Monitoring anionic surfactants in environmental and industrial samples demands rapid, sensitive, and robust sensing. We report a potentiometric sensor based on a poly(vinyl chloride) PVC liquid membrane incorporating the newly prepared ion pair 1,3-didecyl-2-methylimidazolium tetrakis(perfluorophenyl)borate (DDMI-TPFPB). The membrane delivers near-Nernstian responses to sodium dodecyl sulfate (SDS) and sodium dodecylbenzenesulfonate (DBS): slopes of 59.1 and 56.9 mV decade-1, linear ranges of 1 & times; 10(-7)-4 & times; 10(-3 )M (SDS) and 9 & times; 10(-7)-5 & times; 10(-4) M (DBS), and limits of detection of 8.1 & times; 10-8 and 7.3 & times; 10-7 M, respectively. Signal drift is <4 mV/h with response times of <= 1-3 s across the working range. The sensor maintains stable potentials between pH 3-10 and exhibits excellent selectivity versus common inorganic/organic anions, with the expected cross-response to DBS as an anionic surfactant. As an endpoint indicator in potentiometric titrations (cetylpyridinium chloride, Hyamine 1622, and cetyltrimethylammonium bromide), it affords sharp equivalence points and high recoveries for technical-grade SDS/dB (approximate to 97.7-99.8%), in good agreement with standard two-phase titration. Application to commercial detergent products confirms practical utility, and operational lifetime extends to at least six months under extensive use. Computational modeling further showed that hydrophobic interactions drive a dynamic yet stable DDMI-TPFPB association, underpinning the ion pair's robustness and rapid response in sensor operation. Replacing traditional tetraphenylborate anions, the DDMI-TPFPB ion pair enables fast, sensitive, and durable potentiometric quantification of anionic surfactants for environmental monitoring and quality control.

Three centrosymmetric binuclear acetate-bridged copper(II) complexes with square-pyramidal coordination, [Cu-2(L1-3)(2)(& micro;-OAc-kappa O:kappa O)(2)], were prepared and comprehensively characterized, where L represents an imine derived from salicylaldehyde and its 5-halogenated derivatives with 8-aminoquinoline. Complex (1), based on the unsubstituted salicylaldehyde, its 5-bromo analogue (3), alongside with the revisited 5-chloro derivative (2) with significantly improved crystallographic data establish a complete and internally consistent structural series. Structural and spectroscopic analyses were complemented by quantum-chemical calculations, biomolecular binding studies, and antimicrobial assays. According to EPR data, the complexes exist as a mixture of mononuclear and dinuclear species in DMSO solution, while the addition of water shifts the equilibrium toward the dimeric form. Strong binding to bovine serum albumin (K-b > 10(5) M-1) was observed, while calf thymus DNA interactions were moderate, characterized by hypochromism, slight bathochromic shifts, and competitive binding in the CT DNA-EtBr system, consistent with partial intercalation. Reactive oxygen species generation was confirmed spectrophotometrically. All three complexes exhibited broad-spectrum antimicrobial activity against Gram-positive and Gram-negative bacteria, as well as fungi. Docking simulations with Staphylococcus aureus targets including penicillin-binding protein 2a (1 MWR), topoisomerase IV subunit A (2INR), the catalytic core of DNA gyrase (2XCQ), and the pore-forming toxin PVL (6U3F), revealed favourable binding energies at sites crucial for cell wall biosynthesis and DNA replication. Remarkably, complex (2) displayed a fungicidal MFC of 0.039 mg mL(-1) against Candida albicans, over fifteen times lower than that of nystatin.

