Search Results (252)

A novel series of multifunctional tacrine–quinoline hybrids were designed, synthesized, and evaluated as potential anti-Alzheimer’s agents. These compounds incorporate tacrine for cholinesterase’s inhibition and 8-hydroxyquinoline for metal chelation. Piperazine was selected as a linker to provide conformational flexibility and to create favorable cation–π interactions with residues in the mid-gorge region of AChE, enhancing dual-site binding with AChE to inhibit Aβ aggregation. In vitro studies demonstrated submicromolar inhibitory activity toward both AChE and BuChE, particularly for compounds 16e (IC₅₀ = 0.10 μM for AChE, 0.043 μM for BuChE) and 16h (IC₅₀ = 0.21 μM for AChE, 0.10 μM for BuChE). These compounds also exhibited potent inhibition of self-induced Aβ_1–42 aggregation (16e: 80.5% ± 4.4%, 16h: 93.2% ± 3.9% at 20 μM). Kinetic analyses revealed mixed-type inhibition, suggesting dual binding to both CAS and PAS of AChE. UV–vis spectrometry confirmed the chelation of Cu²⁺ and Zn²⁺ ions by the 8-hydroxyquinoline moiety. These findings highlight the tacrine–quinoline scaffold as a promising platform for the discovery of a multitarget-directed anti-AD drug. Full article

With the recent development of accurate protein structure prediction tools, virtually all protein sequences now have an experimental or a modeled structure. It has therefore become essential to develop fast algorithms capable of detecting non-covalent interactions not only within proteins but also in protein-protein, protein-DNA, protein-RNA, and protein-ligand complexes. Interactions involving aromatic compounds, particularly their $\pi$ molecular orbitals, hold unique significance among molecular interactions due to the electron delocalization, which is known to play a key role in processes such as protein aggregation. In this paper, we present PInteract, an algorithm that detects $\pi$-involving interactions in input structures based on geometric criteria, including $\pi$-$\pi$, cation-$\pi$, amino-$\pi$, His-$\pi$, and sulfur-$\pi$ interactions. In addition, it is capable of detecting chains and clusters of $\pi$ interactions as well as particular recurrent motifs at protein-DNA and protein-RNA interfaces, called stair motifs, consisting of a particular combination of $\pi$-$\pi$ stacking, cation/amino/His-$\pi$ and H-bond interactions. Full article

A theoretical study was performed using Density Functional Theory (DFT) to investigate the impact of π-conjugated aliphatic chain growth on the chemical and electronic properties of hybrid antimony pentachloride salts with pyridine- and imidazolium-based cations. Ten molecular systems were optimized to determine their ground-state geometry. Using conceptual DFT, parameters such as chemical hardness, electrophilicity index, electroaccepting power, and electrodonating power were studied. The energy gap was obtained for all ten molecular systems, ranging from −4.038 to −3.706 eV as the chain length increased, favoring intramolecular charge transfer in long-chain systems. Natural bond orbital (NBO) analysis showed charge redistribution between anion and cation as the π-conjugated aliphatic chain grows. At the same time, non-covalent interaction (NCI) studies revealed key attractions and repulsive interactions, such as H···Cl and Cl···π, which are modulated by chain length. These results demonstrate that the structural modification of the cation allows for the fine-tuning of the electronic properties of ionic liquids (ILs). Increasing the conjugated aliphatic chain length was observed to reduce the chemical hardness and electrophilicity index, as well as affecting the Egap of the molecular systems. This work demonstrates that there is an optimal size for the inorganic ion, allowing it to form an optimal IL compound. Full article

