矿物中药自然铜的组成与热稳定性研究

采用X射线粉末衍射、热重-差热分析、等离子体发射光谱等分析手段, 对不同产地自然铜和煅自然铜的结构组成、热稳定性和微量元素进行测定和分析. 结果表明: 自然铜的主要物相为FeS2, 煅自然铜则因产地而异, 出现了FeS2(南京中医药大学样品中约86%, 湖南89%, 四川32%, 山西19%), FeS(湖南11%, 安徽24%, 四川24%), Fe3O4(安徽29%), Fe2O3(安徽14%)和FeO(OH) (南京中医药大学14%, 山西74%)等复杂物相. 自然铜在加热到450～800 ℃时, 逐渐发生了由FeS2转变为FeS的相变. 在这些药材中含有丰富的与人体健康密切相关的微量元素, 既含有对人体有益的Ca, Fe, Zn等微量元素, 也含有As, Cd, Pb等有害微量元素. 实验结果为该矿物药的鉴定和评价提供了科学数据.     

新型介孔羟基磷灰石/壳聚糖-万古霉素药物释放系统复合材料的制备及体外抗菌和成骨能力

采用冷冻干燥法合成了介孔羟基磷灰石(HA)/壳聚糖(CS)-万古霉素(VCM)药物释放系统复合材料, 利用SEM, XRD和FTIR等方法对材料进行了表征. 结果证实CS与HA混合复合材料具有良好的孔径和孔隙率, 万古霉素吸附于复合材料的表面和内部. 细胞毒性实验[噻唑蓝(MTT)比色法]结果表明, 材料可以促进成骨细胞增殖且具有良好的细胞相容性. 体外抑菌实验结果证实此材料可长时间抑制耐甲氧西林金葡菌(MRSA)的生长, 具有良好的抑菌和杀菌能力. 细胞黏附实验结果表明, 成骨细胞附着于材料表面增殖并通过孔道延伸. 实时聚合酶链式反应(RT-PCR)实验结果表明, 在成骨相关标志产物胶原蛋白-1(COL-1)及骨形态发生蛋白-2(BMP-2)基因上均有较高的表达, 表明材料在体外可以促进成骨细胞生长, 具有良好的成骨能力.     

钛材表面疏水图案化对成骨细胞生长的影响

本文通过共沉淀法合成纳米羟基磷灰石,然后采用电泳沉积法在钛材表面沉积羟基磷灰石涂层,并通过氟硅烷浸泡法构建疏水化图案,对制得的样品采用透射电镜、扫描电镜、X射线衍射、红外光谱仪、接触角测量仪进行表征,并与成骨细胞共培养,采用MTT、ALP法检测疏水图案对成骨细胞生长的影响。结果表明,本实验成功在钛材表面构建了疏水图案,且这种图案对成骨细胞生长有一定的抑制作用,通过构建不同的疏水图案,可以达到调控成骨细胞生长方向的作用。     

DyCl_3对原代培养的成骨细胞增殖、分化和矿化功能表达的影响(英文)

采用MTT法、碱性磷酸酶活性测定、油红O的染色和定量测定、矿化功能的测定以及qRT-PCR等手段在细胞和分子水平上研究了DyCl3对原代培养的成骨细胞增殖、分化和矿化功能的影响。研究结果表明,在测试浓度范围内,DyCl3均抑制成骨细胞增殖。浓度为1×10-8,1×10-6和1×10-5mol·L-1的DyCl3促进成骨细胞分化。在测试浓度范围内,DyCl3均抑制成骨细胞横向分化为脂肪细胞。浓度为1×10-5mol·L-1的DyCl3促进成骨细胞矿化结节的形成,而浓度为1×10-7mol·L-1和1×10-6mol·L-1的DyCl3抑制成骨细胞矿化结节的形成,进一步降低浓度为1×10-8mol·L-1,它则对成骨细胞矿化功能没有影响。浓度1×10-6mol·L-1的DyCl3显著降低PPAR-γmRNA表达水平,但相同浓度DyCl3则显著上调RUNX-2mRNA表达水平。实验结果提示,DyCl3对体外培养的成骨细胞增殖、分化及矿化功能的影响与浓度和作用时间有关,而且,它们是影响其生物效应从毒性到活性,从损伤到保护,从上调到下调转变的关键因素。这些结果对深入理解稀土离子对骨代谢的影响具有重要的价值。     

壳聚糖微图形的制备及表征

通过微转移模塑法, 在硅片表面制备了圆形点阵、 方形点阵、 沟槽和波浪等4种形貌的壳聚糖(CS)微图形. CS微图形清晰规整, 成型效果良好. 成骨细胞在圆形点阵和方形点阵上借助伪足多攀附于点阵凸起处. 点阵图形对细胞增殖和分化无影响. 在沟槽和波浪微图形中, 成骨细胞大多被限制在沟区, 且沿着沟槽方向伸展. 沟槽和波浪微图形不利于细胞分化, 但能促进细胞增殖.     