Five neutral heteroleptic mononuclear vanadium(IV) hydrazone complexes ([VOL(bpy)]), derived from 2-hydroxy-5-methylacetophenone and various acid hydrazides (furoic, thiophene, benzoic, nicotinic, and isoniazid), were synthesized and shown to exhibit improved antidiabetic efficacy in streptozotocin-induced diabetic rats, with reduced toxicity and minimal bioaccumulation compared to maltolato- and picolinato-based vanadium species. Structural identity was established by spectroscopic methods. Crystal structures were obtained for four complexes, providing insight into their solid-state chemistry. Stability studies in simulated intestinal and gastric fluids showed that the complexes largely retained their integrity under intestinal conditions, whereas decomposition occurred in the highly acidic gastric environment within several minutes. In vivo experiments revealed a structure-antihyperglycemic activity relationship. The nicotinic-containing complex showed the highest activity, reducing blood glucose levels by 67% within 7 days of treatment, while the remaining complexes improved glycemic control by more than 50%. Bioaccumulation studies demonstrated <1.1% uptake in the liver and kidneys and negligible accumulation in the brain. The presented vanadium compounds enhance antidiabetic potential by addressing key limitations, particularly bioaccumulation and toxicity, associated with vanadium agents previously evaluated in clinical trials.

New coumarin-neurotransmitter hybrids with antioxidant and anti-inflammatory properties.

In this study, potential fungicides were prepared following the principles of green chemistry. The compounds were synthesized in deep eutectic solvents as an alternative medium and compared with syntheses in traditional solvents such as ethanol. The efficiency of the reaction was improved by ultrasonic synthesis in both eutectic solvents and ethanol, resulting in higher yields while reducing reaction energy and time. For the first time, deep eutectic solvents (DES) were used for quaternisation reactions, with choline chloride as a hydrogen bond acceptor and urea, glycerol, malic acid, malonic acid, and levulinic acid as donors. DES, composed of biodegradable, non-toxic, and renewable components, represented a greener alternative to conventional solvents. However, reactions in DES by the conventional method generally resulted in lower yields, probably due to solubility and viscosity limitations inherent in the eutectic medium. The combination of ultrasound and deep eutectic solvents proved to be a good alternative to organic solvents for the quaternisation reaction, as higher yields were achieved in a shorter time compared to conventional methods. The antifungal activity of all 18 synthesized compounds was tested. The compounds exhibited significant antifungal activity against all four pathogens, with varying levels of mycelial growth inhibition. B. cinerea was the most sensitive species (up to 70.7% inhibition), while F. culmorum was the least sensitive (≤32%).

This study reports the design, synthesis, and biological evaluation of novel resveratrol-inspired thieno-benzimidazole and thieno-oxazole derivatives as potential therapeutics for Alzheimer's disease. The research is grounded in the cholinergic hypothesis, which links cognitive decline to reduced acetylcholine levels due to enzymatic degradation by acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Given the increasing relevance of BChE in later disease stages, the focus was placed on developing selective BChE inhibitors. A series of 14 compounds was synthesized using multi-step organic reactions, including Wittig reactions, Vilsmeier formylation, and cyclization strategies. Structural confirmation was achieved through NMR and mass spectrometry. The studied acetylated derivatives exhibit photochemical instability due to efficient trans-cis isomerization and subsequent secondary processes under UV irradiation, necessitating strict light protection during handling, storage, and application. Biological evaluation revealed that all compounds selectively inhibited BChE, with no significant AChE inhibition observed. Among them, carbamate-oxazole derivative 14 exhibited the highest potency (IC50 = 0.248 μM), outperforming the reference drug rivastigmine. Several other derivatives showed moderate to strong activity, with oxazole-based compounds generally outperforming benzimidazole analogs. In addition to enzyme inhibition, antioxidant activity was assessed using the DPPH and CUPRAC assays. Compound 8 exhibited the strongest radical-scavenging activity, comparable to that of Trolox. Molecular docking and dynamics simulations provided insight into binding interactions, highlighting key π-π stacking and hydrogen bonding within the BChE active site. Furthermore, in silico genotoxicity analysis indicated that the most active compounds lack mutagenic potential. Overall, the study identifies promising multifunctional candidates combining selective BChE inhibition, antioxidant properties, and favorable safety profiles, supporting their potential as lead compounds for Alzheimer's disease therapy.

