Synthesis and Crystal Structure of Methyl 3-(5-Bromo-1-ethyl-1H-indole-3-carbonyl)aminopropionate

Methyl 3-（5-bromo-l-ethyl-lH-indole-3-carbonyl）aminopropionate has been synthesized by the acylation of 5-bromo-3-trichloroacetylindole with β-alanine methyl ester, followed by alkylation with ethyl iodide, in 82.6% yield. Its crystal structure was gotten and determined by X-ray diffraction method. The crystal is of monoclinic, space group P2/c with a = 11.7927（8）, b = 14.9342（8）, c = 9.0060（5） A, β = 101.558（6）°, V = 1553.93（16） A3, Z = 4, Dc= 1.510 g/cm3, 2 = 0.71073 A,μ（MoKa） = 2.656 mm-1, Mr = 353.22 and F（000） = 720. The structure was refined to R = 0.0401 and wR = 0.0825 for 1704 observed reflections with I 〉 2σ（I）. In the crystal structure, intermolecular N（2）-H（2）...O（1） hydrogen bond and weak intermolecular bonds （C（1）-H（1）...O（1） and C（10）-H（10B）-O（2）） are formed, and π-π stacking also exists.

Synthesis of Methyl 3-Hydroxypropanoate by Hydroesterification of Ethylene Oxide over Dicobalt Octacarbonyl Catalyst

Methyl 3-hydroxypropanoate was synthesized via hydroesterification of ethylene oxide with CO in the presence of dicobalt octacarbonyl catalyst and methanol solvent. The catalyst exhibited high catalytic activity. The effect of reaction temperature, CO pressure, methanol dosage, catalyst dosage and reaction time on catalytic reaction was investigated. The test results revealed that this reaction was greatly affected by reaction temperature, but it was not significantly affected by the CO pressure, the methanol dosage, the catalyst dosage and the reaction time. Under the optimal conditions, the conversion of ethylene oxide was equal to 92.24%, while the selectivity and yield of methyl 3-hydroxypropanoate reached 88.99% and 84.35%, respectively.

Indirect Electroanalysis of 3-Methyl-4-Nitrophenol in Water Using Carbon Fiber Microelectrode Modified with Nickel Tetrasulfonated Phthalocyanine Complex

Electrochemical detection of 3-methyl-4-nitrophenol (MNP) in direct phenol oxidation occurs at high potentials and generally leads to progressive passivation of the electrochemical sensor. This study describes the use of a carbon fiber microelectrode modified with a tetrasulfonated nickel phthalocyanine complex for the detection of MNP at a lower potential than that of direct phenol oxidation. The MNP voltammogram showed the presence of an anodic peak at -0.11 V vs SCE, corresponding to the oxidation of the hydroxylamine group generated after the reduction of the nitro group. The effect of buffer pH on the peak current and SWV parameters such as frequency, scan increment, and pulse amplitude were studied and optimized to have better electrochemical response of the proposed sensor. With these optimal parameters, the calibration curve shows that the peak current varied linearly as a function of MNP concentration, leading to a limit of detection (LoD) of 1.1 μg/L. These results show an appreciable sensitivity of the sensor for detecting the MNP at relatively low potentials, making it possible to avoid passivation phenomena.

Lipase-catalyzed hydrolysis of methyl-3-phenylglycidate

The enzymatic resolution of racemic methyl 3-phenylgycidate was investigated. It was found that the hydrolysis rate of (2S, 3R)-enantiomer was faster than that of (2R. 3S)-enantiomer by a new lipase. At optimal condition 96% of (2R. 3S)-methyl phenylglycidate with ee of 100% was recovered from the racemic mixture.

