Discovery of novel NSAID hybrids as cPLA2/COX-2 dual inhibitors alleviating rheumatoid arthritis via inhibiting p38 MAPK pathway.

A series of NSAIDs hybrid molecules were synthesized and characterized, and their ability to inhibit NO release in LPS-induced RAW264.7 macrophages was evaluated. Most of the compounds showed significant anti-inflammatory activity in vitro, of which (2E,6Z,9Z,12Z,15Z)-1,1,1-trifluorohenicosa-2,6,9,12,15-pentaen-2-yl 2-(4-benzoylphenyl) propanoate (VI-60) was the most optimal (IC50 = 3.85 ± 0.25 µΜ) and had no cytotoxicity. In addition, VI-60 notably reduced the production of PGE2 in LPS-stimulated RAW264.7 cells compared to ketoprofen. Futhur more, VI-60 significantly inhibited the expression of iNOS, cPLA2, and COX-2 and the phosphorylation of p38 MAPK in LPS-stimulated RAW264.7 cells. The binding of VI-60 to cPLA2 and COX-2 was directly verified by the CETSA technique. In vivo studies illustrated that VI-60 exerted an excellent therapeutic effect on adjuvant-induced arthritis in rats by regulating the balance between Th17 and Treg through inhibiting the p38 MAPK/cPLA2/COX-2/PGE2 pathway. Encouragingly, VI-60 showed a lower ulcerative potential in rats at a dose of 50 mg/kg compared to ketoprofen. In conclusion, the hybrid molecules of NSAIDs and trifluoromethyl enols are promising candidates worthy of further investigation for the treatment of inflammation, pain, and other symptoms in which cPLA2 and COX-2 play a role in their etiology.

Effect of Bimetal Element Doping on the Low-Temperature Activity of Manganese-Based Catalysts for NH3-SCR.

A series of novel Mn6Zr1-xCox denitrification catalysts were prepared by the co-precipitation method. The effect of co-modification of MnOx catalyst by zirconium and cobalt on the performance of NH3-SCR was studied by doping transition metal cobalt into the Mn6Zr1 catalyst. The ternary oxide catalyst Mn6Zr0.3Co0.7 can reach about 90% of NOx conversion in a reaction temperature range of 100-275°C, and the best NOx conversion can reach up to 99%. In addition, the sulfur resistance and water resistance of the Mn6Zr0.3Co0.7 catalyst were also tested. When the concentration of SO2 is 200ppm, the NOx conversion of catalyst Mn6Zr0.3Co0.7 is still above 90%. 5 Vol% H2O has little effect on catalyst NOx conversion. The results showed that the Mn6Zr0.3Co0.7 catalyst has excellent resistance to sulfur and water. Meanwhile, the catalyst was systematically characterized. The results showed that the addition of zirconium and cobalt changes the surface morphology of the catalyst. The specific surface area, pore size, and volume of the catalyst were increased, and the reduction temperature of the catalyst was decreased. In conclusion, the doping of zirconium and cobalt successfully improves the NH3-SCR activity of the catalyst.

Selective catalytic reduction of NO x by low-temperature NH3 over Mn x Zr1 mixed-oxide catalysts.

Mn x Zr1 series catalysts were prepared by a coprecipitation method. The effect of zirconium doping on the NH3-SCR performance of the MnO x catalyst was studied, and the influence of the calcination temperature on the catalyst activity was explored. The results showed that the Mn6Zr1 catalyst exhibited good NH3-SCR activity when calcined at 400 °C. When the reaction temperature was 125-250 °C, the NO x conversion rate of Mn6Zr1 catalyst reached more than 90%, and the optimal conversion efficiency reached 97%. In addition, the Mn6Zr1 catalyst showed excellent SO2 and H2O resistance at the optimum reaction temperature. Meanwhile, the catalysts were characterized. The results showed that the morphology of the MnO x catalyst was significantly changed, whereby as the proportion of Mn4+ and Oα species increased, the physical properties of the catalyst were improved. In addition, both Lewis acid sites and Brønsted acid sites existed in the Mn6Zr1 catalyst, which reduced the reduction temperature of the catalyst. In summary, zirconium doping successfully improved the NH3-SCR performance of MnO x .

Effect of Indium Addition on the Low-Temperature Selective Catalytic Reduction of NO x by NH3 over MnCeO x Catalysts: The Promotion Effect and Mechanism.

A MnCeInO x catalyst was prepared by a coprecipitation method for denitrification of NH3-SCR (selective catalytic reduction). The catalysts were characterized by Fourier transform infrared spectroscopy (FTIR), X-ray diffractometry, scanning electron microscopy, X-ray photoelectron spectroscopy, Brunauer-Emmett-Teller analysis, H2 temperature-programmed reduction, and NH3 temperature-programmed desorption. The NH3-SCR activity and H2O and SO2 resistance of the catalysts were evaluated. The test results showed that the SCR and water resistance and sulfur resistance were good in the range of 125-225 °C. The calcination temperature of the Mn6Ce0.3In0.7O x catalyst preparation was studied. The crystallization of the Mn6Ce0.3In0.7O x catalyst was poor when calcined at 300 °C; however, the crystallization is excessive at a 500 °C calcination temperature. The influence of space velocity on the performance of the catalyst is great at 100-225 °C. FTIR test results showed that indium distribution on the surface of the catalyst reduced the content of sulfate on the surface, protected the acidic site of MnCe, and improved the sulfur resistance of the catalyst. The excellent performance of the Mn6Ce0.3In0.7O x catalyst may be due to its high content of Mn4+, surface adsorbed oxygen species, high specific surface area, redox sites and acid sites on the surface, high turnover frequency, and low apparent activation energy.

Palladium-Catalyzed Asymmetric Trifluoromethylated Allylic Alkylation of Pyrazolones Enabled by α-(Trifluoromethyl)alkenyl Acetates.

The first asymmetric trifluoromethylated allylic alkylation of pyrazolones using α-(trifluoromethyl)alkenyl acetates as a novel trifluoromethylated allylation reagent is described, affording various functionalized chiral pyrazolones containing a trifluoromethylated allyl substituent in high yields with excellent regio-/enantio-/diastereoselectivities. Mechanistically, the double-bond migration of α-(trifluoromethyl)alkenyl acetates in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene is initial and interesting step. More importantly, this study is of significance in providing a novel and widely applicable trifluoromethyl-containing allylation reagent.