Magnetic Nano Cobalt Ferrite Catalyzed Synthesis of 4H-Pyrano[3,2-h]quinoline Derivatives under Microwave Irradiation

A microwave irradiated magnetically separable nano cobalt ferrite catalyzed green method for the synthesis of 4-phenyl-4H-pyrano[3,2-h]quinolin-2-amine and 2-amino-4-phenyl-4H-pyrano[3,2-h] quinoline-3-carbonitrile derivatives through cyclization of aromatic aldehyde, acetonitrile/malononitrile and 8-hydoxyquinoline is developed and presented in this paper. The cubic magnetic cobalt ferrite nano particles were synthesized by sol-gel citrate precursor method and characterized by FT-IR, XRD, SEM and TEM techniques and the structures of the synthesized pyranoquinoline derivatives were assigned by IR, MASS and 1H NMR techniques. The reaction is carried out in a domestic microwave oven with a heat-resistant microwave safe glass container with a lid.

免疫检查点T细胞激活抑制物免疫球蛋白可变区结构域、人内源性逆转录病毒-H长端重复相关蛋白2在子宫内膜癌中的表达及临床意义

目的分析免疫检查点T细胞激活抑制物免疫球蛋白可变区结构域(VISTA)、人内源性逆转录病毒-H长端重复相关蛋白2(HHLA2)在子宫内膜癌(EC)中的表达及临床意义。方法选取2017年9月至2019年10月唐山市妇幼保健院收治的120例的EC患者作为研究对象,收集其的EC组织和癌旁正常组织。检测EC组织和癌旁正常组织VISTA、HHLA2的表达;采用Spearman分析免疫检查点VISTA、HHLA2的相关性;Kaplan-Meier分析VISTA、HHLA2与预后的关系;Cox回归分析影响EC患者预后的危险因素。结果EC组织中VISTA、HHLA2阳性表达率显著高于正常癌旁组织(P<0.05)。Spearman相关性结果显示EC组织中VISTA与HHLA2表达呈正相关性(r=0.587,P<0.05)。EC组织中VISTA、HHLA2表达与临床病理特征有关(P<0.05)。Kaplan-Meier曲线结果显示VISTA阳性表达患者3年生存率低于阴性表达患者(χ^(2)=11.864,P<0.05),HHLA2阳性表达患者3年生存率低于阴性表达患者(χ^(2)=4.975,P<0.05)。Cox回归分析结果显示VISTA和HHLA2是影响EC患者预后的危险因素(P<0.05)。结论免疫检查点VISTA、HHLA2在EC中高表达,其是影响EC预后的危险因素,二者可能是有价值的预后标志物。

人内源性逆转录病毒-H长末端重复关联蛋白2在人食管胃交界腺癌组织中的表达

目的探索新型免疫检查点人内源性逆转录病毒-H长末端重复关联蛋白2(HHLA2)在人食管胃交界腺癌组织中的表达及其临床意义。方法选取2016年3月至2018年6月安阳市肿瘤医院收治的食管胃交界腺癌患者126例作为研究对象,采用免疫组化染色检测食管胃交界腺癌和癌旁正常组织中HHLA2表达,随访终点为患者死亡。采用COX回归风险模型进行多因素生存分析,采用Kaplan-Meier法绘制生存曲线。结果HHLA2在食管胃交界腺癌组织中阳性表达率为68.9%(78/126),高于癌旁正常组织的21.1%(27/126)(χ^(2)=42.465,P<0.001)。多因素COX分析显示,TNM分期、HHLA2表达是患者总生存期的独立预后因素(HR=4.217,P<0.001;HR=2.467,P=0.003)。高表达HHLA2和低表达HHLA2的食管胃交界腺癌患者5 a生存率分别为24.4%和56.3%(χ^(2)=21.140,P<0.001)。结论HHLA2在食管胃交界腺癌组织中表达升高,且与患者总生存期存在相关性;高表达HHLA2和TNM分期进展是导致患者总生存期缩短的独立危险因素。

