Search Results (15,789)

(±)-tiaprofenic acid (TA), marketed as (Surgam^®), belongs to the family of NSAIDs, with the peculiarity of a reduced incidence of ulcer induction in rats compared with parent drugs. However, some adverse effects were observed, and better knowledge of its interaction with biologic substrates is needed. Unfortunately, unlike most commercial NSAIDs, suitable single crystals for an X-ray diffraction study could not be obtained. To fill the gap, the crystal structure of TA was solved by X-ray powder diffraction, and the molecular interactions stabilizing the structure were analyzed by Hirshfeld surface and energy framework analysis. TA crystallizes in the $P{2}_1/c$ space group, with its two enantiomers in the asymmetric unit, further confirming the peculiarity of the crystal structure and the difficulty of solving it. TA packing is characterized by alternating enantiomers connected through hydrogen bonds, forming chains, arranged in layers, stabilized by $\pi$-stacking. First principle modeling revealed several stable conformations within 4 $\mathrm{k}$$\mathrm{J}$/$\mathrm{mol}$ of the global minimum and the relaxed potential energy scans revealed modest (8 $\mathrm{k}$$\mathrm{J}$/$\mathrm{mol}$–15 $\mathrm{k}$$\mathrm{J}$/$\mathrm{mol}$) energy barriers. Such flat energy landscape suggests flexible and dynamic behavior of tiaprofenic acid in solution and in vivo conditions, with multiple suitable docking sites. Full article

The effect of dislocation pile-ups responsible for the generation or annihilation of dislocations during friction of Ag and Ni was considered. The steady-state friction was accompanied by the formation of twin bundles, intersecting twins, dislocations, adiabatic elongated shear bands, and intense dynamic recrystallization. The mechanisms of microstructural stability and friction instability were analyzed. The theoretical models of dislocation generation and annihilation in nanocrystalline FCC metals in the context of plastic deformation and failure development under friction were proposed. The transition to unstable friction was estimated. The damage of Ag was exhibited in the formation of pores, reducing the contact area and significantly increasing the shear stress. The brittle fracture of Ni represents a catastrophic failure associated with the formation of super-hard nickel oxide. Deformation resistance of the dislocation structures in the mesoscale and macroscale was compared. The coefficient of similitude (K) has been introduced in this work to compare plastic deformation at different scales. The model of the strength–ductility trade-off and microstructural instability is considered. The interaction between the migration of dislocation pile-ups and the driving forces applied to the grain boundaries was estimated. Nanostructure stabilization through the addition of a polycrystalline element (solute) to the crystal interiors in order to reduce the free energy of grain boundary interfaces was investigated. The thermodynamic driving force and kinetic energy barrier involved in strengthening, brittleness, or annealing under plastic deformation and phase formation in alloys and composite materials were examined. Full article

Continuous crystallizations have promising potential for effectively controlling and modifying the crystal properties of active pharmaceutical ingredients (APIs). In this study, a continuous antisolvent sonocrystallization process was developed to recrystallize a poorly water-soluble API, mefenamic acid, for microparticle production. This method offers advantages such as efficient sonication, enhanced heat removal, and potential for scalability. The effects of operating parameters, such as sonication intensity, crystallization temperature, antisolvent flow rate, and solution flow rate, were investigated and compared. Using continuous antisolvent sonocrystallization, the particle size of mefenamic acid was controlled within the range of 2.6–3.5 μm, achieving a narrower particle size distribution compared to the unprocessed sample. In addition, scanning electron microscopy (SEM) analysis confirmed that the sonocrystallized mefenamic acid exhibited an improved crystal shape. Analytical results from powder X-ray diffraction (PXRD), Fourier transform infrared spectroscopy (FTIR), and differential scanning calorimetry (DSC) showed that the crystal structure, spectroscopic characteristics, and thermal behavior of mefenamic acid remained unchanged after the sonocrystallization process. Full article