Klebsiella oxytoca originating from shellfish Scapharca subcrenata contains a number of virulence-related genes. In this study, we investigated its pathogenicity using a murine intestinal infection model and predicted its antibacterial compounds and targets via molecular docking analysis. The results revealed that the intake of K. oxytoca 8-2-11 strain (10⁹ CFU/day) via oral gavage for 7 days reduced the average body weight of the mice. The bacterium was present in fecal samples but absent from blood, lung, and liver samples from the mice. The intake of K. oxytoca 8-2-11 significantly altered colon bacteriota, with reduced abundance of Firmicutes, Lachnospiraceae, Lactobacillaceae, Lactobacillus, and Lactobacillus murinus, and increased in Bacteroidota, Muribaculaceae, and Alistipes (p < 0.05). Forty-four bioactive compounds in Scutellaria baicalensis and Forsythia suspensa were screened for docking with 117 potential virulence factors (VFs) in K. oxytoca 8-2-11. The compound baicalin displayed higher binding affinity toward these VFs, with the lowest mean binding energy (−8.4 kcal/mol). Baicalin was able to bind to key VFs in biofilm formation and adherence/motility (e.g., Mrks and EcpA) via forming stable hydrogen bonds, π-stacking, and π-cation interaction. In vitro, baicalin inhibited the bacterial growth and biofilm formation. This study establishes the first murine infection model using aquatic animal-derived K. oxytoca, and it provides candidate antibacterial compounds and targets for control of K. oxytoca infections. Full article

In this study, the design and synthesis of a novel series of cinnamic acid and 1,2,4-triazole hybrids were reported, aiming to enhance antioxidant and lipoxygenase inhibitory activities through pharmacophore combination. Cinnamic acid derivatives and 1,2,4-triazoles exhibit a broad spectrum of biological activities; therefore, by synthesizing hybrid molecules, we would like to exploit the beneficial characteristics of each scaffold. The general synthetic procedure comprises three synthetic steps, starting from the reaction of appropriate substituted cinnamic acid with hydrazine monohydrate in acetonitrile with cyclohexane and resulting in the formation of hydrazides. Consequently, the hydrazides reacted with phenylisothiocyanate under microwave irradiation conditions. Then, cyclization proceeded to the 1,2,4-triazole after the addition of NaOH solution and microwave irradiation. All the synthesized derivatives have been studied for their ability (a) to interact with the free radical DPPH, (b) inhibit lipid peroxidation induced by AAPH, and (c) inhibit soybean lipoxygenase. The synthesized derivatives have shown significant antioxidant activity and have been proved to be very good lipoxygenase inhibitors. Compounds 4b and 4g (IC₅₀ = 4.5 μM) are the most potent within the series followed by compound 6a (IC₅₀ = 5.0 μM). All the synthesized derivatives have been subjected to docking studies related to soybean lipoxygenase. Compound 4g exhibited a docking score of −9.2 kcal/mol and formed hydrophobic interactions with Val126, Tyr525, Lys526, Arg533, and Trp772, as well as a π−cation interaction with Lys526. Full article

Four novel crystalline architectures based on benzo[c]cinnolininium trifluoromethanesulonate salts, [C₁₂H₉N₂]⁺[CF₃SO₃]⁻, have been isolated as single-crystals, and their structures have been determined by X-ray diffraction analysis. The formation of the new salts results from reactions involving the dimeric hydroxo di-n-butylstannane trifluoromethanesulfonato complex [n-Bu₂Sn(OH)(H₂O)(CF₃SO₃)]₂ (1) and benzo[c]cinnoline (C₁₂H₈N₂, BCC). Organic salts I, II, III, and IV were crystallized through slow evaporation at room temperature from a mixture of toluene/dichloromethane. The cystallographic structures of I, II, and IV exhibit the presence of monoprotonated benzo[c]cinnolinium cations in interactions with a free benzo[c]cinnoline molecule through N–H···N hydrogen bonding, while for salt III, the monoprotonated cation directly interacts with the CF₃SO₃⁻ anion via an N–H···O interaction. For all four salts, aromatic π-π interactions involving rings of various components (free benzo[c]cinnoline molecule, benzo[c]cinnolinium cation, toluene molecule), combined with weak C–H···O and C–H···F interactions implying the trifluoromethanesulfonate anion, promote the solid-state self-assembly of supramolecular stacks. In parallel to the formation of benzo[c]cinnolinium based-salts, organotin(IV) 1 was converted into a distannoxane compound, ²_∞{[n-Bu₂(μ-OH)SnOSn(μ-η²-O₃SCF₃)n-Bu₂]₂[n-Bu₂(η¹-O₃SCF₃)SnOSn(μ-OH)n-Bu₂]₂} (3), which was also isolated as a single crystal and whose crystallographic structure was previously established by us. Full article

