BACKGROUND AND PURPOSE:In this study, we evaluated the beneficial vascular effects of a newly semi-synthesized chalcone derived from the Senecio nutans metabolite-1 [4-hydroxy-3-(3-methyl-2-butenyl) acetophenone] in hypertensive rats. We investigated chalcone (CHAL13) through functional assays in spontaneously hypertensive rat (SHR) aorta. We also used fluorescence microscopy, RT-qPCR, molecular docking and X-ray crystallography. KEY RESULTS:CHAL13-induced vasorelaxation was unaffected by endothelial removal or inhibition of the eNOS-NO-sGC-cGMP signalling pathway in SHR. CHAL13 reduced extracellular Ca2+ influx in Ca2+-free medium and decreased KCl-induced intracellular Ca2+ increases in primary vascular smooth muscle cells (pVSMCs). CHAL13 also suppressed the contraction induced by the CaV1.2 agonist Bay-K8644 in SHR aortic rings, supporting a direct inhibitory effect on vascular CaV1.2 channels. Notably, activation of KCa, KV and KATP channels contributed significantly to CHAL13's vasorelaxant effect. Compared with its precursor metabolite, CHAL13 exhibited stronger interactions with the pore-forming α1C subunit of the CaV1.2 channel, near the binding site of voltage-gated calcium channel blockers, and with the α1 subunit of the KCa1.1 channel, near the binding site of known channel activators. CHAL13 also showed predicted interactions with KV1.2 and vascular KATP channels. Aortic tissues treated with CHAL13 showed upregulated expression of Kcnmb1 and Kcna5 transcripts, which are associated with vascular relaxation. CONCLUSIONS AND IMPLICATIONS:CHAL13 exerts a vasorelaxant effect primarily through CaV1.2 channel blockade and coordinated activation of multiple K+ channel subtypes, suggesting membrane hyperpolarization in vascular smooth muscle. Its favourable chemical, pharmacokinetic and toxicological profiles support its potential as a novel antihypertensive scaffold.

This work describes the synthesis and characterization of organometallic N-acylhydrazones (NAHs) of general formula R1-C(O)-NH-NC(R2)(4- or 5-nitrothienyl) (4a,b-7a,b), where R1 = ferrocenyl (a) or cyrhetrenyl (b) and R2 = H or Me. The X-ray crystal structures of 4b, 5a, 5b, and 6b are described. UV-Vis studies confirmed that the compounds remained stable in DMSO/buffer mixtures for 24 h. In vitro studies of the biological activities of 4a,b-7a,b against Trypanosoma cruzi (T. cruzi) and Trypanosoma brucei (T. brucei) showed that the organometallic derivatives were more active against T. brucei (EC50 = 0.18-12.9 μM) than against T. cruzi (EC50 = 4.24-78.8 μM). Except for 5b, cyrhetrenyl derivatives were more potent than their ferrocenyl analogs, showing up to a 7-fold increase in antiparasitic activity. In all cases, the 5-nitrothiophene derivatives (6a,b-7a,b) also outperformed their 4-nitro analogs (4a,b-5a,b), underscoring the strong impact of nitro-group positioning on biological activity. Compound 6b proved to be the most promising anti-T. brucei agent due to its potency (EC50 = 0.47 μM) and selectivity (SI = 110). Comparison of data for 6a and 6b and their isomers 8a and 8b [R1-C(H)N-NH-C(O)(5-nitrothienyl)] revealed that antiparasitic activity and cytotoxicity are strongly influenced by the position of the acylhydrazone group linking the organometallic fragment and the nitroheterocycle. Evaluation of T. brucei susceptibility showed that the 5-nitro derivatives undergo Type I nitroreductase-dependent activation (-tet/+tet ratios: 4.2-5.6), while the 4-nitro counterparts exhibited only minor shifts (1.5-2.0). These results indicate that small structural modifications in NAHs can significantly affect their antiparasitic properties.

