Regioselective Synthesis of 3‐Substituted Isocoumarin‐1‐imines via Palladium‐Catalyzed Denitrogenative Transannulation of 1,2,3‐Benzotriazin‐4(3H)‐ones and Terminal Alkynes

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Regioselective Synthesis of 3-Substituted Isocoumarin-1-imines via Palladium-Catalyzed Denitrogenative Transannulation of 1,2,3-Benzotriazin-4(3H)-ones and Terminal Alkynes

An efficient palladium-catalyzed denitrogenative transannulation strategy to access various 3-substituted isocoumarin-1-imine frameworks using 1,2,3-benzotriazin-4(3H)-ones and terminal alkynes is described.


Abstract

A palladium-catalyzed denitrogenative transannulation strategy to access various 3-substituted isocoumarin-1-imine frameworks using 1,2,3-benzotriazin-4(3H)-ones and terminal alkynes is described. The reaction is highly regioselective and tolerates a wide range of functional groups. The reaction is believed to proceed via a five-membered palladacycle intermediate extruding environmentally benign molecular nitrogen as a by-product. The utility of this method was showcased through the one-pot synthesis of biologically relevant 3-substituted isocoumarin scaffolds.

Preparation of Some New Pyrazolo[1,5‐a]pyrimidines and Evaluation of Their Antioxidant, Antibacterial (MIC and ZOI) Activities, and Cytotoxic Effect on MCF‐7 Cell Lines

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Preparation of Some New Pyrazolo[1,5-a]pyrimidines and Evaluation of Their Antioxidant, Antibacterial (MIC and ZOI) Activities, and Cytotoxic Effect on MCF-7 Cell Lines


Abstract

This study aims to synthesize some novel pyrazolo[1,5-a]pyrimidine derivatives, and investigate their biological activities. These compounds exhibited good to high antioxidant activities [2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging capabilities]. Among them, Ethyl 5-(2-ethoxy-2-oxoethyl)-7-hydroxy-2-methylpyrazolo[1,5-a]pyrimidine-3-carboxylate (3h) showed the highest antioxidant activity [Half-maximal Inhibitory Concentration (IC50)=15.34 μM] compared to ascorbic acid (IC50=13.53 μM) as a standard compound. Their antibacterial activities were investigated against two Gram-positive bacteria (Bacillus subtilis, and Staphylococcus aureus) and two Gram-negative bacteria (Pseudomonas aeruginosa, and Escherichia coli). The results showed that Ethyl 7-hydroxy-5-phenylpyrazolo[1,5-a]pyrimidine-3-carboxylate (3i) has the best antibacterial activity against Gram-positive B. subtilis [Zone of Inhibition (ZOI)=23.0±1.4 mm, Minimum Inhibitory Concentration (MIC)=312 μM]. Also, the cytotoxicity of these compounds was assessed against breast cancer cell lines [human breast adenocarcinoma (MCF-7)], which 7-Hydroxy-2-methyl-5-phenylpyrazolo[1,5-a]pyrimidine-3-carbonitrile (3f) displayed the most cytotoxicity (IC50=55.97 μg/mL), in contrast with Lapatinib (IC50=79.38 μg/mL) as a known drug.

DFT Mechanistic Insights into the Ni(II)‐Catalyzed Enantioselective Arylative Cyclization of Tethered Allene‐Ketones

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DFT Mechanistic Insights into the Ni(II)-Catalyzed Enantioselective Arylative Cyclization of Tethered Allene-Ketones

A detailed DFT mechanistic investigation on redox neutral nickel(II)-catalyzed arylative cyclization reactions of a tethered allene-ketone with arylboronic acids. This work highlights that the transformation consists of three key elementary steps: (i) base-free transmetalation, (ii) cationic terminal allene insertion, and (iii) a diastereo- and enantio-determining cyclization step.