4-F-α-PVP类似物4-F-3-Methyl-α-PVP盐酸盐的结构解析与表征

目的研究在没有对照品的情况下鉴定检材中1-(4-氟苯基)-2-(N-吡咯烷基)-1-戊酮[1-(4-fluorophenyl)-2-(1-pyrrolidinyl)pentan-1-one,4-F-α-PVP]类似物1-(4-氟-3甲基苯基)-2-(N-吡咯烷基)-1-戊酮[1-(4-fluoro-3-methyl phenyl)-2-(1-pyrrolidinyl)pentan-1-one,4-F-3-Methyl-α-PVP]盐酸盐的方法。方法综合利用直接进样电子电离-质谱(electron ionization-mass spectrometry,EI-MS)、GCMS、电喷雾离子化-高分辨质谱(electrospray ionization-high resolution mass spectrometry,ESI-HRMS)、超高效液相色谱-高分辨串联质谱(ultra-high performance liquid chromatography-high resolution tandem mass spectrometry,UPLC-HRMS/MS)、核磁共振(nuclear magnetic resonance,NMR)、离子色谱和傅里叶变换红外光谱法(Fourier transform infrared spectroscopy,FTIR),实现对检材中未知化合物的结构解析与表征,并对该化合物在EI-MS和UPLC-HRMS/MS两种质谱分析方式下生成碎片离子的裂解机制进行推导。结果通过对检材中化合物的直接进样EI-MS、GC-MS、ESI-HRMS和UPLC-HRMS/MS分析,推断出未知化合物为4-F-α-PVP的结构类似物,可能苯环中多了1个甲基。根据核磁共振氢谱(1H-nuclear magnetic reso⁃nance,1 H-NMR)、核磁共振碳谱(13C-nuclear magnetic resonance,13C-NMR)等分析结果,进一步证明了甲基的位置在苯环的3-位。由于1H-NMR分析中实际氢的个数比4-F-3-Methyl-α-PVP中性分子多1个,推断该化合物以盐形式存在。离子色谱法分析结果表明该化合物含氯离子(含量11.14%~11.16%),结合FTIR对主要官能团信息的结构分析,最终确定该未知化合物为4-F-3-Methyl-α-PVP盐酸盐。结论建立了综合利用EI-MS、GC-MS、ESI-HRMS、UPLC-HRMS/MS、NMR、离子色谱和FTIR鉴定检材中4-F-3-Methyl-α-PVP盐酸盐的方法,将有助于法庭科学实验室在案件中鉴定该物质或其他具有类似结构的化合物。

食管鳞癌中microRNA let-7a-3甲基化与IGF-Ⅱ的相关性

目的探讨食管鳞癌组织中microRNA let-7a-3甲基化状态与血浆中类胰岛素样生长因子2(Insulin like growth factor 2,IGF-Ⅱ)表达的相关性。方法采用甲基化特异性PCR法(Methylation specific PCR,qMSP)检测83例食管癌及相对应的癌旁正常组织中let-7a-3甲基化状态,采用酶联免疫吸附试验(Enzyme linked immunosorbent assay,ELISA)检测血浆中IGF-Ⅱ的表达水平。结果83例食管鳞癌患者癌组织中的microRNA let-7a-3甲基化程度显著高于癌旁正常组织(P<0.001)。83例食管鳞癌患者血浆中IGF-Ⅱ的表达水平与let-7a-3基因的甲基化程度总体上呈正相关,具有统计学意义(r=0.600,P<0.001)。结论microRNA let-7a-3可能通过对下游分子的甲基化调控参与食管鳞癌的发生发展,这对了解食管鳞癌形成的机制具有重要意义,可为食管鳞癌的诊断和预后提供依据。

