Photo-induced Coupling Reaction of 1, 1-Diphenyl-2, 2-dicyanoethylene with 10-Methyl-9, 10-dihydroacridine

In a previous communication1, we reported a novel photo-induced coupling of 9-fluorenylidenemalononitrile 1 with the coenzyme NADH model 10-methyl-9, 10-dihydroacridine (AcrH2) to give 9-dicyanomethyl-9-(10-methyl-9-acridinyl)fluorene and proposed a mechanism involving photo-induced electron transfer-proton transfer and radical coupling. This is a scarce mechanism for the reaction of NADH models2, which usually takes place by a formal hydride transfer pathway3. In view of the novelty of t…     

甲基、磺酸基取代的9,9'-双吖啶衍生物的化学发光研究

研究了１０,１０’－二甲基－９,９－双吖啶（ＤＭＢＡ）,２,２‘－二磺酸基－９,９－双吖啶二硝酸盐（ＤＳＢＡＤＮ）,１０,１０’－二甲基－２,２‘－二磺酸基－９,９’－双吖啶（ＤＭＤＳＢＡ）,及１０,１０‘－二甲基－９,９’－双吖啶二硝酸盐９ＤＭＢＡＤＮ,谷称光泽精）等４种９、９‘－双吖啶衍生物的化学发性质,发现１０,１０’－二 磺酸基－９,９‘－双吖啶的化学发光强度是光泽精的２２倍,是迄今为止发     

Determinants of the Inhibition of DprE1 and CYP2C9 by Antitubercular Thiophenes

Mycobacterium tuberculosis (Mtb) DprE1, an essential isomerase for the biosynthesis of the mycobacterial cell wall, is a validated target for tuberculosis (TB) drug development. Here we report the X‐ray crystal structures of DprE1 and the DprE1 resistant mutant (Y314C) in complexes with TCA1 derivatives to elucidate the molecular basis of their inhibitory activities and an unconventional resistance mechanism, which enabled us to optimize the potency of the analogs. The selected lead compound showed excellent in vitro and in vivo activities, and low risk of toxicity profile except for the inhibition of CYP2C9. A crystal structure of CYP2C9 in complex with a TCA1 analog revealed the similar interaction patterns to the DprE1–TCA1 complex. Guided by the structures, an optimized molecule was generated with differential inhibitory activities against DprE1 and CYP2C9, which provides insights for development of a clinical candidate to treat TB.     

2,9-二甲基-1,10-菲罗啉荧光光度法测定痕量铟

本文报道了以2,9-二甲基-1,10-菲罗啉(DMPH)荧光光度法测定痕量铟的新方法。实验表明,钢能很快与DMPH在pH4.0～8.7形成1:1的络合物。络合物的激发和发射波长分别为312nm,423nm。量子产率为0.35。检出限为1.0ng/g,铟量在0～1.0嵋/25mL呈线性关系。该法已成功应用于纯锡和纯铅中痕量铟的测定。     

新型固体电解质La2Mo2O9的制备及其性能

用固相法制备了新型固体电解质La2Mo2O9, 用热膨胀仪、 X射线衍射仪和Raman光谱分析了La2Mo2O9相的形成过程. 用交流阻抗谱和热膨胀仪对合成样品的电学和热学性能进行了研究, 分析了热处理温度对La2Mo2O9相的形成过程和电学性能的影响, 确定了样品获得高电学性能的最佳条件. 研究结果表明: 600 ℃时样品中开始形成La2Mo2O9相, 700 ℃以上烧结的样品可获得具有完整氧空位的La2Mo2O9相. 900 ℃烧结10 h可获得具有高密度和高电导率的La2Mo2O9氧离子导体. 样品的电学性能随烧结温度的升高而增大, 900 ℃时烧结的样品在800 ℃时的电导率为0.067 S·cm-1, 远高于同温度下YSZ的电导率, 与晶粒电阻相比, 晶界电阻非常小. 用热膨胀仪测得La2Mo2O9在555 ℃时有一个一级相变, 对应α-La2Mo2O9到β-La2Mo2O9的相变.     

