自组装共混制备PEG化基因载体

通过含PEG链段的两亲聚合物的自组装共混, 制备了基于疏水作用力的新型PEG化非病毒基因载体. 分别选用胆固醇-聚乙二醇和聚乙二醇-聚丙二醇-聚乙二醇作为共混改性剂, 研究两亲聚合物的种类对组装体在生理盐溶液中的稳定性及基因转染效率的影响. 结果表明, 疏水驱动力的大小是获得稳定的PEG化基因超分子组装体的关键. 通过对两亲聚合物中疏水链段的选择调控, 可制备稳定的PEG化基因超分子组装体, 提高基因传递体系在生理盐溶液中的稳定性及基因转染效率. 通过自组装共混, 为新型PEG化基因超分子组装体的制备提供了切实可行的新方法.     

巯基化透明质酸包封的仿生交联基因微载体的构建

采用超分子组装技术,通过巯基化透明质酸(HA-SH)与聚乙烯亚胺(PEI)/DNA缔合体的界面静电组装,构建了壳层二硫键仿生交联的基因超分子组装体(PEI/DNA/HA-SH).凝胶电泳结果表明,该组装体有很好的DNA缔合特性.壳层的仿生交联使基因超分子组装体在生理盐溶液中的稳定性得到有效改善,细胞毒性显著降低,并能有效转染细胞,为非病毒基因传递体系的设计提供了新途径.     

pH响应性ABC型共聚物的合成与溶液自组装

用单氨基聚乙二醇(m PEG-NH2)引发ε-三氟乙酰基-L-赖氨酸-N-羧酸酐(Lys(TFA)-NCA)开环聚合,得到了聚乙二醇-b-聚(ε-三氟乙酰基-L-赖氨酸)(PEG-b-PTLL)两嵌段共聚物.将PTLL链段末端的NH2与2-溴异丁酰溴反应得到了大分子引发剂,通过原子转移自由基聚合(ATRP)的方法分别分别引发苯乙烯(St)和N-异丙基丙烯酰胺(NIPAM)聚合,制备了结构明确、聚合度可控的聚乙二醇-b-聚(ε-三氟乙酰基-L-赖氨酸)-b-聚苯乙烯(PEG-b-PTLL-b-PS)和聚乙二醇-b-聚(ε-三氟乙酰基-L-赖氨酸)-b-聚(N-异丙基丙烯酰胺)(PEG-b-PTLL-b-PNIPAM)三嵌段杂化共聚肽.将PEG-b-PTLL-b-PNIPAM去保护后得到温度和p H响应三嵌段共聚物;将PEG-b-PTLL-b-PS去保护后得到p H响应的两亲性三嵌段共聚物.研究了PEG45-b-PLL106-b-PS20在混合溶剂H2O/DMF中的p H诱导胶束化行为.TEM结果表明,当水溶液p H小于PLL的p Ka时,PEG45-bPLL106-b-PS20形成球状胶束,当水溶液p H大于PLL的p Ka时,PLL转变成α-螺旋,PEG45-b-PLL106-b-PS20组装成盘状胶束.     

基于卤键的选择性吸附层层组装多层膜

以超支化聚乙烯亚胺为构筑基元、以卤键为推动力制备了可以选择性吸附带有负电荷小分子的层层组装多层膜. 为了将超支化聚乙烯亚胺引入多层膜体系中, 我们首先制备了接枝有卤键给体分子-碘全氟苯的超支化聚乙烯亚胺(BPEI-I). 然后将BPEI-I和含有卤键受体的聚(4-乙烯吡啶)(PVPy)在四氢呋喃和三氯甲烷的混合溶剂中组装成膜, 并用紫外可见光谱、AFM和XPS对膜的组装过程、形貌、厚度和推动力进行了表征. 制备得到的BPEI-I和PVPy多层膜可以吸附含有负电荷的2-蒽甲酸钠小分子, 而对有类似结构但带有正电荷的溴化-N-(2-蒽甲基)吡啶盐却没有吸附作用. 这种选择性吸附能力主要得益于包覆在多层膜中的超支化聚乙烯亚胺基元的正电荷空腔和由卤键构筑的弱极性微环境. 本文的研究为制备选择性吸附薄膜提供了一种新的思路, 在传感、富集分离和微接触印刷等领域都有潜在应用价值.     