METTL3通过mRNA m6A甲基化促进类风湿关节炎滑膜成纤维细胞增殖、迁移及分泌炎症因子

目的探讨甲基转移酶样3(METTL3)对类风湿关节炎(RA)滑膜成纤维细胞增殖、迁移及分泌炎症因子的作用及机制。方法本研究纳入类风湿关节炎及骨关节炎患者各25例,留取滑膜组织,分别用RT-qPCR及免疫组化法检测METTL3表达水平,ELISA检测RNA m6A浓度;分离培养RA滑膜成纤维细胞,分为NC组、hi-METTL3(过表达METTL3)组、si-METTL3(敲低METTL3)组、STM2457(METTL3抑制剂)干预组,用CCK-8法检测细胞增殖,流式细胞仪检测细胞凋亡、ELISA检测细胞培养上清液白介素-6(IL-6)、白介素-17A(IL-17A)、肿瘤坏死因子-κB活化受体配体(RANKL)、骨保护素(OPG)的浓度。结果与骨关节炎滑膜组织相比,RA滑膜组织RNA m6A表达显著增高(P<0.05),METTL3的表达显著增高(P<0.05)。过表达METTL3后,滑膜成纤维细胞m6A表达增加,细胞增殖、迁移能力显著提高,凋亡无明显变化,分泌细胞因子IL-6、RANKL显著增加,OPG显著减少(P<0.05)。干扰METTL3表达后,滑膜成纤维细胞m6A表达减少,细胞增殖、迁移显著减低,分泌细胞因子IL-6、RANKL显著降低,OPG显著增高(P<0.05);使用METTL3抑制剂STM2457干预后,滑膜成纤维细胞增殖、迁移显著减低,分泌细胞因子IL-6、RANKL显著降低,OPG显著增高(P<0.05);各组表达IL-17A无显著差异。结论METTL3可能通过RNA m6A甲基化修饰促进RA滑膜成纤维细胞增殖、迁移及促进IL-6、RANKL的表达,抑制OPG的表达。

Peripheral Concentration of Hydroxyproline and 3-methyl-histidine in Postpartum Cow

A total of 16 Friesian cows were used in the study to determine the peripheral concentration of hydroxyproline(HYPRO) and 3 methyl histidine(3 MEHIS).The objectives of the experiment were to find out the relationship between collagen and myosin degradation and uterine involution in the postpartum cow.The results showed tht the mean concentrations of HYPRO and 3 MEHIS were 13.47±2.38 and 18.35±2.77 n mole/mL,respectively,for the cows during the days 60～90 postpartum.And for the cows immediately after calving the concentrations of HYPRO and 3 HEHIS reduced from 34.29 and 28.06 nmole/mL on the day one after calving to the normal lever of 13.23 and 17.97 n mole on the day 50 postpartum,respectively.There was a good correlation between the peripheral concentrations of both HYPRO and 3 MEHIS and the diameters of the involuting uterus(r=0.8128).

Dissolution Properties of 2-(Dinitromethylene)-5-methyl-1,3-diazacyclopentane in Dimethyl Sulfoxide and N-Methyl Pyrrolidone

The molar enthalpies of dissolution for 2-（dinitromethylene）-5-methyl-1,3-diazacyclopentane（DNMDZ） in dimethyl sulfoxide（DMSO） and N-methyl pyrrolidone（NMP） were measured using an RD496-2000 Calvet microcalorimeter at 298.15 K under atmospheric pressure.Empirical formulae for the calculation of the molar enthalpies of dissolution（Δ diss H） were obtained from the experimental data of the dissolution processes of DNMDZ in DMSO or NMP.The relationships between the rate constant（k） and the molality（b） and between the reaction order（n） and the molality（b） were determined.The corresponding kinetic equations describing the two dissolution processes were dα/dt=10^-2.16（1-α） ^1.01 for the dissolution of DNMDZ in DMSO,and dα/dt=10^-2.02（1-α）^ 0.85 for the dissolution of DNMDZ in NMP,respectively.

Crystal Structure and Anticancer Properties of Cinobufagin 3-Hemisuberate Methyl Ester

