The vapor-phase synthesis of 3-methylindole over Ag/SiO2 doped with ZnO was investigated. The catalysts were characterized by XRD, H2- TPR, NH3-TPD and TG techniques. The results indicated that ZnO promoter greatly en...The vapor-phase synthesis of 3-methylindole over Ag/SiO2 doped with ZnO was investigated. The catalysts were characterized by XRD, H2- TPR, NH3-TPD and TG techniques. The results indicated that ZnO promoter greatly enhanced the initial activity of the catalyst but disfavored its stability. H2-TPR and XRD results showed that the reduction peak of Ag2O shifted to higher temperature and the intensity of silver diffraction peaks was much weaker after the addition of ZnO promoter to Ag/SiO2. This indicated that there existed the interaction between Ag2O and SiO2-ZnO which promoted the silver particles dispersing on the support and inhibited the sintering of silver during the reaction. NH3-TPD and TG results revealed that the acid amounts of the catalyst and coking increased after adding ZnO to Ag/SiO2, which resulted in the deactivation of Ag/SiO2-ZnO catalyst rapidly.展开更多
Drugs SPD-304（6,7-dimethyl-3-{[methyl-（2-{methyl-[1-（3-trifluoromethyl-phenyl）-1H-indol-3-ylme thyl]-amino}-ethyl）-amino]-methyl}-chromen-4-one） and zafirlukast contain a common structural element of 3-substitut...Drugs SPD-304（6,7-dimethyl-3-{[methyl-（2-{methyl-[1-（3-trifluoromethyl-phenyl）-1H-indol-3-ylme thyl]-amino}-ethyl）-amino]-methyl}-chromen-4-one） and zafirlukast contain a common structural element of 3-substituted indole moiety which closely relates to a dehydrogenated reaction catalyzed by cytochrome P450s（CYPs）. It was reported that the dehydrogenation can produce a reactive electrophilic intermediate which cause toxicities and inactivate CYPs. Drug L-745,870（3-{[4-（4-chlorophenyl）piperazin-1-yl]-methyl}-1H-pyrrolo 2,3-β-pyridine） might have similar effect since it contains the same structural element. We used molecular docking approach combined with molecular dynamics（MD） simulation to model three-dimensional（3D） complex structures of SPD-304, zafirlukast and L-745,870 into CYP3A4, respectively. The results show that these three drugs can stably bind into the active site and the 3-methylene carbons of the drugs keep a reasonable reactive distance from the heme iron. The complex structure of SPD-304-CYP3A4 is in agreement with experimental data. For zafirlukast, the calcu lation results indicate that 3-methylene carbon might be the dehydrogenation reaction site. Docking model of L-745,870-CYP3A4 shows a potential possibility of L-745,870 dehydrogenated by CYP3A4 at 3-methylene carbon which is in agreement with experiment in vivo. In addition, residues in the phenylalanine cluster as well as S119 and R212 play a critical role in the ligands binding based on our calculations. The docking models could provide some clues to understand the metabolic mechanism of the drugs by CYP3A4.展开更多
The vapor-phase synthesis of 3-methylindole from glycerol and aniline over Cu/NaY modified by K2O was investigated. The catalysts were characterized by X-ray diffraction （XRD） and the temperature- programmed desorpt...The vapor-phase synthesis of 3-methylindole from glycerol and aniline over Cu/NaY modified by K2O was investigated. The catalysts were characterized by X-ray diffraction （XRD） and the temperature- programmed desorption of ammonia （NH3-TPD）. The effect of the reaction temperature on the activity and selectivity of Cu]NaY-K2O catalyst was also investigated. The results indicated that the addition of K2O to Cu/NaY increased the selectivity of the catalyst remarkably because the amount of middle-strong acid sites decreased clearly. The decrease of the reaction temperature was beneficial for the increase of 3- methylindole selectivity. Over Cu/NaY-K2O, the selectivity of 3-methylindole reached 75% and the yield of the target product was up to 47% at 220 ℃. A probable catalytic mechanism for the synthesis of 3- methylindole from glycerol and aniline was proposed.展开更多
基金supported by the Innovative Research Team in University of Liaoning (No. 2008T106)
文摘The vapor-phase synthesis of 3-methylindole over Ag/SiO2 doped with ZnO was investigated. The catalysts were characterized by XRD, H2- TPR, NH3-TPD and TG techniques. The results indicated that ZnO promoter greatly enhanced the initial activity of the catalyst but disfavored its stability. H2-TPR and XRD results showed that the reduction peak of Ag2O shifted to higher temperature and the intensity of silver diffraction peaks was much weaker after the addition of ZnO promoter to Ag/SiO2. This indicated that there existed the interaction between Ag2O and SiO2-ZnO which promoted the silver particles dispersing on the support and inhibited the sintering of silver during the reaction. NH3-TPD and TG results revealed that the acid amounts of the catalyst and coking increased after adding ZnO to Ag/SiO2, which resulted in the deactivation of Ag/SiO2-ZnO catalyst rapidly.
