionally, providing the potential for applications as organic semiconductors and pyroelectric materials. This unusual structural feature, molecular packing, and properties are most likely associated with the assistance of the methyl group and the sp3 carbon atom in the backbone. [ABSTRACT FROM AUTHOR]

2,2,2-trifluronate (TF) infiltrates into the solvated sheath of hydrated Zn2+ and adheres to the surface of Zn anode, guiding the homogeneous deposition of Zn2+ along the Zn(0 0 2) crystal surface, significantly inhibiting the formation of Zn dendrites and mitigrating side reactions. [Display omitted] Aqueous zinc-ion batteries (AZIBs) have attracted significant attention owing to their inherent security, low cost, abundant zinc (Zn) resources and high energy density. Nevertheless, the growth of zinc dendrites and side reactions on the surface of Zn anodes during repeatedly plating/stripping shorten the cycle life of AZIBs. Herein, a simple organic molecule with abundant polar functional groups, 2,2,2-trifluoroether formate (TF), has been proposed as a high-efficient additive in the ZnSO 4 electrolyte to suppress the growth of Zn dendrites and side reaction during cycling. It is found that TF molecules can infiltrate the solvated sheath layer of the hydrated Zn2+ to reduce the number of highly chemically active H 2 O molecules owing to their strong binding energy with Zn2+. Simultaneously, TF molecules can preferentially adsorb onto the Zn surface, guiding the uniform deposition of Zn2+ along the crystalline surface of Zn(0 0 2). This dual action significantly inhibits the formation of Zn dendrites and side reactions, thus greatly extending the cycling life of the batteries. Accordingly, the Zn//Cu asymmetric cell with 2 % TF exhibits stable cycling for more than 3,800 cycles, achieving an excellent average Columbic efficiency (CE) of 99.81 % at 2 mA cm−2/1 mAh cm−2. Meanwhile, the Zn||Zn symmetric cell with 2 % TF demonstrates a superlong cycle life exceeding 3,800 h and 2,400 h at 2 mA cm−2/1 mAh cm−2 and 5 mA cm−2/2.5 mAh cm−2, respectively. Simultaneously, the Zn//VO 2 full cell with 2 % TF possesses high initial capacity (276.8 mAh/g) and capacity retention (72.5 %) at 5 A/g after 500 cycles. This investigation provides new insights into stabilizing Zn metal anodes for AZIBs through the co-regulation of Zn2+ solvated structure and surface crystallography. [ABSTRACT FROM AUTHOR]

Investigation of the fruits of Rhododendron molle G. Don led to the isolation of three new grayanane-type diterpenoids, rhodomolleins LIV-LVI (1-3). The structures and absolute configurations of new compounds were fully elucidated by spectroscopic analysis and single-crystal X-ray diffraction, including HRESIMS, 1 D and 2 D NMR data. Compounds 1-3 were evaluated for analgesic activities utilizing an acetic acid-induced writhing test in mice. Compound 1 showed a significant antinociceptive effect with writhe inhibition rates of 72.9% and 100% at doses of 6 mg/kg and 20 mg/kg in mice, respectively. The binding mode of 1 to N-ethylmaleimide-sensitive factor (NSF, PDB: 6IP2) was explored by molecular docking, indicating the presence of hydrogen bond interactions which account for its analgesic activity. [ABSTRACT FROM AUTHOR]

Nickel (Ni) is an interesting candidate for corrosion protection of copper (Cu) due to its present passive area. Ni films with larger passive areas have better corrosion protection than those with smaller ones. In the present research, Ni films were produced over Cu. A barreling apparatus was employed to support the produced films in the sulphate solution. Various spinning speeds (0, 50, and 100 rpm) were used on the barrel while it was being processed. Several investigations were conducted, such as deposition rate, current efficiency, surface morphology, phase, film thickness, crystallographic orientation, and electrochemical properties. Increased spinning speed resulted in a decrease in the deposition rate, current efficiency, grain size, thickness, crystallite size, and exchange current density. Compared to a higher spinning speed, the decrease in spinning speed caused an increase in the oxygen content, surface roughness, and micro-strain. The higher speed of the barrel apparatus resulted in a lower corrosion rate Ni film of 0.147 mmpy. Moreover, the lower speed of the barrel apparatus resulted in a higher exchange current density Ni film of 0.997 A/cm². [ABSTRACT FROM AUTHOR]