Enhanced oil recovery (EOR) via CO₂ flooding is a promising strategy for improving hydrocarbon recovery and carbon sequestration, yet the influence of pH on solid–liquid interfacial interactions in quartz-dominated reservoirs remains poorly understood. This study employs molecular dynamics (MD) simulations to investigate the pH-dependent adsorption behavior of crude oil components on quartz surfaces and its impact on CO₂ displacement mechanisms. Three quartz surface models with varying ionization degrees (0%, 9%, 18%, corresponding to pH 2–4, 5–7, and 7–9) were constructed to simulate different pH environments. The MD results reveal that aromatic hydrocarbons exhibit significantly stronger adsorption on quartz surfaces at high pH, with their maximum adsorption peak increasing from 398 kg/m³ (pH 2–4) to 778 kg/m³ (pH 7–9), while their alkane adsorption peaks decrease from 764 kg/m³ to 460 kg/m³. This pH-dependent behavior is attributed to enhanced cation–π interactions that are facilitated by Na⁺ ion aggregation on negatively charged quartz surfaces at high pH, which form stable tetrahedral configurations with aromatic molecules and surface oxygen ions. During CO₂ displacement, an adsorption–stripping–displacement mechanism was observed: CO₂ first forms an adsorption layer on the quartz surface, then penetrates the oil phase to induce the detachment of crude oil components, which are subsequently displaced by pressure. Although high pH enhances the Na⁺-mediated weakening of oil-surface interactions, which leads to a 37% higher diffusion coefficient (8.5 × 10⁻⁵ cm²/s vs. 6.2 × 10⁻⁵ cm²/s at low pH), the tighter packing of aromatic molecules at high pH slows down the displacement rate. This study provides molecular-level insights into pH-regulated adsorption and CO₂ displacement processes, highlighting the critical role of the surface charge and cation–π interactions in optimizing CO₂-EOR strategies for quartz-rich reservoirs. Full article

This study focuses on the search for new effective synthetic antimicrobial compounds as a tool against the widespread presence of microorganisms resistant to existing drugs. Five derivatives of [1,3]thiazolo[3,2-b][1,2,4]triazoles were synthesized using an accessible protocol based on electrophilic heterocyclization and were characterized using infrared (FTIR) and nuclear magnetic resonance (NMR) spectroscopies, and their in vitro antimicrobial and antifungal activities were evaluated using the agar plate diffusion method and the microdilution plate procedure. Both antibacterial (Gram-positive and Gram-negative) and antifungal activities were found for the examined samples. The minimum inhibitory concentration (MIC) varied from 0.97 to 250 µg/mL, and the minimum bactericidal concentration (MBC) from 1.95 to 500 µg/mL. Compound 2a showed good antifungal action against Candida albicans and Saccharomyces cerevisiae with minimum fungicidal concentration (MFC) 125 and MIC 31.25 µg/mL. The molecular docking revealed that the 2-heptyl-3-phenyl-6,6-trimethyl-5,6-dihydro-3H-[1,3]thiazolo[3,2-b][1,2,4]triazol-7-ium cation stands out as a highly promising candidate for further investigation due to a wide range of interactions, including conventional hydrogen bonds, π–σ, π–π T-shaped, and hydrophobic alkyl interactions. The synthesis and preliminary evaluation of [1,3]thiazolo[3,2-b][1,2,4]triazoles yielded promising antimicrobial and antifungal candidates. The diverse interaction profile of the 2-heptyl derivative salt allows this compound’s selection for further biological studies. Full article

