Search Results (90)

This study focuses on the synthesis, properties, and comparative analysis of new flame-retardant compounds: coumarins and isophosphinolines. These compounds feature a diarylphosphine oxide (DAPO) substituent at the β-position relative to both the carbonyl and the phosphoryl groups. Various derivatives with halogens, phosphorus, and/or aromatics substituents were synthetized and their thermal stability and flammability were evaluated at the microscale by thermogravimetric analysis (TGA) and pyrolysis–combustion flow calorimetry (PCFC) in order to identify the most promising molecules for use as flame-retardant (FR) additives or comonomers. FTIR-coupled PCFC analysis was also carried out to study the combustion profiles of the molecules. Beyond the confirmation of some expected trends, such as the char promotion of phosphorus and flame inhibition of halogens, the study revealed some unexpected findings that warrant further investigation. These include the prominent role of the chlorine substitution position on the aromatic ring, as well as significant differences in FR performance between diastereoisomers. Full article

Type 2 diabetes mellitus (T2DM) demands safer and more effective therapies to control postprandial hyperglycemia. Here, we report the synthesis and in vitro evaluation of ten salicylic acid-derived Schiff base derivatives (4a–4j) as α-glucosidase inhibitors. Compounds 4e, 4g, 4i, and 4j exhibited potent enzyme inhibition, with IC₅₀ values ranging from 14.86 to 18.05 µM—substantially better than acarbose (IC₅₀ = 45.78 µM). Molecular docking and 500 ns molecular dynamics simulations revealed stable enzyme–ligand complexes driven by π–π stacking, halogen bonding, and hydrophobic interactions. Density Functional Theory (DFT) calculations and molecular electrostatic potential (MEP) maps highlighted key electronic factors, while ADMET analysis confirmed favorable drug-like properties and reduced nephrotoxicity. Structure–activity relationship (SAR) analysis emphasized the importance of halogenation and aromaticity in enhancing bioactivity. Full article

Background/Objectives: Diabetes mellitus is a group of chronic metabolic disorders characterized by persistent hyperglycemia. Aldose reductase, the first enzyme in the polyol pathway, plays a key role in the onset of long-term diabetic complications. Aldose reductase inhibition has been widely established as a potential pharmacotherapeutic approach to prevent and treat diabetes mellitus-related comorbidities. Although several promising aldose reductase inhibitors have been developed over the past few decades, they have failed in clinical trials due to unacceptable pharmacokinetic properties and severe side effects. This paper describes the design, synthesis, and pharmacological evaluation of four novel 5-halogenated N-indolylsulfonyl-2-fluorophenol derivatives (3a-d) as aldose reductase inhibitors. Methods: The design of compounds was based on a previously published lead compound (IIc) developed by our research group to enhance its inhibitory capacity. Compounds 3a-d were screened for their ability to inhibit in vitro partially purified aldose reductase from rat lenses, and their binding modes were investigated through molecular docking. Results: The presence of a sulfonyl linker between indole and o-fluorophenol aromatic rings is mandatory for potent aldose reductase inhibition. The 5-substitution of the indole core with halogens resulted in a slight decrease in the inhibitory power of 3a-c compared to IIc. Among halogens, bromine was the most capable of filling the selectivity pocket through hydrophobic interactions with Thr113 and Phe115 residues. Conclusions: Although our strategy to optimize the inhibitory potency of IIc via inserting halogen atoms in the indole scaffold was not fruitful, aromatic ring halogenation can be still utilized as a promising approach for designing more potent aldose reductase inhibitors. Full article

We present a simple and cost-effective method for generating a dielectric barrier discharge (DBD) plasma using a commercially available ozone generator power supply. By coupling the plasma source to the extended ion transfer tube of an ambient mass spectrometer, we achieved stable plasma discharge, enabling the post-ionization of nonpolar compounds during the electrospray ionization process. Using this approach, we successfully detected polycyclic aromatic hydrocarbons (PAHs), halogenated PAHs (HPAHs), and other nonpolar pollutants in liquid mixtures, with detection limits on the order of 10 ng/mL. In fish exposed to HPAHs, both polar metabolites and lipids, as well as the nonpolar pollutant 1-chloronaphthalene, were simultaneously detected. Notably, 1-chloronaphthalene accumulated at the highest concentration in gill tissue. This straightforward plasma-assisted technique offers a reliable strategy for expanding the detection capabilities of electrospray mass spectrometry to include nonpolar molecules. Full article

