Visible-light-induced three-component reactions of α-diazoesters, quinazolinones and cyclic ethers toward quinazoline-based hybrids.

An effective approach for the construction of 4-short-chain ether attached carbonyl group-substituted quinazolines was developed. Visible-light-induced three-component reactions of α-diazoesters, quinazolinones, and cyclic ethers, with a broad substrate scope and excellent functional group tolerance, under extremely mild conditions without the need for any additional additives and catalysts, selectively led to quinazoline-based hybrids in good to excellent yields. The synthesized hybrids, which are a conglomeration of a quinazoline, a short-chain ether, and a carbonyl group in one molecular skeleton, have potential for application in the development of new drugs or drug candidates.

Design, synthesis and mechanistic studies of novel arylformylhydrazone butylphenyltin complexes as potential anticancer agents.

Many diorganotin complexes with various alkyl groups exhibit excellent in vitro anticancer activity. However, most diorganotin is the same alkyl group, and the asymmetric alkyl R group has been rarely reported. Hence, in this paper, twenty butylphenyl mixed dialkyltin arylformylhydrazone complexes have been synthesized by microwave "one-pot" reaction with arylformylhydrazine, substituted α-keto acid or its sodium salt and butylphenyltin dichloride. The crystal structures of nine complexes were determined, indicating that the complexes C1, C2, C11, C12, and C16 âˆ¼ C19 possessed a central symmetric structure of a dinuclear Sn2O2 tetrahedral ring; while the complex C9 is a trinuclear tin-oxygen cluster with a 6-membered ring encased in a 12-membered macrocyclic structure. The inhibiting activity of complexes was tested against the human cell lines NCI-H460, MCF-7, HepG2, Huh-7 and HL-7702. Complex C2 demonstrated the optimal inhibitory effect on HepG2 cells, with an IC50 value of 0.82 ± 0.03 µM. Cellular biology experiments revealed that complex C2 could induce apoptosis and G2/M phase cell cycle arrest in HepG2 and Huh-7 cells. The complex also caused the collapse of the mitochondrial membrane potential and increased intracellular reactive oxygen species in HepG2 and Huh-7 cells. Western blot analysis further clarified that complex C2 could induce cell apoptosis through the mitochondrial pathway along with the release of reactive oxygen species.

Experimental Study on NOx Reduction of Diesel Engine by EGR Coupled with SCR.

Exhaust gas recirculation (EGR) and selective catalytic reduction (SCR) are crucial technologies for mitigating nitrogen oxide (NOx) emissions in diesel engines. Although EGR reduces engine outlet NOx emissions, it simultaneously increases diesel consumption, leading to a poor economic performance. SCR requires AdBlue consumption; thus, striking the right balance for overall engine economy is of utmost importance. This study aims to evaluate NOx emission control and fluid cost in diesel engines. The total fluid cost of the diesel engine includes diesel and AdBlue. The engine is equipped with an aftertreatment system comprising a diesel oxidation catalyst (DOC), diesel particulate filter (DPF), selective catalytic reduction (SCR), and ammonia slip catalyst (ASC). The study was carried out at 1600 and 2100 rpm (25, 50, 75, and 100% load). The results show that with the increase of EGR valve opening, the exhaust temperature increased, the brake-specific fuel consumption (BSFC) increased, and the NOx emission decreased. With the increased AdBlue dosage, the NOx conversion efficiency gradually improved, ultimately approaching near-zero NOx emissions. However, as NOx emissions decreased, the equivalent diesel fluid cost rose. At 1600 r/min (100% load), when the NOx emissions were reduced by zero, the maximum fluid costs were 235, 223, and 218g/(kW·h) under the AdBlue/diesel price ratios of 1/1, 1/2, and 1/3, respectively. As the AdBlue/diesel price ratio decreases, the influence of EGR on the fluid cost diminishes. Coordinated control of EGR and AdBlue allows for reduced NOx emissions while mitigating the overall cost of diesel engines and aftertreatment systems. This research provides valuable guidance for EGR and urea control in diesel engines and contributes to the field of diesel engine emission control.

Synthesis of 2,4-Dicyanoalkylated Benzoxazines through the Radical-Mediated Cascade Cyclization of Isocyanides with AIBN under Metal- and Additive-Free Conditions.

A general and novel method for the radical cascade cyclization of aryl isocyanides with AIBN has been described. This strategy provides straightforward access to various 2,4-dicyanoalkylated benzoxazines in moderate to good yields under metal- and additive-free conditions. The reaction can apply to a gram scale and tolerate diverse functional groups. 2,4-Dicyanoalkylated benzoxazine derivatives feature a large Stokes shift and intramolecular charge transfer properties.