La2-xSrxMo2O9-α仅的制备及氧离子导电性能

用固相反应法合成了立方相陶瓷样品La2-xSrxMo2O9-α(x=0.05,0.10,0.15).采用交流阻抗谱、气体浓差电池和氧泵(氧的电化学透过)等多种电化学方法研究了样品在550～1000℃下氧离子的导电性质.结果表明:La2-xSrxMo2O9-α陶瓷在氧化性气氛中几乎是纯的氧离子导体;在还原性气氛中为氧离子和电子的混合导体;掺杂量x对样品的电导率有着明显影响,其中x=0.10的样品La1.9Sr0.1Mo2O9具有最高的氧离子电导率,1000℃时的氧离子电导率约为0.17 S·cm-1.     

Palladium-Catalysed Amination of Hindered Aryl Halides with 9H-Carbazole

Palladium-catalysed Buchwald–Hartwig amination of ortho-substituted hindered aryl bromides or chlorides with 9H-carbazole has been investigated. In the amination of 1-bromo- or chloronaphthalene with 9H-carbazole, the combined use of Pd₂(dba)₃ as a Pd precursor, Buchwald ligands with two tert-butyl groups and LiOtBu or lithium hexamethyldisilazide as a base led to satisfactory yields. N,N’-Bis[2,6-bis(diphenylmethyl)-4-methoxyphenyl]imidazol-2-ylidene (IPr*^OMe), which is a bulky N-heterocyclic carbene ligand, showed similar activity as Buchwald ligands with two tert-butyl groups. In contrast, only IPr*^OMe provided satisfactory yields in the amination of 2-bromo-1,1′-biphenyl with 9H-carbazole. The amination of 2-bromo- or chlorotoluene and 1-(2-bromo- or chlorophenyl)naphthalene with 9H-carbazole proceeded smoothly when the IPr*^OMe ligand was used.     

一种含三氟甲基和呫吨结构聚酰胺的合成与性能

在浓硫酸和3-巯基丙酸催化下,3′-三氟甲基苯基-2,2,2-三氟苯乙酮(1)和甲苯于40～50℃下缩合反应8 h,制得中间体-1,1-二(4-甲基苯基)-1-(3′-三氟甲基苯基)-2,2,2-三氟甲基乙烷(2),继而在光照和N-溴代丁二酰亚胺促进下,将中间体氧化得到二羧酸-1,1-二(4-羧基苯基)-1-(3′-三氟甲基苯基)-2,2,2-三氟甲基乙烷(3),二步反应总收率为77.4%.采用Yamazaki体系,3和9,9-二[(4-氨基苯氧基)苯基]呫吨进行溶液亲核缩聚反应,制得了一种高分子量的(数均分子量为43000,分子量分布为1.8)新型含三氟甲基和呫吨结构的聚酰胺.该聚酰胺为非晶态结构并具有良好的透光率(λcutoff=330 nm),其玻璃化转变温度(Tg)为242℃,在氮气气氛中5%的热失重温度(Td5)为465℃,800℃时的残炭率为50%.聚合物易溶于N,N-二甲基乙酰胺(DMAc)、N-甲基吡咯烷酮(NMP)、间甲酚、吡啶(Py)和四氢呋喃(THF)等有机溶剂中,并可浇注得到韧性好和透明的薄膜,其拉伸强度为85 MPa,拉伸模量为2.0 GPa,断裂伸长率为10%.同时,该聚合物的体积电阻、表面电阻和介电常数分别为2.85×1015Ωcm,4.23×1014Ω和3.55(100 Hz),呈现了良好的电绝缘性能.     

1,1-二氘代-3,6,9,12-四氧代-1-二十四烷醇的合成

二缩三乙二醇在金属钠存在下与溴代十二烷反应生成3，6，9－三氧代－二十烷醇，收率86％；该醇与氯乙酸甲酯反应生成3，6，9，12－四氧化二十四烷酸甲酯，收率60％，3，6，9，12－四氧代二十四烷酸甲酯与氘代铝锂氢在乙醚中反应生成1，1－二氘代－3，6，9，12－四氧代－1－二十四烷醇，收率95％。     

Comparison of different fluorimetric HPLC methods for analysis of acidic polyether toxins in marine phytoplankton