Synthesis and Crystal Structure of exo-4-(3,4-Dichlorophenyl)-8-ethyl-3,3a,4,5,8, 12d-hexahydro-2H-furo[3,2-c]indolo[3,2-f]quinoline

The title compound exo-4-（3,4-dichlorophenyl）-8-ethyl-3,3a,4,5,8,12d-hexahydro-2H-furo[3,2-c]indolo[3,2-f]quinoline （C25H22Cl2N2O, Mr = 437.35） was synthesized and crystallized. The crystal belongs to tetragonal, space group I4（1）/a with a = 17.4903（3）, b = 17.4903（3）, c = 28.3403（5） , Z = 16, V = 8669.6（3） 3, Dc = 1.340 g·cm-3, μ（MoKɑ） = 0.319 mm-1, F（000） = 3648, R = 0.0429 and wR = 0.711 for 2714 observed reflections I 2σ（I）. X-ray analysis reveals that atoms C（1）, C（2）, C（3）, C（4）, C（5） and N（1） on the new pyridine ring are slightly distorted, forming a distorted boat conformation.

Synthesis and Crystal Structure of Ethyl(2-amino-4-(3-nitrophenyl)-1,4-dihydro-2H-pyrano[3,2-h]quinolin-3-)carboxylate

The title compound ethyl(2-amino-4-(3-nitrophenyl)-1,4-dihydro-2H-pyrano[3,2- h]quinolin-3-)carboxylate (C21H17N3O5, Mr = 391.38) was synthesized and crystallized. The crystal belongs to triclinic, space group P?with a = 7.886(1), b = 9.896(2), c = 12.575(3) ? a = 77.81(2), b = 82.69(2), g = 73.86(2), Z = 2, V = 919.0(3) ?, Dc = 1.414 g/cm3, m(MoKa) = 0.103 mm-1, F(000) = 408, R = 0.0421 and wR = 0.0973 for 2007 observed reflections (I > 2s(I)). X-ray analysis reveals that the C(6), C(7), C(10), C(11), C(12) and O(1) atoms form a six-membered ring which adopts a boat conformation. In the ring, the bond lengths of C(6)C(7) and C(10)C(11) are 1.360(2) and 1.361(2) ? respectively, indicating they are C=C double bonds.

Syntheses, Crystal Structures and Photoluminescence Properties of Cadmium(Ⅱ) and Nickel(Ⅱ) Complexes with 2-(2-Benzimidazolyl)quinoline

Two novel complexes, [Cd2（BMQU）2Cl4] （1） and [Ni（BMQU）2HPO4]·1.5H2O （2） （BMQU = 2-（2-benzimidazolyl）quinoline）, were synthesized by the hydrothermal method and characterized by elemental analysis, IR, and TG-DTG. The crystal structures were determined by single-crystal X-ray diffraction. Both 1 and 2 crystallize in the triclinic system, space group P . The data for 1： a = 0.8342（7）, b = 0.9226（9）, c = 1.0646（8） nm, α = 90.819（2）, β = 97.466（2）, γ = 98.280（2）°. The Cd（Ⅱ） is coordinated with three chlorine atoms and two nitrogen atoms of a BMQU molecule, generating a distorted square-pyramidal geometry. The dinuclear Cd（Ⅱ） complex is formed by two chlorine bridge bonds, and the one-dimensional chain structure is constructed with the hydrogen bond N-H…Cl and π-π stacking interaction. The data for 2： a = 1.2251（1）, b = 1.2451（1）, c = 1.2868（1） nm, α = 107.510（2）, β = 98.630（1）, γ = 109.921（2）°. The Ni（Ⅱ） is coordinated with four nitrogen atoms of two BMQU molecules and two oxygen atoms of a HPO42-, forming a distorted-octahedral geometry. The two-dimensional layer structure is formed by the hydrogen bonds and π-π stacking interaction between neighboring molecules. Complex 1 shows a strong blue fluorescence emission （λmax= 456 nm） at solid state.