Endoplasmic Reticulum-Targeting Quinazolinone-Based Lipophilic Probe for Specific Photoinduced Ferroptosis and Its Induced Lipid Dynamic Regulation.

Lethal lipid peroxidation caused by reactive oxygen species occurs in different types of programmed cell death, especially in ferroptosis. Ferroptosis inducers, which serve as small-molecule probes, can provide insight into the mechanism of ferroptosis and facilitate drug discovery. The classical ferroptosis inducers indirectly lead to lipid peroxidation; thus, it is difficult to explore lipid regulation during the ferroptotic process. In this study, we designed two quinazolinone-based lipophilic probes BODIQPy-TPA and QPy-TPA, which proved to directly induce lipid peroxidation by light irradiation in vitro. The probe BODIQPy-TPA, which was mainly distributed in the endoplasmic reticulum (ER), specifically triggered ferroptosis in B16 and HepG2 cells upon light irradiation. As a comparison, the probe QPy-TPA, which was mainly distributed in lipid droplets (LDs), induced cell death by a nonferroptotic pathway. Further lipidomic analysis revealed that these two probes caused different patterns of lipid regulation and lipid peroxidation, suggesting that ferroptosis might activate distinct lipid regulation.

Synthesis of Selenium-Containing N-Quinazolinyl Acroleins via a 3,3-Radical Rearrangement Cascade Reaction.

An effective approach for the construction of 2-aryl-3-(3-oxo-1-aryl-2-(organoselanyl)prop-1-en-1-yl)quinazolin-4(3H)-ones was developed. Excellent to almost quantitative yields were obtained by the cascade reaction of propargyl quinazoline-4-yl ethers, diselenides, and 70% tert-butyl hydrogen peroxide aqueous solution under metal-free and mild conditions. The synthesized hybrids, with conglomeration of quinazolinone, organoselenium, aldehyde, and fully substituted alkene moieties in one molecule, will have the potential for applications in development of new drugs or drug candidates.

Toxic Effects of Copper Fungicides on the Development and Behavior of Zebrafish in Early-Life Stages.

Copper-based fungicides have been used to control various plant diseases for more than one hundred years and play very important roles in agriculture. Accumulation of copper in freshwater and environment pose severe threats to human health and the environment. The current study evaluated the developmental and behavioral toxicity of PEG@Cu NCs (copper nanoclusters), Kocide® 3000 (copper hydroxide), and Cu(CH3COO)2 (copper acetate) to zebrafish in early-life stages. The developmental toxicity was evaluated according to the parameters of mortality, hatching rate, autonomous movement and heartbeat of embryos, and body length of larvae. The 9 dpf (days postfertilization)-LC50 (50% lethal concentration) of embryonic mortality was 0.077, 0.174 or 0.088 mg/L, and the 9 dpf-EC50 (effective concentration of 50% embryos hatching) of hatching rate was 0.079 mg/L, 0.21 mg/L and 0.092 mg/L when the embryos were exposed to PEG@Cu NCs, Kocide® 3000 or Cu(CH3COO)2, respectively. Kocide® 3000 and Cu(CH3COO)2 obviously decreased the spontaneous movements, while PEG@Cu NCs had no adverse effects on that of embryos. The reduced heartbeat can return to normal after exposure to PEG@Cu NCs for 96 h, while it cannot recover from Kocide® 3000. In addition, Kocide® 3000 (≥0.2 mg/L), PEG@Cu NCs and Cu(CH3COO)2 with 0.05 mg/L or higher concentration exhibited obvious behavioral toxicity to zebrafish larvae according to the parameters of movement distance, average velocity, absolute sinuosity, absolute turn angle and absolute angular velocity.

Transition metal-free regioselective direct acylation of quinazolines for the synthesis of acylquinazoline derivatives.

An efficient, mild method for direct regioselective acylation of quinazolines under metal-free conditions was developed with bis(trifluoroacetoxy)iodobenzene and trimethylsilyl azide at ambient temperature. The acylation reaction of quinazolines with aldehydes gave the corresponding acyl quinazolines in ethyl acetate with good to excellent yields and excellent functional group tolerance and site selectivity. In addition, the mechanism of the direct acylation of quinazolinone was investigated through HPLC-HRMS (high pressure liquid chromatography-high resolution mass spectrometry) and EPR (electron paramagnetic resonance) strategies.

Study on Nanomaterials with Inhibitory Effects on the Growth of Aspergillus niger.

