聚[碳酸(亚丁酯-co-ε-己内酯)酯]的制备及其载药微球性能的研究

采用阴离子配位聚合方法, 合成了二氧化碳、1,2-环氧丁烷与ε-己内酯的三元共聚物: 聚[碳酸(亚丁酯-co-ε-己内酯)酯](PBCL). 并采用复相乳液(W/O/W)溶剂挥发法制备了包裹抗菌药物甲磺酸帕珠沙星的可降解微球. 对聚合物进行了FTIR, ¹H NMR, ¹³C NMR, DSC, TGA和WAXD等表征, 以及降解性能和载药微球特性的研究. 结果表明, PBCL热稳定性及降解性能优于聚碳酸亚丁酯(PBC). 所得PBCL微球球形规整、表面光滑. 大部分微球粒径在0.5～1 μm的范围内, 载药量和包封率分别达到38.21%和87.9%. 微球的体外释药性能研究在pH 7.4的磷酸缓冲溶液中进行, 释放21 d后, PBCL微球的累积释药量为84.74%, PBC微球的释药量仅为17.29%. 药物的体外释放行为符合Higuchi方程. PBCL载药微球具有长效缓释作用.     

温度敏感性壳聚糖基聚电解质载药纳米粒子的制备及表征

以天然高分子壳聚糖(CS)、羧甲基纤维素(CMC)和温度敏感性单体N-异丙基丙烯酰胺(NIPAM)为原料,通过自组装制备了温度敏感性聚电解质复合纳米粒子CS-g-PNIPAM/CMC-g-PNIPAM,并以5-氟尿嘧啶(5-FU)为模型药物研究了纳米粒子对药物的负载与可控释放性能。当CMC-g-PNIPAM与CS-g-PNIPAM的质量比为3:7时,形成的纳米粒子结构最稳定,动态光散射(DLS)测得其平均粒径为116nm,粒径分布较窄。载药纳米粒子对5-FU具有较高的载药量和包封率。在磷酸盐缓冲溶液中的释药行为表明,其累积药物释放量随pH和温度的增加而增大,表现出良好的pH与温度可控性能。     

水包油包固体乳化法制备蛋白药物缓释微球

以牛血清白蛋白(BSA)为模型药物, 研究了一种新型载药微球的水包油包固体(S/O/W)乳化法. 用纳米尺寸的SiO2吸附溶液中的BSA, 得到粒径约为30 nm的含药粒子, 再用PLGA包裹含药粒子. 考察不同制备条件对载药量和包封率的影响, 并与传统的双乳法(W/O/W)进行了对比, 发现该制备方法提高了药物的载药量(由2.5%到3.1%)和包封率(由72%到90%以上), 同时提高了药物活性.     

可生物降解固体脂质纳米粒的制备、表征及药物的体外释放

以可生物降解材料硬脂酸为载体, 以葛根总黄酮为模型药物, 采用乳化蒸发-低温固化法制备固体脂质纳米粒. 采用透射电镜研究载药纳米粒形态, 激光粒度分析仪测定其粒径, X射线衍射仪进行物相鉴别, 并对纳米粒的包封率及体外释药特性等进行了研究. 分析结果表明, 所制备硬脂酸固态脂质纳米粒为类球实体, 粒径分布比较均匀, 平均粒径为(263.82±3.6) nm, 包封率为(67.53±0.12)%. X射线衍射分析证明药物以分子或细小粒子分散于脂质骨架中. 体外释药研究结果表明, 纳米粒体外释药先快后慢, 12 h累积释药50%, 包封于降解材料骨架内的药物通过骨架溶蚀缓慢释放. 药物的体外释放符合Higuchi方程.     

以电化学方法在离子液体[DEME][BF4]中合成铂纳米粒子

通过恒电位电沉积法在离子液体N,N-二乙基-N-甲基-N-（2-甲氧基乙基）铵四氟硼酸铵（[DEME][BF₄]）中,在玻碳电极上制备了铂纳米颗粒。首先探究了不同沉积电势和不同沉积时间对铂纳米粒子微观形貌的影响,由SEM和TEM图发现在-2.5 V下沉积480 s制备的铂纳米粒子的平均粒径约为2.38 nm。使用高分辨率透射电子显微镜（HRTEM）和电子衍射（SAED）对其晶体结构进行表征,证明了铂纳米粒子为面心立方（fcc）晶体结构。在硫酸中测试铂纳米粒子的催化性能,发现其暴露出明显的（110）和（100）晶面。进一步对铂的电沉积行为进行研究发现,Pt（Ⅳ）的两步还原是由扩散过程和电化学过程共同控制。     

