Exploring the Molecular Interactions of 7,8-Dihydroxyflavone and Its Derivatives with TrkB and VEGFR2 Proteins

7,8-Dihydroxyflavone (7,8-DHF) is a TrkB receptor agonist, and treatment with this flavonoid derivative brings about an enhanced TrkB phosphorylation and promotes downstream cellular signalling. Flavonoids are also known to exert an inhibitory effect on the vascular endothelial growth factor receptor (VEGFR) family of tyrosine kinase receptors. VEGFR2 is one of the important receptors involved in the regulation of vasculogenesis and angiogenesis and has also been implicated to exhibit various neuroprotective roles. Its upregulation and uncontrolled activity is associated with a range of pathological conditions such as age-related macular degeneration and various proliferative disorders. In this study, we investigated molecular interactions of 7,8-DHF and its derivatives with both the TrkB receptor as well as VEGFR2. Using a combination of molecular docking and computational mapping tools involving molecular dynamics approaches we have elucidated additional residues and binding energies involved in 7,8-DHF interactions with the TrkB Ig2 domain and VEGFR2. Our investigations have revealed for the first time that 7,8-DHF has dual biochemical action and its treatment may have divergent effects on the TrkB via its extracellular Ig2 domain and on the VEGFR2 receptor through the intracellular kinase domain. Contrary to its agonistic effects on the TrkB receptor, 7,8-DHF was found to downregulate VEGFR2 phosphorylation both in 661W photoreceptor cells and in retinal tissue.     

3-氨基-1,2-苯并-α-吡喃酮类衍生物的合成及抗氧化研究

以2,3,4-三甲氧基苯甲醛为原料,经4步反应合成了两个未见文献报道的1,2-苯并-α-吡喃酮类衍生物,其结构经NMR和MS确证。体外抗氧化性能测试结果显示,3-苯乙酰氨基-7,8-二甲氧基-1,2-苯并-α-吡喃酮在高浓度时显示出比对照品和3-氨基-7,8-二甲氧基-1,2-苯并-α-吡喃酮更好的DPPH自由基清除活性,在低浓度时则对羟自由基表现出比对照品及3-氨基-7,8-二甲氧基-1,2-苯并-α-吡喃酮更好的抑制活性,在ABTS自由基清除实验中,低浓度的3-氨基-7,8-二甲氧基-1,2-苯并-α-吡喃酮展现出较对照品更佳的清除活性,两者具有进一步研究的价值。     

3-氨基-7,8-二甲氧基-2(1H)-喹诺酮的合成

为了改进和优化3-氨基-2(1H)-喹诺酮环的合成工艺,从芳草醛出发,依次经过乙酰化、硝化、甲基化、还原,制备出2-氨基-3,4-二甲氧基苯甲醛(Ⅴ),Ⅴ与硝基乙酸甲酯环合得3-硝基-7,8-二甲氧基-2(1H)喹诺酮(Ⅵ),还原Ⅵ,得到3-氨基-7,8-二甲氧基-2(1H)-喹诺酮。优化后的环合条件为:以体积比7∶3的甲苯和环己烷为混合溶剂,哌啶为催化剂;Ⅵ最佳还原条件为:乙醇为溶剂,5%钯碳和甲酸铵为还原剂。在该条件下,3-氨基-7,8-二甲氧基-2(1H)-喹诺酮合成总收率从邻氨基苯甲醛(Ⅴ)计可达70%以上。     

General rate equations and their applications for cyclic reaction networks: pyramidal systems

The King-Altman-Hill graphic method has been widely used to derive the rate laws of enzymatic reactions, but the compilation of all the possible pathways is very time-consuming and the reaction rates are not given explicitly. In this study, the network reduction and Y-to-delta transformation techniques were systematically used to derive the general rate equations for pyramidal reaction networks in homogeneous catalysis. The enzymatic reaction of 7,8-dihydrofolate and NADPH to form 5,6,6,8-tetrahydrofolate and NADP, catalyzed by dihydrofolate reductase was taken as an example to illustrate the application of the general reaction rate equations. The calculated overall reaction rate was compared with that obtained from the exact solution by matrix algebra and those obtained from the King-Altman-Hill graphic method.     