To characterize the temporal variation in and source contribution of volatile organic compounds (VOCs) in a polymer industrial park, a two-year offline monitoring campaign (2018–2019) at Shangyu Industrial Park in the Yangtze River Delta was conducted. The study quantified the VOCs composition, seasonal variation, and ozone formation potential (OFP), with source apportionment performed using the Positive Matrix Factorization (PMF) model. During the observation period, the average concentration of total VOCs in 2019 was 286.1 ppb, showing a 22.6% reduction compared to that in 2018. Seasonal analysis revealed decreases in the total VOCs concentration by 41.8%, 38.4%, and 6.1% during spring, summer and winter, respectively, while an increase of 13.8% was observed in autumn, primarily attributed to industrial restructuring in the second half of 2019. Notable reductions were observed in specific VOCs components: oxygen-containing volatile organic compounds (OVOCs), alkane, halogenated hydrocarbon, alkene, and alkyne decreased by 34.5%, 27.9%, 26.3%, 24.6%, and 20.4%, respectively. The average OFP in 2019 was 2402.0 μg/m³, representing a 1.8% reduction from 2018. Contributions to total OFP from alkane, OVOCs, alkyne, and alkene decreased by 32.9%, 26.0%, 20.7%, and 15.0%, respectively, while halogenated hydrocarbons and aromatic hydrocarbons increased by 50.1% and 7.0%. PMF analysis identified four major VOCs sources: industrial production (44.9%), biomass combustion (17.8%), vehicle exhaust (11.0%), and solvent usage (26.3%). From 2018 to 2019, contributions from vehicle exhaust and solvent usage increased by 4.8% and 5.9%, respectively, while industrial production and biomass combustion decreased by 10.5% and 0.3%. Full article

The synthesis of (E)-1-(1-benzyl-5-methyl-1H-1,2,3-triazol-4-yl)-3-phenyl-2-propen-1-one derivatives was carried out in two steps, using benzylic chloride derivatives as starting material. The structural determination of intermediates and final products was performed by spectroscopic methods: infrared spectroscopy, nuclear magnetic resonance spectroscopy and mass spectrometry (IR, NMR, and MS). In vitro evaluation of cytotoxic activity on adherent and non-adherent cells showed that triazole chalcones exhibited significant activity against three of the five cell lines studied: non-Hodgkin lymphoma U937, glioblastoma multiform tumor T98G, and gallbladder cancer cells Gb-d1. In contrast, the cytotoxic activity observed for cervical cancer HeLa and gallbladder adenocarcinoma G-415 was considerably lower. Additionally, in the cell lines where activity was observed, some compounds demonstrated an In vitro inhibitory effect superior to that of the control, paclitaxel. Molecular docking studies revealed specific interactions between the synthesized ligands and therapeutic targets in various cell lines. In U937 cells, compounds 4a and 4c exhibited significant inhibition of vascular endothelial growth factor receptor (VEGFR) kinase, correlating with their biological activity. This effect was attributed to favorable interactions with key residues in the binding site. In T98G cells, compounds 4r and 4w showed affinity for transglutaminase 2 (TG2) protein, driven by their ability to form hydrophobic interactions. In Gb-d1 cells, compounds 4l and 4p exhibited favorable interactions with mitogen-activated protein kinase (MEK) protein, similar to those observed with the known inhibitor selumetinib. In HeLa cells, compounds 4h and 4g showed activity against dihydrofolate reductase (DHFR) protein, driven by hydrogen bonding interactions and favorable aromatic ring orientations. On the other hand, compounds 4b and 4t exhibited no activity, likely due to unfavorable interactions related to halogen substitutions in the aromatic rings. Full article