This study describes a facile one-pot solvothermal method for the synthesis of heterostructured (HS) Bi2S3–TiO2 (BT) nanoparticles (NPs) and utilizes its potential for sensing the nitrobenzene (NB) as a fluorescent probe. The characterization of as-synthesized BT NPs endorses the mixed morphology with an average particle size of 14 nm and the crystallography study depicted the orthorhombic Bi2S3 and tetragonal anatase TiO2 phases. The selectivity and sensitivity of BT NPs toward NB were examined by comparing the fluorescence quenching with a few other selected organic aromatic compounds. The appreciable quenching efficiency of 97% was achieved with NB. The visual response of the BT/NB mixture was noticed under UV light (λ = 3 6 5 nm). The quenching parameters of the BT/NB system have been evaluated by modifying Stern–Volmer and double logarithmic equations. The results attribute the prevalence of dynamic quenching within the concentration range (0.4 mM to 5 mM) and beyond 5 mM, both static and dynamic quenching coexist. Further, thermodynamic studies of the BT/NB system indicate the spontaneous hydrophobic interaction. Moreover, a reliable outcome has been demonstrated in the sensing application of BT NPs in real water samples. [ABSTRACT FROM AUTHOR]

AbstractX-ray diffraction (XRD) is an analytical technique that has found several applications focusing on the identification of crystal structure, space groups, plane, and orientation, in addition to qualitative and quantitative phase identification, and polymorphism behavior. An XRD diffractogram pattern/Bragg’s peak can also provide valuable information that can be used for various food applications. While this review details the fundamental principles of XRD, the types of XRD systems, instrumentation, and the components thereof, the focus is to serve as a structured resource on explored applications of XRD in food, majorly revolving around food quality and safety. While recent studies relevant to the field are highlighted, leads for futuristic prospects are presented. With its unique approach, the XRD analysis can prove to be a rapid, robust, and sensitive nondestructive approach to food quality evaluation. Recent reports indicate its scope for nonconventional applications such as the assessment of 3D printability of foods, ice crystal formation, and screening food adulterants. Studies also highlight its scope to complement or replace conventional food quality testing approaches that involve the usage of chemicals, extensive sample preparation procedures, derivatization steps and demand long testing times. [ABSTRACT FROM AUTHOR]

Thiocarbonyl dithiocyanate (1) and chlorothiocarbonyl thiocyanate (2) were synthesized from thiophosgene and ammonium or silver thiocyanate, respectivley. Their crystal structures show syn‐anti (1) and syn (2) conformations, which were confirmed in the bulk phases by powder X‐ray diffraction, vibrational spectroscopy and DFT calculations. Further calculations explain the isolation of the kinetic reaction products by a lower transition states opposed to the thermodynamic reaction products. Reaction of 1 with ethanol gave a dithiobiuret derivative (3). In a proof‐of‐principle study we show that it in turn can be used for the complexation of nickel to yield (4). [ABSTRACT FROM AUTHOR]

Direct methods have practically solved the phase problem for small–medium‐size molecules but have substantially failed in macromolecular crystallography. They have two main limitations: a strong dependence on structural complexity and the need to work with atomic‐resolution data. Many attempts have been made to broaden their field of applicability, for example the use of some a priori information to make the estimate of the triplet invariant phases more effective. Unfortunately none of these new approaches allowed the successful application of direct methods to proteins and nucleic acids. Direct methods are still a niche tool in macromolecular crystallography. In a recent publication [Giacovazzo (2019). Acta Cryst. A75, 142–157] the method of joint probability distributions has been modified to take into account new sources of prior information, one of which is relevant to this article: the Patterson map. In practice, it has been shown that with prior knowledge of the interatomic vectors one is able to modify the classic Cochran reliability parameter for estimating the triplet invariant phases. The article was essentially theoretical in nature, and no attempt was described to test the practical usefulness of the new probabilistic formulas. This work is therefore the first application of the new method. It is shown that the use of the Patterson map as prior information substantially improves the Cochran estimate of triplet phases; the phase error distribution for the new estimates, even if it is related to macromolecular structures, becomes similar to that obtained for medium‐size structures. In some ways, it is as if the use of the Patterson information reduces the structural complexity, thus allowing a more general use of direct methods in macromolecular crystallography. Atomic resolution no longer seems to be a necessary ingredient for the applicability of direct methods; tests show that the apparent reduction in structural complexity also occurs in macromolecular structures with experimental data having a resolution of 2.3 Å. A number of test structures have been used to show the potential of the new technique. [ABSTRACT FROM AUTHOR]