Abstract

Density functional theory (DFT) has provided a detailed mechanistic picture for the redox neutral nickel(II)-catalyzed arylative cyclization reactions of a tethered allene-ketone with arylboronic acids. A mechanistic rationale for the high diastereo- and enantioselectivity achieved experimentally at high reaction temperature was uncovered through modeling the reaction with a chiral ligand and the predicted stereochemical outcome corroborates with experimental results. An unprecedented mechanism for the base-free organoboron transmetalation was revealed and the regioselectivity of migratory insertion of tethered allene-ketones as well as the stability of the possible allylnickel isomers (σ-allyl vs π-allyl) were clarified. The multifaceted nature of the reaction is revealed with certain elementary steps preferring cationic compared to the neutral state.

Advances in the Research of Photo, Electrical, and Magnetic Responsive Smart Superhydrophobic Materials: Synthesis and Potential Applications

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Advances in the Research of Photo, Electrical, and Magnetic Responsive Smart Superhydrophobic Materials: Synthesis and Potential Applications

This paper presents recent advances in photo, electro, and magneto responsive smart superhydrophobic materials, focusing on the synthesis, modification, properties, and responsive behaviours of photo, electro, and magneto responsive smart superhydrophobic materials in response to different external stimuli, and also explores the challenges associated with different types of responsive superhydrophobic materials, as well as the unique prospects for the application of photo, electro, and magneto responsive superhydrophobic materials.


Abstract

With the rapid advancement of technology, the wettability of conventional superhydrophobic materials no longer suffice to meet the demands of practical applications. Intelligent responsive superhydrophobic materials have emerged as a highly sought-after material in various fields. The exceptional superhydrophobicity, reversible wetting, and intelligently controllable characteristics of these materials have led to extensive applications across industries, including industry, agriculture, defense, and medicine. Therefore, the development of intelligent superhydrophobic materials with superior performance, economic practicality, enhanced sensitivity, and controllability assumes utmost importance in advancing technology worldwide. This article provides a summary of the wettability principles of superhydrophobic surfaces and the mechanisms behind intelligent responsive superhydrophobicity. Furthermore, it reviews and analyzes the recent research progress on light, electric, and magnetic responsive superhydrophobic materials, encompassing aspects such as material synthesis, modification, performance, and responses under diverse external stimuli. The article also explores the challenges associated with different types of responsive superhydrophobic materials and the unique application prospects of light, electric, and magnetic responsive superhydrophobic materials. Additionally, it outlines the future directions for the development of intelligent responsive superhydrophobic materials.

Jellyfish‐type Dinuclear Hafnium Azido Complexes: Synthesis and Reactivity

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Jellyfish-type Dinuclear Hafnium Azido Complexes: Synthesis and Reactivity

A jellyfish-like tetraazide Hf2(μ-1,1-N3)2(N3)2 supported by a new pyrazolate-bridged ligand was designed and synthesized from a dihafnium chloride precursor reacting with NaN3, which further generated a tetranuclear hafnium imido complex from a putative dinuclear HfIV-nitridyl intermediate under reduction conditions.


Abstract

Di- and multinuclear hafnium complexes bridged by ligands have been rarely reported. In this article, a novel 3,5-disubstituted pyrazolate-bridged ligand LH5 with two [N2N]2−-type chelating side arms was designed and synthesized, which supported a series of dinuclear hafnium complexes. Dinuclear hafnium azides [LHf2(μ-1,1-N3)2(N3)2][Na(THF)4] 3 and [LHf2(μ-1,1-N3)2(N3)2][Na(2,2,2-Kryptofix)] 4 were further synthesized and structurally characterized, featuring two sets of terminal and bridging azido ligands like jellyfishes. The reactivity of 3 under reduction conditions was conducted, leading to a formation of a tetranuclear hafnium imido complex [L1Hf2(μ1-NH)(N3){μ2-K}]2 5. DFT calculations revealed that the mixed imido azide 5 was generated via an intramolecular C−H insertion from a putative dinuclear HfIV-nitridyl intermediate.

