4-单取代-1H-1,2,3-三氮唑的合成研究

以甲氧基聚乙二醇(mPEG)为起始原料通过磺酰化、叠氮化反应合成叠氮基甲氧基聚乙二醇(mPEG-N_3,2);在铜催化下和芳香炔、脂肪炔发生1,3-偶极环加成反应合成甲氧基聚乙二醇-1,2,3-三氮唑(mPEG-1,2,3-triazoles,3);再于酸性条件下脱除甲氧基聚乙二醇(mPEG)制备4-单取代-1H-1,2,3-三氮唑(4),其结构经过MS及~1H NMR、~(13)C NMR确证。     

非糖基化促红细胞生成素的聚乙二醇定点修饰及修饰产物性质

临床用重组人促红细胞生成素(rhEpo)是中国仓鼠卵巢细胞(Chinese hamster ovary cell, CHO)表达的糖蛋白, 糖基对稳定蛋白的结构和生物活性非常重要, 但CHO表达体系生产成本高、产量低. 以大肠杆菌表达的促红细胞生成素为非糖基化蛋白(rh-ngEpo), 对其进行聚乙二醇(PEG)修饰可以提高蛋白稳定性和体内循环半衰期. 本文采用分子量为20000的N-末端专一性的单甲氧基聚乙二醇-丙醛(mPEG-ALD)修饰rh-ngEpo, 对影响修饰反应的因素进行了考察. 结果表明, 在最佳反应条件下, 单修饰率可达55%. 修饰混合物经离子交换层析分离, 获得了纯度大于95%的单修饰产物, 其二、三级结构证明与原蛋白相似. 肽图分析结果表明, PEG绝大部分修饰在蛋白N-末端的氨基酸残基上. ELISA分析表明, 单修饰产物的体外活性虽然比修饰前减少30%, 但热稳定性得到显著增强, 在SD大鼠体内的药代动力学性质得到显著提高. 研究结果表明, PEG可以在一定程度上替代糖基的作用, PEG修饰的非糖基化Epo有望成为一种新型的促红细胞生成蛋白药物.     

巯-炔加成可控修饰的两亲性嵌段共聚肽及其溶液自组装

以单甲氧基聚乙二醇伯胺(m PEG-NH2)作为大分子引发剂,引发γ-炔丙基-L-谷氨酸-N-羧基-环内酸酐(NCA)开环聚合的方法,合成了侧链上含有炔基的聚乙二醇-b-聚(γ-炔丙基-L-谷氨酸)两嵌段共聚物(PEG-b-PPLG).进一步通过巯基-炔基加成的"点击"化学方法,对两嵌段共聚物中聚氨基酸PPLG嵌段分别修饰了普通疏水性的饱和烷烃、具有超疏水性质的全氟代烷烃,并利用红外光谱、圆二色光谱、动态光散射和透射电子显微镜等技术,对合成的两嵌段共聚物在水溶液及有机溶剂四氢呋喃(THF)中的自组装性质进行了研究.研究发现两嵌段共聚物修饰前后,聚氨基酸嵌段在水和THF中都能保持一定的α-螺旋的构象,并进一步自组装形成以α-螺旋的聚氨基酸嵌段为内核、PEG嵌段为外壳的纳米聚集结构.     

甲氧基聚乙二醇-1,2-二硬脂酰甘油磷酰乙醇胺的合成

以1,2-二硬脂酸甘油酯为原料,依次与三氯氧磷和乙醇胺反应,得到1,2-二硬脂酰甘油磷酰乙醇胺(DSPE),其在N,N’-羰基二咪唑作用下与甲氧基聚乙二醇(mPEG2000)反应,生成甲氧基聚乙二醇2000-1,2-二硬脂酰甘油磷酰乙醇胺(mPEG2000-DSPE)。产物结构经过红外光谱、质谱及核磁氢谱等表征确证。     

两相体系检测聚乙二醇化粒细胞集落刺激因子的修饰度

研究了温度、平衡时间等对硫氰铁铵-氯仿两相体系检测不同分子量聚乙二醇(PEG)的影响因素,优化检测条件是温度30℃、平衡时间2h,检测限是6.65μg.利用PEG(30000)修饰粒细胞集落刺激因子(GCSF),分离纯化得到纯度大于97%的单修饰PEG30k-GCSF,建立了检测其修饰度的方法,得出PEG修饰度为19.4%,与理论值(20%)接近.此法能准确检测蛋白质或多肽的聚乙二醇修饰度.     