肾上腺髓质素微球复合PLGA/纳米羟基磷灰石支架材料的制备及生物活性评价

利用离子乳化交联法制备了负载肾上腺髓质素的壳聚糖微球,应用热致相分离法制备了乳酸和乙醇酸共聚物/纳米羟基磷灰石(PLGA/nHA)支架材料并在其中包覆载药微球.通过扫描电子显微镜、体外释放行为、材料溶血行为、碱性磷酸酶(ALP)活性的测定、支架材料表面细胞荧光染色和MTT[3-(4,5-二甲基噻唑-2)-2,5-二苯基四氮唑溴盐]比色法等手段综合评价载药支架材料的性能及生物活性.结果表明,微球直径均匀,载药支架孔径大小合适并相互穿通.支架材料的溶血率小于5%,符合医用材料的溶血实验要求.载药支架及支架材料本身对成骨细胞及血管内皮细胞的增殖以及成骨细胞的分化均有一定的促进作用.     

UO22+对某些细胞毒性的初探

建立了由多种金属离子和小分子配体组成的多相细胞液热力学平衡模型,模拟研究了UO22+在组织液和细胞液的形态。体外培养了SD大鼠成骨细胞和人肾小管上皮细胞,通过体外细胞生长抑制实验探索了UO22+对成骨细胞及肾小管上皮细胞的毒性。研究表明,在细胞液中,当各形态UO22+物质总浓度[U]=8.4×10-6mol/L时,当pH为6.0～6.5时,UO22+主要以固相(UO2)3(PO4)2存在,当pH为6.8～7.5时,UO22+主要以水溶性[UO2(CO3)3]4-存在;当[U]=1.3×10-3mol/L时,在整个细胞液pH范围内,固相(UO2)3(PO4)2占主导地位。体外细胞生长抑制实验表明,UO22+对成骨细胞的生长具有抑制作用,能显著降低肾小管上皮细胞的存活率,具有明显的细胞毒性。     

中药黄芩中神经氨酸酶抑制剂的超滤质谱筛选研究

采用超滤质谱分析技术, 结合体外酶活性实验方法, 从传统中药黄芩提取物中筛选神经氨酸酶抑制剂. 研究结果表明, 中药黄芩提取物具有较强的神经氨酸酶抑制活性, 利用超滤质谱方法从中筛选并鉴定出了六种具有潜在神经氨酸酶抑制活性的化合物, 为开发神经氨酸酶抑制剂提供了实验依据.     

聚乳酸/聚苯胺/富勒烯静电纺丝纤维的制备与表征

以富勒烯C_(60)作为聚苯胺的导电掺杂剂,采用乳液聚合-复合法制备了聚乳酸/聚苯胺/富勒烯复合体系(PLA81/PANI14/C_(60)5),并对其结构和性能进行了表征与理论分析.通过静电纺丝-编织法制备了PLA/PANI/C_(60)导电纤维管.利用555定时器原理设计自制了多谐振荡信号的电刺激装置,将其用于导电纤维管的细胞培养,以考察电刺激作用下导电纤维管上成骨细胞的生长和增殖情况.结果表明,PLA/PANI/C_(60)薄片的电阻率为104Ω·cm数量级;C_(60)能够促进苯胺乳液聚合的链增长,提高聚苯胺产物的聚合度;PLA/PANI/C_(60)纤维管形貌规整,具有良好的亲水性;在18μA/1 Hz/500 ms电刺激的作用下,PLA/PANI/C_(60)纤维对成骨细胞的生长具有明显的促进作用.加载适当电流电刺激能够加强生长因子对成骨细胞的分化作用,有利于促进成骨细胞的生长和繁殖.     