Alloyed nanoclusters have been widely reported, but controllable synthesis of predesigned nanoclusters with specific structures remains challenging. We used [Cu(MeCN)4]PF6 intercept (AgtBuC≡C)n polymer to form Ag(I)-Cu(II) oligomer precursors which serve as the starting point of co-reduction reaction, leading to the generation of a new [Ag8Cu7(tBuC≡C)12]PF6 (Ag8Cu7) nanocluster. Single-crystal diffraction result reveals its Cu@Ag8@Cu6(tBuC≡C)12 three-layer structure similar to the previously reported Ag9Cu6 nanocluster except for the different core atom and shorter bond distance around. The identification of Ag8Cu7 was further confirmed by ESI-MS, XPS, PXRD, and TG characterizations. Besides, the nonemissive Ag8Cu7 cluster was subject to ligand exchange of bulky ligand 3,5-bis(trifluoromethyl)phenylacetylide (ArC ≡ CH) giving a novel Ag10Cu4(ArC ≡ C)14(DPPB)2 (Ag10Cu4) with a 634 nm red light emission, which provides another example of the breakage-reassembly mechanism. [ABSTRACT FROM AUTHOR]

Effects of transformation temperature and carbon content on the effective grain bounded by high‐angle boundary, i.e., "Bain size", in bainite structure are studied in Fe–2Mn–(0.05–0.75)C (mass%) alloys transformed isothermally between 773 and 673 K. Bainitic ferrite (BF) nucleates at austenite (γ) grain boundary with strong variant selection for carbon content less than 0.2 mass%, resulting in formation of coarse BF regions consisting of the Kurdjumov–Sachs (K–S) variants belonging to the same Bain variant. As temperature is lowered, K–S variant pairs with large misorientation are frequently formed. Variant selection at γ grain boundary becomes weaker for higher carbon content due to frequent intragranular nucleation particularly at 673 K. The Bain size decreases generally as transformation temperature is lowered, which is ≈15 μm at 773 K but down to ≈5 μm at 673 K, and also slightly decreases at 773 K with increasing carbon content. At lower temperatures, it decreases with the increase of carbon content in low carbon range less than 0.2 mass%C but inversely increases in higher carbon range. The observed changes in the variant paring and the Bain size are well understood in terms of the driving force of BF formation and self‐accommodation of transformation strain. [ABSTRACT FROM AUTHOR]

Growing high‐quality crystals remains a necessary part of crystallography and many other techniques. This article tabulates and describes several techniques and variations that will help individuals grow high‐quality crystals in preparation for crystallographic techniques and other endeavors, such as form screening. The discussion is organized to focus on low‐tech approaches available in any laboratory. [ABSTRACT FROM AUTHOR]

The highly cytotoxic macrocyclic trichothecene Isororidin A (C29H40O9) was isolated from the fungus Myrothesium verrucaria endophytic on the wild medicinal plant 'Datura' (Datura stramonium L.) and was characterized by one‐ (1D) and two‐dimensional (2D) NMR spectroscopy. The three‐dimensional structure of Isororidin A has been confirmed by X‐ray crystallography at 0.81 Å resolution from crystals grown in the orthorhombic space group P212121, with one molecule per asymmetric unit. Isororidin A is the epimer of previously described (by X‐ray crystallography) Roridin A at position C‐13′ of the macrocyclic ring. [ABSTRACT FROM AUTHOR]

Preparation of biomacromolecules for structural biology studies is a complex and time‐consuming process. The goal is to produce a highly concentrated, highly pure product that is often shipped to large facilities with tools to prepare the samples for crystallization trials or for measurements at synchrotrons and cryoEM centers. The aim of this article is to provide guidance and to discuss general considerations for shipping biomacromolecular samples. Details are also provided about shipping samples for specific experiment types, including solution‐ and cryogenic‐based techniques. These guidelines are provided with the hope that the time and energy invested in sample preparation is not lost due to shipping logistics. [ABSTRACT FROM AUTHOR]