Four new heteroleptic neutral paramagnetic mononuclear oxidovanadium(IV) complexes, designated as [VOL (phen)], where L corresponds to acetophenone isoniazid hydrazone or its 5-halogenated derivatives and phen stands for 1,10-phenanthroline, were synthesized and thoroughly characterized using chemical analysis, various spectroscopic techniques, and diffraction methods. Single-crystal X-ray diffraction revealed the molecular and crystal structures of two complexes, showing an octahedral coordination environment around the vanadium(IV) center. The coordination includes a tridentate ONO donor hydrazone ligand in its deprotonated enol-imine form, 1,10-phenanthroline as a bidentate NN donor ternary ligand, and one terminal oxygen atom. The biochemical and hematological effects of these complexes were evaluated in a streptozotocin-induced diabetic rat model. All synthesized complexes showed cholesterol-lowering effects compared to the diabetic rat group, with the vanadium complex lacking a substituent on the acetophenone ring of hydrazone showing the strongest effect. Complexes exhibited comparable and significant antidiabetic activity in vivo, effectively reducing hyperglycemia within 1 week of treatment. Additionally, the histopathological effects of complex (4) on liver, kidney, and brain tissues were investigated. All four complexes were found to have low bioaccumulation levels, with total absolute bioaccumulation in all tested organs less than 0.35% of the administered dose.

Metal complexes remain central to modern inorganic chemistry due to their structural diversity [...]

A novel heterobimetallic ruthenium(II)–gold(I) complex featuring a bridging bis(diphenylphosphino)butane (dppb) ligand was prepared and fully characterized. Single-crystal X-ray diffraction revealed a piano-stool geometry around Ru(II) with η6-cymene, two chlorido ligands, and one phosphorus atom from dppb, while the Au(I) center adopts a linear P–Au–Cl coordination. Structural integrity in the solution was confirmed by 1D and 2D NMR spectroscopy, while solution behavior was further monitored by variable solvent 31P NMR and UV/Vis spectroscopy, indicating that the organometallic Ru–arene core remains intact, whereas the chlorido ligands coordinated to Ru exhibit partial lability. Complementary characterization included elemental analysis, FTIR, and UV/Vis spectroscopy. Spectrofluorimetric and FRET analyses showed that Au(dppb), Ru(dppb), and the heterobimetallic AuRu complex bind to BSA with apparent constants of 1.41 × 105, 5.12 × 102, and 2.66 × 104 M−1, respectively, following a static quenching mechanism. In vivo biological evaluation in Wistar rats revealed no significant hepatotoxicity or nephrotoxicity, with only mild and reversible histological alterations and preserved hepatocyte nuclear morphology. Hematological analysis indicated a statistically significant reduction in leukocyte populations, suggesting immunomodulatory potential, while elevated serum glucose levels point to possible endocrine or metabolic activity. These findings highlight compound structural stability and intriguing bioactivity profile, making it a promising platform for further organometallic drug development and testing.

A series of fourteen novel phenol carbamates was synthesized and evaluated as potential selective butyrylcholinesterase (BChE) inhibitors targeting cholinergic dysfunction in Alzheimer's disease (AD). The compounds were prepared efficiently from resveratrol analogs via a Wittig reaction followed by carbamoylation, and their structures were confirmed by NMR, MS, and HRMS analyses. All derivatives were screened for inhibitory activity against acetylcholinesterase (AChE) and BChE using a modified Ellman method. None of the compounds inhibited AChE, whereas all selectively inhibited BChE, with IC50 values ranging from 0.045 to 6.840 μM. The most potent inhibitor, compound 13, bearing a pyrrolidine moiety, exhibited an IC50 value of 0.045 μM, outperforming the reference drug galantamine by more than two orders of magnitude. Molecular docking and dynamics simulations confirmed strong π-π and alkyl-π interactions between the ligands and the enzyme's active site, accounting for their high affinity and selectivity. In silico ADME(T) analysis predicted excellent intestinal absorption, blood-brain barrier penetration, and low cytotoxicity, while minor genotoxicity alerts were observed for a few derivatives. In vitro cytotoxicity assays in HepG2 cells confirmed the absence of toxicity at concentrations up to 30 μM. These results highlight methoxy-substituted phenol carbamates, particularly compound 13, as promising lead structures for the design of selective BChE inhibitors and potential therapeutic agents for the treatment of AD.