Fe3+和Fe2+对原代培养的成骨细胞增殖、分化和矿化功能的影响

采用噻唑蓝(MTT)法、碱性磷酸酶(ALP)比活性测定、油红O染色和茜素红染色及定量分析,研究了不同浓度的Fe3+和Fe2+对原代培养的成骨细胞增殖、分化及矿化功能的影响.结果表明:浓度为1×10-9～1×10-4 mol·L-1的Fe3+和Fe2+促进成骨细胞增殖,但是在较高浓度1×10-3 mol·L-1时,它们则抑制成骨细胞增殖.与成骨细胞作用48 h,浓度为1×10-8～1×10-4 mol·L-1的Fe3+和Fe2+抑制其分化,但在较低的浓度1×10-9 mol·L-1时则对其分化没有影响:进一步延长作用时间为72 h,Fe3+对成骨细胞分化没有影响,除1×10-6mol·L-1浓度的Fe2+促进成骨细胞分化外,其他浓度的Fe2+则抑制其分化;测试浓度下的Fe3+对成骨细胞向脂肪细胞的横向分化表现为抑制或没有影响,而Fe2+的影响则依赖于浓度和作用时间.在1×10-8～1×10-5mol·L-1浓度范围内,Fe3+和Fe2+对矿化结节的影响表现出相反的效应.在较高浓度(1×10-4mol·L-1)下,它们促进矿化节结的形成,而在较低浓度(1×10-9mol·L-1)下,Fe3+抑制矿化节结的形成,Fe2+则没有影响.结果提示:浓度.作用时间和铁离子的价态都是影响Fe3+和Fe2+生物效应(从毒性到活性,从损伤到保护,从上调到下调)转变的关键因素.     

二氧化碳和丙烯直接合成甲基丙烯酸的NiPMo/TiO2催化剂的研究

用溶胶-凝胶法以磷钼酸(MPA)的镍盐溶液水解钛酸四丁酯制备了NiPMo/TiO2催化剂.使用ICP、 XRD、 TG-DTA、 IR、 TPD-MS和微反应技术研究了催化剂的化学组成、热稳定性、化学吸附性质和催化反应性能.杂多钼酸盐与TiO2通过O2-在TiO2表面发生了键合.在623 K下,杂多阴离子仍保持原有的Keggin结构.CO2在Lewis酸位Ni(Ⅱ)和Lewis碱位Ni-O-Mo的桥氧协同作用下生成CO2卧式吸附态Ni(Ⅱ)←O-(CO)←(O--Ni).丙烯有多种吸附态在催化剂上吸附.在563 K、 1 MPa和空速1500 h-1的反应条件下,丙烯的摩尔转化率为3.2%,产物MAA选择性为95%.     

CoFe2O4自形成磁性液体场致结构化对磁化的影响

The Langevin paramagnetic theory can’t describe the relation between magnetization of ferrofluids and applied magnetic field. The structuralization of ferrofluids, which is considered the main influence factor of the magnetization, is regarded. The part of magnetization works is deposited when the structure is forming. This action influences the magnetization of ferrofluids directly or indirectly. On the base of the “compressing” model, the Langevin function that usually describes the magnetization of ferrofluid is modified, and a well-fitted curve is obtained. An equation of the relation between the equivalent volume fraction after being “compressed” and the intensity of magnetic field is discovered, which approximately describes the process of magnetization. The relation between the approximate initial susceptibility and the volume fraction can be obtained from modified formula.     

Highly regioselective Buchwald–Hartwig amination at C-2 of 2,4-dichloropyridine enabling a novel approach to 2,4-bisanilinopyridine (BAPyd) libraries

The highly regioselective Buchwald–Hartwig amination at C-2 of the cheap and readily accessible reagent, 2,4-dichloropyridine with a range of anilines and heterocyclic amines is described. This new methodology is robust and provides a facile access to 4-chloro-N-phenylpyridin-2-amines on 0.25 mol scale. These intermediates undergo a further Buchwald–Hartwig amination at higher temperature to enable rapid exploration of the chemical space at C-4 and to provide a library of 2,4-bisaminopyridines.     

Sulfur-directed metal-free and regiospecific methyl C(sp3)–H imidation of thioanisoles

Regiospecific and direct imidation of the methyl C(sp³)–H bond of thioanisoles is realized under mild and metal-free conditions with N-fluorobis(benzenesulfonyl)imide as an oxidant and nitrogen source. Proposed mechanism suggests that thionium ion intermediates and a Pummerer-type reaction are involved. The imidation has advantages such as high step-economy, excellent functionality tolerance, and regiospecificity, giving structurally diverse imidation products.     