Phospholipases and galactolipases trigger oxylipin-mediated wound-activated defence in the red alga Gracilaria chilensis against epiphytes

We investigated the wound response of the commercially important red alga, Gracilaria chilensis, in order to obtain insight into its interaction with epiphytic pests. After wounding, the host releases free fatty acids as well as the hydroxylated eicosanoids, 8R-hydroxy eicosatetraenoic acid (8-HETE) and 7S,8R-dihydroxy eicosatetraenoic acid (7,8-di-HETE). While the release of free arachidonic acid and subsequent formation of 8-HETE is controlled by phospholipase A, 7,8-di-HETE production is independent of this lipase. This dihydroxylated fatty acid might be directly released from galactolipids. Physiologically relevant concentrations of oxylipins reduced spore settlement of Acrochaetium sp. (Rhodophyta, Acrochaetiaceae) and suppressed the development of hapteria in Ceramium rubrum (Rhodophyta, Ceramiaceae) when these model epiphytes were exposed to artificial surfaces that contained 8-HETE or 7,8-di-HETE. Thus, the immediate release of oxylipins can be seen as G. chilensis defence against epiphytes.     

天然产物Penicilliazine类似物的合成

以7-甲氧基-4,4a,5,6,8a-五氢-1,2-苯并口恶嗪-3-羧酸乙酯(1a)为起始原料,经NaOH醇溶液和酸化处理,再通过二甲基氨基吡啶(DMAP)催化、1,3-双环己基碳二亚胺(DCC)脱水与7,8-二甲氧基-3-羟基-2(1氢)-喹诺酮(2)的酯化反应,成功合成了天然产物Penicilliazine的类似物P-1,总收率为54.4%,用1HNMR、13CNMR、MS和元素分析等对P-1进行了结构表征;对DCC投料量等反应条件进行了初步优化;对水解反应过程的研究发现,烯醇醚结构的化合物1a可水解失去甲基得到酮式结构的化合物7-羰基-4,4a,5,6,8,8a-六氢-1,2-苯并口恶嗪-3-羧酸(1c),而使用酮式结构1c的乙酯,未发现相应酮式结构羧酸1c的生成。     

New oxidation products of α-tocopherol

A major product of the reaction between α-tocopherol andt-butyl hydroperoxide in chloroform is 5-ethoxymethyl-7,8-dimethyl tocol, the source of the ethoxy group being the ethanol that is used to stabilize the chloroform. Two new products of this oxidation have now been identified as 2-(3′-hydroxy-3′,7′,11′,15′-tetramethylhexadecyl), 3-ethoxymethyl-5,6-dimethylbenzo-1,4-quinone and 5-ethoxycarbonyl-7,8-dimethyl tocol. These two compounds and another major product, 5-formyl-7,8-dimethyl tocol appear to be formed by further oxidation of 5-ethoxymethyl-7,8-dimethyl tocol.     

The Aldo-Keto Reductases and Polycyclic Aromatic Hydrocarbon Activation

The aldo-keto reductases (AKRs), are monomeric 37 kDa oxidoreductases that catalyze the NADP + -dependent oxidation of PAH trans -dihydrodiol proximate carcinogens to their reactive and redox-active o -quinones. Five human isoforms have been cloned and expressed as purified recombinant enzymes (AKR1C1-AKR1C4 and AKR1A1). Of these the general metabolic enzyme aldehyde reductase (AKR1A1) displays the highest utilization ratio for the oxidation of ( m ) R,R -benzo[ a ]pyrene-7,8-diol (BP-7,8-diol) to benzo[ a ]pyrene-7,8-dione (BP-7,8-dione). AKR1A1 is coexpressed with CYP1A1 and epoxide hydrolase suggesting that it is exposed to its trans -dihydrodiol substrates in situ. PAH o -quinones produced by AKRs are highly electrophilic yielding bimolecular rate constants for the addition of GSH of at least 1.3 2 10 3 M m 1 min m 1 . By reacting with DNA, PAH o -quinones form both stable and depurinating adducts in vitro. By entering into futile redox-cycles the PAH o -quinones can amplify the production of reactive oxygen species and increase 7,8-dihydro-8-oxo-2-deoxyguanosine (8-oxo-dGuo) formation. The spectrum of DNA-adducts and generation of prooxidants (reactive oxygen) may explain how PAHs can act as complete carcinogens.     

环虫酰肼的合成

乙酰乙酸乙酯与甲醛缩合,然后脱羧得到2-甲基-4-氧-2-环己烯甲酸乙酯,在四乙基溴化铵催化下与1-溴-3-氯丙烷反应,得到5-甲基-7,8-2H-6-苯并二氢吡喃甲酸乙酯,再在硫粉的催化下脱氢得到5-甲基苯并二氢吡喃-6-甲酸乙酯,然后经水解、酰肼化得到关键中间体N-5-甲基苯并二氢吡喃-6-甲酰-N'-特丁基肼,最后与3,5-二甲基苯甲酰氯反应得到环虫酰肼,总收率23.3%。     

