Producing 2-ethyl-1-hexyl thioglycolate(ETE)via esterification reaction with thioglycolic acid(TGA)aqueous solution as raw material by reactive-separation coupling technology is a promising process intensification met...Producing 2-ethyl-1-hexyl thioglycolate(ETE)via esterification reaction with thioglycolic acid(TGA)aqueous solution as raw material by reactive-separation coupling technology is a promising process intensification method.To choose suitable reactive-separation coupling strategy,the kinetic studies of the esterification of TGA with 2-ethyl-1-hexanol(EHL)were carried out in a batch system.The commercial ion exchange resin was employed as an eco-friendly catalyst.The effects of temperature,catalyst concentration and molar ratio were determined.It was interesting to observe that the equilibrium conversion of TGA increased with the increase of catalyst mass fraction due to the adsorption of product water onto resin surface.The activity-based pseudo-homogeneous(PH),Eley-Rideal(ER)and Langmuir-Hinshelwood-Ho ugen-Watson(LHHW)models were used to fit the kinetics data of the resin-catalyzed reaction.The models of ER and LHHW performed better than the PH model.The kinetics of the TGA-self-catalyzed reaction was also determined.An activity-based homogeneous kinetics model could well describe this self-catalyzed reaction.These results would be meaningful to the selection and design of an appropriate reactionseparation strategy for the production of ETE,to realize the process intensification.展开更多
Phthalates have been used in a wide variety of consumer goods. Their versatility as plasticizers has translated into worldwide use in a vast array of consumer products. These compounds can leach into matrices, such as...Phthalates have been used in a wide variety of consumer goods. Their versatility as plasticizers has translated into worldwide use in a vast array of consumer products. These compounds can leach into matrices, such as food and liquids that can be routed for human exposure. One of the most used phthalates is Diethylhexyl phthalate (DEHP). Diethylhexyl phthalate and its metabolite 2-ethyl-1-hexanol (2-EH) have demonstrated biological effects which merit further evaluation. In this work, we expand on our previous work with DEHP and screen the 2-EH metabolite for different cell death endpoints such as growth inhibition, apoptosis, autophagy, caspase activation, DNA fragmentation, and cell cycle arrest using fluorophores and the NC3000 instrument. Significant results (p 0.05) revealed higher toxicity for the 2-EH metabolite when compared to DEHP. Also, 2-EH presented apoptosis induction with characteristic hallmarks, such as loss of mitochondrial membrane potential, caspase activation, DNA fragmentation and cell cycle arrest at the S phase. In addition, the presence of autophagosome was detected through L3CB protein staining. We conclude that 2-EH presents differences in cell death endpoints that interestingly differ from the DEHP parent compound. Further studies are needed to establish the molecular pathways responsible for the observed effects.展开更多
2-硝基咪唑是一种重要的医药中间体,可用于合成多种抗癌药物,通过对其结构进行修饰,有望开发新型活性药物分子。以2-氨基嘧啶和3-溴丙酮酸乙酯为起始原料,经过缩合环化、肼解、氧化和取代合成了一系列1-烷基-2-硝基-1 H-咪唑-5-甲酸乙酯...2-硝基咪唑是一种重要的医药中间体,可用于合成多种抗癌药物,通过对其结构进行修饰,有望开发新型活性药物分子。以2-氨基嘧啶和3-溴丙酮酸乙酯为起始原料,经过缩合环化、肼解、氧化和取代合成了一系列1-烷基-2-硝基-1 H-咪唑-5-甲酸乙酯(7a~7d)及其同分异构体1-烷基-2-硝基-1 H-咪唑-4-甲酸乙酯(8a~8d),该方法克服了传统合成路线中氮原子上取代基仅为甲基的局限性。研究不同取代基对2种异构体比例的影响,结果表明:随着取代基团的给电子能力增强,更加有利于化合物7的生成。所有合成化合物的结构都经过1 H NMR,13 C NMR和MS(ESI)确证或表征。展开更多
The title complex [Cu3L3(H2O)]DMFH2O (H2L = 4-(3-hydroxy-2-ethyl-4- pyridinone-1-yl)-aniline condensation salicylaldehyde) was obtained. The single-crystal X-ray study shows that it is a trinuclear compound [Cu3(C20H1...The title complex [Cu3L3(H2O)]DMFH2O (H2L = 4-(3-hydroxy-2-ethyl-4- pyridinone-1-yl)-aniline condensation salicylaldehyde) was obtained. The single-crystal X-ray study shows that it is a trinuclear compound [Cu3(C20H15N2O3)3(H2O)]DMFH2O. The coordi- nation sphere about each copper ion in the complex consists of two oxygen atoms from hydroxylpyridinone moiety of one ligand and one oxygen and one nitrogen atoms from salicyladehyde Schiff-base moiety of another ligand arranged in a slightly distorted square planar geometry. Among the three copper ions, one (Cu(2)) is coordinated by the other oxygen