The human toxic syndrome, diarrhetic shellfish poisoning (DSP), is caused by polyether toxins that are present in bivalve molluscs but originate from some species of marine phytoplankton. During the last few years different HPLC methods with fluorescence detection (FLD) have been proposed for analysis of marine toxins, including polyether toxins, in shellfish and phytoplankton. Several derivatization reagents have been proposed in the literature, with the aim of converting the acidic DSP toxins into their corresponding fluorescent derivatives. In this work we report results obtained from HPLC–FLD analysis of extracts from phytoplankton, including Dinophysis spp., harvested off the south-west coast of Ireland. Three different reagents were used for fluorescent derivatization: 3-bromomethyl-6,7-dimethoxy-1-methyl-2(1H)-quinoxalinone (BrDMEQ), 9-chloromethylanthracene (CA), and in situ 9-anthracenyldiazomethane (ADAM). Derivatization was performed under conditions previously optimised. The DSP derivatives were cleaned using different SPE procedures then analysed by HPLC–FLD. In this study, the use of BrDMEQ, CA, and in situ ADAM was compared in terms of sensitivity and selectivity. Evaluation of HPLC methods for analysis of DSP toxin derivatives was also conducted; the presence of okadaic acid (OA), dinophysistoxin-2 (DTX-2), and pectenotoxin-2 seco acids (PTX1SAs) was detected in the sample extracts studied.     

Nondoped-type White Organic Light-Emitting Diode Using Star-Shaped Hexafluorenylbenzene as an Energy Transfer Layer

White organic light-emitting diodes (WOLEDs) with a structure of indium-tin-oxide (ITO)/N,N'-bis-(1-naphthyl)-N,N'-diphenyl-(1,1'-biphenyl)-4,4'-diamine (NPB)/1,2,3,4,5,6-hexakis(9,9-diethyl-9H-fluoren-2-yl)benzene (HKEthFLYPh)/5,6,11,12 -tetraphenylnaphtacene (rubrene)/tris(8-hydroxyquinoline) aluminum (Alq3)/Mg:Ag were fabricated by vacuum deposition method, in which a novel star-shaped hexafluorenylbenzene HKEthFLYPh was used as an energy transfer layer, and an ultrathin layer of rubrene was inserted between HKEthFLYPh and Alq3 layers as a yellow light-emitting layer instead of using a time-consuming doping process. A fairly pure WOLED with Commissions Internationale De L'Eclairage (CIE) coordinates of (0.32, 0.33) was obtained when the thickness of rubrene was 0.3 nm, and the spectrum was insensitive to the applied voltage. The device yielded a maximum luminance of 4816 cd/m2 at 18 V.     

A functional comparison between the HER2(high)/HER3 and the HER2(low)/HER3 dimers on heregulin-β1-induced MMP-1 and MMP-9 expression in breast cancer cells

Overexpression of HER2 correlates with more aggressive tumors and increased resistance to cancer chemotherapy. However, a functional comparison between the HER2(high)/HER3 and the HER2(low)/HER3 dimers on tumor metastasis has not been conducted. Herein we examined the regulation mechanism of heregulin- β1 (HRG)-induced MMP-1 and -9 expression in breast cancer cell lines. Our results showed that the basal levels of MMP-1 and -9 mRNA and protein expression were increased by HRG treatment. In addition, HRG-induced MMP-1 and -9 expression was significantly decreased by MEK1/2 inhibitor, U0126 but not by phosphatidylinositol 3-kinase (PI-3K) inhibitor, LY294002. To confirm the role of MEK/ERK pathway on HRG-induced MMP-1 and -9 expression, MCF7 cells were transfected with constitutively active adenoviral- MEK (CA-MEK). The level of MMP-1 and -9 expressions was increased by CA-MEK. MMP-1 and -9 mRNA and protein expressions in response to HRG were higher in HER2 overexpressed cells than in vector alone. The phosphorylation of HER2, HER3, ERK, Akt, and JNK were also significantly increased in HER2 overexpressed MCF7 cells compared with vector alone. HRG-induced MMP-1 and -9 expressions were significantly decreased by lapatinib, which inhibits HER1 and HER2 activity, in both vector alone and HER2 overexpressed MCF7 cells. Finally, HRG-induced MMP-1 and MMP-9 expression was decreased by HER3 siRNA overexpression. Taken together, we suggested that HRG-induced MMP-1 and MMP-9 expression is mediated through HER3 dependent pathway and highly expressed HER2 may be associated with more aggressive metastasis than the low expressed HER2 in breast cancer cells.     