Synthesis of Some Benzothiazole Derivatives Based on 3‐Hydroxypyridine‐4‐one and Benzaldehyde and Evaluation of Their β‐Amyloid Aggregation Inhibition Using both Experimental Methods and Molecular Dynamic Simulation

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Synthesis of Some Benzothiazole Derivatives Based on 3-Hydroxypyridine-4-one and Benzaldehyde and Evaluation of Their β-Amyloid Aggregation Inhibition Using both Experimental Methods and Molecular Dynamic Simulation


Abstract

Some novel inhibitors based on the (benzo[d]thiazol-2-yl)-1-phenylmethanimine derivatives were designed to reduce the aggregation process in Alzheimer's disease. These structures seem to mimic stilbene-like scaffold, while the benzothiazole moiety “locks” the thioflavin T binding site. Other inhibitors were designed based on 2-((benzo[d]thiazol-2-ylimino)methyl)-5-(benzyloxy)-1-methylpyridin-4(H)-one derivatives.

Benzo[d]thiazol-2-amine derivatives were prepared by the reaction of aniline derivatives with ammonium thiocyanate in the presence of bromine/acetic acid. Then, the reaction of amines with benzaldehyde derivatives and 5-(benzyloxy)-1-methyl-4-oxo-1,4-dihydropyridine-2-carbaldehyde gave the desired compounds. The plate reader-based fibrillation assay was done to evaluate the inhibition of Aβ aggregation. Also, molecular dynamic simulation was carried out to clarify the interaction manner of the designed compounds with Aβ formation.

The biological evaluation proved 5a and 7e as the best inhibitor of the Aβ aggregation. compound 5a in the concentration of 50 μM inhibited Aβ fibril formation better than 7e. MD simulation elucidated that the Aβ aggregation inhibitors in different concentrations represented different binding conformations throughout the entire or in one area of Aβ. MD showed the ligands in lower concentrations accumulate in an area of Aβ aggregations and separate one fibril from the aggregated Aβ. On the contrary, in higher concentrations, the ligands tend to be located through the entire Aβ.

Improving low‐temperature CO2 methanation by promoting Ni‐Al LDH‐derived catalysts with alkali metals

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Fossil fuels depletion and environmental impacts caused by greenhouse gas emissions such as CO2 are significant issues to secure the nature preservation within a sustainable economy. CO2 methanation is a promising process to mitigate CO2 emissions and reuse it to produce CH4, serving as fuel, chemical feedstock, and energy source. A series of LDH-derived Ni-Al catalysts promoted by Li, Mg, Ca, and La were prepared via the co-precipitation method. Characterization by N2 physisorption, X-ray diffraction (XRD) and photoelectron spectroscopy (XPS), as well as thermal techniques as temperature programmed reduction (H2-TPR), desorption (CO2-TPD, H2-TPD), and oxidation (TPO) analyses were performed. Low-temperature catalytic tests (200-400 °C) revealed that alkali metal modification improves performance even at 200 °C, where Ni55Ca11Al33 catalyst achieved 74% CO2 conversion with 100 % CH4 selectivity by enhancing basicity and metal-support interaction, high Ni dispersion and small crystallite sizes, providing proper sites to adsorb and activate CO2. Moreover, the catalysts presented excellent resistance to deactivation, maintaining high stability during 10 h on stream. These results prove that Ni-Al mixed oxides, LDH-derived catalysts performances can be further improved by incorporating alkali metals into less energy-spending, low-temperature CO2 methanation processes.

Metal‐free Photocatalytic [4+2] Annulation of Acrylamides with 2‐Benzyl‐2‐bromocarbonyls to Assemble Tetralin‐1‐carboxamides

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Comprehensive Summary

Tetralin-1-carboxamides are frequently incorporated in myriad medicinally important molecules. However, their existing synthetic routes not only suffer from some drawbacks such as tedious procedures, harsh reaction conditions, narrow substrate scope, low yields, and environmental problems, and are also based upon the elaboration of uneasily available non-linear tetralin derivatives. Herein we describe a metal- and additive-free visible light-induced [4+2] annulation of two simple linear starting materials, namely acrylamides and 2-benzyl-2-bromocarbonyls, through a cascade C(sp3)−Br/C(sp2)−H bond cleavage, double C−C bond formation, and aromatization sequence. The developed protocol provides a convenient, efficient, and green approach to a variety of tetralin-1-carboxamide derivatives with good functional group compatibility. Importantly, the resulting products could also undergo the LiCl-mediated mono-decarboxylative cyclization process to further furnish the architecturally novel bridged polycyclic imides with excellent cis-diastereoselectivities.