atom of water molecule on the fifth coordinate position to form a distorted square pyramid geometry. The crystal is of monoclinic, space group P21/c with a = 12.9202(5), b = 27.197(1), c = 17.0116(7) ? b = 100.588(1), V = 5875.9(4) 3, Z = 4, C63H57N7O12Cu3, Mr = 1294.78, Dc = 1.464 g/cm3, m = 1.146 mm-1, F(000) = 2668, R = 0.0784 and wR = 0.1546 for 6926 observed reflections with I > 2s(I). The differences of coordinate bond lengths are observed between anhydrous and hydrous units: in the former unit, the average bond lengths are 1.978 ?for CuN (azomethine), 1.883 ?for CuO (phenolic) in Schiff-base moiety, 1.959 ?for CuO (keto), and 1.919 ?for CuO (hydroxy) in hydroxypyridinone moiety; while those in the latter are longer with the following corresponding values: 1.985(5), 1.908(5), 1.993(5) and 1.919(4) ? respectively. The Cu(2)O (water) bond length is 2.375(6) ?展开更多
Tumor necrosis factor-alpha (TNF-α) is a potent inflammatory cytokine and its exaggerated production has been implicated in acute, chronic and autoimmune inflammatory diseases. Proteinaceous and non-proteinaceous ant...Tumor necrosis factor-alpha (TNF-α) is a potent inflammatory cytokine and its exaggerated production has been implicated in acute, chronic and autoimmune inflammatory diseases. Proteinaceous and non-proteinaceous anti-TNF-α agents have been developed to reduce its circulating levels either by neutralizing, binding or inhibiting the de novo synthesis with the aim of achieving desirable therapeutic effects. In the present study, we compared the effects of a protein-based anti-TNF-α drug, etanercept, and a non-protein-based anti-TNF-α small molecule, 5-ethyl-1-phenyl-2-(1H) pyridone (5-EPP), on the LPS-stimulated secretion of TNF-α in the medium and TNF-α associated with the THP-1 cells in vitro. Both drugs had marked concentration-dependent inhibitory effects on the LPS-stimulated secretion of TNF-α. However, their effects on the LPS-stimulated cell-associated TNF-α were diametrically opposed to each other. For instance, etanercept further increased the level by up to 12-fold, whereas 5-EPP inhibited the level in a dose dependent manner. In addition, 5-EPP caused a significant reduction in the elevated level of cell associated TNF-α caused by LPS + etanercept. The differences in the levels of cell-associated TNF-α as reported in the present study may partly explain the adverse effects of some protein-based anti-TNF-α drugs including etanercept as opposed to a non-protein-based anti-TNF-α drug such as pirfenidone, a structural analogue of 5-EPP, for treatment of some TNF-α mediated diseases. It was concluded from the findings of this study that drugs which elevate the levels of cell associated-TNF-α will potentially have more adverse events even after reducing the secreted levels of TNF-α than the drugs which reduce both the secreted and cell-associated TNF-α levels.展开更多
The title complex, (1S)-1,1'-bis{[N-ethyl-N-(1-methylethyl)-amino]carbonyl}-2- (hydroxyldiphenylmethyl)-ferrocene ([Fe(C24H22NO2)(C11H16NO)]2·H2O, Mr = 1207.13), was synthesized via (-)-Sparteine-m...The title complex, (1S)-1,1'-bis{[N-ethyl-N-(1-methylethyl)-amino]carbonyl}-2- (hydroxyldiphenylmethyl)-ferrocene ([Fe(C24H22NO2)(C11H16NO)]2·H2O, Mr = 1207.13), was synthesized via (-)-Sparteine-mediated enantioselective directed ortho-lithiation of 1,1‘-bis{[N- ethyl-N-(1-methylethyl)-amino]carbonyl}-2-(hydroxydiphenylmethyl)-ferrocene. The structure of the rifle compound was determined by X-ray single-crystal diffraction. The crystal belongs to the orthorhombic system, space group P212121, with a = 10.266(2), b = 17.676(4), c = 34.097(7)A, V = 6187(2)A3, Z = 4, C70H86Fe2N4O7, Dc = 1.296 g/cm^3,μ = 0.527 mm^-1, T= 113(2) K, F(000) = 2568, the final R = 0.0469 and wR = 0.0984 for 13940 observed reflections with I 〉 2σ(I). The neighboring ferrocene derivatives are joined into dimers via O-H…O=C intermolecular hydrogen bonding by a water molecule. Besides, the dimers form neat rows along the a axis.展开更多
基金the financial support for this work from the National Natural Science Foundation of China(No.21706034)the Guiding Project of Fujian Province(No.2018H0016)+1 种基金the Open Foundation of State Key Laboratory of Chemical Engineering(No.SKL-ChE-18B02)the Integration of Industry,Education and Research of Fujian Province(No.2018Y4008).