Two-dimensional (2D) crystals which present unconventional stoichiometries on graphene surfaces in ambient conditions, such as Na₂Cl, Na₃Cl, and CaCl, have attracted significant attention in recent years due to their electronic structures and abnormal cation–anion ratios, which differ from those of conventional three-dimensional crystals. This unconventional crystallization is attributed to the cation–π interaction between ions and the π-conjugated system of the graphene surface. Consequently, their physical and chemical properties—including their electrical, optical, magnetic, and mechanical characteristics—often differ markedly from those of conventional crystals. This review summarizes the recent progress made in the fabrication and analysis of the structures, distinctive features, and applications of these 2D unconventional stoichiometry crystals on graphene surfaces in ambient conditions. Their special properties, including their piezoelectricity, metallicity, heterojunction, and room-temperature ferromagnetism, are given particularly close attention. Finally, some significant prospects and further developments in this exciting interdisciplinary field are proposed. Full article

The one-dimensional (1D) Sb(III)-based organic–inorganic hybrid perovskite (AImd)₂¹_∞[SbI₅] (AImd = 1-allylimidazolium) crystallizes in the orthorhombic, centrosymmetric space group Pnma. The structure consists of corner-sharing [SbI₆] octahedra forming 1D chains separated by allylimidazolium cations. Void analysis through Mercury CSD software confirmed a densely packed lattice with a calculated void volume of 1.1%. Integrated quantum theory of atoms in molecules (QTAIM) and non-covalent interactions index (NCI) analyses showed that C–H···I interactions between the cations and the ¹_∞[SbI₅]²⁻ network predominantly stabilize the supramolecular assembly followed by N–H···I hydrogen bonds. The calculated growth morphology (GM) model fits very well to the experimental morphology. UV–Vis diffuse reflectance spectroscopy allowed us to determine the optical band gap to 3.15 eV. Density functional theory (DFT) calculations employing the B3LYP, CAM-B3LYP, and PBE0 functionals were benchmarked against experimental data. CAM-B3LYP best reproduced Sb–I bond lengths, while PBE0 more accurately captured the HOMO–LUMO gap and the associated electronic descriptors. These results support the assignment of an inorganic-to-organic [Sb–I] → π* charge-transfer excitation, and clarify how structural dimensionality and cation identity shape the material’s optoelectronic properties. Full article

Given the adverse effects of organic dyes from aqueous solutions on human physiology and the ecological system, establishing an effective system for their elimination is imperative. This study employs the in situ thermal (IST) method to synthesize nanocomposites comprising zeolitic imidazole frameworks, specifically Fe-ZIF-8 and Fe-ZIF-67. The investigation offers a comprehensive evaluation of the properties of these nano-adsorbents for the removal of malachite green (MG). The results indicate a significantly increased adsorption capacity of up to 495 and 552 mg g⁻¹ for Fe-ZIF-8 and Fe-ZIF-67, respectively. Furthermore, they demonstrate removal efficiencies of up to 90% and 95% for MG, respectively. Parameters associated with the adsorption process are derived from isotherms and removal kinetics, specifically the Freundlich model and the pseudo-second-order kinetics model, respectively. The enhanced adsorption capacity observed in Fe-ZIF-8 and Fe-ZIF-67 can be attributed to π–π stacking interactions, hydrogen bonding, and electrostatic attraction. After undergoing three cycles, both adsorbents consistently exhibit a high removal efficiency of approximately 85%, indicating notable structural integrity and outstanding potential for repeated use. The examined adsorbents display exceptional efficacy, favorable stability, and substantial specific surface area, underscoring their remarkable adsorption capabilities. The nanocomposites comprising Fe-ZIF-8 and Fe-ZIF-67 demonstrate considerable potential as highly favorable options for the elimination of MG and other cationic organic dyes from aqueous environments. Full article

A group of sulfonium and selenonium salts bearing diverse benzylidene acetal substituents on their side chain moiety were designed and synthesized. Compared with our previous study, structural modifications in this study focused on multi-substitution of the phenyl ring and bioisosteric replacements at the sulfonium cation center. In vitro biological evaluation showed that selenonium replacement could significantly improve their α-glucosidase inhibitory activity. The most potent inhibitor 20c (10.0 mg/kg) reduced postprandial blood glucose by 48.6% (15 min), 52.8% (30 min), and 48.1% (60 min) in sucrose-loaded mice, outperforming acarbose (20.0 mg/kg). Docking studies of 20c with ntMGAM presented a new binding mode. In addition to conventional hydrogen bonding and electrostatic interaction, amino residue Ala-576 was first identified to contribute to binding affinity through π-alkyl and alkyl interactions with the chlorinated substituent and aromatic ring. The selected compounds exhibited a high degree of safety in cytotoxicity tests against normal cells. Kinetic characterization of α-glucosidase inhibition confirmed a fully competitive inhibitory mode of action for these sulfonium salts. Full article