Tuberculosis, the deadliest human lung disease caused by Mycobacterium tuberculosis, continues to be a global health threat, and finding new drugs and drug targets seems an ongoing battle. The cytochrome P450 CYP125A1 enzyme of M. tuberculosis H37Rv, which is involved in cholesterol metabolism, is a well-established target for drug development. Research is ongoing to identify new compounds that target this enzyme. Understanding the structure–activity relationship of CYP125 family members is crucial for developing a specific and efficient inhibitor. In this direction, this study analyzed 21 crystal structures of CYP125 family enzymes, unraveling the factors responsible for substrate specificity and the amino acids that play a key role in catalysis. One of the unique features of CYP125A1 is its active site cavity shape, which determines the specificity of substrates and inhibitors. The active site cavity is shaped like a letter box, lined by hydrophobic residues, and it transitions into a funnel-like shape with a progressive narrowing as it approaches the heme. Due to this shape, the cholesterol and cholest-4-en-3-one serve as substrates, but not androstenedione, as the former molecules have an alkyl side chain that extends down the narrow funnel channels, interacting with the heme iron. Different binding patterns were observed for substrates and indole-derived inhibitors. Both type I and type II interactions were observed with the non-azole P450 inhibitor LP10 and indole-derived compounds, where the side chain of the indole-derived compound determined the type of interaction. This study provides a comprehensive understanding of the structure–function analysis of P450 enzymes and the interactions of CYP125A members with various ligands. Our findings pave the way for designing new and specific CYP125A1 inhibitors that will ultimately be developed into novel anti-TB drugs. Full article

Background: Theophylline, which is biologically important and found in tea, coffee, and cocoa beans, can be synthesized chemically or by direct extraction and concentration from natural sources. Theophylline derivatives have garnered attention in recent years for their potential therapeutic effects on Mycobacterium tuberculosis, antihistaminic, anti-inflammatory, and anticancer. Also, trifluoromethyl (CF₃) group has also been widely used in drug and agrochemical design. Methods: In this study, a series of new theophylline derivatives containing substituted trifluoromethyl and trifluoromethoxy groups were synthesized. The structures of these new compounds were confirmed by NMR, FT-IR, and elemental analyses. Additionally, the anticancer activities of the molecules were analyzed against VEGFR-2, CYP P450, and estrogen receptor by molecular docking method. Furthermore, in vitro biological effects of the compounds were comprehensively evaluated in cancer (A549 and HeLa) and normal (BEAS-2B) cells. Cell viability was assessed by MTT assay, and selectivity index (SI) values were calculated to determine tumor-specific toxicity. Results: N(7)-substituted theophyllines were prepared by the reaction of 1,3-dimethyl-3,7-dihydro-1H-purine-2,6-dione (theophylline) and trifluoromethyl substituted benzyl halide compounds. The synthesized N(7)-substituted theophyllines were obtained as white powder in high yield. The structure of synthesized compounds was confirmed by various spectroscopic techniques such as ¹H, ¹³C, ¹⁹F NMR, and FT-IR spectroscopy, and elemental analysis. The highest interaction was recorded as −5.69 kcal/mol for 3-CF₃ substituted against VEGFR-2 structure while the best binding affinity was determined for 4-OCF₃ substituted with −6.69 kcal/mol against Human Cytochrome P450 with in silico analysis. The in vitro anticancer activities of the molecules were also evaluated against A549 and HeLa cells, and displayed considerably higher cytotoxicity with 2-CF₃, 3-CF_3, and 4-CF₃ substituted molecules in Hela and A549 cell line. To elucidate the molecular mechanism, apoptosis-related gene expression changes were analyzed by RT-qPCR in A549 and HeLa cells treated with compound 2-CF₃. Significant upregulation of pro-apoptotic markers and downregulation of anti-apoptotic genes were observed. Consistently, ELISA-based quantification confirmed increased protein levels of Caspase-3, BAX, and Cytochrome C, and decreased BCL-2, validating the apoptotic mechanism at the protein level. Also, the antibacterial and antibiofilm activity details of the molecules were evaluated against DNA Gyrase, and SarA crystal structures by molecular docking method. The highest interaction was recorded as −5.56 kcal/mol for 2-CF₃ substituted with H-bonds with Asn46, Val71, Asp73, and Thr165 against DNA Gyrase crystal structure while 3-CF₃ substituted has the best binding affinity against SarA. The in vitro antimicrobial effects of the molecules were also evaluated. Conclusions: The synthesized molecules may provide insight into the development of potential therapeutic agents to the increasing antimicrobial resistance and biofilm-forming capacity of microorganisms. Additionally, compound 2-CF₃ substituted exhibited promising and selective anticancer activity through apoptosis induction, supported by gene and protein level evidence. Full article