Synthesis, Structure and Quantum Chemical Study on the Organotin Complex [Di(2,4,6-trichlorobenzyl)]tin Bis(quinoline-2-formate)

The title compound was prepared by the reaction of di（2,4,6-trichlorobenzyl） stannic chloride with quinoline-2-formate and characterized with elemental analysis, ^1H NMR, IR and X-ray diffraction methods. It crystallizes in monoclinic, space group P21/n with a = 1.3138（3）, b = 1.8756（4）, c = 1.4599（3） nm, β = 92.731（3）°, V = 3.5933（12） nm^3, Z = 4, Dc = 1.795 g/cm^3, μ（MoKa） = 1.425 mm^-1, F（000） = 1920, R = 0.0778, wR = 0.2286 （for Ⅰ〉 2σ（Ⅰ）） and R = 0.0932, wR = 0.2415 （for all data）. The independent reflections were 6359, among which 5030 were observed （Ⅰ〉 2σ（Ⅰ）） and used in the succeeding refinement. Structural analysis indicates that Sn is in a distorted octahedral coordination environment, and a three-dimensional network could be observed via intermolecular hydrogen bonds. Finally, the stability, frontier orbital composition and energy of the title compound were discussed with Lanl2dz basis set and G98W program.

2-芳基喹唑啉衍生物的合成

喹唑啉类化合物作为药物研发中的优势骨架结构,被广泛用于抗肿瘤药物的研究开发中。尤其是2-取代喹唑啉类化合物具有多种生理活性,其衍生物的设计合成引起了广大科研工作者的关注。本研究以邻氨基苄胺为起始原料,和不同的芳基醛反应,在碱性条件下,一锅法得到4种2-芳基取代喹唑啉类化合物,目标产物结构经^(1)H NMR确证。

EphA2与B7-H3在结直肠癌组织中表达及其与临床病理和预后的相关性

目的探讨促红细胞生成素肝细胞A2(Erythropoietin-producing hepatocellular A2,EphA2)与免疫调节分子B7-H3在结直肠癌(colorectal cancer,CRC)中的表达及其临床预后价值。方法收集行手术治疗的110例CRC患者的石蜡包埋组织,通过免疫组织化学染色检测CRC组织中EphA2与B7-H3的表达,分析两者与CRC临床病理参数的关系。此外,通过Kaplan-Meier生存曲线和Cox风险比例模型评估EphA2与B7-H3表达在CRC患者中的预后意义。结果在所分析的110例CRC样本中,65.5%(72/110)呈现EphA2高表达,而61.8%(68/110)有B7-H3高表达。EphA2高表达者肿瘤直径更大(P=0.043)、淋巴结转移(P=0.034)和淋巴血管侵犯较低表达者更为频繁(P=0.026)。此外,与低表达组相比,B7-H3高表达者具有更为进展的T分期(P=0.024)和更高的淋巴结转移率(P=0.045)。生存分析显示,EphA2高表达与低表达患者的5年总体生存(overall survival,OS)率分别为43.9%和66.1%(P=0.014)。B7-H3高表达组的5年OS率显著低于低表达组,分别为33.2%和66.7%(P=0.028)。单、多变量Cox回归分析表明EphA2高表达(HR=2.576,95%CI:1.040-6.384,P=0.041)、B7-H3高表达(HR=2.305,95%CI:1.051~5.057,P=0.037)是CRC患者的独立预后因素。结论EphA2和B7-H3高表达与侵袭性生物学特征及不良预后显著相关,二者或许是结直肠癌患者可靠的预后分子标志。

Copper-catalyzed C(sp)-H aryl amination enables modular synthesis of quinolines and 2-quinolinones

Herein,we disclose a novel copper-catalyzed C(sp)-H aryl amination of terminal alkynes with anthranils,enabling the rapid generation of highly reactive secondary N-aryl ynamines for the modular synthesis of structurally diverse C2-substituted quinolines and 2-quinolinones.The in-situ formed carbonyl-ynamines are prone to tautomerize to carbonyl-ketenimines,which can efficiently react with a series of nucleophiles,including amines,alcohols,phenols,thiols,thiophenols,active-methylene compounds,and even water to produce various quinoline derivatives with the generation of H_(2)O as a sole and green byproduct.This method also unlocks a practical route to create various quinoline-fused heterocycles and can be successfully applied to the late-stage modification of complex molecules and the concise synthesis of bioactive targets.Mechanistic studies reveal a coppercatalyzed inner-sphere nitrene transfer process by using anthranils as novel aryl nitrene precursors.