文摘Producing 2-ethyl-1-hexyl thioglycolate(ETE)via esterification reaction with thioglycolic acid(TGA)aqueous solution as raw material by reactive-separation coupling technology is a promising process intensification method.To choose suitable reactive-separation coupling strategy,the kinetic studies of the esterification of TGA with 2-ethyl-1-hexanol(EHL)were carried out in a batch system.The commercial ion exchange resin was employed as an eco-friendly catalyst.The effects of temperature,catalyst concentration and molar ratio were determined.It was interesting to observe that the equilibrium conversion of TGA increased with the increase of catalyst mass fraction due to the adsorption of product water onto resin surface.The activity-based pseudo-homogeneous(PH),Eley-Rideal(ER)and Langmuir-Hinshelwood-Ho ugen-Watson(LHHW)models were used to fit the kinetics data of the resin-catalyzed reaction.The models of ER and LHHW performed better than the PH model.The kinetics of the TGA-self-catalyzed reaction was also determined.An activity-based homogeneous kinetics model could well describe this self-catalyzed reaction.These results would be meaningful to the selection and design of an appropriate reactionseparation strategy for the production of ETE,to realize the process intensification.
文摘Phthalates have been used in a wide variety of consumer goods. Their versatility as plasticizers has translated into worldwide use in a vast array of consumer products. These compounds can leach into matrices, such as food and liquids that can be routed for human exposure. One of the most used phthalates is Diethylhexyl phthalate (DEHP). Diethylhexyl phthalate and its metabolite 2-ethyl-1-hexanol (2-EH) have demonstrated biological effects which merit further evaluation. In this work, we expand on our previous work with DEHP and screen the 2-EH metabolite for different cell death endpoints such as growth inhibition, apoptosis, autophagy, caspase activation, DNA fragmentation, and cell cycle arrest using fluorophores and the NC3000 instrument. Significant results (p 0.05) revealed higher toxicity for the 2-EH metabolite when compared to DEHP. Also, 2-EH presented apoptosis induction with characteristic hallmarks, such as loss of mitochondrial membrane potential, caspase activation, DNA fragmentation and cell cycle arrest at the S phase. In addition, the presence of autophagosome was detected through L3CB protein staining. We conclude that 2-EH presents differences in cell death endpoints that interestingly differ from the DEHP parent compound. Further studies are needed to establish the molecular pathways responsible for the observed effects.
文摘2-硝基咪唑是一种重要的医药中间体,可用于合成多种抗癌药物,通过对其结构进行修饰,有望开发新型活性药物分子。以2-氨基嘧啶和3-溴丙酮酸乙酯为起始原料,经过缩合环化、肼解、氧化和取代合成了一系列1-烷基-2-硝基-1 H-咪唑-5-甲酸乙酯(7a~7d)及其同分异构体1-烷基-2-硝基-1 H-咪唑-4-甲酸乙酯(8a~8d),该方法克服了传统合成路线中氮原子上取代基仅为甲基的局限性。研究不同取代基对2种异构体比例的影响,结果表明:随着取代基团的给电子能力增强,更加有利于化合物7的生成。所有合成化合物的结构都经过1 H NMR,13 C NMR和MS(ESI)确证或表征。
基金This work was supported by the foundation of Natural Science Research of Jiangsu Education Department (02KJB150007)
文摘The title complex [Cu3L3(H2O)]DMFH2O (H2L = 4-(3-hydroxy-2-ethyl-4- pyridinone-1-yl)-aniline condensation salicylaldehyde) was obtained. The single-crystal X-ray study shows that it is a trinuclear compound [Cu3(C20H15N2O3)3(H2O)]DMFH2O. The coordi- nation sphere about each copper ion in the complex consists of two oxygen atoms from hydroxylpyridinone moiety of one ligand and one oxygen and one nitrogen atoms from salicyladehyde Schiff-base moiety of another ligand arranged in a slightly distorted square planar geometry. Among the three copper ions, one (Cu(2)) is coordinated by the other oxygen atom of water molecule on the fifth coordinate position to form a distorted square pyramid geometry. The crystal is of monoclinic, space group P21/c with a = 12.9202(5), b = 27.197(1), c = 17.0116(7) ? b = 100.588(1), V = 5875.9(4) 3, Z = 4, C63H57N7O12Cu3, Mr = 1294.78, Dc = 1.464 g/cm3, m = 1.146 mm-1, F(000) = 2668, R = 0.0784 and wR = 0.1546 for 6926 observed reflections with I > 2s(I). The differences of coordinate bond lengths are observed between anhydrous and hydrous units: in the former unit, the average bond lengths are 1.978 ?for CuN (azomethine), 1.883 ?for CuO (phenolic) in Schiff-base moiety, 1.959 ?for CuO (keto), and 1.919 ?for CuO (hydroxy) in hydroxypyridinone moiety; while those in the latter are longer with the following corresponding values: 1.985(5), 1.908(5), 1.993(5) and 1.919(4) ? respectively. The Cu(2)O (water) bond length is 2.375(6) ?