The multifunctional catalytic hemoglobin from the terebellid polychaete Amphitrite ornata, also named dehaloperoxidase (AoDHP), utilizes the typical oxygen transport function in addition to four observed activities involved in substrate oxidation. The multifunctional ability of AoDHP is presently a rare observation, and there exists a limitation for how novel dehaloperoxidases can be identified from macrobenthic infauna. In order to discover more infaunal DHP-bearing candidates, we have devised a facilitated method for an accurate taxonomic identification that places visual and molecular taxonomic approaches in parallel. Traditional visual taxonomic species identification by the non-specialist, at least for A. ornata or even for other marine worms, is a very difficult and time-consuming task since a large diversity is present and the method is restricted to adult worm specimens. The work herein aimed to describe a method that simplifies the taxonomic identification of A. ornata in particular through the assessment of its mitochondrial cytochrome c oxidase subunit I gene by employing the DNA barcoding technique. Furthermore, whole-worm specimens of A. ornata were used to extract and purify AoDHP followed by an H₂O₂-dependent peroxidase activity assay evaluation against substrate 2,4,6-trichlorophenol. AoDHP isoenzyme A was also overexpressed as the recombinant protein in Escherichia coli, and its peroxidase activity parameters were compared to AoDHP from the natural source. The activity assay assessment indicated a tight correlation for all Michaelis–Menten parameters evaluated. We conclude that the method described herein exhibits a streamlined approach to identify the polychaete A. ornata, which can be adopted by the non-specialist, and the full procedure is predicted to facilitate the discovery of novel dehaloperoxidases from other marine invertebrates. Full article

Increased levels and detrimental effects of volatile organic compounds (VOCs) on air quality and human health have become an important issue in the environmental field. Benzene is classified as one of the most hazardous air pollutants among non-halogenated aromatic hydrocarbons with toxic, carcinogenic, and mutagenic effects. Various technologies have been applied to decrease harmful emissions from various sources such as petrochemistry, steel manufacturing, organic chemical, paint, adhesive, and pharmaceutical production, vehicle exhausts, etc. Catalytic oxidation to CO₂ and water is an attractive approach to VOC removal due to high efficiency, low energy consumption, and the absence of secondary pollution. However, catalytic oxidation of the benzene molecule is a great challenge because of the extraordinary stability of its six-membered ring structure. Developing highly efficient catalysts is of primary importance for effective elimination of benzene at low temperatures. This review aims to summarize and discuss some recent advances in catalyst composition and preparation strategies. Advantages and disadvantages of using noble metal-based catalysts and transition metal oxide-based catalysts are addressed. Effects of some crucial factors such as catalyst support nature, metal particle size, electronic state of active metal, redox properties, reactivity of lattice oxygen and surface adsorbed oxygen on benzene removal are explored. Thorough elucidation of reaction mechanisms in benzene oxidation is a prerequisite to develop efficient catalysts. Benzene oxidation mechanisms are analyzed based on in situ catalyst characterization, reaction kinetics, and theoretical simulation calculations. Considering the role of oxygen vacancies in improving catalytic performance, attention is given to oxygen defect engineering. Catalyst deactivation due to coexistence of water vapor and other pollutants, e.g., sulfur compounds, is discussed. Future research directions for rational design of catalysts for complete benzene oxidation are provided. Full article

The prevalence of small multi-target drugs containing a fluorinated aromatic moiety among approved drugs in the market is due to the unique properties of this halogen atom. With the aim to develop potent antidiabetic agents, a series of phenylsulfonic esters based on the conjugation of the 5-substituted 2-hydroxy-3-nitroacetophenones 1a–d with phenylsulfonyl chloride derivatives substituted with a fluorine atom or fluorine-containing (-CF₃ or -OCF₃) group were prepared. Their structures were characterized using a combination of spectroscopic techniques complemented with a single-crystal X-ray diffraction (XRD) analysis on a representative example. The compounds were, in turn, assayed for inhibitory effect against α-glucosidase, α-amylase, protein tyrosine phosphatase 1 B (PTP1B) and the vascular endothelial growth factor receptor-2 (VEGFR-2) all of which are associated with the pathogenesis and progression of type 2 diabetes mellitus (T2DM). The antigrowth effect of selected compounds was evaluated on the human breast (MCF-7) and lung (A549) cancer cell lines. The compounds were also evaluated for cytotoxicity against the African Green Monkey kidney (Vero) cell line. The results of an in vitro enzymatic study were augmented by molecular docking (in silico) analysis. Their ADME (absorption, distribution, metabolism and excretion) properties have been evaluated on the most active compounds against α-glucosidase and/or α-amylase to predict their drug likeness. Full article

