多重响应性超支化星形聚合物的合成与组装以及控制释放研究

含二硫键的自引发单体与2-(2-甲氧基乙氧基)乙基甲基丙烯酸酯(MEO₂MA)进行自缩合乙烯基共聚合得到超支化PMEO₂MA(H-PMEO₂MA). 以它作大分子引发剂, 引发二甲氨基乙基甲基丙烯酸酯(DMAEMA)进行原子转移自由基聚合, 合成了具有温度、pH以及氧化还原多重响应性的超支化星形聚合物H-PMEO₂MA-star-PDMAEMA. 证明了H-PMEO₂MA有低临界溶液温度(LCST); 研究了PDMAEMA 链段的长度和溶液的pH值对超支化星形聚合物的LCST的影响. 当H-PMEO₂MA-star-PDMAEMA水溶液温度从2 ℃升高至室温, H-PMEO₂MA变成疏水性而发生聚集, 形成以H-PMEO₂MA为核, PDMAEMA为壳的胶束. 在胶束形成过程中, 将尼罗红装载到这种聚合物胶束中, 形成释药系统, 研究了pH、氧化还原响应性释药性能.     

pH响应性超支化星形共聚物的合成及基因转染研究

通过两步ATRP制备了两亲性p H响应性超支化星形共聚物HP(DMAESP-co-BS2MOE)-(POEGMA)n.首先,以2-(2'-溴异丙酰氧基)乙基2″-甲基丙烯酰氧基乙基二硫化物(BS2MOE)为自引发单体,与甲基丙烯酰氧基-3-硫代己酸二甲氨基乙酯(DMAESP)共聚,得到超支化共聚物HP(DMAESP-coBS2MOE).然后以HP(DMAESP-co-BS2MOE)作为大分子引发剂引发甲基丙烯酸寡聚乙二醇酯(OEGMA)的聚合,得到超支化星形共聚物HP(DMAESP-co-BS2MOE)(POEGMA)n.在DMAESP中,叔胺基团和甲基丙烯酸酯基团通过酸敏感的β-硫丙酯键连接,由于该键在酸性条件下能够缓慢水解,形成羧基末端,最终得到的聚合物具有p H响应性.同时,由于BS2MOE中含有二硫键,能够被细胞中的谷胱甘肽还原,该聚合物同时具有氧化还原响应性.HP(DMAESP-co-BS2MOE)(POEGMA)n在水中能够自组装成以HP(DMAESP-co-BS2MOE)为核,以POEGMA为壳的纳米级胶束,并能负载DNA,可作为基因转染的载体.     

光交联Pickering乳液中的粒子稳定剂制备胶体体微胶囊

研究了光敏性聚合物刷修饰二氧化硅纳米粒子的制备及其乳化行为, 提供了一种制备新颖“胶体体”微胶囊的方法. 首先, 在二氧化硅纳米粒子表面引入原子转移自由基聚合(ATRP)引发剂分子, 通过表面引发ATRP得到含有香豆素侧基聚合物刷光敏性的纳米二氧化硅粒子(SiO₂-PMMA-PCMA); 然后, 以该粒子为乳化剂制备油包水型的皮克林乳液; 最后, 在紫外光的照射下引发香豆素侧基的交联反应从而得到“胶体体”微胶囊. 结果表明, 香豆素单体7-(2-甲基丙烯酰乙氧基)-4-甲基香豆素(CMA)和SiO₂-PMMA-PCMA在紫外光作用下都可以发生交联反应, 以SiO₂-PMMA- PCMA纳米粒子作乳化剂可以制备稳定的皮克林乳液, 光交联后得到的“胶体体”微胶囊的平均粒径约为170 μm.     

双亲水性超支化接枝共聚物的pH响应性药物释放

首先利用阳离子开环聚合合成了超支化聚缩水甘油醚（HPG）,然后通过酯化反应制备了低接枝率的大分子引发剂HPG-Br,并进一步引发甲基丙烯酸-2-（N,N-二甲氨基）乙酯（DMAEMA）单体的原子转移自由基聚合,合成了低接枝率的双亲水性超支化接枝共聚物HPG-g-PDMAEMA,用1HNMR和GPC对聚合物结构进行了表征.并采用芘荧光探针法,HNMR和DLS研究了HPG-g-PDMAEMA在不同pH水溶液中的组装行为.以1香豆素102为模型药物研究了HPG-g-PDMAEMA聚合物在不同pH条件下的药物释放行为,发现在pH连续振荡刺激下HPG-g-PDMAEMA聚合物胶束对药物分子能实现部分＂可逆＂的释放和再包载.     

通过自缩合乙烯基氧阴离子聚合制备超支化聚甲基丙烯酸羟丙酯

由甲基丙烯酸羟丙酯通过自缩合乙烯基氧阴离子聚合(self-condensing vinyl oxyanionic polymerization)制备了端羟基的超支化聚甲基丙烯酸酯. 以氢化钾(KH)和冠醚的复合物为引发剂时, 可以得到高分子量的聚合物. 用¹H NMR和¹³C NMR谱图证实了聚合物的超支化结构. 由于在聚合过程中存在质子转移反应, 引发剂与单体的摩尔比会影响所得聚合物的结构. 超支化聚合物的玻璃化转变温度在58.1～81.4 ℃之间, 且随着引发剂与单体的比例的减小而降低. 当引发剂与单体等摩尔比时, 所得聚合物的支化度为0.49.     