Background/Objectives: This research reports the synthesis and evaluation of novel charged thienobenzo-triazoles as non-selective cholinesterase inhibitors (AChEs and BChEs), their anti-inflammatory properties, and a computational study. Methods: Fifteen derivatives were created through photochemical cyclization and quaternization of the triazole core. The compounds were tested for AChE and BChE inhibition. They showed greater potency and selectivity toward BChE. Results: The most potent compound, derivative 14, inhibited BChE with an IC50 of 98 nM, while derivative 9 also displayed significant anti-inflammatory activity by inhibiting LPS-induced TNF-α production (IC50 = 0.66 µM). Molecular docking revealed that triazolinium salts form key π-π and electrostatic interactions within enzyme active sites. In silico predictions indicated favorable ADME-Tox properties for compounds 9 and 11, including low mutagenicity and moderate CNS permeability. Conclusions: These findings highlight the potential of new charged triazolinium salts as peripherally selective cholinesterase inhibitors with additional anti-inflammatory potential.

Three new complexes of copper(II) and chromone-2-carboxylic acid, a ligand from the group of hydroxypyrones, were synthesised according to the principles of green chemistry. The complexes were characterised by FT–IR and NMR spectroscopy, thermal and electrochemical analysis, and their structures are proposed. The results show the formation of mononuclear (1) and dinuclear hydroxo-bridged dinuclear copper(II) complexes (2 and 3). The results of cyclic voltammetry show that the copper in all complexes is in the +2-oxidation state. The antiproliferative activity was determined by MTT assay on 2D cell models in vitro on seven cell lines. The activity spectrum of complexes 1–3 ranged from the highest to the lowest value in the tumour cell lines tested, in the following order: Hep G2 > NCI-H358 > HT-29 > KATO III > MDA-MB 231 > Caco-2. The most effective concentration was 10−5 mol dm−3, which suppressed the growth of Hep G2 cells as follows: 69.5% (1), 64.8% (2) and 64% (3). The calculated selectivity index clearly shows that Hep G2 is the most sensitive cell line to copper complexes (SI = 1.623 (1); 1.557 (2), 1.431 (3).

The growing prevalence of Alzheimer's disease calls for a drug that can simultaneously act towards several targets involved in the pathophysiology of the disease. In our study, we evaluated the potential of hydrazone and N-acylhydrazone derivatives of vitamin B6 and pyridine-4-carbaldehyde to be used as multi-target directed ligands targeting cholinergic system by inhibiting acetyl- and butyrylcholinesterase, lowering the accumulation of β-amyloid plaques by inhibiting both the β-secretase activity and amyloid self-aggregation, and maintaining the biometal balance by chelating certain biometals. Our results showed that all of the tested hydrazones were potent inhibitors of human cholinesterases with inhibition constants (Ki) in micromolar range able to lower the activity of β-secretase, inhibit amyloid aggregation, chelate biometals and act as antioxidants. Also, most of them were estimated to be able to cross the blood-brain barrier by passive transport and to be absorbed in human intestines as well as with moderate metabolic stability in liver microsomes.

The incorporation of different ferrocene scaffolds into the peptide sequences induces the formation of hydrogen-bond-based secondary structural elements that are frequently observed in natural peptides and proteins. There are three simple ferrocene scaffolds for conjugation with amino acids and peptides that serve as templates for ferrocene peptidomimetics, namely ferrocene-1,1′-dicarboxylic acid (Fcd, I), 1′-aminoferrocene-1-carboxylic acid (Fca, III), and ferrocene-1,1′-diamine (Fcda, V). Here, we have investigated their ability to induce the turn structure upon conjugation with Val, Leu, and Phe. Furthermore, we also wanted to determine whether the branched side chains of Val, Leu, and Phe interfere with intramolecular hydrogen bonding (IHB). For these purposes, we performed a detailed spectroscopic analysis by measuring the concentration, temperature, and solvent dependence of the IR, NMR, and CD spectra. The effect of the different ferrocene scaffolds on the antioxidant activity of the prepared peptides was tested using the DPPH and ABTS methods, and was further rationalized using electrochemical measurements. It was found that the ferrocene scaffold has the greatest influence on the hydrogen bonding pattern, while the influence of the side branches of the amino acids is less relevant.