Synthesis and optical and thermal properties of poly[methyl(2,9‐diphenyl‐ 7,8‐benzophenanthryl)silylene‐co‐1,4‐bis(methylphenylsilyl)phenylene]

Poly[methyl(2,9‐diphenyl‐7,8‐benzophenanthryl)silylene‐co‐1,4‐bis(methylphenylsilyl)phenylene] (PMBS‐co‐BSP) was synthesized by the condensation reaction of dichloromethyl(2,9‐diphenyl‐7,8‐benzophenanthryl)silane and 1,4‐bis(chloromethylphenylsilyl)benzene with sodium in toluene. Optical and thermal behavior of the polymer was investigated. Because of the introduction of substituted benzophenanthryl groups into the Si atoms of the polymer, the UV absorption wavelength of the PMBS‐co‐BSP red‐shifted significantly in the UV region, and a strong photoluminescence band was observed in the visible region other than the near‐UV photoluminescence typical of normal polysilane. The photochemical behavior was examined both in solution and in thin film by fluorescence and UV spectroscopy. Irradiation of the PMBS‐co‐BSP with a low‐pressure mercury lamp in solution resulted in homolytic scission of silicone–silicone bonds; the fluorescence emission intensities decreased gradually with increasing UV irradiation time and the maximum emission wavelength blue‐shifted significantly. Irradiation of thin solid films of the PMBS‐co‐BSP in air led to the formation of photoproducts containing Si? OH and Si? O? Si groups. The PMBS‐co‐BSP began to weigh less at about 300 °C and the weight loss of the polymer at 700 °C was calculated to be 75% of the initial weight in N₂. Copyright © 2006 Society of Chemical Industry     

在单壁碳纳米管上自动沉积金纳米粒子时所用润湿剂的研究

在用单壁碳纳米管直接自动沉积Au纳米粒子的时候,可以使用不同的溶剂与水混合配制氯金酸溶液,此时这些溶剂所起的作用是润湿碳管表面,从而使Au纳米粒子可以更好地沉积在碳管上。通过将Au沉积在单壁碳纳米管一系列的实验比较,最后发现,润湿碳管的溶剂不仅可用乙醇,还可以使用甲醇、丙酮、异丙醇等,其中沉积效果较好的是：50％的乙醇和30％的丙酮的水溶液。     

聚酰胺吸附硝基苯酚的热力学与机理探讨

探讨了水溶液中聚酰胺树脂吸附硝基苯酚的热力学特性及其机理，测定了不同温度下的吸附等温线。结果表明：在稀溶液中吸附硝基苯酚均符合Freundlich或Langmuri模型；聚酰胺对苦味酸、2，4—二硝基苯酚的吸附为熵驱动的吸热、熵增的自发过程；对对硝基苯酚的吸附为焓驱动的放热、熵减的自发过程；硝基苯酚主要以酚羟基及邻位硝基与聚酰胺中的酰胺基形成氢链吸附；吸附过程均具有物理吸附特征，主要为氢链吸附和范德华吸附。     

Benzo(a)pyrene metabolites formed by the action of yeast cytochrome P-450/P-448

Benzo(a)pyrene metabolites have been identified by high-pressure liquid chromatography after production by a cytochrome P-450 in brewer's yeast disruptates. The major metabolites are 7,8-dihydro-7,8-dihydroxy-benzo(a)pyrene, 9-hydroxybenzo(a)-pyrene and 3-hydroxybenzo(a)pyrene. Pretreatment of the yeast with benzo(a)-pyrene, during its growth decreases the Michaelis constant (K_m) of the enzyme for benzo(a)pyrene, using either NADPH or cumene hydroperoxide as a cofactor.     

Benzo[ a ]pyrene-7,8-dione is More Mutagenic than Anti -BPDE on p53 and is Dependent on the Generation of Reactive Oxygen Species

Polycyclic aromatic hydrocarbons (PAHs) may cause lung cancer via metabolic activation. p53 is one of the most commonly mutated tumor suppressor genes in this disease. To determine whether PAH o -quinones cause change-in-function mutations in p53 , we employed a yeast reporter system. Treatment of p53 cDNA with ( - )- anti -7,8-dihydroxy-9 f ,10 f -epoxy-7,8,9,10-tetrahydro-benzo[ a ]pyrene, ( anti -BPDE, an ultimate carcinogen) or submicromolar concentrations of BP-7,8-dione under redox-cycling conditions (NADPH and CuCl 2 ) also caused p53 mutagenesis in a dose-dependent manner. It was found that BP-7,8-dione was 80 times more mutagenic than anti -BPDE under these conditions. p53 mutagenesis by BPQ was attenuated by ROS scavengers and completely abrogated by a combination of superoxide dismutase and catalase, indicating that both superoxide anion and hydroxyl radicals were the responsible mutagens. DNA sequencing demonstrated that over 46% of BPQ-induced mutations were G:C to T:A transversions. Together these data suggest that PAH o -quinones generate an endogenous mutagen (ROS) which leads to p53 inactivation.     