Confirmation of okadaic acid, dinophysistoxin-1 and dinophysistoxin-2 in shellfish as their anthrylmethyl derivatives using UV radiation

A rapid and simple method for confirmation of the diarrhetic shellfish poisons (DSP): okadaic acid (OA), dinophysistoxin-1 (DTX-1) and dinophysistoxin-2 (DTX-2) using fluorescence detection following derivatization with 9-chloromethylanthracene, has been established as an alternate to LC/MS. Exposure of the anthrylmethyl derivatives of OA, DTX-1 and DTX-2 to near UV light (300-400 nm) resulted in the loss of these compounds to below detection limits within 30 min, with a concurrent appearance of two additional compounds. Based on the mass spectral evidence, we propose that these newly formed compounds are the decarboxylation products of the derivatized diarrhetic shellfish poisons. UV radiation is, therefore, proposed as a rapid and simple confirmation technique for these DSP in mussel samples.     

The hit-to-lead optimization of 1,2,3,4,4a,9a-hexahydro-1H-xanthenes as glucocorticoid receptor antagonists

The structure–activity relationship(SAR) study of a 1 2 3 4 4a 9a-hexahydro-1H-xanthene series of selective,human glucocorticoid receptor a(hGRa) antagonists is reported.Compounds were screened using hydroxyapatite-based GR binding and MMTV-Luc co-transfection reporter gene assays.Four different regions of the scaffold were modified to assess the effects on hGRa antagonism and related potency.Compound 8d exhibits an 8-fold better bioactivity than the original hit 1a,as well as an improved chemical stability,which make it a promising lead for the subsequent optimization.     

Human liver dihydrodiol dehydrogenase 1-catalyzed reaction generating 9alpha,11beta-prostaglandin F2 from prostaglandin D2 followed by micellar electrokinetic chromatography

An enzyme reaction converting prostaglandin D2 (PGD2) into 9alpha,11beta-prostaglandin F2 (9alpha,11beta-PGF2) by a human liver-originated recombinant dihydrodiol dehydrogenase 1 (DD1) has been studied using CE. Four prostaglandins, viz. PGD2, 9alpha,11beta-PGF2, PGE2, and PGF2a (see Fig. 1, the latter two major PGs are possibly coexisting compounds in the assay mixtures), were completely separated by using SDS or PEG as buffer additives. Because analysis times in the SDS system were shorter than in the PEG system, SDS was employed in measurements of the enzyme activity of DD1. The pH dependence and the reaction temperature dependence of enzyme activity have been studied. The present method enabled us to detect all of the participants in the enzyme reaction: PGD2, 9alpha,11beta-PGF2, nicotinamide adenine dinucleotide phosphate (NADPH), and NADP+. Thus, direct, comprehensive, and reliable analysis of the enzyme reaction becomes possible. Enzyme activity has hitherto been estimated indirectly from the decrease of fluorescence derived from NADPH as an index of progress of the enzyme reactions in batch methods employed in conventional studies. In addition, the low sample consumption characteristic of CE should be a significant advantage of the present method in characterization of less commonly available enzymes such as the recombinant species used in this work.     

Iridoid glycosides-Kutkin,Picroside I,and Kutkoside from Picrorrhiza kurroa Benth inhibits the invasion and migration of MCF-7 breast cancer cells through the down regulation of matrix metalloproteinases: 1st Cancer Update