Background:Sorafenib is a tyrosine kinase inhibitor (TKI) used to treat hepatocellular carcinoma (HCC), but this drug causes clinically significant toxicities in approximately 50% of patients. Given the high frequency and severity of these side effects, it is necessary to develop new, safer drugs to treat this cancer. Purpose:Novel 2,6,9-trisubstituted pyrimidine derivatives were synthesised and evaluated as potential antitumour agents for HCC. Materials and Methods:Twelve compounds (6a-l) were obtained by a four-step synthetic procedure using a simple and efficient methodology in which two key reactions were promoted by microwave irradiation. Subsequently, compounds 6a-l were evaluated in vitro for cytotoxic activity against the HCC cell line HepG2 and other cell lines; in vivo in the HepG2 xenograft tumour model; and in silico (docking and dynamic simulations). Results and discussion:Compound 6e proved to be the most promising of this series (IC50 = 5.6 µM), as well as being more index selective than sorafenib and with lower cytotoxicity in Vero cells (18.92 µM). In addition, 6e was further evaluated in Huh-7 cells and demonstrated selectivity for HCC. Docking studies on the proposed targets, VEGFR-2 and B-raf, indicated that 6e could bind to them with binding energies and interaction patterns similar to those of sorafenib. The 6e interaction pattern at the VEGFR-2 binding site was corroborated by dynamic studies over 100 ns. A possible mechanism of 6e-induced HepG2 cell death was investigated. Experiments on caspases-3, -7, -8, -9, Apaf-1, Cyt-c, ERK1/2, and p53 showed that they were all activated, whereas Bcl-2 was inhibited by 6e in HepG2 cells. Furthermore, 6e induced the accumulation of reactive oxygen species (ROS) in HepG2 cells. These results suggest that apoptosis in HepG2 was caused by: (i) a caspase-dependent pathway and (ii) changes in the cellular levels of Bcl-2 family proteins and ROS. In addition, 6e attenuated the growth of HepG2 xenograft tumours in mice at a dose of 1 mg/kg for 3 weeks. Conclusion:Based on these results, this pyrimidine derivative could be an interesting compound for the design of new agents against HCC.

In this study, we report the synthesis and characterization of three Cu(I) complexes bearing functionalized dipyridylamine ligands and DPEphos. Structural analysis confirms a distorted tetrahedral coordination environment around the metal center. Photophysical studies in DMSO show similar absorption profiles (lambda abs approximate to 341-343 nm) with ligand-centered and MLCT transitions, while emission spans the visible region (lambda emi = 410-483 nm) and is strongly influenced by ligand substitution, with the CF3 derivative displaying a marked red shift. Emission is insensitive to oxygen and exhibits short lifetimes (tau approximate to 14.9-15.3 ns), suggesting short-lived 1MLCT excited states. Biological evaluation in A375 melanoma cells reveals that all complexes exhibit low-micromolar cytotoxicity under dark conditions (IC50 = 3.33-4.92 mu M). Notably, only the CF3-substituted complex shows a significant light-induced enhancement of activity upon irradiation at 390 nm (IC50 = 1.18 mu M), indicating photoactivation.

Lichens are mutualistic symbiosis between a fungus (mycobiont) and an alga or cyanobacteria (photobiont), forming metabolically versatile holobionts capable of producing diverse secondary metabolites that facilitate their survival in extreme environments. Chrysothrix species, commonly known as “gold dust lichens,” are characterized by their vivid yellow thalli and their production of pulvinic acid derivatives, although their bioactive potential remains poorly explored. In this study, using organic chemistry techniques, we characterized the methanolic extract of Chrysothrix sp.—collected from the Paposo Fog Oasis in northern Chile, a unique coastal ecosystem sustained by persistent fog (“camanchacas”) within the Atacama Desert—and identified calycin as its major secondary metabolite through chromatographic purification and single-crystal X-ray diffraction. Antibacterial assays revealed that both the crude methanolic extract and purified calycin exhibited selective inhibitory activity against multidrug-resistant Gram-positive ESKAPE-E pathogens. Minimum Inhibitory Concentrations (MICs) ranged from 125 to 500 μg/mL, with the strongest effects observed against Enterococcus faecium (MDR, VRE) and Staphylococcus aureus (MDR, MRSA). No meaningful activity was detected against Gram-negative bacteria, consistent with the known permeability barrier conferred by the outer membrane. This work provides the first evidence of antibacterial activity for calycin isolated from Chrysothrix sp., highlighting the relevance of pulvinic acid derivatives as promising scaffolds for antimicrobial development. These findings highlight the potential of lichen-derived agents and alternative sources of antibacterial agents to address the global challenge of antimicrobial resistance.