Spontaneous formation of discrete arrangement of particles by dipping ultraviolet/ozone‐treated poly(dimethylsiloxane) substrate in solution

The spontaneous formation of well‐ordered microstructures is an interesting research topic because such formation is useful for cost‐effective production of functional materials. In this article, we report a novel method for spontaneous formation of a discrete arrangement of particles using an ultraviolet/ozone‐treated poly(dimethylsiloxane) substrate. The substrate was first dipped in a solution (solvent: mixture of methanol and water, solute: sucrose or lithium perchlorate) in a sealed vessel filled with the vapor of the solvent, and was then dried in air to precipitate the solute as particles. In spite of the simplicity of the procedure, the particles were regularly and discretely arranged in a triangular lattice with a distance between the neighboring particles of about 48 µm. The mechanism of formation of the array was explained by considering the formation of regular dimples due to swelling of the substrate surface with the solution and the dewetting of the liquid film of the solution on the surface. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 43506.     

Synthesis and Characterization of Mono‐, Di‐, and Tetranitrated 7,8‐Disubstituted Glycolurils

Three 7,8‐disubstitited glycolurils were synthesized and subjected to various nitration conditions yielding the corresponding mono‐, di‐, and tetranitro derivatives. Prior to their synthesis, these nitrated compounds were evaluated computationally to determine their densities and heats of formation, from which explosive performance was predicted. Details on the methods used for the synthesis as well as the results from their computational analysis are discussed.     

Synthesis and characterization of carbon/AlOOH composite for adsorption of chromium(VI) from synthetic wastewater

In this work, flake like carbon/AlOOH composite has been synthesized and evaluated as a new adsorbent for the removal of Cr(VI) from synthetic wastewater. Different characterization tools such as, SEM, EDAX, XRD and XPS were performed to characterize the composite material. Batch adsorption studies for Cr(VI) removal were performed under the influence of various operational parameters such as solution pH, contact time, initial solution concentration and temperature. Results obtained revealed that adsorption of Cr(VI) onto carbon/AlOOH composite followed the pseudo-second order kinetics and Freundlich isotherm model. Thermodynamic results suggests that adsorption of Cr(VI) onto carbon/AlOOH composite was spontaneous and endothermic in nature.     

D201树脂吸附硝基苯酚的热力学研究

探讨了水溶液中D201强碱阴离子交换树脂吸附硝基苯酚的等温吸附规律及吸附热力学特性,测定了不同温度下的吸附等温线。结果表明：D201树脂吸附硝基苯酚均服从Freundlich经验式,均为优惠吸附,吸附能力大小排序为：苦味酸〉2,4-二硝基苯酚〉对硝基苯酚。树脂对苦味酸的吸附为吸热、熵增的自发过程;对2,4-二硝基苯酚和对硝基苯酚的吸附为放热、熵减的自发过程。     

GSS362/TX-100复配体系在水中的溶液行为研究

研究了1,3-丙二醇双子琥珀酸二异辛酯磺酸钠(GSS362)和辛基酚聚氧乙烯醚(TX-100)复配物在水中的表面性质和胶束化行为,并对理想混合临界胶束浓度以及混合体系中各组分在表面吸附层和胶束中的组成、相互作用参数和热力学参数进行分析计算。结果表明,复配物在水溶液中不存在协同效应,但是TX-100的加入明显降低了GSS362的临界胶束浓度,混合胶束的形成为自发过程,胶束中GSS362与TX-100分子具有较弱的相互作用,胶束中富含非离子表面活性剂TX-100。     

Equilibrium and Kinetic Studies on the Adsorption of Lignans from Schisandra chinensis by Commercial Macroporous Resins

Seventeen resins were evaluated by their adsorption capacities from two solvent systems, ethanol aqueous solution and surfactant emulsifiable solution, prepared from Schisandra chinensis. The adsorption of lignans from surfactant emulsifiable solution on LS-305, XAD-16, HPD-100, and XAD-4 as a function of contact time, initial adsorbate concentration, and temperature was investigated by using batch experiments. LS-305 and XAD-16 exhibited higher lignans adsorption capacity than HPD-100 and XAD-4. The adsorption kinetics and Freundlich isotherm model of lignans on the four resins were well described by a pseudo-second-order and Freundlich isotherm models, respectively. The adsorption of lignans on the resins was spontaneous.