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Structure−Activity Relationship and Solubility Studies of N1‐Substituted Quinoxaline‐2,3‐diones as Kainate Receptor Antagonists

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Structure−Activity Relationship and Solubility Studies of N1-Substituted Quinoxaline-2,3-diones as Kainate Receptor Antagonists

This study presents the synthesis and structure-activity analysis of 21 new quinoxaline-2,3-dione derivatives as glutamate receptor ligands. Solubility studies focused on strategic structural modifications and resulted in increased solubility in water and alkaline conditions. These findings provide the potential for the development of active compounds with improved solubility.


Abstract

Kainate receptors are a class of ionotropic glutamate receptors that respond to the excitatory neurotransmitter glutamate in the central nervous system and play an important role in the development of neurodegenerative disorders and the regulation of synaptic function. In the current study, we investigated the structure- activity relationship of the series of quinoxaline-2,3-diones substituted at N1, 6, and 7 positions, as ligands of kainate homomeric receptors GluK1-3 and GluK5. Pharmacological characterization showed that all derivatives obtained exhibited micromolar affinity at GluK3 receptors with K i values in the range 0.1–4.4 μM range. The antagonistic properties of the selected analogues: N-(7-fluoro-6-iodo-2,3-dioxo-3,4-dihydroquinoxalin-1(2H)-yl)-3-sulfamoylbenzamide, N-(7-(1H-imidazol-1-yl)-6-iodo-2,3-dioxo-3,4-dihydroquinoxalin-1(2H)-yl)-3-sulfamoylbenzamide and N-(7-(1H-imidazol-1-yl)-2,3-dioxo-6-(phenylethynyl)-3,4-dihydroquinoxalin-1(2H)-yl)-3-sulfamoylbenzamide at GluK3 receptors, were confirmed by an intracellular calcium imaging assay. To correlate in vitro affinity data with structural features of the synthesized compounds and to understand the impact of the substituent in N1 position on ability to form additional protein-ligand interactions, molecular modeling and docking studies were carried out. Experimental solubility studies using UV spectroscopy detection have shown that 7-imidazolyl-6-iodo analogues with a sulfamoylbenzamide moiety at the N1 position are the best soluble compounds in the series, with molar solubility in TRISS buffer at pH 9 more than 3-fold higher compared to NBQX, a known AMPA/kainate antagonist.

Metabolism of (R)‐Praziquantel versus the Activation of a Parasite Transient Receptor Potential Melastatin Ion Channel

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Metabolism of (R)-Praziquantel versus the Activation of a Parasite Transient Receptor Potential Melastatin Ion Channel

Praziquantel is an anthelmintic drug activating schistosome worms’ Transient Receptor Potential Melastatin ion channel for which the cyclohexyl moiety is a key pharmacophore and also the main site of CYP-mediated oxidative metabolism. While attempting to limit metabolism, the contribution to the overall activity of both the parent and the main metabolite of praziquantel in humans is discussed.


Abstract

Praziquantel (PZQ) is an essential anthelmintic drug recently established to be an activator of a Transient Receptor Potential Melastatin (TRPMPZQ) ion channel in trematode worms. Bioinformatic, mutagenesis and drug metabolism work indicate that the cyclohexyl ring of PZQ is a key pharmacophore for activation of trematode TRPMPZQ, as well as serving as the primary site of oxidative metabolism which results in PZQ being a short-lived drug. Based on our recent findings, the hydrophobic cleft in schistosome TRPMPZQ defined by three hydrophobic residues surrounding the cyclohexyl ring has little tolerance for polarity. Here we evaluate the in vitro and in vivo activities of PZQ analogues with improved metabolic stability relative to the challenge of maintaining activity on the channel. Finally, an estimation of the respective contribution to the overall activity of both the parent and the main metabolite of PZQ in humans is reported.