酸性离子液体中铂纳米粒子的制备、表征及应用

基于功能化离子液体的特性,开发出不使用聚合物保护剂制备铂纳米粒子并同时获得具有金属和酸活性中心双功能催化剂的新方法。首先,设计并合成出了一种新型季铵型质子(Br?nsted)酸性离子液体(N, N, N-三甲基-N-磺丁基硫酸氢铵([HSO₃-b-N(CH₃)₃]HSO₄)),然后,利用化学还原方法在该离子液体中制备了金属铂纳米粒子,并采用紫外光谱、傅立叶红外光谱、X-光电子能谱、透射电子显微镜和X射线衍射等方法对所制备的金属铂纳米粒子进行了结构表征。结果表明,所制备的铂纳米粒子具有面心立方结构,离子液体作为修饰剂修饰在铂纳米粒子的表面,有效地阻止了铂纳米粒子的团聚;将该含有铂纳米粒子的酸性离子液体作为双功能催化剂,直接用于硝基苯加氢合成对氨基苯酚反应,发现其具有良好的催化性能,在85 ℃、4 h、0.4 MPa条件下,硝基苯转化率为98.6%,对氨基苯酚收率为75.8%,回收的酸性离子液体纳米铂双功能催化体系中铂纳米粒子依然具有很好的分散性和稳定性。     

以电化学方法在离子液体[DEME][BF4]中合成铂纳米粒子

通过恒电位电沉积法在离子液体N,N-二乙基-N-甲基-N-（2-甲氧基乙基）铵四氟硼酸铵（[DEME][BF₄]）中,在玻碳电极上制备了铂纳米颗粒。首先探究了不同沉积电势和不同沉积时间对铂纳米粒子微观形貌的影响,由SEM和TEM图发现在-2.5 V下沉积480 s制备的铂纳米粒子的平均粒径约为2.38 nm。使用高分辨率透射电子显微镜（HRTEM）和电子衍射（SAED）对其晶体结构进行表征,证明了铂纳米粒子为面心立方（fcc）晶体结构。在硫酸中测试铂纳米粒子的催化性能,发现其暴露出明显的（110）和（100）晶面。进一步对铂的电沉积行为进行研究发现,Pt （Ⅳ）的两步还原是由扩散过程和电化学过程共同控制。     

5-氟尿嘧啶/壳聚糖载药纳米微球的制备及性能

以三聚磷酸钠为交联剂,采用离子交联法制备了5-氟尿嘧啶/壳聚糖纳米微球,评价其性能、体外释药性能及对人肺癌细胞GLC-82的体外杀伤效应,并通过Zeta电位和红外光谱分析载药纳米微球形成机理.结果表明,所制备的5-Fu/CS纳米微球平均包封率为32.3%,平均载药量为25.6%,平均粒径为253nm,平均zeta电势为+8.38mV,成球性及分散性良好.CS载药纳米微球具有缓释性能,体外释药行为符合双向动力学规律.在体外作用72h,CS载药纳米微球对人肺癌细胞GLC-82的杀伤率达66.6%,杀伤效果明显优于5-Fu对照组.     

壳聚糖基多功能纳米药物载体的体外研究

制备了一种壳聚糖基多功能纳米药物载体系统, 并探讨了其体外释药性质. 合成了甲氨蝶呤-壳聚糖偶联物(MTX-CS), 甲氨喋呤(MTX)的取代度为6.3%; MTX-CS具有两亲性, 在水性介质中能自组装形成纳米粒子, 平均粒径为(269.5±18.3) nm, zeta电位为(25.7±0.9) mV. MTX-CS纳米粒子能有效包载抗血管生成药Combretastatin A-4(CA-4), 当药物/载体材料投料比为1∶4 时, 载药量为15.7%, 包封率为62.8%. 体外释放实验结果显示, CA-4释放较快, MTX释放缓慢, 有利于发挥2种药物的协同抗肿瘤作用.     