Seawater electrolysis offers a promising route for sustainable hydrogen production in coastal areas, leveraging solar energy while reducing freshwater consumption. Yet, chloride-induced corrosion severely limits conventional electrodes such as titanium, which depend on passive titanium dioxide films and display minimal hydrogen evolution reaction activity (|i0,H2| approximate to 0.001-0.01 A/m2). Here, we report for the first time the use of copper-based coordination compounds-a triazole-derived polymer (CCCu) and a Prussian Blue Analogue (CuHCF)-as dual-function electrodes combining corrosion resistance with electrocatalytic activity. Structural integrity was verified by FTIR, TGA, XRD, and SEM/EDS analyses. Electrochemical tests in 0.5 M NaCl, interpreted using mixed potential theory, revealed corrosion potentials (Ecorr) of -40 mV versus Standard Hydrogen Electrode (CuHCF) and -23 mV versus Standard Hydrogen Electrode (CCCu), and corrosion current densities of 0.259 and 0.379 A/m2, respectively. Both exhibited hydrogen evolution reaction exchange current densities significantly higher than titanium (0.019 A/m2 for CuHCF and 0.062 A/m2 for CCCu). CuHCF achieved a Tafel slope of 222 mV/dec, comparable to NiMoP alloys and carbon steel. Complementary density functional theory calculations elucidated how metal-ligand interactions and electronic redistribution govern both catalytic performance and degradation. These findings introduce a new concept of semi-electrocatalysts, where copper coordination compounds act as structurally adaptive, low-cost materials bridging corrosion resistance and hydrogen evolution in seawater systems.

Two new Cu(II) (CP1) and Co(II) (CP2) coordination polymers (CPs) with the triazole ligand 5-methyl-1-(pyridin-4-yl-methyl)-1H-1,2,3-triazole-4-carboxylate (L1) have been synthesized and structurally characterized by SCXRD (Single Crystal X-Ray Difraccion), PXRD (Power X-Ray Difracction), FT-IR (Fourier Transform Infrared), TG (Theermo Gravimetric), and electrochemical techniques. Both CPs were obtained at the water/n-butanol interface by reacting nitrate salts of each metal with the NaL1 ligand. SCXRD analysis revealed that CP1 (Coordination Polymer 1) and CP2 (Coordination Polymer 2) crystallize in the monoclinic space groups C2/c (No. 15) and P21/n (No. 14), respectively, forming 1D zigzag chain structures, which further lead to a 2D supramolecular network through O-H⋯O and C-H⋯O hydrogen bond interactions, respectively. In CP1, the supramolecular structure is assembled by hydrogen bonds involving water molecules. In contrast, CP2 forms its supramolecular network mainly through hydrogen bonds between adjacent triazole ligand molecules. Hirshfeld surface analysis revealed that the most significant contributions to the crystal packing come from H⋯O/O⋯H, H⋯H, H⋯N/N⋯H, and H⋯C/C⋯H interactions. In addition, FT-IR provided information on the functional groups involved in the coordination, while the decomposition patterns of both CPs were evaluated by TGA. Electrochemical studies conducted in a saline environment showed that CP1 exhibits superior hydrogen evolution reaction (HER) kinetics compared to CP2, as evidenced by a higher exchange current density and a lower Tafel slope. Density functional theory calculations and experimental bandgap measurements provided a deeper understanding of the electronic properties influencing the electrochemical behavior. The results highlight the potential of CP1 as an efficient catalyst for HER under saline conditions.