The detection of zinc ions plays an essential role in protecting public health and maintaining ecological balance. However, traditional fluorescent probes for Zn²⁺ are limited in their specificity, especially under complex environments, due to their single-mode optical signal and inadequate recognization capacities. Herein we report a dual-mode supramolecular sensing system constructed from a unique three-component assembly involving a terpyridine platinum (II) complex, oxalate, and Zn²⁺, enabling highly specific detection performance for Zn²⁺. The supramolecular sensing system exhibits excellent selectivity among various interfering substances, accompanied by ultra-low detection limit (0.199 μM) and fast response (<3 s). The high recognization capacity comes from tri-component-based supramolecular assembly, while the dual-mode response arises from the generation of intermelcular Pt-Pt and π-π interactions, which yields absorption and emission originating from low-energy metal–metal-to-ligand charge transfer (MMLCT) transitions. This work marks a pioneering demonstration for highly specific detection of Zn²⁺ and inspires an alternative strategy for designing cation probes. Full article

Background: The 2C protein of foot-and-mouth disease virus (FMDV), a member of helicase superfamily 3 (SF3), drives viral genome replication and serves as a critical target for antiviral drug development. Methods: A fluorescence resonance energy transfer (FRET)-based high-throughput screening (HTS) platform was developed to identify 2C helicase inhibitors. Primary screening evaluated 4424 compounds for helicase inhibition. Molecular docking analyzed inhibitor interactions with the N207 residue within the catalytic core and helicase inhibition assays classified the inhibitor type (mixed, competitive, noncompetitive). Differential scanning fluorimetry (nanoDSF) quantified 2C thermal destabilization. Antiviral activity was assessed via indirect immunofluorescence, RT-qPCR, and plaque reduction assays. Results: Six compounds inhibited 2C helicase activity at >620 μM. Molecular docking revealed hydrogen bonding, hydrophobic interactions, and π-cation stabilization at the catalytic core. 2-MPO and MPPI were classified as mixed-type inhibitors, 5-TzS⁻ and 2-PyOH as competitive, and DCMQ/Spiro-BD-CHD-dione as noncompetitive. NanoDSF showed a ΔT_m ≥ 1.5 °C (2.5 mM compounds), with reduced destabilization in N207A mutants. Antiviral assays identified 2-MPO and MPPI as optimal inhibitors. MPPI achieved effective FMDV suppression at 160 μM, exhibiting two orders of magnitude higher potency than 2-MPO (400 μM). Conclusions: The established FRET-based HTS platform targeting 2C helicase facilitates anti-FMDV lead discovery, while 2C inhibitors may serve as an effective therapeutic strategy against other picornaviruses. Full article

Single-phase white-light-emitting materials, particularly 2D hybrid organic–inorganic halide perovskites, have garnered significant attention due to their strong electron–phonon interactions, which lead to broad luminescence and a notable Stokes shift resulting from self-trapped exciton recombination. However, 2D lead iodide perovskites typically display these characteristics poorly, restricting their efficiency as white-light emitters. This study presents a 2D lead iodide perovskite that incorporates a fluorinated π-conjugated aggregation-induced enhanced emission luminophore, FPCSA, as a bulky organic cation to create a quasi-2D perovskite. The FPCSA cation establishes a Type II energy level alignment with the lead iodide layer in the 2D perovskite, and a significant energy offset effectively suppresses charge transfer, enabling independent emission from both the organic and inorganic layers while facilitating self-trapped exciton formation. Under 315 nm UV excitation, this material demonstrates warm white-light emission with RGB triple-band photoluminescence stemming from the electronically decoupled FPCSA and perovskite layers. These findings provide a promising new method for designing efficient single-phase white-light-emitting materials for optoelectronic applications. Full article