聚乙二醇和叶酸对层状双金属氢氧化物颗粒的表面修饰

以具有伪装隐形作用的聚乙二醇(PEG)和具有靶向作用的叶酸(FA)为修饰剂, 以氨丙基三甲氧基硅烷(APTMS)为连接剂, 对Mg₃Al-NO₃层状双金属氢氧化物(LDH)进行了表面修饰, 制备了LDH-PEG-FA纳米颗粒, 并通过X射线衍射(XRD)、 透射电子显微镜(TEM)、 紫外-可见光谱(UV-Vis)、 傅里叶变换红外光谱(FTIR)、 粒度分布分析和元素分析等技术对其结构进行了表征. 结果表明, PEG和FA的修饰量可由其原料配比调控, 修饰后的产物具有良好的水再分散性, 这主要源于修饰层的空间位阻效应. 预期LDH-PEG-FA同时具有伪装隐形性和靶向性, 可用于药物载体等领域.     

选择性聚乙二醇化赖氨酸的合成

以单甲氧基聚乙二醇(mPEG)和Fmoc-Lys(Boc)-OH(1)为主要原料,经过羧基苄酯化、侧链Boc脱除、ε-氨基丁二酸酐修饰得到功能化的赖氨酸化合物N-α-芴甲氧羰基-N-ε-(γ-氧代丁酸)-L-赖氨酸苄酯(4);1和4分别与mPEG在偶联剂D IC/HOB t的作用下联接,最终分别实现了赖氨酸主链和侧链的mPEG定点修饰,合成了新型的N-α-芴甲氧羰基-N-ε-(γ-氧代丁酸聚乙二醇酯)-L-赖氨酸苄酯(5,总收率52.6%)和N-ε-叔丁氧羰基-N-α-芴甲氧羰基-L-赖氨酸聚乙二醇酯(6,收率93.7%),其结构经1H NMR,IR和MS表征。     

几种修饰剂共价修饰L—门冬酰胺酶降低其抗原性的对比研究

选用单甲氧基聚乙二醇、右旋糖苷、磺化右旋糖苷,肝素及小分子醋酸酐对酶分子进行了共价修饰,研究了不同修饰剂对酶分子的酶活力及其抗原性的影响。结果表明,大分子,特别是单甲氧基聚乙二醇的降低抗原性效果很好,但活力损失较大;修饰剂分子量越大,酶表面氨基修饰程度越高,解除抗原性效果越好。     

一种新型枝化聚乙二醇的合成

以谷氨酸作为中心分子,首先对谷氨酸的氨基进行Boc保护,然后在4-二甲基氨基吡啶-二环己基碳二亚胺催化体系的作用下,将两条线性的单甲氧基聚乙二醇(mPEG)链连接到谷氨酸的两个羧基上,合成出含有两条聚乙二醇(PEG)链及一个活性氨基的新型枝化PEG[Glu(PEG)2],其结构经1H NMR,IR,GPC和VPO表征。     

基于低分子量聚乙烯亚胺和油酸的负电性基因载体

构建负电性的基因载体、发展基于低分子量聚乙烯亚胺(PEI)的基因载体对基因传递研究具有重要意义. 本文基于低分子量聚乙烯亚胺(2 kDa)和油酸构建了负电性的基因载体. 它通过混合聚乙烯亚胺(2 kDa)、dsDNA和油酸胶束而自发形成. 该基因载体在血清中很稳定,细胞毒性非常低,可包封80%以上DNA. 通过1,2-二硬脂酰-sn-甘油-3-磷酸乙醇胺-N-[甲氧基(聚乙二醇2000)]铵盐(DSPE-PEG)对其表面进行修饰,发现多达90%的基因可被细胞摄取.     

Dichroism of absorption and polarization of phosphorescence of molecules of the closed form of nitrobenzospirothiopyran

The spectral-polarization characteristics of absorption and phosphorescence of molecules of the initial form of nitro-substituted indolinospirobenzothiopyran were studied in oriented polyethylene films and in solutions with different polarity. An oscillator model of the electron transitions responsible for the formation of absorption and luminescence spectra was suggested. It was established that the principal differences in the spectral and photophysical properties of the compound studied and its oxygen-containing analog are associated with the fact that the electronegativity of the S atom is lower than that of the O atom. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 6, pp. 1143–1146, June, 1997.     