Multicomponent cyclocondensations of 5-amino-3-methyl-1-phenyl-1H-pyrazole (AMPZ), thiobarbituric acid, and p-formaldehyde under conventional thermal heating or ultrasonic irradiation were studied. Treatment of the reaction mixture in ethanol in an ultrasonic bath for 3 h produced azocine compound 4b, while the same mixture in ethanol under reflux conditions for 15 h produced spiro compound 4a. This work encompasses intricate experimental details, X-ray diffraction measurements, and multifaceted computational analyses employing methods such as the density functional theory and Hirshfeld surface analysis. Crystallographic investigations revealed the molecular structure of the compound and clarified its interactions involving hydrogen bonds and weak intermolecular forces. This article describes the synthesis and characterization of a novel spirocyclic compound. The study also evaluated the antioxidant potential in vitro using the DPPH and ABTS methods. The results showed that these compounds showed the best free radical scavenging ability, even in very small amounts, and that even at very low concentrations, these compounds showed excellent radical scavenging potential. Surprisingly, these compounds exhibited strong (ABTS+) radical scavenging activities, mainly attributed to the HAT mechanism, indicating their potential as therapeutic agents. Facile multipurpose, three-component selective procedures for new spiroheterocycles have been proposed, presenting intriguing perspectives in the field of medicine, particularly in the field of antioxidants. The geometric values of the computationally optimized structure were calculated using the density functional theory in LC-BLYP/6-31(d), aligned with the X-ray diffraction data, reinforcing the precision of our findings.

One of the most urgent threats to public health worldwide is the ongoing rise of multidrug-resistant (MDR) bacterial strains. Among the most critical pathogens are MDR-Klebsiella pneumoniae strains. The lack of new antibiotics has led to an increased need for non-antibiotic antimicrobial therapies. Photodynamic therapy (PDT) has become increasingly significant in treating MDR bacteria. PDT uses photosensitizer compounds (PS) that generate reactive oxygen species (ROS) when activated by light. These ROS produce localized oxidative stress, damaging the bacterial envelope. A downside of PDT is the limited bioavailability of PSs in vivo, which can be enhanced by conjugating them with carriers like nanoparticles (NPs). Zinc nanoparticles possess antibacterial properties, decreasing the adherence and viability of microorganisms on surfaces. The additive or synergistic effect of the combined NP-PS could improve phototherapeutic action. Therefore, this study evaluated the effectiveness of the copper(I)-based PS CuC1 compound in combination with Zinc Oxide NP, ZnONP, to inhibit the growth of both MDR and sensitive K. pneumoniae strains. The reduction in bacterial viability after exposure to a PS/NP mixture activated by 61.2 J/cm2 of blue light photodynamic treatment was assessed. The optimal PS/NP ratio was determined at 2 µg/mL of CuC1 combined with 64 µg/mL of ZnONP as the minimum effective concentration (MEC). The bacterial gene response aligned with a mechanism of photooxidative stress induced by the treatment, which damages the bacterial cell envelope. Additionally, we found that the PS/NP mixture is not harmful to mammalian cells, such as Hep-G2 and HEK-293. In conclusion, the CuC1/ZnONP combination could effectively aid in enhancing the antimicrobial treatment of infections caused by MDR bacteria.

Hybrid halide compounds of formula A2BX4 represent a promising class of materials for tuning structural and electronic properties via halide substitution. Here, we report the synthesis and comprehensive characterization of the (CH3NH3)2ZnX4 (X = Cl, Br, I) series, including the first full structural resolution of the iodide analogue. Single-crystal X-ray diffraction revealed a halide-driven transition from a three-dimensional monoclinic structure (P21/c) for Cl and Br to a layered orthorhombic structure (Pbca) for I. Raman spectroscopy showed redshifts in lattice phonons and N-H stretching broadening along the series, indicating weaker hydrogen bonding and enhanced vibrational coupling with heavier halides. Thermal analysis confirmed phase transitions associated with CH3NH3+ dynamics, followed by complete decomposition below 300 degrees C, largely independent of halide identity. Diffuse reflectance spectroscopy revealed wide bandgap semiconducting behavior, with values decreasing systematically from 5.55 eV (Cl) to 4.25 eV (I). These findings establish a clear structure-property correlations in the (CH3NH3)2ZnX4 family and provide a foundation for future bandgap and lattice engineering in hybrid halide systems.