Ethnopharmacological relevanceIridoid glycosides have been associated with decreased risks of cancer, such as hepatocarcinoma. Although Picrorrhiza kurroa has shown activity against hepatocarcinogenesis, its mechanism of action is poorly understood, further the anticancer activity of iridoid glycosides present in this plant has not been tested so far.Aim of the studyHere, MCF-7 cell lines (Human breast cancer) were used to test whether P. kurroa extract (PE) and its isolated iridoid glycosides Picroside I (PS), Kutkoside (KS), and Kutkin (KT) exerts the anti-invasion activity via down-regulation of the expression of matrix metalloproteinases (MMPs). MMPs play an important role in solid tumor invasion and migration.Materials and methodsThe activity and expression of gelatinases (MMP-2 and MMP-9) and collagenases (MMP-1 and MMP-13), protein, and mRNA were detected by gelatin zymography, and RT-PCR. The migratory and invasive capacities of MCF-7 cell lines were measured by the wound scratch migration assay. The preliminary cytotoxicity testing was done by MTT assay and propidium iodide staining. Further the inhibition of inflammatory mediators was also done by quantification of nitrite inflammatory mediators.ResultsThe study showed that PE and its isolated iridoids glycosides PS, KS, and KT exhibited considerable cytotoxic potential in a dose-dependent manner. Further PE, PS, KS, and KT inhibited MCF-7 cell invasion and migration, and decreased MMP-2, 9 and MMP-1, 13 activities. Furthermore, PS, KS, and KT reduced MMPs expression at protein and mRNA levels, and suppression of the inflammatory mediators was also exhibited.ConclusionsOur results suggest that PS, KS, and KT may be the valuable anti-invasive drug candidates for cancer therapy by suppressing Collagenases and Gelatinases. PS, KS, and KT showed good results in comparison with PE. PS and KS exhibit almost comparable down regulation while KT exhibited maximum suppression of invasion, migration, and expression of MMPs.     

Electronic Properties of Two Series of Blue-Emitting Conjugated Oligomers and Polymers Based on Cyanostilbene： A Quantum Chemistry Study

One of the drawbacks of the electroluminescence （EL） polymers is that they are usually much better at accepting and transporting holes than electrons due to their inherent richness of π-electrons. One approach improving electron injection and transport in conjugated polymers is to incorporate moieties with high electron affinities. In this theoretical work, to gain an insight into the chemical structure-property relationships was aimed by controllable modification of the main chain structures. Two cyanovinylene derivatives with 2,7-fluorenylene and p-phenylene moieties in the main chains, namely, poly { （2,5-dimethoxy-p-phenylene- 1,4-ylene）-alt-[ 1,2-bis（p-phenylene）- 1- cyanovinylene]} （PPhCN） and poly{[9,9-dimethyl-2,7-fluorenylene]-alt-[1,2-bis（p-phenylene）-1-cyanovinylene]} （PFCN）, were studied employing density functional theory （DFT） and time dependent density functional theory （TD-DFT） with B3LYP functional. The electronic properties of the neutral molecules, extrapolated ionization potentials （IP） and electron affinities （EA）, and energy gaps were investigated in comparison with pristine poly（2,7- fluorenylene）. From comparison with poly（2,7-fluorenylene） （PF）, the 1,2-bis（p-phenylene）-1-cyanovi-nylene unit was found to be a good electron-withdrawing moiety for electronic materials and the incorporation of 1,2-bis（p- phenylene）-1-cyanovinylene resulted in a narrow band gap and a red shift of both the absorption and photoluminescence emission peaks. Most importantly, the LUMO energies of PFCN are around 1 eV lower than those of PF, which results in the decrement of EA about 0.9 eV, indicating that the 1,2-bis（p-phenylene）-1-cyanovinylene unit has significantly improved the electron-accepting properties of the copolymer PFCN. Substitution of 2,5-dimethoxy-p-phenylene for 9,9-dimethyl-2,7-fluorenylene induced larger band gaps and thus a blue-shift in absorption and emission peaks, which can be attributed to the better conjugated backbone in PFCN.     

Synthesis of anthraoxaza- and anthradioxaphosphorine derivatives

Anthraoxaza- and anthradioxaphosphorine sulfides were obtained by treatment of 1-amino- and 1-hydroxy-9-anthrones with Lawesson's reagent.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 1, pp. 142–144, January, 1995.     

2—氨基—9,10—蒽醌及其衍生物的光谱电化学研究

用循环伏安法研究了２－氨基－９，１０－蒽醌及其衍生物在ＤＭＦ－０．１ｍｏｌ／ＬＴＢＡＰ溶液中的电化学行为，结果表明它们在铂电极上均发生两步连续的单电子还原过程，取代基Ｒ及水和苯甲酸等质子性试剂的加对伏安曲线有很大的影响。