In this paper, the inhibitory effect of various nanomaterials on the growth of Aspergillus niger was studied. Among them, copper nanorods had the most obvious inhibitory effect on the growth of Aspergillus niger. The phase of copper nanorods was modified by chitosan, and its inhibitory effect on the expansion of Aspergillus niger was measured. 1. Preparation of copper nanorods and chitosan@copper nanorods: Copper nanorods with a diameter of about 300-350 nm and a length of about 100-800 nm were prepared by the liquid-phase reduction method. The chitosan solution was prepared by using the characteristics of chitosan dissolved in dilute acid to prepare chitosan@copper nanorods and modify the phase of copper nanorods. 2. Determination of the inhibitory effect of various copper nanomaterials on the growth of Aspergillus niger, including Cuprous Oxide nanoparticles, copper nanorods, nano copper oxide, and copper hydroxide, which have certain inhibitory effects on the growth of Aspergillus niger. Among them, copper nanorods have a better effect. On this basis, chitosan@copper nanorods are obtained by modifying the phase of copper nanorods with chitosan. The measured antibacterial effect is that the EC50 value is 344 mg/L.

Catalytic Desymmetrizing Baeyer-Villiger Oxidation of Quaternary Carbon-Containing Cyclobutane-1,3-diones.

The first highly enantioselective Baeyer-Villiger oxidation of quaternary carbon-containing cyclobutane-1,3-diones using chiral phosphoric acid catalysis and commercially available oxidants was reported. According to the structure of the substrates, two optimized reaction conditions were developed to afford the corresponding chiral tetronic acid products in ≤93% and ≤95% ee values. This reaction offers the first catalytic asymmetric approach to chiral 5,5-disubstituted tetronic acid derivatives. The synthetic potential of this method has been demonstrated by the formal asymmetric synthesis of (-)-vertinolide and the first catalytic asymmetric total synthesis of plakinidone B.

One-pot synthesis of 11-sulfenyl dibenzodiazepines via tandem sulfenylation/cyclization of o-isocyanodiaryl amines and diaryl disulfides.

A one-pot sulfenylation/cyclization of o-isocyanodiaryl amines has been described for the preparation of 11-sulfenyl dibenzodiazepines. This AgI-catalyzed reaction covers an unexplored tandem process to give seven-membered N-heterocycles. This transformation shows a broad range of substrate scope, simple operation, and moderate to good yields under aerobic conditions. Diphenyl diselenide can also be produced in an acceptable yield.

Mn(III)-Mediated Radical Addition/Cyclization of Isocyanides with Aryl Boronic Acids/Diarylphosphine Oxides: Access to 11-Functionalized Dibenzodiazepines.

A Mn(III)-mediated radical addition/cyclization reaction of isocyanides with aryl boronic acids/diarylphosphine oxides has been developed. A series of 11-arylated/-phosphorylated dibenzodiazepines were efficiently constructed in moderate to excellent yields under mild reaction conditions via imidoyl radical process. The present protocol offers novel access to functionalized seven-membered N-heterocycles.

Tetrabutylammonium Chloride-Induced Cascade Radical Addition/Cyclization of O-Isocyanodiaryl Amines: A Novel Protocol for the Synthesis of 11-Trifluoromethylated Dibenzodiazepines.

A straightforward protocol for the synthesis of 11-trifluoromethylated dibenzodiazepines has been developed via TBAC-induced trifluoromethylation/cyclization of o-isocyanodiaryl amines using Togni's reagent as the trifluoromethyl source. This is the first report on the one-step construction of CF3-containing dibenzodiazepine drug skeletons. Additionally, a series of 11-trifluoromethylated dibenzodiazepines were afforded in moderate to excellent yields under transition-metal-free conditions.

Fe(acac)2/TBHP-promoted synthesis of 11-functionalized dibenzodiazepines via alkoxycarbonylation and carboxamidation of o-isocyanodiaryl amines.

A radical addition/cyclization reaction of o-isocyanodiaryl amines has been developed for the efficient synthesis of potentially bioactive dibenzo[b,e][1,4]diazepine-11-carboxylates and dibenzo[b,e][1,4]diazepine-11-carboxamides. This Fe(acac)2/TBHP-promoted radical cascade process involves an unexplored isocyanide addition and the following cyclization to form 11-functionalized dibenzodiazepines. Moreover, the alkoxycarbonylation and carboxamidation of o-isocyanodiaryl amines show broad substrate scope and good functional group compatibility under mild conditions.

DMF-Assisted Radical Cyclization of o-Isocyanodiaryl Ethers via 1,5-Aryl Migration: Construction of 2-Arylbenzoxazoles.