Selective syntheses of 2H-1,3-oxazines and 1H-pyrrol-3(2H)-ones via temperature-dependent Rh(II)-carbenoid-mediated 2H-azirine-ring expansion

The Rh(II)-catalyzed reaction of 2-carbonyl-substituted 2H-azirines with ethyl 2-cyano-2-diazoacetate or 2-diazo-3,3,3-trifluoropropionate provides an easy access to 2H-1,3-oxazines and 1H-pyrrol-3(2H)-ones. These compounds can be selectively prepared from the same starting material using temperature as the only varied parameter. The 2-azabuta-1,3-diene intermediate, a common precursor for both heterocyclic products, isomerizes into 2H-1,3-oxazine under kinetic control, while 1H-pyrrol-3(2H)-one is the sole product of the reaction at elevated temperatures. According to DFT-calculations a one-atom oxazine ring contraction involving ring-opening to a 2-azabuta-1,3-diene intermediate, followed by a 1,5- and 1,2-prototropic shift leads to the consecutive formation of imidoylketene and azomethine ylide, which then further undergo cyclization to the pyrrole derivative.     

Copper catalyzed/mediated synthetic methodology for ebselen and related isoselenazolones

Scope of the copper catalyzed/mediated selenium-nitrogen coupling reaction has been studied for the synthesis of isoselenazolones. It is noticed that the 2-chloro, 2-bromo-, and 2-iodo-aryl amides substrates can be exploited in the selenium-nitrogen coupling reaction by employing 25-100 mol % of CuI/1,10-phenanthroline (L) and potassium carbonate as a base in DMF. Furthermore, electron rich 2-chloro-arylamides also underwent selenium-nitrogen coupling reaction to give biologically important selenium-nitrogen heterocycles. Also, copper-catalyzed selenium-nitrogen coupling reaction has been meticulously applied for the synthesis of diaryl diselenides having methoxy, amine, and amide functionality from respective aryl iodides in the presence of stoichiometric amount of succinimide as an external Se-N coupling partner.     

Knoevenagel condensation catalyzed by novel Nmm-based ionic liquids in water

A series of novel N-methyl morpholine (Nmm) based ionic liquids with 1,2-propanediol group were synthesized and used as catalysts for Knoevenagel condensation at room temperature in water. Under the effect of the catalyst, various aldehydes or aliphatic ketones could react with a wide range of activated methylene compounds well, including malononitrile, alkyl cyanoacetate, cyanoacetamide, β-diketone, barbituric acid, 2-arylacetonitrile and thiazolidinedione. Furthermore, most of the products could be separated just by filtrating and washing with water. Additionally, the catalyst is recyclable and applicable for the large-scale synthesis.     

Construction of polyheterocyclic spirotetrahydrothiophene derivatives via sulfa-Michael/aldol cascade reaction

A series of polyheterocyclic spirotetrahydrothiophene derivatives were obtained in moderate to excellent yields via a catalyst-free sulfa-Michael/aldol cascade reaction of chalcones 1 and commercially available 1,4-dithiane-2,5-diol 2 under mild conditions. We also present the first asymmetric sulfa-Michael/aldol cascade reaction of chalcones 1 and commercially available 1,4-dithiane-2,5-diol 2 with moderate to good enantioselectivities catalyzed by readily available chiral phase-transfer catalysts (PTCs).     

Suzuki-Miyaura reactions of the soluble guanylate cyclase inhibitor NS2028: a non-product specific route to C-8 substituted analogues

Both soluble guanylate cyclase (sGC) inhibitors ODQ 1 and NS2028 2 are synthesized via improved protocols. In the former case treating 3,4-dihydroquinoxalin-2(1H)-one oxime 8, which can be prepared in two steps from 1,2-benzenediamine, with 1,1′-carbonyldiimidazole (CDI) gives the dihydro-ODQ 10 that in the presence of KMnO₄ oxidises to give ODQ 1 in an overall yield of 46% starting from 1,2-benzenediamine. In the latter case, the synthesis affords NS2028 2 from 2-amino-4-bromophenol 3 in three steps with an overall yield of 85% and avoids the need for chromatography. Furthermore, Suzuki-Miyaura reaction conditions are described that enable the preparation of 8-aryl and 8-heteroaryl derivatives of NS2028 directly from NS2028 2. Finally, demethylation of the 8-(methoxyphenyl) substituted analogues afforded the 8-(hydroxyphenyl) derivatives 40-42. All new products are fully characterised.