The chirality of the protein backbone influences both self-assembly and biological activity. In ferrocene-containing peptides, the sequence and chirality of the constitutive amino acids as well as the structure of the ferrocene scaffold strongly influence the conformational properties, whereas the biological activity is more strongly influenced by lipophilicity. A joint spectroscopic and computational study has shown that a relatively simple structural modification, such as changing the order of two amino acids in the dipeptide sequence from Pro–Ala (III) to Ala–Pro (IV), also alters the hydrogen bonding patterns from a mostly ten-membered (β-turn) to a seven-membered ring (γ-turn), which affects the antiproliferative activity of the ferrocene peptidomimetics studied. A systematic approach presented in this study allowed us to highlight the relevant structural variations that could lead to increased biological activity in similar ferrocene-based bioconjugates.

BACKGROUND:Computational research plays an important role in predicting the chemical and physical properties of biologically active compounds important in future structural modifications to improve or modify biological activity. OBJECTIVE:This research focuses on quantum chemical and spectroscopic investigations properties of synthesized 4-hydroxycoumarin derivatives. METHODS:Quantum chemical calculations were obtained using B3LYP, HF, and M06-2x level methods with the 6-31++G (d,p) basis set. Afterward, IR, 1H, 13C, UV-Visible experimentally parameters were compared with the results obtained using the B3LYP/6-31+G*(d) basis set of the molecules to be able to characterize the structures. RESULTS:Based on the quantum chemical calculations compound with acetamido group on the phenyl ring is the most reactive, and compound with nitro substituent is the least reactive and the the strongest electrophile among tested compounds. With the exception of compounds with dimethylamino group, all other compounds have a pronounced tautomer between OH and C = O group. The calculated and experimental values are in agreement with each other. CONCLUSION:The molecular structure in the ground state of six 3-cinnamoyl 4-hydroxycoumarin derivatives was optimized using density functional theory. The observed and computed values were compared and it can be concluded that the theoretical results were in good linear agreement with the experimental data.

The biological properties of five aroylhydrazones derived from salicylaldehyde and its 5-substituted derivatives with 2-furoic acid hydrazide were thoroughly investigated. NMR analysis confirmed the predominant existence of the aroylhydrazones in the keto-amine form in aqueous solution. Geometries of these compounds were optimized using density functional theory (DFT) calculations with the B3LYP hybrid functional, while ADMET analysis predicted their pharmacokinetic and toxicological properties. Substituent effects on the interactions between the salicyl aroylhydrazones and BSA and DNA were elucidated through experimental and molecular docking studies, revealing the bromo-substituted hydrazone as the most potent binder to both biomolecular targets. Experimental results aligned well with theoretical predictions, indicating that salicyl hydrazones predominantly act as DNA groove binders. Thermodynamic analysis suggested that the hydrazones predominantly interact with BSA through hydrogen bonding and van der Waals forces. Moreover, antioxidant potential assessment using DPPH, ABTS, FRAP, and metal chelating assays demonstrated the potent antioxidant power of nitro and hydroxy-substituted derivatives. Additionally, the antimicrobial properties of hydrazone against Gram-positive and Gram-negative bacteria, as well as fungi, were thoroughly explored, highlighting the nitro derivative as the most prominent candidate with broad-spectrum antimicrobial potential.