A novel DMF-assisted radical cyclization of o-isocyanodiaryl ethers via 1,5-aryl migration has been developed for the synthesis of a series of 2-arylbenzoxazoles by the FeCl3/TBHP/Et3N catalytic system in DMF. However, N,N-dimethylbenzo[d]thiazole-2-carboxamide and N,N-dimethylbenzo[d]selenazole-2-carboxamide were obtained from the corresponding substrate 2-isocyanophenyl p-methoxyphenyl thioether and 2-isocyanodiphenyl selenoether under the same conditions. A possible mechanism may involve aryl 1,5-migration and DMF-assisted radical cyclization of o-isocyanodiaryl ethers.

Aroylhydrazone Diorganotin Complexes Causes DNA Damage and Apoptotic Cell Death: From Chemical Synthesis to Biochemical Effects.

Under microwave irradiation, eighteen new aroylhydrazone diorganotin complexes (1a-9b) were produced through the reaction of aroylhydrazine, 2-ketobutyric acid, and the corresponding diorganotin. Fourier transform infrared spectroscopy, 1H, 13C, and 119Sn nuclear magnetic resonance spectroscopies, high-resolution mass spectroscopy, X-ray crystallography, and thermogravimetric analysis (TGA) were performed to characterize the complexes. The in vitro anticancer activity for complexes were assessed using a CCK-8 assay on human cancer cells of HepG2, NCI-H460, and MCF-7. Complex 4b revealed more intensive anticancer activity against MCF-7 cells than the other complexes and cisplatin. Flow cytometry analysis and transmission electron microscope observation demonstrated that complex 4b mediated cell apoptosis of MCF-7 cells and arrested cell cycle in S phase. Western blotting analysis showed that 4b induced DNA damage in MCF-7 cells and led to apoptosis by the ATM-CHK2-p53 pathway. The single cell gel electrophoreses assay results showed that 4b induced DNA damage. The DNA binding activity of 4b was studied by UV-Visible absorption spectrometry, fluorescence competitive, viscosity measurements, gel electrophoresis, and molecular docking, and the results show that 4b can be well embedded in the groove and cleave DNA.

Recent advances in the tandem annulation of 1,3-enynes to functionalized pyridine and pyrrole derivatives.

Great progress has been made in the tandem annulation of enynes in the past few years. This review only presents the corresponding reactions of 1,3-enyne structural motifs to provide the functionalized pyridine and pyrrole derivatives. The functionalization reactions cover iodination, bromination, trifluoromethylation, azidation, carbonylation, arylation, alkylation, selenylation, sulfenylation, amidation, esterification, and hydroxylation. We also briefly introduce the applications of the products and the reaction mechanisms for the synthesis of corresponding N-heterocycles.

Transient Directing Group Strategy as a Unified Method for Site Selective Direct C4-H Halogenation of Indoles.

A unified method for direct C4-H halogenation of indoles has been accomplished with the assistance of anthranilic acids as suitable transient directing groups. Exclusive site selectivity (one out of five potential reactive sites) as well as good functional group tolerance was obtained to install three kinds of halogen atoms (Cl, Br and I, respectively) by using inexpensive N-halosuccinimides (NXS) as halogen sources under mild conditions. Taking advantage of the rich functional groups in the product, a diversity of nitrogen-containing heterocycles were facily constructed via one-step late-stage derivations.

α-Keto Acids as Triggers and Partners for the Synthesis of Quinazolinones, Quinoxalinones, Benzooxazinones, and Benzothiazoles in Water.

A general and efficient method for the synthesis of quinazolinones, quinoxalinones, benzooxazinones, and benzothiazoles from the reactions of α-keto acids with 2-aminobenzamides, benzene-1,2-diamines, 2-aminophenols, and 2-aminobenzenethiols, respectively, is described. The reactions were conducted under catalyst-free conditions, using water as the sole solvent with no additive required, and successfully applied to the synthesis of sildenafil. More importantly, these reactions can be conducted on a mass scale, and the products can be easily purified through filtration and washing with ethanol (or crystallized).

Catalytic Enantioselective Desymmetrization of Cyclobutane-1,3-diones by Carbonyl-Amine Condensation.

A chiral phosphoric acid-catalyzed enantioselective condensation of 2,2-disubstituted cyclobutane-1,3-diones with a primary amine is described. This reaction offered a mild and efficient protocol for constructing quaternary carbon-containing cyclobutanes in good to high yields and enantioselectivities. This reaction is the first catalytic desymmetrizing carbonyl-amine condensation reaction and also represents the first catalytic desymmetrizing reaction of prochiral cyclobutane-1,3-dione.