The title compound cinobufagin 3-hemisuberate methyl ester（1） was isolated from the venom of Bufo bufo gargarizans CANTOR. The crystal structure of 1, C35H48O9, was determined by single-crystal X-ray diffraction analysis. It belongs to orthorhombic, space group P212121 with a = 8.9338（3）, b = 16.2970（4）, c = 22.4019（6） , V = 3261.59（16） 3, Mr = 612.73, Z = 4, Dc = 1.248 g/cm3, μ = 0.725 mm-1, F（000） = 1320, S = 1.040, the final R = 0.0374 and wR = 0.0412 for 4458 unique reflections, of which 4088 were observed（I 〉 2σ（I））. In the solid state, short intermolecular C-H...O interactions involving a methine and the ester carbonyl group in cinobufagin moiety and a methyl in the suberate moiety linked adjacent molecules into a three-dimensional network. Detailed analysis of the 1H-NMR data showed that X-ray structure of 1 would be expected to closely resemble the solution conformation in chloroform. Compound 1 was inactive for the inhibition of PC3 and HepG2 cancer cells, but the parent compound cinobufagin showed potent inhibition with IC50 values of 0.145 and 5.48 μM, respectively, indicating that esterification at C（3） decreased the cytotoxic effect of 1.

Auxiliary Ligands Mediated One- and Two-dimensional Cd(Ⅱ) Coordination Polymers Incorporating Methyl-3- hydroxy-5-carboxy-2-Thiophenecarboxylate Ligand

Two N-donor ligands mediated Cd（Ⅱ） coordination polymers, namely,[Cd（L）（dmpz）2]n （1） and {[Cd（L）（atr）05（H20）]（H2O）}n （2） （H2L = methyl-3-hydroxy-5-carboxy-2-thiophenecarboxylate, dmpz = 3,5-dimethylpyrazole, and atr= 4-amino-l,2,4-triazole）, havebeen produced. Their structures were characterized by single-crystal X-ray diffraction analysis,elemental analyses and infrared spectra. Compound 1 possesses a one-dimensional （1D） chainstructure and is finally extended into a three-dimensional （3D） supramolecular architecturethough hydrogen bonding interactions. Compound 2 features a two-dimensional （2D） networkwith 4-connected sql topology based on dinuclear Cd（Ⅱ） clusters as nodes, which is alsoassembled into a 3D supramolecular architecture through hydrogen bonding interactions.Furthermore, compounds 1 and 2 exhibit high thermal stabilities and intense fluorescent emissionin the solid, and can be explored as potential luminescent materials.

Investigation of liquid–liquid equilibrium of the ternary system(water +1,6-diaminohexane + 2-methyl-1-propanol or 3-methyl-1-butanol) at different temperatures

In this study, the LLE data of ternary system(water + 1,6-diaminohexane + 2-methyl-1-propanol) and(water +1,6-diaminohexane + 3-methyl-1-butanol) were measured at 293.15, 303.15 and 313.15 K under atmospheric pressure. Reliability of the experimental tie-line data was checked by empirical Hand, Othmer-Tobias and Bachman equations. Distribution coefficient(D) and selectivity(S) were calculated in order to investigate capability of the studied organic solvents for 1,6-diaminohexane extraction. The high values of separation factors demonstrated that 2-methyl-1-propanol and 3-methyl-1-butanol were applicable for this purpose. The experimental data were correlated by nonrandom two-liquid(NRTL) and universal quasi-chemical(UNIQUAC) models.The percent-root-mean-square deviation(RMSD) values for NRTL and UNIQUAC models were less than 0.15,which indicated that the experimental data have been sufficiently correlated.

Synthesis, Crystal Structure and Antitumor Activity of 2-(3-Methyl-5-(methylthio)-4H-1,2,4-triazol-4-yl)isoindoline-1,3-dione

The title compound 2-（3-methyl-5-（methylthio）-4H-1,2,4-triazol-4-yl）isoindoline- 1,3-dione （C12H10NaO2S, Mr= 274.30） has been synthesized by a three-step procedure including the cyclization, hydrazinolysis and substitution reactions, and its crystal structure was determined by X-ray single-crystal diffraction. The crystal belongs to the monoclinic system, space group P2/c with a = 12.264（3）, b = 14.646（3）, c = 14.349（4） A,β = 91.69（3）°,μ = 0.255 mm1, Mr = 274.30, V = 2576.2（10） A3, Z =8, Dc = 1.414 g/cm3, F（000） = 1136, R = 0.0487 and wR = 0.1329 for 4048 observed reflections with I 〉 2σ（I）. In addition, the preliminary bioassay suggested that the title compound 6 exhibits relatively good antitumor activity against HT-29 and MCF-7.