G26-H2井钻井施工技术

G26-H2井是一口低孔、特地渗透的致密储层油井,在进行井身结构与井眼轨道介绍后,对施工中直井段轨迹控制、造斜段轨迹控制、水平段轨迹控制及井下安全措施进行详细探讨,该井能够顺利完成,为二开次致密储层油井施工积累了施工经验。

Studies on the Synthesis, Crystal Structure and Quantum Chemistry of Di(o-cyanobenzyl)tin Bis(quinoline-2-carboxylate)

Di（o-cyanobenzyl）tin bis（quinoline-2-carboxylate） was synthesized by the reaction of tri（o-cyanobenzyl）tin chloride with quinoline-2-carboxylic acid. The molecular structure of the compound was characterized by elemental analysis, IR, 1H NMR and X-ray diffraction. Crystal data for the compound： tficlinic, space group P1, a = 0.80734（7）, b = 1.00681（9）, c = 1.04811（9） nm, a = 81.7570（10）, β = 7.7240（10）,γ = 81.2850（10）°, V = 0.77581（12） nm3, Z = 1, Dc = 1.488 g/cm3, μ（MoKa） = 0.870 mm^-1 and F（000） = 350. The final R= 0.0204 and wR= 0.0530 for 2677 observed reflections with I 〉2σ（I）, and R = 0.0208 and wR = 0.0532 for all reflections. The molecular structure adopts a distorted octahedral geometry around the Sn atom. The title compound molecules are connected via hydrogen bonding interactions to form a 3D network structure. Quantum chemistry calculation study on the title compound has been performed by means of G98W package at the Lanl2dz basis set. The stability of the compound, orbital energies and some frontier molecular orbital composition characteristics have also been investigated.

Anti-Cancer Activity and Molecular Docking of Some Pyrano[3,2&#8209;c]quinoline Analogues

Quinoline analogues exhibited diversified biological activities depending on the structure type. A number of natural products with pyrano[3,2-c]quinolone structural motifs and patented chromenes were reported as promising cytotoxic agents. A molecular docking study was employed to investigate the binding and functional properties of 3-amino pyranoquinolinone 2a-c as anti-cancer agents. The three 3-amino pyranoquinolinone 2a-c showed an interesting ability to intercalate the DNA-topoisomerase complex and were able to obtain energetically favorable binding modes (&#8722;8.3 - &#8722;7.5 kcal/mol). Compound 2c containing butyl chain superiority over the other two compounds 2a-b which appeared to be involved in arene-H interactions with the two dG13 aromatic centers. The butyl chain also appeared to be immersed into a side subpocket formed by the side chains of Asn520 and Glu522 and the backbone amide of Arg503, Gly504, Lys505 and Ile506. Hence, the 3-amino pyranoquinolinone 2c used as starting material to prepare derivatives of pyrano[3,2-c]quinolone containing 1,2,4-triazine ring 4a-b which will enhance the anti-cancer activity. Pyrano[3,2-c]quinoline-2,5-diones 2a-c and 4a-b were evaluated in vitro on cell lines Ehrlich Ascites carcinoma cells (EAC), liver cancer cell line Hep-G2 and breast cancer cell line MCF-7 for the development of novel anticancer agents. The screening results revealed that compounds 4a-b were found most active candidates as anticancer agents.

