Restoration of catalytic activity by the preservation of ligand structure: Cu-catalysed asymmetric conjugate addition with 1,1-diborylmethane

Reported herein is a novel reaction engineering protocol to enhance the efficiency of a transition metal-catalysed process by strategically preventing ligand degradation. Based on spectroscopic investigations, a decomposition pathway of a chiral phosphoramidite ligand during a Cu-catalysed reaction was identified. The involvement of the destructive process could be minimized under the modified reaction conditions that control the amount of nucleophilic alkoxide base, which is the origin of ligand decomposition. Overall, the strategy has been successfully applied to a new class of asymmetric conjugate addition reactions with bis[(pinacolato)boryl]methane, in which α,β-unsaturated enones are utilised as substrates.

A novel Cu-catalysed asymmetric conjugate addition reaction with bis[(pinacolato)boryl]methane using α,β-unsaturated enones as substrates has been developed on the basis of strategic preservation of the supporting ligand.     

Sensitive Determination of Felodipine in Human and Dog Plasma by Use of Liquid–Liquid Extraction and LC–ESI–MS–MS

Summary A sensitive and selective liquid chromatographic method coupled with electrospray ionization tandem mass spectrometry (LC–ESI–MS–MS) has been developed for quantification of felodipine in human and dog plasma. Compounds were separated on a 2.0 mm × 150 mm, 5.0 m particle, C₈ column with 1 m m ammonium acetate–acetonitrile, 20:80, pH 6.0, as mobile phase at a flow rate of 200 L min^–1. Nifedipine was used as internal standard. Plasma samples were extracted with diethyl ether, the centrifuged upper layer was evaporated, the residue was reconstituted with mobile phase, and the reconstituted samples were injected. The analytical column lasted for at least 1000 injections. By use of multiple reaction monitoring (MRM) mode in MS–MS felodipine and nifedipine were detected without severe interference from the human or dog plasma matrix. Felodipine produced a protonated precursor ion ([M + H]⁺) at m/z 384 and a corresponding product ion at m/z 338. And internal standard (nifedipine) produced a protonated precursor ion ([M + H]⁺) at m/z 347 and a corresponding product ion at m/z 315. Detection of felodipine in human and dog plasma was accurate and precise, with a limit of quantification of 0.05 ng mL^–1. The method has been successfully applied to preliminary pharmacokinetic study of felodipine in human and dog plasma.     

Complete 1H and 13C NMR spectral assignment of symmetric and asymmetric bis-spiropyran derivatives

(1)H and (13)C NMR spectra of symmetric and asymmetric bis-spiropyrans, Series 1-3, were completely assigned. Especially, the (1)H assignment of asymmetric spiropyrans was achieved by utilizing (1)H-(1)H COSY and nOe experiments. All of the carbons in the dye molecules were investigated through a combination of heteronuclear 2D-shift correlation spectroscopy (HETCOR), together with an attached proton test (APT).     

Induction of nitric oxide synthase (NOS) by soluble glucocorticoid induced tumor necrosis factor receptor (sGITR) is modulated by IFN-gamma in murine macrophage

Earlier study showed that glucocorticoid induced tumor necrosis factor receptor (GITR), a new TNFR family, activated murine macrophages to express inducible nitric oxide synthase (iNOS) and to generate nitric oxide (NO). A possible involvement of pro-inflammatory cytokines on NO production by GITR was investigated in vitro systems and signaling molecules contributing to sGITR-induced iNOS production are determined in Raw 264.7 cells, a murine macrophage cell line. The result showed that the synergy was afforded by the combination of GITR with IFN-g in a dose-dependent manner but IFN-gamma alone was not able to induce NOS. No effects were observed with TNF-alpha, IL-1beta, or IL-6 co-treated with GITR. To determine signaling molecules contributing to sGITR-induced iNOS production, a specific inhibitor for signal pathway proteins tested showed that PDTC (NF-kappaB) and genistein (tyrosine kinase) inhibited NOS induction significantly, while sodium orthovanadate (tyrosine phosphatase) potentiated NOS expression. These results suggest that activations of NF-kappaB were involved in induction of iNOS by GITR and IFN-gamma priming caused earlier and stronger NF-kappaB activation.     

Design,Synthesis and Biological Evaluation of 1,3,5-Triazine Derivatives Targeting hA1 and hA3 Adenosine Receptor

Adenosine mediates various physiological activities in the body. Adenosine receptors (ARs) are widely expressed in tumors and the tumor microenvironment (TME), and they induce tumor proliferation and suppress immune cell function. There are four types of human adenosine receptor (hARs): hA₁, hA_2A, hA_2B, and hA₃. Both hA₁ and hA₃ AR play an important role in tumor proliferation. We designed and synthesized novel 1,3,5-triazine derivatives through amination and Suzuki coupling, and evaluated them for binding affinities to each hAR subtype. Compounds 9a and 11b showed good binding affinity to both hA₁ and hA₃ AR, while 9c showed the highest binding affinity to hA₁ AR. In this study, we discovered that 9c inhibits cell viability, leading to cell death in lung cancer cell lines. Flow cytometry analysis revealed that 9c caused an increase in intracellular reactive oxygen species (ROS) and a depolarization of the mitochondrial membrane potential. The binding mode of 1,3,5-triazine derivatives to hA₁ and hA₃ AR were predicted by a molecular docking study.     