Carbazole is an aromatic heterocyclic organic compound consisting of two fused benzene rings and a pyrrole ring and is a very valuable building structure for the design of many compounds for use in various fields of chemistry and medicine. This study presents three new carbazole-based thiazole derivatives that differ in the presence of a different halogen atom: chlorine, bromine, and fluorine. Experimental studies and quantum-chemical simulations show the effect of changing a halogen atom on the physicochemical, biological, and linear and nonlinear optical properties. We have also found that carbazoles C-Cl, C-Br, and C-F exhibit high tyrosinase inhibitory activity, with IC₅₀ values in the range of 68–105 µM with mixed mechanism of action. Finally, molecular docking to the active site of Concanavalin A (ConA) and bioavailability for all compounds were evaluated. Full article

Polycyclic aromatic compounds (PACs) exhibit rat aryl hydrocarbon receptor (rAhR) activities, leading to diverse biological or toxic effects. In this study, the key amino residues and molecular interactions that govern the rAhR activity of PACs were investigated using in silico strategies. The homology model of rAhR was first docked with 90 PACs to yield complexes, and the results of the molecular dynamics simulations of 16 typical complexes showed that the binding energies of the complexes range from −7.37 to −26.39 kcal/mol. The major contribution to the molecular interaction comes from van der Waals forces, and Pro295 and Arg316 become the key residues involved in most complexes. Two QSAR models were further developed to predict the rAhR activity of PACs (in terms of log IEQ for PACs without halogen substitutions and log%-TCDD-max for halogenated PACs). Both models have good predictive ability, robustness, and extrapolation ability. Molecular polarizability, electronegativity, size, and nucleophilicity are identified as the important factors affecting the rAhR activity of PACs. The developed models could be employed to predict the rAhR activity of other reactive PACs. This work provides insight into the mechanisms and interactions of the rAhR activity of PACs and assists in the assessment of their fate and risk in organisms. Full article

With the rapid development of society, more and more unknown halogenated disinfection byproducts (DBPs) enter into drinking water and pose potential risks to humans. To explore the unknown halogenated DBPs in tap water, a selectively nontargeted analysis (SNTA) method was developed by conducting micro-liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (micro-LC-QTOFMS). In this method, two runs were employed: in the first run, the modes of TOFMS and precursor ion (the fragments were set as Cl³⁵/Cl³⁷, Br⁷⁹/Br⁸¹, and I^126.9) were performed, and the molecular ions or precursor ions of the halogenated organics could be obtained; in the second run, the product ion mode was conducted by setting the molecular ion screened above, and the MS/MS spectrums could be acquired to speculate concerning the structure. Two kinds of model DBPs (one kind had an aliphatic structure and the other was an aromatic compound) were used to optimize the parameters of the MS, and their MS characteristics were summarized. With this SNTA method, 15 halogenated DBPs were screened in two tap water samples and their structures were proposed. Of them, six DBPs had not been reported before and were assumed to be new DBPs. Overall, the detected halogenated DBPs were mostly acidic substances. Full article