New and Facile Synthesis of Substituted Pyrrole, Pyridine, Pyrazolo[4,3-b] Pyridine, Pyrano[3,2-c] Quinoline, Napthopyran, Naphthodipyran and Coumarin Derivatives

Several new pyrazolo[4,3-b] pyridines 7a, b were prepared by reacting arylidenemalononitriles 1a, c or 1i, j with 4-nitrosoantipyrine 4. Reacting 1a, b, d with 4-azidomethylcarbonylantipyrine 8 give 2-aminopyrrole 14. Pyrano[3,2-c] quinolines 20a, b and 23 were obtained by reacting 4-hydroxyquinoline 15 with 1g, h, 2b respectively. Reaction of 1 with naphthalenediols 24, 27 and 29 yield naphthodipyrans 26a, b, 28a, b and 30a。

Design, Synthesis and Antifungal Activity of 6-Fluoro-3,3a,4,5-tetrahydro-2H-pyrazolo[4,3-c]-quinoline-2-carboxamide Derivatives

A series of 6-fluoro-3,3a,4,5-tetrahydro-2H-pyrazolo[4,3-c]quinoline-2-carboxamide derivatives was designed based on the bioisosterism and combination principle in drug design. The target compounds were synthesized from substituted aniline through Michael addition, cyclization, Mannich reaction and condensation with 4-substituted semicarbazides, and the structures were confirmed by mass spectrometry（MS） and 1H NMR. The antifungal assay was carried out in vitro by two-fold dilution. The result shows that all the compounds are of antifungal activities against the tested fungi at different levels.

KF-Al_2O_3催化下3,4-二氢-2H-吡喃[3,2-h]喹啉衍生物的合成

芳醛、8 羟基喹啉与丙二腈或氰乙酸乙酯在KF Al2 O3催化下反应生成一系列新的 3,4 二氢 2H 吡喃 [3,2 h]喹啉衍生物 。

CO_2-H_2O流体不混溶对Au溶解度的影响——以贵州省贞丰县水银洞金矿床为例

运用热力学原理和方法,研究了CO2-H2O流体不混溶作用对Au的溶解度的影响。结果表明,贵州水银洞金矿床的成矿流体是一种富含挥发分(fCO2=70.79MPa)、酸性(pH=3.71)、还原性(fO2=0.50×10-36MPa)、中温(267℃)、具有超压(180MPa)性质的含Au(a∑Au=3.744×10-8mol/L)流体。当超压流体的封闭层——炭质页岩因断裂作用而被破坏时,热液体系的压力发生骤降(28.50～35.30MPa),CO2-H2O流体发生不混溶作用,并有大量CO2溢出。CO2的流失可使成矿溶液的CO2逸度和O2逸度降低(fCO2=0.80MPa、fO2=2.512×10-42MPa),酸碱度升高(pH=4.32),同时伴随温度的下降(224℃),成矿热液中Au溶解度的降低(a∑Au=3.790×10-9mol/L),从而快速沉淀下来成矿。

Al_2O_3-H_2O纳米流体相变蓄冷特性研究

在水介质中悬浮少量的纳米氧化铝颗粒(粒径20nm),通过添加分散剂和超声波振荡,制备成均匀分散的Al2O3-H2O纳米流体。对水和Al2O3-H2O纳米流体的相变蓄冷特性进行了实验比较。结果表明,加入纳米Al2O3可降低水的过冷度,缩短结冰时间;在相同的时间内,纳米流体的蓄冷量要大于纯水。

原位低温拉曼光谱技术在人工合成CaCl_2-H_2O和MgCl_2-H_2O体系流体包裹体分析中的应用Ⅱ:低温下流体包裹体相变行为的研究

本文利用低温原位拉曼技术,对 CaCl_2-H_2O 体系和 MgCl_2-H_2O 体系人工合成流体包裹体进行了研究。结果表明:对于盐浓度不同的溶液而言,可采用不同的冷冻方式有效采集低温拉曼光谱;通过系统采集不同温度下的拉曼光谱,可以直接准确地测定包裹体中流体的成分和低温相变过程。人工合成包裹体原位低温拉曼光谱的研究,为将该技术应用于天然包裹体分研究奠定了理论基础,可以预见,该技术必将在流体包裹体研究领域发挥其它方法不可替代的重要作用。