In vitro Studies of Chitosan-based Muitifunctional Drug Delivery Nanosystem

制备了一种壳聚糖基多功能纳米药物载体系统,并探讨了其体外释药性质.合成了甲氨蝶呤-壳聚糖偶联物(MTX-CS),甲氨喋呤(MTX)的取代度为6.3％;MTX-CS具有两亲性,在水性介质中能自组装形成纳米粒子,平均粒径为(269.5±18.3) nm,zeta电位为(25.7±0.9) mV.MTX-CS纳米粒子能有效包载抗血管生成药Combretastatin A-4(CA-4),当药物/载体材料投料比为1∶4时,载药量为15.7％,包封率为62.8％.体外释放实验结果显示,CA-4释放较快,MTX释放缓慢,有利于发挥2种药物的协同抗肿瘤作用.     

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%.     

Synthesis of 1-benzyloxypyrazin-2(1H)-one derivatives

Different approaches for the synthesis of 1-benzyloxypyrazin-2(1H)-one derivatives from simple amino acids have been investigated. A library of 33 precursors for the preparation of N-hydroxy pyrazinones was obtained in moderate to good yields.     

Toward new camptothecins. Part 6: Synthesis of crucial ketones and their use in Friedländer reaction

In the context of the preparation of camptothecin and luotonin A analogs, the synthesis of some key keto-precursors and their use in Friedländer condensation are described. This paper also focuses on the stability of these keto intermediates and emphasizes the major differences between indolizinones and pyrroloquinazolinones series. Noteworthy is also the report of some original structures isolated as by-products of some experiments.     

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.     

KMnO4-mediated oxidative CN bond cleavage of tertiary amines: Synthesis of amides and sulfonamides

KMnO₄-mediated oxidative CN bond cleavage of tertiary amines producing secondary amine was introduced, which was trapped by electrophiles (acyl chloride and sulfonyl chloride) to form amides and sulfonamides. The reaction could take place at mild condition, tolerating a wide range of function groups and affording products in moderate to excellent yields.     

Chemistry of heterocyclic compounds at the A. E. Favorsky Irkutsk Institute of Chemistry, Siberian Branch of the Russian Academy of Sciences, over 50 years (Review)

The review contains a concise historical account and information on the most significant researches undertaken by the staff at the A. E. Favorsky Irkutsk Institute of Chemistry, Siberian Branch of the Russian Academy of Sciences on the Chemistry of Heterocyclic Compounds. Dedicated to Academician of the Russian Academy of Sciences B. A. Trofimov on his 70th jubilee. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1443–1502, October, 2008.     

A general and convenient synthesis of 4-(tosylmethyl)semicarbazones and their use in amidoalkylation of hydrogen,heteroatom, and carbon nucleophiles

A general synthesis of previously unknown semicarbazone-based α-amidoalkylating reagents, 4-(tosylmethyl)semicarbazones, has been developed. The synthesis involved three-component condensation of semicarbazones of aliphatic or aromatic aldehydes with the same or other aldehydes and p-toluenesulfinic acid. The scope and limitations of this reaction were investigated. The compounds obtained were demonstrated to be an efficient α-(4-semicarbazono)alkylating agents. They were reacted with H- (sodium borohydride), O- (sodium methylate), S- (sodium phenylthiolate), N- (pyrrolidine, sodium succinimide), P- (trialkyl phosphites), and C-nucleophiles (sodium diethyl malonate) to give the corresponding products of the tosyl group substitution, 4-substituted semicarbazones, including analogues of nitrofurazone. Among the prepared compounds tested in vitro for antibacterial and antifungal activity, three nitrofuryl-containing semicarbazones exhibited high biological activities with minimum inhibitory concentration (MIC) values of 8–32 μg/mL.     

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.     

Synthesis of novel chiral bidentate hydroxyalkyl-N-heterocyclic carbene ligands and their application in palladium-catalyzed Mizoroki–Heck couplings and asymmetric addition of diethylzinc to benzaldehyde

A small library of new chiral bidentate hydroxyalkyl-imidazolium salts 1 is conveniently synthesized on multi-gram scale from inexpensive and commercially available chiral pool amino acids. The corresponding carbenes, generated by deprotonation of imidazolium salts 1, in combination with palladium(II) chloride were tested in the Mizoroki–Heck coupling reaction. The most significant results in terms of yields and reactivities were achieved with low catalyst loading. The catalytic activities of these imidazolium salts were also investigated in the asymmetric addition of diethylzinc to benzaldehyde. The use of MgO nanoparticles as an additive in conjunction with these ligands played a crucial role in increasing the efficiency of these reactions.