Organophosphorus flame retardants (OPFRs) are abundant and persistent in the environment but have limited toxicity information. Their similarity in structure to organophosphate pesticides presents great concern for developmental neurotoxicity (DNT). However, current in vivo testing is not suitable to provide DNT information on the amount of OPFRs that lack data. Over the past decade, an in vitro battery was developed to enhance DNT assessment, consisting of assays that evaluate cellular processes in neurodevelopment and function. In this study, behavioral data of small model organisms were also included. To assess if these assays provide sufficient mechanistic coverage to prioritize chemicals for further testing and/or identify hazards, an integrated approach to testing and assessment (IATA) was developed with additional information from the Integrated Chemical Environment (ICE) and the literature. Human biomonitoring and exposure data were identified and physiologically-based toxicokinetic models were applied to relate in vitro toxicity data to human exposure based on maximum plasma concentration. Eight OPFRs were evaluated, including aromatic OPFRs (triphenyl phosphate (TPHP), isopropylated phenyl phosphate (IPP), 2-ethylhexyl diphenyl phosphate (EHDP), tricresyl phosphate (TMPP), isodecyl diphenyl phosphate (IDDP), tert-butylphenyl diphenyl phosphate (BPDP)) and halogenated FRs ((Tris(1,3-dichloro-2-propyl) phosphate (TDCIPP), tris(2-chloroethyl) phosphate (TCEP)). Two representative brominated flame retardants (BFRs) (2,2′4,4′-tetrabromodiphenyl ether (BDE-47) and 3,3′,5,5′-tetrabromobisphenol A (TBBPA)) with known DNT potential were selected for toxicity benchmarking. Data from the DNT battery indicate that the aromatic OPFRs have activity at similar concentrations as the BFRs and should therefore be evaluated further. However, these assays provide limited information on the mechanism of the compounds. By integrating information from ICE and the literature, endocrine disruption was identified as a potential mechanism. This IATA case study indicates that human exposure to some OPFRs could lead to a plasma concentration similar to those exerting in vitro activities, indicating potential concern for human health. Full article

In this study, Fe₃O₄ nanoparticles (FeNPs) decorated with halogenated perylene diimides (PDIs) have been used for capturing VOCs (volatile organic compounds) through noncovalent binding. Concretely, we have used tetrachlorinated/brominated PDIs as well as a nonhalogenated PDI as a reference system. On the other hand, methanol, ethanol, propanol, and butanol were used as VOCs. Experimental studies along with theoretical calculations (the BP86-D3/def2-TZVPP level of theory) pointed to two possible and likely competitive binding modes (lone pair–π through the π-acidic surface of the PDI and a halogen bond via the σ-holes at the Cl/Br atoms). More in detail, thermal desorption (TD) experiments showed an increase in the VOC retention capacity upon increasing the length of the alkyl chain, suggesting a preference for the interaction with the PDI aromatic surface. In addition, the tetrachlorinated derivative showed larger VOC retention times compared to the tetrabrominated analog. These results were complemented by several state-of-the-art computational tools, such as the electrostatic surface potential analysis, the Quantum Theory of Atoms in Molecules (QTAIM), as well as the noncovalent interaction plot (NCIplot) visual index, which were helpful to rationalize the role of each interaction in the VOC···PDI recognition phenomena. Full article

The accurate prediction of adverse drug reactions (ADRs) is essential for comprehensive drug safety evaluation. Pre-trained deep chemical language models have emerged as powerful tools capable of automatically learning molecular structural features from large-scale datasets, showing promising capabilities for the downstream prediction of molecular properties. However, the performance of pre-trained chemical language models in predicting ADRs, especially idiosyncratic ADRs induced by marketed drugs, remains largely unexplored. In this study, we propose MoLFormer-XL, a pre-trained model for encoding molecular features from canonical SMILES, in conjunction with a CNN-based model to predict drug-induced QT interval prolongation (DIQT), drug-induced teratogenicity (DIT), and drug-induced rhabdomyolysis (DIR). Our results demonstrate that the proposed model outperforms conventional models applied in previous studies for predicting DIQT, DIT, and DIR. Notably, an analysis of the learned linear attention maps highlights amines, alcohol, ethers, and aromatic halogen compounds as strongly associated with the three types of ADRs. These findings hold promise for enhancing drug discovery pipelines and reducing the drug attrition rate due to safety concerns. Full article