This article discloses the synthesis of four new positional isomeric zwitterionic ligands exhibiting semi-flexible and flexible characteristics—n-pyridinium-1,2,3-triazole-4-carboxy-5-Acetate (n-PTCA), and n-methylpyridinium-1,2,3-triazole-4-carboxy-5-Acetate (n-MPTCA; where n = 3, 4)—which were derived from an aqueous solution of the corresponding sodium salts in an acidic medium (HCl). These compounds are successfully synthesized and characterized with FT-IR and multinuclear NMR spectroscopy; likewise, proper single crystals are obtained for each compound. All compounds adopt zwitterionic forms in the solid state, which are stabilized via intermolecular proton transfer processes involving HCl and solvent molecules. A single-crystal X-ray analysis revealed how positional isomerism and molecular flexibility influence the supramolecular topology. Specifically, 3-PTCA and 4-PTCA exhibit isomorphic hydrogen bond networks, while 3-MPTCA and 4-MPTCA display distinct packing motifs, attributed to the presence of a methylene spacer between the pyridinium and triazole rings. The Hirshfeld surface analysis quantitatively confirmed the dominance of O···H/H···O and N···H/H···N interactions in the solid-state architecture. These strong hydrogen-bonding networks are indicative of the potential proton-conductive behavior in the crystalline state, positioning these compounds as promising candidates for applications in proton-conducting materials. The structural insights gained underscore the pivotal role of molecular topology in tailoring crystal packing, with implications for the rational design of zwitterionic ligands in functional materials, including MOFs and coordination polymers. The calculated HOMO-LUMO energy gaps reveal a significant electronic variability among the ligands, influenced primarily by the positional isomerism and structural flexibility introduced by the methylene spacer.

The increase in and concern about neurodegenerative diseases continue to grow in an increasingly long-lived world population.

The crystal structure of the title compound was determined at 120 K. It crystallizes in the triclinic space group P\overline{1} with four independent molecules in the asymmetric unit. In the crystal, each symmetry-unique molecule forms π–π stacks on itself, giving four unique π–π stacking interactions. Intermolecular hydrogen bonding is observed between each pair of independent molecules, where each hydroxy group can act as a hydrogen-bond donor and acceptor.

This article details the synthesis, full characterization, optical properties, theoretical analysis, evaluation of nonlinear optical properties (NLO), and determination of the hemolytic capacity of quinoline-1,3-benzodioxole chalcone(5).

The cation of the title hydrated salt, C17H17BN3+·I−·H2O, is a diazaborinane featuring substitution at the 1, 2, and 3 positions in the nitrogen–boron six-membered heterocycle. The cation is approximately planar with a dihedral angle between the pyridyl ring and the diazaborinane ring system of 5.40 (5)°. In the crystal, the cations stack along [100] in an alternating head-to-tail manner, while the iodide ion and water molecule form one-dimensional hydrogen-bonded chains beside the cation stack. The cation stacks and I−–water chains are crosslinked by N—H...I and N—H...O hydrogen bonds.

This study presents the synthesis and characterization of a series of 13 novel acetamides. These were subjected to Ellman's assay to determine the efficacy of the AChE and BChE inhibitors. Finally, we report their antioxidant activity as an alternative approach for the search for drugs to treat AD. These studies revealed that compounds 1a-1k and 2l-2m were obtained in moderate yield. Four amides (1h, 1j, 1k, and 2l) were selective for one of the enzymes (BChE); thus, those that inhibited BChE were more active than the positive control (galantamine) and showed better IC50 values (3.30-5.03 µM). The theoretical free binding energies calculated by MM-GBSA indicated that all inhibitors were more stable than rivastigmine, and the inhibition mechanisms involved the entire active site: peripheral anionic site, oxyanion hole, acyl-binding pockets, and catalytic site. We examined the cytotoxicity of compounds 1h, 1j, 1k, and 2l in human dermal cells and found that they did not exhibit any toxic effects under the tested conditions. Additionally, these compounds, which also inhibited BChE, displayed mixed inhibition and did not exhibit hemolytic effects on human erythrocytes. Furthermore, the ABTS and DPPH assays indicated that, although none of the compounds showed activity in the DPPH assay, the EC50 values for radical trapping by the ABTS method showed that compounds 1a, 1d, 1e, and 1g had EC50 values lower than 10 µg/mL, indicating their strong radical scavenging capacity. We also report the crystal structures of compounds 1c, 1d, 1f, and 1g, which are found in monoclinic crystal systems.