莱啉酰亚胺类化合物的邻位C—H键功能化研究进展

莱啉酰亚胺是一类重要的功能有机染料.独特的缺电性共轭骨架与优异的光电性质使其成为多环芳烃家族中的重要成员,在有机场效应晶体管、有机光伏器件和生物医学传感等领域具有广阔的应用前景.对莱啉酰亚胺骨架的精准修饰不仅可以有效调控分子能级,还有利于实现分子间的可控组装,是高效创制新型π-分子材料的有效手段.早期,受合成方法的限制,莱啉酰亚胺骨架母核修饰的位点主要局限于电子云密度稍高的湾位,但在该位点引入取代基会扭曲π-平面,不利于π-分子之间的有效堆积.莱啉酰亚胺骨架邻位选择性修饰不影响母核的平面性,近年来受到广泛关注,催生出系列莱啉酰亚胺邻位C—H键功能化的新策略.根据成键类型不同,以苝二酰亚胺和萘二酰亚胺为例,系统总结了莱啉酰亚胺骨架邻位C—H键功能化的方法,以及邻位修饰对莱啉骨架光电性质和组装的影响.     

主客体组装构建环糊精修饰基因微载体的研究

合成了二茂铁接枝聚乙烯亚胺( PEI-Fc),利用二茂铁与β-环糊精的主客体嵌套作用制备了环糊精修饰聚乙烯亚胺,核磁测定结果显示,每条PEI-Fc链上通过主客体作用嵌套的CD平均为26个.这种基于弱相互作用力的β-环糊精修饰聚乙烯亚胺能有效诱导DNA分子的缔合,在N/P值达到3以上时,可形成表面为正电荷、粒径为150 ～ 250 nm的球形粒子.在含10％胎牛血清的DMEM体外细胞培养基中,由于培养基中的蛋白质能够在粒子表面发生静电吸附,PEI-Fc/CD/DNA基因微载体显示出良好的稳定性.HEK293细胞培养结果显示,以表达绿色荧光蛋白的质粒pEGFP为模型,以N/P值为10的PEI/DNA组装体作为对照,N/P值为3、5和10的PEI-Fc/CD/DNA组装体的转染效率均达到对照组的2～3倍,这种基于主客体组装构建的环糊精修饰基因微载体显著提高了基因转染效率.     

pH响应型苯硼酸酯缀合物的制备、表征和智能释放研究

以葡聚糖(Dextran)作为主链,将罗丹明B(Rh B,荧光智能释放药物模型/示踪显像)、3-羟基苯硼酸(PBA)酯化后,缀合到葡聚糖上,形成一种新型p H响应的高分子缀合物.由于该高分子缀合物中存在硼酸酯键,使得其负载模型药物到达肿瘤细胞的溶酶体之后释放出罗丹明B,不仅降低了药物毒性,还能够示踪药物的递送过程.体外模拟释放结果表明,缀合物在癌细胞的溶酶体/内涵体(p H 5)内能很好地释放出罗丹明B,而在药物输送过程(p H 7.4)中有很少的罗丹明B释放出来.另外,高分子载体葡聚糖的存在,使聚合物体现出良好的生物相溶性,从而减少了对正常组织的伤害,在抗癌药物的智能释放方面具有很好的应用前景.     

刺激响应共负载药物/基因微载体的制备

合成了聚乙烯亚胺接枝二茂铁(PEI-Fc)两亲聚合物, 采用水包油法制备包埋疏水性抗癌药阿霉素(DOX)的载药胶束, 并利用胶束表面正电荷的PEI链段有效缔合DNA, 获得尺寸合适、 表面带正电荷的阿霉素与基因共负载微载体. 在磷酸盐(PBS)缓冲溶液中, 共负载微载体能够缓慢释放出DOX. 在硝酸铈铵存在下, 二茂铁从疏水性转变为亲水性, 使载药胶束完全解离, 由于PEI-Fc与DNA之间的静电作用, 使基因超分子组装体稳定存在, 显示出很好的氧化响应特性. 细胞培养结果表明, 表面带正电荷的共负载微载体易被HepG2细胞内吞, 并可转染, 且随着DOX的释放逐渐杀死HepG2肝癌细胞, 为安全稳定、 具有刺激响应的药物与基因共负载微载体的制备提供了可行的途径.     