Phosphagen kinases are vital for energy buffering and ATP regeneration in cells with high or fluctuating energy demands. Phosphagens are small, high-energy phosphate-storage molecules, such as arginine phosphate or creatine phosphate, that serve as immediate phosphate donors for rapid ATP production. Among them, arginine kinase plays a central role in invertebrates, while creatine kinase is predominant in vertebrates. This review presents a comprehensive structural analysis of arginine kinases and their homologs across diverse species, ranging from invertebrates like Daphnia magna, Scylla paramamosain, and Limulus polyphemus to the bacterial kinase McsB from Staphylococcus aureus. High-resolution crystal and cryo-EM structures reveal a common two-domain architecture and shed light on substrate-induced conformational changes, domain cooperativity, and catalytic mechanisms. Mutational studies highlight conserved residues such as His284 and their impact on enzyme dynamics. Importantly, the structure of bacterial arginine kinase-like kinases, such as McsB, unveils regulatory mechanisms mediated by activators like McsA. This structural diversity and functional specificity underscore the evolutionary adaptability of phosphagen kinases and their relevance as potential drug targets or diagnostic markers. Full article

Europium mononuclear complexes are able to form organic molecular crystals by aggregation of molecules through non-covalent bonding interactions. These crystals have many unique optical properties. However, this kind of crystal still faces some difficulties and challenges in the process of research and application, such as the high difficulty of synthesis and purification, and the difficulty of spectral property modulation. In this work, an europium-containing rare-earth molecular crystal material [Eu(BA)₄(pip)], was prepared via a solvothermal method. It is characterized by low melting point, low polarity, stable structure, high luminescence intensity, and has the potential for the preparation of quantum optical devices. After that, optimized the structure of the molecular crystals by petroleum ether solvent. Through the recrystallization process, a uniform and continuous film was formed, which resulted with a more regular surface morphology, and the changes in the optimized crystal structure had an effect on the europium ion electron-leap energy level, the fluorescence emission spectra also showed higher fluorescence resolving ratio. This study particular emphasis on enhancing the quality of [Eu(BA)₄(pip)] molecular crystals and investigating their impact on their spectral properties. Full article

Background: Bispecific antibodies have emerged as a promising class of therapeutics, enabling simultaneous targeting of two distinct antigens. Single-domain antibodies (sdAbs) comprising camelid variable heavy chains (VHHs) provide a compact and adaptable platform for bispecific antibody design due to their small size and ease of linkage. Methods: Here we investigate structure-activity relationship of VHH-based cytokine surrogates by combining cell signaling and functional assays with x-ray crystallography and other biophysical techniques. Results: We describe crystal structures of four unique bispecific VHHs that engage and activate the cytokine receptor pairs IL-18Rα/IL-18Rβ and IL-2Rβ/IL-2Rγ. These bispecific VHH molecules, referred to as surrogate cytokine agonists (SCAs), create unique cytokine signals that can be tuned by linker engineering. Our structural analysis reveals multiple dimeric conformations for these bispecific SCAs, where the two VHH domains can interact to form a compact structure. We demonstrate that the dimeric conformation can be enforced via engineering of a non-native disulfide bond between the VHH subunits, thus enhancing molecular thermostability. Conclusion: Our findings have important implications for the design and engineering of bispecific VHHs or sdAbs, offering a novel strategy for tuning their activity and increasing their stability. Full article

We demonstrate that selective electrochemical etching is a reliable method for detecting and observing the uneven concentration distribution of impurities in indium phosphide crystals, which accompanies the growth of highly doped crystals using the Czochralski method. Even though selective electrochemical etching, as a method of detecting defects in the crystal lattice, has been discussed many times in the literature, it has not yet been described for indium phosphide. In this work, we investigated etching in compositions of various selective electrolytes for InP of n- and p-type conductivity with different surface orientations. We present in detail the features of detecting the striped inhomogeneity of impurity distribution. The mechanisms and peculiarities of the formation of oxide crystallites on the surface of InP during electrochemical processing are presented, including structures like flower-like and parquet crystallites. The formation of porous surfaces, terraces, tracks, and crystallites is explained from the perspective of the defect-dislocation mechanism. Full article