Protein crystallography is an established method to study the atomic structures of macromolecules and their complexes. A prerequisite for successful structure determination is diffraction‐quality crystals, which may require extensive optimization of both the protein and the conditions, and hence projects can stretch over an extended period, with multiple users being involved. The workflow from crystallization and crystal treatment to deposition and publication is well defined, and therefore an electronic laboratory information management system (LIMS) is well suited to management of the data. Completion of the project requires key information on all the steps being available and this information should also be made available according to the FAIR principles. As crystallized samples are typically shipped between facilities, a key feature to be captured in the LIMS is the exchange of metadata between the crystallization facility of the home laboratory and, for example, synchrotron facilities. On completion, structures are deposited in the Protein Data Bank (PDB) and the LIMS can include the PDB code in its database, completing the chain of custody from crystallization to structure deposition and publication. A LIMS designed for macromolecular crystallography, IceBear, is available as a standalone installation and as a hosted service, and the implementation of key features for the capture of metadata in IceBear is discussed as an example. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Serial crystallography, born from groundbreaking experiments at the Linac Coherent Light Source in 2009, has evolved into a pivotal technique in structural biology. Initially pioneered at X‐ray free‐electron laser facilities, it has now expanded to synchrotron‐radiation facilities globally, with dedicated experimental stations enhancing its accessibility. This review gives an overview of current developments in serial crystallography, emphasizing recent results in time‐resolved crystallography, and discussing challenges and shortcomings. [ABSTRACT FROM AUTHOR]

A new 14-membered resorcylic acid lactone (RAL14), chaetolactone A (1), along with three known ones (2−4), was obtained from the fermentation of the soil-derived fungus Chaetosphaeronema sp. SSJZ001. Their structures were established based on extensive spectroscopic data analyses (UV, IR, HRESIMS, 1D, and 2D NMR),13C NMR chemical shifts calculations coupled with the DP4+ probability method, theoretical calculations of ECD spectra, as well as X-ray diffraction analysis. All compounds were evaluated for their cytotoxic effects against A549, HO-8910, and MCF-7 cell lines. [ABSTRACT FROM AUTHOR]

A report from the International Union of Crystallography Commission on Magnetic Structures outlining the recommendations for communicating commensurate magnetic structures. [ABSTRACT FROM AUTHOR]

Quantum crystallography is an emerging research field of science that has its origin in the early days of quantum physics and modern crystallography when it was almost immediately envisaged that X‐ray radiation could be somehow exploited to determine the electron distribution of atoms and molecules. Today it can be seen as a composite research area at the intersection of crystallography, quantum chemistry, solid‐state physics, applied mathematics and computer science, with the goal of investigating quantum problems, phenomena and features of the crystalline state. In this article, the state‐of‐the‐art of quantum crystallography will be described by presenting developments and applications of novel techniques that have been introduced in the last 15 years. The focus will be on advances in the framework of multipole model strategies, wavefunction‐/density matrix‐based approaches and quantum chemical topological techniques. Finally, possible future improvements and expansions in the field will be discussed, also considering new emerging experimental and computational technologies. [ABSTRACT FROM AUTHOR]

This study aims to establish the methods of evaluating cosmetic foundation in vitro from four dimensions: concealment, dullness, migration resistance as well as the ability of water resistance, sweat resistance and sebum resistance. The automatic film coating machine was used to evenly coat the samples in the first steps. The concealment and dullness sections were evaluated by MetaVue VS3200 spectrophotometer, which measured the hiding rate of the samples and the color characterization values of the foundation (ΔL, Δa, Δb). The coverage rate of sample E1 is 90.98 cr, which is the highest coverage. The ΔL value of sample D2 has the largest change of -2.73 as well as the highest dullness. Combined with the result of consumer testing for further verification, the overall score results are consistent with in vitro test results. Also, the ability of migration resistance was determined and compared by the image analysis of software Image-Pro Plus 6.0 through the testing of the amount of rubbed powder. Moreover, through the contact angle measuring device, the capabilities of water, sweat, and sebum resistance of the foundation samples could be compared based on the measurement of the contact angles of deionized water, artificial sweat, and artificial sebum on the sample surface. The contact angles of sample B1 and D2 with deionized water and artificial sweat are greater than 90° for removal of lipophilicity. The contact angles of all samples are less than 90° for removal of lipophilicity, among which sample E1 and sample F are relatively lower in removal of lipophilicity, and the contact angles are respectively 40.8° and 40.0°. The results of water resistance, sweat and sebum tested in this study are generally consistent with the test results based on existing literature. The results show that four methodologies of scientific measurement with instruments are feasible and valid, and they help develop the convenience and scientific rigor of in vitro evaluation. [ABSTRACT FROM AUTHOR]