非那雄胺合成工艺改进

非那雄胺能抑制5α-还原酶的活性,明显降低二氢睾酮水平,是一种治疗良性前列腺增生的有效药品。该合成工艺以甾烯酮酸为原料,将其与氯化亚砜反应,无须分离即与叔丁胺反应得17β-酰胺化合物,再氧化开环,环合,氢化,脱氢合成了非那雄胺。经元素分析、IR、1HNMR、13CNMR、MS分析表征了其结构。该法无须使用昂贵的2,2-二吡啶二硫化物和剧毒药品苯亚硒酸酐,且以乙酸铵代替氨气,降低了对设备的要求和腐蚀,更适用于工业生产。     

Determination of heats of detonation and influence of components of composite explosives on heats of detonation of high explosives

The heats of detonation of 20 simple high explosives and explosive mixtures were determined by means of an adiabatic detonation calorimeter designed by the authors. The results indicated that the performance of the instrument was reliable and the experimental data were very accurate. For explosive mixtures, there was a linear accumulative relationship between the heats of detonation of the explosive mixture and its components. Accordingly, the heats of detonation of explosive mixtures could be calculated directly from the heats of detonation of simple explosives and the characteristic heats of other components. The experiments showed that the gold or brass shell of the cylindrical charge could be substituted by a thick-walled porcelain shell, which had the advantage of cheapness.

     

Synthesis of phenolic components of Grains of Paradise

Two vanilloids, (5E)-8-(4-hydroxy-3-methoxyphenyl)oct-5-en-4-one (1) and 4-[3-hydroxydecyl]-2-methoxyphenol (2), isolated from the dried seeds of Grains of Paradise (Aframomum melegueta), were synthesized; the latter compound was made as the S-enantiomer and the material derived from the seeds was found to be a 1:1.7 mixture of the R and S isomers. The synthetic route used should allow the preparation of analogs having extended alkyl chains and consequently different lipophilicity, and 3, a homolog of 2, was also prepared.     

Summary of development of the theory of stability of colloids and thin films

In this review, the research of the author in the field of colloidal systems is summarized. The factors influencing colloidal stability are systematized and analyzed. Examples are presented to illustrate the practical utilization of the theory of stability of colloids and thin films.This review was prepared on the basis of the works of the author, which were awarded the State Premium for 1991 in the field of science and technology, chemistry section.Institute of Physical Chemistry, Russian Academy of Sciences, 117915 Moscow. Translated from Izvestiya Akademii Nauk, Seriya Khimicheskaya, No. 8, pp. 1708–1717, August, 1992.     

Study of hydration of two cements of different strengths

Main hydration products of two cement pastes, i.e. CSH-gel, portlandite (P) (and specific surface S) were studied by static heating, and by SEM, TEM and XRD, as a function of cement strength (C-33 and C-43) hydration time (th) and subsequent hydration in water vapour.Total change in mass on hydration and air drying, M_o, increased with strength of cement paste and with hydration time. Content of water escaping at 110 to 220°C, defined as water bound with low energy, mainly interlayer and hydrate water, was independent on cement strength but its content increased with (th). Content of chemically bound (zeolitic) water in CSH-gel, escaping at 220-400°C, was slightly dependent on strength and increased with (th). It was possibly derived from the dehydroxylation of CSH-gel and AFm phase. Portlandite water, escaping at 400-500°C, was independent on cement strength and was higher on longer hydration. Large P crystals were formed in the weaker cement paste C-33. Smaller crystals were formed in C-43 but they increased with (th). Carbonate formated on contact with air (calcite, vaterite and aragonite), decomposed in cement at 600-700^oC. It was high in pastes C-33(1 month) and C-43(1 month), i.e. 5.7 and 3.3%, respectively; it was less than 1% after 6 hydration months (low sensitivity to carbonation) in agreement with the XRD study showing carbonates in the air dry paste (1month), and its absence on prolonged hydration (6 months) and on acetone treatment. Water vapour treatment of (6 months) pastes or wetting-drying increased this sensitivity.Nanosized P-crystals, detected by TEM, could contribute to the cement strength; carbonate was observed on the rims of gel clusters.This revised version was published online in November 2005 with corrections to the Cover Date.     

氯氧化镁生成热的研究

用氧化镁氯化镁水溶液制备了8水合氯氧化镁[nMg(OH)2·MgCl2·8H2O], 并测定了其在盐酸中的溶解热, 实验结果表明, 氯氧化镁溶解热与n值呈线性关系, 根据溶解热求出5Mg(OH)2·MgCl2·8H2O和3Mg(OH)2·MgCl2·8H2O的生成热分别为-7727.1和5888.1kJ·mol^1^-。     

Thermodynamics of the formation of oxosulfides of rare-earth elements

The enthalpies of solution of several oxosulfides of rare-earth elements and the high-temperature enthalpies of oxosulfides and oxosulfates of lanthanum and yttrium were measured using solution calorimetry and high-temperature microcalorimetry techniques. Standard enthalpies of formation and some thermodynamic properties of oxosulfides and oxosulfates were calculated. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 2 pp. 294–297, February, 1997.     

恶臭嗅辨实验室建设探讨

针对恶臭测试的环境影响问题,提出了解决的实例方案,并对方案的要点及优缺点进行讨论,此方案在实际操作中具有较好的效果。