Theoretical Studies on the Aminolysis of Ester: Effects of the Catalysis and Substituent to the Reaction of Methyl Indole-3-acetate with Ammonia

A comprehensive exploration of the aminolysis mechanism for methyl indole-3-acetate with ammonia is carried out by employing the B3 LYP/6-311++G(d,p), M06-2 X/6-311++G(d,p) and MP2/6-311++G(d,p)//M06-2 X/6-311++G(d,p) levels. Two alterative reaction channels of the concerted and addition/elimination stepwise processes including the uncatalyzed, base-catalyzed reactions are taken into consideration. Subsequently, the substituent effects and solvent effects in methanol are also evaluated at the M06-2 X/6-311++G(d,p) level. The calculated results indicate that the calculated values of M06-2 X level are quite close to those of MP2, the stepwise pathway has more advantages to the concerted one for all of the reaction processes and the catalyst facilitates the proton migration and decreases the energy barriers as well. It is shown that the most preferred mechanism is the based-catalyzed stepwise process, the substituent of NH2 group slightly accelerates all the aminolysis reaction processes, and the solvent effect does not remarkably change the mechanism of the reaction.

Urinary Concentrations of Hydroxyproline and 3-Methyl Histidine in Postpartum Cow

The urinary concentrations of hydroxyproline (HYPRO)and 3 -methyl histidine (3 - MEHIS) were de- termined in 16 Chinese-Holstein cows. The objectives of the experiment were to find out thhe relationship between collagen and myosin ddegradation and uterine involution in the postpartum cow. The results in the experiment showed that the mean concentrations of HYPRO and 3-MEHIS were 138.32±22.99 and 37.09 ±3.90 nmol·mL-1,respectively,for the cows during the days between 60-90 postpartum,and for the cows immediately after calving the concentrations of HYPRO and 3 -MEHIS reduced from 284.30 and 65.48 nmol ·mL-1 on the day one after calving to the normal level of 109.18 and 33.51 nmol·mL^-1 on the day 50 post- partum,respectively. There was a good correlation between the urinary concentrations of both HYPRO and 3 -MEHIS and the diameters of the involuting uterus (r = 0. 79).

Treatment of 2-phenylamino-3-methyl-6-di-n-butylaminofluoran production effluent by combination of biological treatments and Fenton's oxidation

High strength refractory organic stream is produced during the production of 2-phenylamino-3-methyl-6-di-n-butylaminofluoran （One Dye Black 2, abbr. ODB 2）, a novel heat-sensitive material with a promising market. In this study, a combination of acidificationprecipitation, primary biological treatment, Fenton＇s oxidation and another biological treatment was successfully used for the removal of COD from 18000-25000 mg/L to below 200 mg/L from the ODB 2 production wastewater in a pilot experiment. A COD removal of 70%-80% was achieved by acidification-precipitation under a pH of 2.5-3.0. The first step biodegradafion permitted an average COD removal of 70% under an hydraulic residence time （HRT） of 30 h. By batch tests, the optimum conditions of Fenton＇s oxidation were acquired as： Fe^2＋ dose 6.0 mmol/L; H2O2 dose 3000 mg/L; and reaction time 6 h. The second step biological treatment could ensure an effluent COD below 200 mg/L under an HRT of 10 h following the Fenton＇s treatment.