基金Supported by the National Natural Science Foundation of China(No.20903045)the Specialized Research Fund for the Doc-toral Program of Higher Education, China(No.20070183046)the Specialized Fund for the Basic Research of Jilin University, China(No.200810018)
文摘Drugs SPD-304（6,7-dimethyl-3-{[methyl-（2-{methyl-[1-（3-trifluoromethyl-phenyl）-1H-indol-3-ylme thyl]-amino}-ethyl）-amino]-methyl}-chromen-4-one） and zafirlukast contain a common structural element of 3-substituted indole moiety which closely relates to a dehydrogenated reaction catalyzed by cytochrome P450s（CYPs）. It was reported that the dehydrogenation can produce a reactive electrophilic intermediate which cause toxicities and inactivate CYPs. Drug L-745,870（3-{[4-（4-chlorophenyl）piperazin-1-yl]-methyl}-1H-pyrrolo 2,3-β-pyridine） might have similar effect since it contains the same structural element. We used molecular docking approach combined with molecular dynamics（MD） simulation to model three-dimensional（3D） complex structures of SPD-304, zafirlukast and L-745,870 into CYP3A4, respectively. The results show that these three drugs can stably bind into the active site and the 3-methylene carbons of the drugs keep a reasonable reactive distance from the heme iron. The complex structure of SPD-304-CYP3A4 is in agreement with experimental data. For zafirlukast, the calcu lation results indicate that 3-methylene carbon might be the dehydrogenation reaction site. Docking model of L-745,870-CYP3A4 shows a potential possibility of L-745,870 dehydrogenated by CYP3A4 at 3-methylene carbon which is in agreement with experiment in vivo. In addition, residues in the phenylalanine cluster as well as S119 and R212 play a critical role in the ligands binding based on our calculations. The docking models could provide some clues to understand the metabolic mechanism of the drugs by CYP3A4.
基金fnancial support provided by the National Natural Science Foundation of China (No. 21173110)
文摘The vapor-phase synthesis of 3-methylindole from glycerol and aniline over Cu/NaY modified by K2O was investigated. The catalysts were characterized by X-ray diffraction （XRD） and the temperature- programmed desorption of ammonia （NH3-TPD）. The effect of the reaction temperature on the activity and selectivity of Cu]NaY-K2O catalyst was also investigated. The results indicated that the addition of K2O to Cu/NaY increased the selectivity of the catalyst remarkably because the amount of middle-strong acid sites decreased clearly. The decrease of the reaction temperature was beneficial for the increase of 3- methylindole selectivity. Over Cu/NaY-K2O, the selectivity of 3-methylindole reached 75% and the yield of the target product was up to 47% at 220 ℃. A probable catalytic mechanism for the synthesis of 3- methylindole from glycerol and aniline was proposed.