The molecular weight, surface tension, and the particle size distribution of micellar aggregates of a polyetherpolyacrylate polymeric surfactant, HS-PA, were characterized on gel permeation chromatograph, surface tension meter, and laser particle size analyzer, respectively. The thickening properties, detergency, liquid crystal morphology, suspension properties, and rheological behaviors of HS-PA in unstructured/structured detergents with LAS/AES/AEO9 as the main surfactants, respectively, were also investigated. The characterization results showed that, the weight-average molecular weight of HS-PA was 4 244, the critical micelle concentration was 3x10-7 mol/L, and the equilibrium surface tension was 42.06 mN/m; the average particle size of aggregates was increased when LAS, AES and AEO9 formed mixed micelles with HS-PA, respectively. The application test in unstructured detergents showed that, HS-PA had viscosityenhancing effects on all the LAS/AES/AEO9-based systems, and meanwhile it was beneficial to the improvement of the detergency to sebum. The application test in structured detergents showed that, HS-PA would help the formation of lamellar liquid crystals in the LAS/AES/AEO9 systems, and the more HS-PA used, the more the liquid crystals in the AES system; the centrifugal separation results showed that the structured detergents containing HS-PA had the ability to stabilize the suspension of microcapsules; HS-PA could increase the yield stress of the LAS formulation system as determined by rotational rheometer. [ABSTRACT FROM AUTHOR]

The different structures and behaviors of UO2+x observed in crystallographic and local structure measurements were examined by extended X-ray absorption fine structure (EXAFS) measurements of pristine UO2.0, p+ and He2+ irradiated UO2.0, and, at multiple temperatures, bulk U4O9 and U3O7 and thin film U4O9-δ on an epitaxial substrate. The disorder caused by irradiation is mostly limited to increased widths of the existing U-O/U pair distributions, with any new neighbor shells being minor. As has been previously reported, the disorder caused by oxidative addition to U4O9 and U3O7 is much more extensive, resulting in multisite U-O distributions and greater reduction of the U-U amplitude with different distributions in bulk and thin-film U4O9. This includes the significant spectral feature near R = 1.2 Å for all U4O9 and U3O7 samples fit with a U-oxo type moiety with a U-O distance around 1.7 Å. In addition to indicating that these anomalies only occur in mixed valence materials, this work confirms the continuous rearrangement of the U-O distributions from 10 to 250 K. Although these variations of the structure are not observed in crystallography, their prominence in the EXAFS indicates that the dynamic structure underlying these effects is an essential factor of these materials. [ABSTRACT FROM AUTHOR]

AbstractThree new copper(II) complexes with the general formula Cu4X6O(L)4 (1, X = chloride, L = 2-amino-5-chloropyridine; 2, X = chloride, L = 2-amino-5-bromopyridine and 3, X = bromide, L= 2-aminopyridine) with an adamantane-like core structure are reported. 1 and 2 crystallize in the space group P-1, while 3 crystallizes in the space group P21/c. We also report comparisons between the structures of these compounds and ones found in a literature review of compounds with similar structures and organic ligands. The members of this family all exhibit antiferromagnetic interactions and the possibility of magnetic frustration due to their geometries. [ABSTRACT FROM AUTHOR]