This study systematically investigates the effects of aging treatment (AT) on the microstructure and properties of Cr/DLC coatings deposited via cathodic arc ion plating onto the surface of ECAP-7075 aluminum alloy. Utilizing a comprehensive approach combining performance tests (nanoindentation, nanoscratch testing, dynamic polarization analysis) with characterization tests (scanning electron microscopy, energy dispersive spectroscopy, X-ray diffraction, and X-ray photoelectron spectroscopy), the synergistic effects of equal channel angular pressing (ECAP) and aging treatment(AT) were elucidated. The results demonstrate that the combined ECAP and AT significantly enhance the coating’s performance. Specifically, AT promotes the precipitation of η’ phase within the 7075 aluminum alloy substrate, increases the size of Cr₇C₃ crystallites in the Cr-based interlayer, improves the crystallinity of the Cr₇C₃ phase on the (060) or (242) crystal planes, and elevates the sp³-C/sp²-C ratio in the diamond-like carbon(DLC) top layer, leading to partial healing of defects and a denser overall coating structure. These microstructural transformations, induced by AT, result in substantial improvements in the mechanical properties (hardness reaching 5.2 GPa, bond strength achieving 15.1 N) and corrosion resistance (corrosion potential increasing to -0.698 V) of the Cr/DLC-coated ECAP-7075 aluminum alloy. This enhanced combination of properties makes these coatings particularly well-suited for high-performance aerospace components requiring both wear resistance and corrosion protection in demanding environments. Full article

We developed dye-sensitized solar cells based on anatase–titanium dioxide (A-TiO₂) nanotubes (TiNTs) and nanocubes (TiNcs) with {001} crystal facets generated using simple and facile electrochemical anodization. We also demonstrated a simple way of developing one-dimensional, two-dimensional, and three-dimensional self-assembled TiO₂ nanostructures via electrochemical anodization, using them as an electron-transporting layer in DSSCs. TiNTs maintain tubular arrays for a limited time before becoming nanocrystals with {001} facets. Using FESEM and TEM, we observed that the TiO₂ nanobundles were transformed into nanocubes with {001} facets and lower fluorine concentrations. Optimizing the reaction approach resulted in better-ordered, crystalline anatase TiNTs/Ncs being formed on the Ti metal foil. The anatase phase of as-grown TiO₂ was confirmed by XRD, with (101) being the predominant intensity and preferred orientation. The nanostructured TiO₂ had lattice values of a = 3.77–3.82 and c = 9.42–9.58. The structure and morphology of these as-grown materials were studied to understand the growth process. The photoconversion efficiency and impedance spectra were explored to analyze the performance of the designed DSSCs, employing N719 dye as a sensitizer and the I⁻/I³⁻ redox pair as electrolytes, sandwiched with a Pt counter-electrode. As a result, we found that self-assembled TiNTs/Ncs presented a more effective photoanode in DSSCs than standard TiO₂ (P25). TiNcs (0.5 and 0.25 NH₄F) and P25 achieved the highest power conversion efficiencies of 3.47, 3.41, and 3.25%, respectively. TiNcs photoanodes have lower charge recombination capability and longer electron lifetimes, leading to higher voltage, photocurrent, and photovoltaic performance. These findings show that electrochemical anodization is an effective method for preparing TiNTs/Ncs and developing low-cost, highly efficient DSSCs by fine-tuning photoanode structures and components. Full article