罗丹明B与基因共负载纳米粒子的制备与性能

药物/基因共负载的智能微载体的制备是肿瘤多元复合治疗的关键科学问题。本文以疏水性荧光染料罗丹明B为模型药物,采用聚乙烯亚胺－接枝－胆固醇两亲聚合物作为药物载体,成功制备了罗丹明与基因共负载的超分子组装体。通过组装条件的调控,获得了尺寸为150 nm、表面电位33 mV的球形纳米粒子,并依然具有很好的DNA缔合特性。细胞培养结果表明：表面正电荷的罗丹明与基因共负载纳米粒子很容易被细胞内吞,并能有效转染细胞,为高效安全的药物/基因共负载微载体的制备提供了切实可行的途径。 关键词 非病毒基因载体;超分子组装;药物/基因共负载     

单根DNA短链构筑pH响应超分子水凝胶

设计合成了一条包含两段自互补序列和一段富含胞嘧啶(C)序列的DNA单链.在碱性条件下,两段自互补序列可通过分子间自组装形成一维DNA纳米线,调节p H至酸性条件后,胞嘧啶序列通过形成双分子i-motif结构将纳米线交联,从而形成DNA水凝胶.当加入酸或碱调节体系的p H时,水凝胶的力学强度会发生变化.在p H为5.3时,水凝胶力学强度达到最大,增大或减小p H都会使水凝胶强度降低.同时,改变DNA单链浓度也能够调节水凝胶的力学强度.此凝胶制备过程原料合成简便,无需涉及不同DNA链定量配比的问题,大大简化了实验操作;另外i-motif结构在形成与解离两态之间的转换非常迅速,在几秒钟之内便可完成,也赋予该凝胶快速p H响应的特性.     

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%.     

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.     

α-Amino acid derived enaminones and their application in the synthesis of N-protected methyl 5-substituted-4-hydroxypyrrole-3-carboxylates and other heterocycles

A new and simple synthesis of novel N-protected methyl 5-substituted-4-hydroxypyrrole-3-carboxylates, which exist in equilibrium with their 4-oxo tautomers, has been developed in two steps starting from N-protected α-amino acids. The key intermediates are enaminones, which can also be isolated, characterized, and used for the construction of other functionalized heterocycles, before they spontaneously decompose to pyrrole products. 4-Hydroxypyrroles are prone to partial aerial oxidation but can be efficiently alkylated or reduced to stable polysubstituted pyrrolidine derivatives.     

Specific intramolecular aromatic CH insertion of diazosulfonamides

The chemoselectivity in the intramolecular CH insertion of various diazosulfonamides has been experimentally studied. The results reveal that the aliphatic 1,4-, 1,5-, or 1,6-C(sp³)?H insertions of diazosulfonamides are not accessible, while the aromatic 1,5-C(sp²)?H insertion can be realized specifically by adjusting the diazo-adjacent group. In addition, the general chemoselectivities in the intramolecular CH insertions of diazosulfonyl compounds are summarized. Generally, diazosulfones undergo both aromatic 1,5-C(sp²)?H and aliphatic 1,5- and 1,6-C(sp³)?H insertions, while diazosulfonates undergo aliphatic 1,5- and 1,6-C(sp³)?H insertions. However, diazosulfonamides only undergo aromatic 1,5-C(sp²)?H insertion.     

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.     

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.     

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.     

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.     

N-Heterocyclic carbene-palladacyclic complexes: synthesis,characterization and their applications in the C-N coupling and α-arylation of ketones using aryl chlorides

N-Heterocyclic carbene-palladacyclic complexes 3 were successfully achieved in a one-pot procedure under mild conditions. The structure of 3a was unambiguously confirmed by X-ray single crystal diffraction and it was an active catalyst in the Buchwald-Hartwig amination and α-arylation of ketones even at very low catalyst loadings (0.01?mol%).     

Iodine-mediated oxidative Pictet-Spengler reaction using terminal alkyne as the 2-oxoaldehyde surrogate for the synthesis of 1-aroyl-β-carbolines and fused-nitrogen heterocycles

An efficient iodine-mediated oxidative Pictet-Spengler reaction in dimethyl sulphoxide (DMSO) using terminal alkynes as the 2-oxoaldehyde surrogate for the synthesis of aryl (9H-pyrido[3,4-b]indol-1-yl)methanones is described. The scope of the protocol includes the total synthesis of Fascaplysin, Eudistomins Y₁ and Y₂. The methodology is extended for preparing pyrrolo[1,2-a]-quinoxaline and indolo[1,5-a]quinoxaline derivatives. The utility of 1-aroyl-β-carbolines was demonstrated by performing palladium-catalyzed β-carboline directed ortho-C(sp2)-H functionalization of the phenyl ring with thiomethyl (SMe) group using DMSO as source and for accessing 4-aryl-canthin-6-ones.