文摘Tumor necrosis factor-alpha (TNF-α) is a potent inflammatory cytokine and its exaggerated production has been implicated in acute, chronic and autoimmune inflammatory diseases. Proteinaceous and non-proteinaceous anti-TNF-α agents have been developed to reduce its circulating levels either by neutralizing, binding or inhibiting the de novo synthesis with the aim of achieving desirable therapeutic effects. In the present study, we compared the effects of a protein-based anti-TNF-α drug, etanercept, and a non-protein-based anti-TNF-α small molecule, 5-ethyl-1-phenyl-2-(1H) pyridone (5-EPP), on the LPS-stimulated secretion of TNF-α in the medium and TNF-α associated with the THP-1 cells in vitro. Both drugs had marked concentration-dependent inhibitory effects on the LPS-stimulated secretion of TNF-α. However, their effects on the LPS-stimulated cell-associated TNF-α were diametrically opposed to each other. For instance, etanercept further increased the level by up to 12-fold, whereas 5-EPP inhibited the level in a dose dependent manner. In addition, 5-EPP caused a significant reduction in the elevated level of cell associated TNF-α caused by LPS + etanercept. The differences in the levels of cell-associated TNF-α as reported in the present study may partly explain the adverse effects of some protein-based anti-TNF-α drugs including etanercept as opposed to a non-protein-based anti-TNF-α drug such as pirfenidone, a structural analogue of 5-EPP, for treatment of some TNF-α mediated diseases. It was concluded from the findings of this study that drugs which elevate the levels of cell associated-TNF-α will potentially have more adverse events even after reducing the secreted levels of TNF-α than the drugs which reduce both the secreted and cell-associated TNF-α levels.
基金supported by the Major Program of National Natural Science Foundation of China (200572009)Beijing Natural Science Foundation Program and Scientific Research Key Program of Beijing Municipal Commission of Education (KZ200610011006)
文摘The title complex, (1S)-1,1'-bis{[N-ethyl-N-(1-methylethyl)-amino]carbonyl}-2- (hydroxyldiphenylmethyl)-ferrocene ([Fe(C24H22NO2)(C11H16NO)]2·H2O, Mr = 1207.13), was synthesized via (-)-Sparteine-mediated enantioselective directed ortho-lithiation of 1,1‘-bis{[N- ethyl-N-(1-methylethyl)-amino]carbonyl}-2-(hydroxydiphenylmethyl)-ferrocene. The structure of the rifle compound was determined by X-ray single-crystal diffraction. The crystal belongs to the orthorhombic system, space group P212121, with a = 10.266(2), b = 17.676(4), c = 34.097(7)A, V = 6187(2)A3, Z = 4, C70H86Fe2N4O7, Dc = 1.296 g/cm^3,μ = 0.527 mm^-1, T= 113(2) K, F(000) = 2568, the final R = 0.0469 and wR = 0.0984 for 13940 observed reflections with I 〉 2σ(I). The neighboring ferrocene derivatives are joined into dimers via O-H…O=C intermolecular hydrogen bonding by a water molecule. Besides, the dimers form neat rows along the a axis.
基金supported by the National High-Tech Research and Development Program of China(863)(2012AA101806)National Natural Science Foundation of China(21306195,51276183)~~