Fly ash, as the main solid waste of coal-fired power plants, is an environmental problem that needs to be solved due to its massive accumulation. The mechanical properties and optimization mechanism of lightweight aggregate concrete prepared by using new single-cylinder rotary kiln fly ash ceramic granules as aggregate were systematically investigated. Through orthogonal experimental design, combined with macro-mechanical testing and microscopic characterization techniques, the effects of cement admixture and ceramic granule admixture on the properties of concrete, such as compressive strength, split tensile strength, and modulus of elasticity, were analyzed, and the optimization scheme of key parameters was proposed. The results show that the new single rotary kiln fly ash ceramic particles significantly improve the mechanical properties of concrete by optimizing the porosity (water absorption ≤ 5%), and its 28-day compressive strength reaches 46~50.9 MPa, which is 53.3~69.7% higher than that of the ordinary ceramic concrete, and the apparent density is ≤1900 kg/m³, showing lightweight and high-strength characteristics. X-ray diffraction (XRD) analysis shows that the new ceramic grains form a more uniform, dense structure through the synergistic effect of internal mullite crystals and dense glass phase; computed tomography (CT) scanning shows that the total volume rate of cracks of the new ceramic concrete was reduced by up to 63.8% compared with that of ordinary ceramic concrete. This study provides technical support for the utilization of fly ash resources, and the prepared vitrified concrete meets the demand of green building while reducing structural deadweight (20~30%), which has significant environmental and economic benefits. Full article

This study investigates the influence of RE elements on the room- and high-temperature properties of magnesium alloys. The effects of RE type, addition level, and multi-element alloying strategies were systematically analyzed to clarify the underlying strengthening mechanisms and processing pathways for optimizing Mg–RE alloys. RE elements enhance the mechanical and thermal properties of Mg alloys through crystal structure modification, formation of thermally stable dispersed phases, precipitation strengthening, and solid-solution strengthening. Compared with conventional alloying elements, RE additions offer distinct advantages in strengthening efficiency and overall performance. To fully exploit these benefits, new research paradigms that integrate machine learning and other advanced techniques are required, enabling the intelligent design of multicomponent alloy systems tailored to specific application requirements. Full article

Background/Objectives: Malaria is a prominent vector-borne disease, with a high mortality rate, particularly in children under five years old. Despite the use of various insecticides for its control, the emergence of resistant mosquitoes poses a significant public health threat. Acetylcholinesterase (AChE) is a crucial enzyme in nerve transmission and a primary target for insecticide development due to its role in preventing repeated nerve impulses. Recent studies have identified difluoromethyl ketone (DFK) as a potent inhibitor of both sensitive and resistant Anopheles gambiae acetylcholinesterase (AgAChE). This study aimed to identify novel AgAChE inhibitors that could be explored for malaria prevention. Methods: We performed a virtual screening on the PubChem database using a pharmacophore model from difluoromethyl ketone-inhibited AgAChE’s crystal structure. The most promising compound was then subjected to molecular docking and dynamics studies with AgAChE to confirm initial findings. ADMET and agrochemical likeness (ag-like) properties were also analyzed to assess its potential as an agrochemical agent. Results: PubChem18463786 was identified as the most suitable compound from the virtual screening. Molecular docking and molecular dynamics studies confirmed its strong interaction with AgAChE. The ADMET and ag-like analyses indicated that PubChem18463786 possesses physicochemical properties suggesting a high probability of non-absorption in humans and meets the criteria for agrochemical similarity. Conclusions: Our findings suggest that PubChem18463786 is a potential AgAChE inhibitor candidate. After validation through in vitro and in vivo experiments, it could be exploited for malaria prevention and serve as a lead compound for the synthesis of new, more effective, and selective agrochemical agents. Full article

Soybean residue, kudzu root residue, astragalus residue and pomegranate peel residue are byproducts of food processing with high yield. In the food processing industry in Northwest China, these waste residues contain a large amount of nutrients and have a large amount of emissions. In this study, cellulose was extracted from four kinds of waste residue and characterized to study its emulsification performance and application effect. The results are as follows: The extracted cellulose had typical cellulose crystal structure and good thermal stability. Among the four kinds of cellulose, the physical, chemical and functional properties of the soybean byproduct were significantly better than those of standard cellulose and other sources of cellulose. The Pickering emulsions fixed by four kinds of cellulose and soybean lecithin have similar properties. The emulsification performance of the immobilized soybean byproduct cellulose Pickering emulsion is the best. Soybean byproduct cellulose was used as an oil substitute for the development of new mayonnaise. The results showed that when 8% soybean byproduct cellulose Pickering emulsion was used to replace vegetable oil, the quality of reduced-fat mayonnaise was better. This soybean byproduct cellulose has potential development and application value in industrial food. Full article