垃圾气化分析及其对中国实现碳中和与无废城市建设的贡献

气化是实现化学利用碳资源(尤其是煤)生产化学品和燃料的关键工艺.目前,全球拥有超过272套气化装置,主要应用于煤化工,尤其在中国.由于在一个化工厂通过技术集成达到工业规模的集中生产可实现减少二氧化碳排放并促进碳密集型行业的循环经济,如废物管理、化学和交通行业,因此,近年来全球对垃圾气化的兴趣日益浓厚,尤其是那些在煤气化...     

Structural and functional stabilities of artificially designed DNA ultra-thin films grown by silica Assistance

We report the structural and functional stabilities of artificially synthesized DNA ultra-thin films. Fully covered DNA ultra-thin films on a silica substrate were fabricated by the silica-assisted growth method and those samples were then incubated in various chemicals and physical conditions. The DNA ultra-thin films showed high maintainability under those harsh conditions and these results would aid to facilitate the use of artificial DNA ultra-thin films in advanced research areas such as biophotonics and bioelectronics.     

One-pot synthesis of 1-substituted-5-alkylselanyl-1H-tetrazoles from isoselenocyanates: unexpected formation of N-alkyl-N-arylcyanamides and (Z)-Se-alkyl-N-cyano-N,N′-diarylisoselenoureas

1-Substituted-5-alkylsulfanyl-1H-tetrazoles are well known class of organic substances with various applications in medicinal chemistry or photographic industry. Their selenium analogues, 1-substituted-5-alkylselanyl-1H-tetrazoles are, however, much less explored because of the lack of suitable methods for their preparation. In this work we investigated the synthesis of 1-alkyl/aryl-5-alkylselanyl-1H-tetrazoles from synthetically available alkyl/arylisoselenocyanates. One-pot reactions of arylisoselenocyanates with sodium azide and alkylating agent led to the target 5-alkylselanyl-1-aryl-1H-tetrazoles but also to interesting side products, namely N-alkyl-N-arylcyanamides and (Z)-Se-alkyl-N-cyano-N,N′-diarylisoselenoureas. Nevertheless, when alkylisoselenocyanates were utilized as the substrates, the reactions led exclusively to the formation of 1-alkyl-5-alkylselanyl-1H-tetrazoles in good yields. This simple one-pot procedure brings new possibilities for the preparation of variously substituted selenium compounds. It also opens the way to further investigations of selenium isosteres of the widely utilized 5-thiotetrazole moiety in biomedical applications.     

Isolation of an Organic Solvent-Tolerant Lipolytic Enzyme from Uncultivated Microorganism

Although the use of lipases as biocatalysts has frequently been proposed, it is yet scarcely being implemented in industrial processes. This is mainly due to the difficulties associated with the discovery and engineering of new enzymes and the lack of versatile screening methods. In this study, we screened the available strategy from a metagenomic pool for the organic solvent-tolerant lipase with enhanced performance for industrial processes. A novel lipase was identified through functional screening from a metagenomic library of activated sludge in an Escherichia coli system. The gene encoding the lipase from the metagenomic pool, metalip1, was sequenced and cloned by PCR. Metalip1 encoding a polypeptide of 316 amino acids had typical residues essential for lipase such as pentapeptide (GXSXGG) and catalytic triad sequences (Ser160, Asp260, and His291). The deduced amino acid sequence of metalip1 showed high similarity to a putative lipase from Pseudomonas sp. CL-61 (80 %, ABC25547). Metalip1 was expressed in E. coli BL21 (DE3) with a his-tag and purified using a Ni-NTA chelating column and characterized. This enzyme showed high expression level and solubility in the heterologous E. coli host. This enzyme was active over broad organic solvents. Among organic solvents examined, dimethyl formamide was the best organic solvent for metalip1. We showed that function-based strategy is an effective method for fishing out an organic solvent-tolerant lipase from the metagenomic library. Also, it revealed high catalytic turnover rates, which make them a very interesting candidate for industrial application.     

Nanosilver‐Decorated TiO2 Nanofibers Coated with a SiO2 Layer for Enhanced Light Scattering and Localized Surface Plasmons in Dye‐Sensitized Solar Cells

Enhanced harvesting of visible light is vital to the development of highly efficient dye‐sensitized solar cells (DSSCs). Nanosilver‐decorated TiO₂ nanofibers (Ag@TiO₂ NFs) were synthesized by depositing chemically reduced Ag ions onto the surface of electrospun TiO₂ nanofibers (TiO₂ NFs). The prepared Ag@TiO₂ NFs were coated with SiO₂ (SiO₂@Ag@TiO₂ NFs) by using PVP as coupling agent for protecting corrosion of Ag nanoparticle by I^?/${{\rm I}{{- \hfill \atop 3\hfill}}}$ solution. The fabricated SiO₂@Ag@TiO₂ NFs demonstrated a synergistic effect of light scattering and surface plasmons, leading to an enhanced light absorption. Moreover, an anode consisting of SiO₂@Ag@TiO₂ NFs incorporating TiO₂ nanoparticles (NPs) increased light harvesting without substantially sacrificing dye attachment. The power conversion efficiency increased from 6.8 to 8.7 % for a thick film (10 μm), that is, 28 %. These results suggest that SiO₂@Ag@TiO₂ NFs are promising materials for enhanced light absorption in dye‐sensitized solar cells.