Acid Mine Drainage (AMD) is a significant environmental problem in the mining industry due to its high concentration of hazardous metals and metalloids, sulfate compounds, and low pH levels. Despite the attention that iron oxide magnetic nanoparticles (MNP) have received for AMD remediation, there is still a lack of understanding of the physicochemical mechanisms behind their non-specific adsorption, particularly in distinct variations of AMD, such as Cu-rich AMD. In this study, we synthesized, characterized, and applied MNP to the two-step treatment of Cu-rich AMD. The chemical and physical properties of the MNP and magnetically separated sludges after AMD treatment are characterized. Additionally, the chemical species adsorbed onto the MNP, the oxidation state of the resultant sludge after Cu-rich AMD treatment, and the short-range ordering of metal contaminant species on the surface of the MNP are identified. Finally, first-principles calculations using Density Functional Theory were conducted to understand how different Cu ion species adsorb to the MNP surface depending on the pH of the Cu-rich AMD. The bonding between MNP and Cu species occurs primarily through metal cation-oxygen bonds on the surface of MNP, and this bonding is influenced by the pH of the solution. A combination of experimental and theoretical approaches was the key to arrive at this conclusion. This information can aid in the comprehension of how metal contaminants adhere to the surfaces of MNP and in the precise engineering of these nanoparticles.

An important finding is that the ketalization of 2-bromo-3-(3,5-di-tert-butyl-4-hydroxyphenyl)-1-phenylprop-2-en-1-one in the presence of amine has been presented. The structure of obtained 2-(3,5-di-tert-butyl-4-hydroxyphenyl)-3,3-diethoxy-1-phenylpropan-1-one is fully characterized by IR, MS, 1H, 13C NMR spectrometry, as well as X-ray diffractometry. Experimental spectrum values of the molecule were compared with experimental data. Optimized structures of the molecule were obtained on the B3LYP, HF, M062X methods and 6-31++G(d,p) basis set. Additionally, Hirshfeld surface analyses was performed in order to obtain information about the interactions in the crystal packing.

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.

The title compound, 1,5,5-trimethyl-imidazolidine-2,4-dione was characterized by FT-IR, 1H NMR, and 13C NMR spectroscopy techniques. The crystal structure was established by single-crystal X-ray diffraction. The powder Xray powder diffraction analysis confirms the phase purity of the crystalline sample. The hydantoin with formula C6H10N2O2 crystallizes in the tetragonal space group I4/m (N degrees 87), Z=8, and unit cell parameters a=15.554(2) angstrom, c=6.623(6) angstrom. This space group is very infrequent to find in purely organic molecules and is since, in the asymmetric unit, the hydantoin ring lies on a mirror plane m. The crystalline packing is stabilized by the formation of intermolecular interactions of the strong hydrogen bond type of the N-H & sdot;& sdot;& sdot;O between the neighboring hydantoin rings. In addition, the crystalline structure presents the formation of weaker unconventional hydrogen bonds of the C-H & sdot;& sdot;& sdot;O type. These hydrogen bonds give rise to the formation of 8, 24, and 36-membered ring-type supramolecular structures described by the graphs R22(8), R44(24), and R88(36), respectively, which govern the packing of the supramolecular structure of 1,5,5-trimethyl-imidazolidine-2,4-dione. Hirshfeld surface analysis of the crystal structure shows that the most important contributions for the crystal packing are from H & sdot;& sdot;& sdot;H (58.3%) and H & sdot;& sdot;O/O & sdot;& sdot;H (34.0%) interactions, which indicate that van der Waals interactions are the dominant forces in the crystal packing. Energy framework calculations suggest that the contacts formed between molecules are slightly electrostatic. These intermolecular interactions were also investigated through topological analysis of the electron density (rho) employing the NCI method. Experimental and theoretical results obtained for this new hydantoin compound suggest that N-H & sdot;& sdot;& sdot;O and C-H & sdot;& sdot;& sdot;O interactions play an important role in the stabilization of its supramolecular structure.