Simple Summary: Breast cancer ranks as the most prevalent cancer among women. Current screening includes regular mammography and subsequent biopsy if the mammography results are abnormal. These procedures are costly and uncomfortable. We propose an alternative non-invasive method based on X-ray scattering. Using a machine learning approach, we have examined almost 3000 measurements of cancerous and non-cancerous samples belonging to 110 patients and shown excellent results on cancer/non-cancer separation. This can lead to patient-friendly, fast, and economical solutions for breast cancer screening to complement mammography and reduce biopsy. It should be emphasized that this approach can be readily extended to other types of cancer and even other diseases. With breast cancer being one of the most widespread causes of death for women, there is an unmet need for its early detection. For this purpose, we propose a non-invasive approach based on X-ray scattering. We measured samples from 107 unique patients provided by the Breast Cancer Now Tissue Biobank, with the total dataset containing 2958 entries. Two different sample-to-detector distances, 2 and 16 cm, were used to access various structural biomarkers at distinct ranges of momentum transfer values. The biomarkers related to lipid metabolism are consistent with those of previous studies. Machine learning analysis based on the Random Forest Classifier demonstrates excellent performance metrics for cancer/non-cancer binary decisions. The best sensitivity and specificity values are 80% and 92%, respectively, for the sample-to-detector distance of 2 cm and 86% and 83% for the sample-to-detector distance of 16 cm. [ABSTRACT FROM AUTHOR]

The emergence and spread of antibiotic resistance represent a growing threat to public health. Of particular concern is the appearance of β-lactamases, which are capable to hydrolyze and inactivate the most important class of antibiotics, the β-lactams. Effective β-lactamase inhibitors and mechanistic insights into their action are central in overcoming this type of resistance, and in this context boronate-based β-lactamase inhibitors were just recently approved to treat multidrug-resistant bacteria. Using boric acid as a simplified inhibitor model, time-resolved serial crystallography was employed to obtain mechanistic insights into binding to the active site serine of β-lactamase CTX-M-14, identifying a reaction time frame of 80–100 ms. In a next step, the subsequent 1,2-diol boric ester formation with glycerol in the active site was monitored proceeding in a time frame of 100–150 ms. Furthermore, the displacement of the crucial anion in the active site of the β-lactamase was verified as an essential part of the binding mechanism of substrates and inhibitors. In total, 22 datasets of β-lactamase intermediate complexes with high spatial resolution of 1.40–2.04 Å and high temporal resolution range of 50–10,000 ms were obtained, allowing a detailed analysis of the studied processes. Mechanistic details captured here contribute to the understanding of molecular processes and their time frames in enzymatic reactions. Moreover, we could demonstrate that time-resolved crystallography can serve as an additional tool for identifying and investigating enzymatic reactions. Boronate-based ß-lactamase inhibitors play an important role in treating multidrug-resistant bacteria infection, however, the molecular mechanism of inhibition remains unclear. Here, the authors use time-resolved serial crystallography to investigate the binding process by using boric acid as a model against β-lactamase CTX-M-14, revealing the binding to the active site serine within 80–100 ms, a subsequent 1,2-diol boric ester formation with glycerol within 100–150 ms, as well as the displacement of the sulfate anion in the active site. [ABSTRACT FROM AUTHOR]

The Bifidobacterium bifidum SAM-VI riboswitch undergoes dynamic conformational changes that modulate downstream gene expression. Traditional structural methods such as crystallography capture the bound conformation at high resolution, and additional efforts would reveal details from the dynamic transition. Here, we revealed a transcription-dependent conformation model for Bifidobacterium bifidum SAM-VI riboswitch. In this study, we combine small-angle X-ray scattering, chemical probing, and isothermal titration calorimetry to unveil the ligand-binding properties and conformational changes of the Bifidobacterium bifidum SAM-VI riboswitch and its variants. Our results suggest that the SAM-VI riboswitch contains a pre-organized ligand-binding pocket and stabilizes into the bound conformation upon binding to SAM. Whether the P1 stem formed and variations in length critically influence the conformational dynamics of the SAM-VI riboswitch. Our study provides the basis for artificially engineering the riboswitch by manipulating its peripheral sequences without modifying the SAM-binding core. [ABSTRACT FROM AUTHOR]

Synchrotron protein crystallography (PX) remains an indispensable tool for uncovering the atomic structures of biomolecules. TLS 15A1, operated by the protein diffraction group of NSRRC, has been accessible to both academic and industrial users since January 2013. This beamline is energy‐tunable within a range between 5.6 and 15.5 keV, which is suitable for phasing experiments. Over the past 11 years, TLS 15A1 has supported 657 projects and facilitated 1523 experiments across 41,656 h of beamtime. This article describes the beamline layout, studies of factors influencing data quality, and significant scientific contributions. [ABSTRACT FROM AUTHOR]