锆改性Cu/SiO_(2)催化剂催化3-羟基丙酸甲酯选择性加氢

采用蒸氨法制备了锆(Zr)改性的Cu/SiO_(2)催化剂,用于3-羟基丙酸甲酯(3-HMP)气相加氢制1,3-丙二醇(1,3-PDO)。采用比表面积及孔分布测试、XRD、ICP-OES、H_(2)-TPR、NH_(3)-TPD、CO_(2)-TPD、FTIR、TGDTG、HRTEM、XPS和AES等手段对催化剂进行了详细表征,发现Zr物种的加入使得Cu和Zr物种之间发生了强相互作用,产生了较多的层状硅酸铜,在结构方面提高了催化剂的比表面积,降低了铜物种的粒径,促进铜物种的分散,且在电子调控方面提高了Cu^(+)的含量,增强了催化剂吸附酰基和甲氧基的能力。与未改性的Cu/SiO_(2)催化剂相比,在相同反应条件下,Zr掺杂量为0.5%的Cu/SiO_(2)催化剂表现出更高的催化性能,获得3-羟基丙酸甲酯转化率为96.0%和1,3-丙二醇选择性为84.3%,1,3-PDO的总收率达80.9%。这是目前在高液时空速0.10h^(-1)的条件下取得的最佳结果。

3-羟基丙酸甲酯加氢合成1,3-丙二醇反应中La对Cu/SiO_(2)催化剂的修饰作用

[目的] 3-羟基丙酸酯加氢制备1,3-丙二醇(1,3-PDO)过程中存在β-羟基脱除等副反应,导致1,3-PDO的选择性和收率不高,其中高效催化剂的开发是解决该问题的关键.[方法]采用蒸氨法制备了不同添加量La修饰的20Cu/SiO_(2)催化剂,对其进行催化性能评价,并通过H_(2)程序升温还原(H_(2)-TPR)、X射线衍射(XRD)、透射电子显微镜(TEM)、X射线光电子能谱(XPS)和N_(2)物理吸附-脱附对其进行表征.[结果] 20Cu-0.50La/SiO_(2)的催化性能最佳,它显著地提高了3-羟基丙酸甲酯(3-HMP)加氢制1,3-PDO的催化活性和稳定性,其中3-HMP转化率为91.8%,1,3-PDO的选择性和收率分别为85.2%和78.2%.这是在高液时空速(LHSV=0.10 h^(-1))的条件下取得的最佳结果.[结论] La的加入与Cu产生了强相互作用,增强了催化剂中Cu的分散性,同时提高了Cu^(+)物种表面浓度,使活性Cu的比表面积增加,从而提高了加氢反应的活性和稳定性.

Lysine-specific demethylase 1 inhibitor rescues the osteogenic ability of mesenchymal stem cells under osteoporotic conditions by modulating H3K4 methylation

Bone tissue engineering may be hindered by underlying osteoporosis because of a decreased osteogenic ability of autologous seed cells and an unfavorably changed microenvironment in these patients. Epigenetic regulation plays an important role in the developmental origins of osteoporosis; however, few studies have investigated the potential of epigenetic therapy to improve or rescue the osteogenic ability of bone marrow mesenchymal stem cells(BMMSCs) under osteoporotic conditions. Here, we investigated pargyline, an inhibitor of lysine-specific demethylase 1(LSD1), which mainly catalyzes the demethylation of the di- and mono-methylation of H3K4. We demonstrated that 1.5 mmol·Lpargyline was the optimal concentration for the osteogenic differentiation of human BMMSCs. Pargyline rescued the osteogenic differentiation ability of mouse BMMSCs under osteoporotic conditions by enhancing the dimethylation level of H3K4 at the promoter regions of osteogenesis-related genes. Moreover, pargyline partially rescued or prevented the osteoporotic conditions in aged or ovariectomized mouse models, respectively. By introducing the concept of epigenetic therapy into the field of osteoporosis, this study demonstrated that LSD1 inhibitors could improve the clinical practice of MSC-based bone tissue engineering and proposes their novel use to treat osteoporosis.

Organic Synthesis in Ionic Liquids: Condensation of 3-Methyl-1-phenyl-5-pyrazolone with Carbonyl Compounds Catalyzed by Ethylenediammonium Diacetate (EDDA)

An efficient and environmental benign method is reported for the condensation of 3-methyl-1-phenyl-5-pyrazolone with carbonyl compounds in ionic liquids [Bmim]BF4 and [Bmim]PF6 catalyzed by ethylenediammonium diacetate.