The pyrimidine heterocycle plays an important role in anticancer research. In particular, the pyrimidine derivative families of uracil show promise as structural scaffolds relevant to cervical cancer. This group of chemicals lacks data-driven machine learning quantitative structure-activity relationships (QSARs) that allow for generalization and predictive capabilities in the search for new active compounds. To achieve this, a dataset of pyrimidine and uracil compounds from ChEMBL were collected and curated. A workflow was developed for data-driven machine learning QSAR using an intuitive dataset design and forwards selection of molecular descriptors. The model was thoroughly externally validated against available data. Blind validation was also performed by synthesis and antiproliferative evaluation of new synthesized uracil-based and pyrimidine derivatives. The most active compound among new synthesized derivatives, 2,4,5-trisubstituted pyrimidine was predicted with the QSAR model with differences of 0.02 compared to experimentally tested activity.

The need for a systematic approach in developing new metal-based drugs with dual anticancer-antimicrobial properties is emphasized by the vulnerability of cancer patients to bacterial infections. In this context, a novel organometallic assembly was designed, featuring ruthenium(II) coordination with p-cymene, one chlorido ligand, and a bidentate neutral Schiff base derived from 4-methoxybenzaldehyde and N,N-dimethylethylenediamine. The compound was extensively characterized in both solid-state and solution, employing single crystal X-ray diffraction, nuclear magnetic resonance, infrared, ultraviolet-visible spectroscopy, and density functional theory, alongside Hirshfeld surface analysis. The hydrolysis kinetic was thoroughly investigated, revealing the important role of the chloro-aqua equilibrium in the dynamics of binding with deoxyribonucleic acid and bovine serum albumin. Notably, the aqua species exhibited a pronounced affinity for deoxyribonucleic acid, engaging through electrostatic and hydrogen bonding interactions, while the chloro species demonstrated groove-binding properties. Interaction with albumin revealed distinct binding mechanisms. The aqua species displayed covalent binding, contrasting with the ligand-like van der Waals interactions and hydrogen bonding observed with the chloro specie. Molecular docking studies highlighted site-specific interactions with biomolecular targets. Remarkably, the compound exhibited wide spectrum moderate antimicrobial activity against Staphylococcus aureus, Pseudomonas aeruginosa, and Candida albicans, coupled with low micromolar cytotoxic activity against human colorectal adenocarcinoma cells and significant activity against human leukemic monocyte lymphoma cells. The presented findings encourage further development of this compound, promising avenues for its evolution into a versatile therapeutic agent targeting both infectious diseases and cancer.

Wet synthesis approach afforded four new heteroleptic mononuclear neutral diamagnetic oxidovanadium( V ) complexes, comprising salicylaldehyde-based 2-furoic acid hydrazones and a flavonol coligand of the general composition [VO(fla)(L- ONO )]. The complexes were comprehensively characterized, including chemical analysis, conductometry, infrared, electronic, and mass spectroscopy, as well as 1D 1 H and proton-decoupled 13 C( 1 H) NMR spectroscopy, alongside extensive 2D 1 H - 1 H COSY, 1 H - 13 C HMQC, and 1 H - 13 C HMBC NMR analyses. Additionally, the quantum chemical properties of the complexes were studied using Gaussian at the B3LYP, HF, and M062X levels on the 6 - 31 ++g(d,p) basis sets. The interaction of these hydrolytically inert vanadium complexes and the BSA was investigated through spectrofluorimetric titration, synchronous fluorimetry, and FRET analysis in a temperature -dependent manner, providing valuable thermodynamic insights into van der Waals interactions and hydrogen bonding. Molecular docking was conducted to gain further understanding of the specific binding sites of the complexes to BSA. Complex 2 , featuring a 5-chloro-substituted salicylaldehyde component of the hydrazone, was extensively examined for its biological activity in vivo . The effects of complex administration on biochemical and hematological parameters were evaluated in both healthy and diabetic Wistar rats, revealing antihyperglycemic activity at millimolar concentration. Furthermore, histopathological analysis and bioaccumulation studies of the complex in the brain, kidneys, and livers of healthy and diabetic rats revealed the potential for further development of vanadium( V ) hydrazone complexes as antidiabetic and insulin -mimetic agents.