温敏性超支化多臂共聚物的自组装和可控的药物释放（摘要）

采用core-first的策略以超支化聚3-乙基-3-羟甲基环氧丁烷（HBPO）作为前体,通过原子转移自由基聚合的方法合成了以HBPO为核,以聚N-异丙基丙烯酰胺（PNIPAM）为臂的新型温敏性星形多臂共聚物HBPO-star-PNIPAM.^1HNMR、FTIR以及SEC表征证明了PNIPAM成功的接到了HBPO核上.超支化HBPO-star-PNIPAM的自组装行为通过芘探针荧光光谱、^1HNMR、TEM和DLS等方法表征,结果表明该聚合物在纯水中以＂MMA＂机理直接组装形成大的多分子胶束.     

基于苯氧基联烯的两亲性嵌段共聚物的合成

运用机理转换策略,结合自由基聚合和原子转移自由基聚合(ATRP),制备了含有聚联烯链段的两亲性三嵌段共聚物.设计合成了含有偶氮和ATRP引发基团的双官能团引发剂,先用该双官能团引发剂引发苯氧基联烯单体的自由基聚合,得到了含有ATRP引发基团的聚联烯大分子引发剂,然后该大分子引发剂引发亲水性单体N,N-二乙基氨乙基甲基丙烯酸酯(DEAEMA)的ATRP聚合,制得了聚N,N-二乙基氨乙基甲基丙烯酸酯-聚联烯-聚N,N-二乙基氨乙基甲基丙烯酸酯(PDEAEMA-b-PPOA-b-PDEAEMA).该三嵌段共聚物能在水溶液中形成胶束,通过荧光探针技术分别测定了它在不同离子浓度、不同p H值条件下的临界胶束浓度.实验结果表明,该聚合物胶束的cmc随着p H值增大而减小,随着离子浓度的增大而增大.     

基于原子转移自由基聚合技术的偶氮苯星形液晶聚合物的合成与表征

利用原子转移自由基聚合(ATRP)技术合成了含不同端基取代基的偶氮苯三臂星形侧链液晶聚合物. 均苯三酚与2-溴异丁酰溴通过酯化反应制备三官能团引发剂, 引发偶氮苯单体6-[4-(4-甲氧基苯基偶氮)酚氧基]己基甲基丙烯酸酯(MMAzo)或6-[4-(4-乙氧基苯基偶氮)酚氧基]己基甲基丙烯酸酯(EMAzo)的ATRP反应. 利用核磁共振氢谱(¹H NMR)、凝胶色谱(GPC)、差示扫描量热法(DSC)和偏光显微镜(POM)等手段对星形聚合物进行表征. 星形聚合物的液晶性与相应均聚物相似, 但偶氮苯端基取代基的不同导致星形聚合物的液晶性差别显著. 在紫外/可见光照射下星形聚合物呈现明显的异构化转变.     

双亲性光敏感遥爪聚合物C-PNIPAAm的合成与性能

以7-羟基-4-甲基香豆素为原料,依次与环氧氯丙烷、二硫化钠反应得一含香豆素基元的二硫化物(C-S-S-C),并以其与三丁基膦复合体系为链转移剂,偶氮二异丁腈(AIBN)为引发剂,N-异丙基丙烯酰胺(NIPAAm)为单体制备了末端为香豆素光响应基元的双亲性遥爪聚合物(C-PNIPAAm).用傅里叶变换红外(FT-IR)光谱、凝胶渗透色谱(GPC)、氢核磁共振(1H-NMR)等对该聚合物进行了结构表征.研究显示该双亲性遥爪聚合物可在水中直接形成胶束,并以荧光素为疏水性客体考察了聚合物胶束的光控释放行为.在波长大于310 nm的紫外光照射下,聚合物链末端的香豆素单元可进行光二聚,胶束结构随之改变,因而所负载的荧光素可得到逐步有效释放.动态激光光散射(DLS)检测显示,光二聚反应使聚合物胶束平均粒径从56.6 nm增大至101.0 nm.     

氧负离子聚合在超支化聚合物合成中的应用

近年来,氧负离子聚合得到较快发展,单体种类已经由酯基的β位上含有供电性杂原子的甲基丙烯酸酯类扩展到环氧类、甲基丙烯酸羟酯类单体.氧负离子引发这两类单体聚合,可以得到新型结构的超支化聚合物.对氧负离子引发合成超支化聚合物的机理及其应用进行了综述.     

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.     

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.     

Facile synthesis of bicyclic 1-arylpyrazol-5-ones

In this Letter, we described a facile method for constructing fused bicyclic 1-arylpyrazol-5-one ring system. We employed various methylene-containing carboxylic acids as the substrates and proved that the pyrazolone ring closure requires activated methylene group in intermediate II. Accordingly, a series of structurally diversified, fused bicyclic 1-arylpyrazol-5-ones was prepared in moderate to high yields using the requisite substrates.     

Synthesis of pyrrolo[1,2-a]pyrazines and pyrazino[1,2-a]indoles by Curtius reaction in Morita-Baylis-Hillman derivatives

Synthesis of substituted pyrrolo[1,2-a]pyrazines and pyrazino[1,2-a]indoles from the Morita-Baylis-Hillman derivatives of acrylates via saponification followed by Curtius reaction is described.     

正丁胺对激光染料荧光谱影响的研究

用正丁胺作为碳源,采用射频辉光放电制备碳膜,选用激光染料R6G和聚乙二醇混合液作为蒸气源,采用单源热蒸发,在蒸发室与染料同时沉积得到混合膜,用拉曼光谱和红外光谱分析了碳膜的结构和键合方式,分析表明:碳膜中存在胺基团和氢原子.混合膜的荧光谱测量结果表明,认为正丁胺对染料荧光谱的影响是因为胺基和氢原子的存在.     

Cu0-catalysed 1,3-dipolar cycloadditions of α-amino acid derived N,N-cyclic azomethine imines to ynones

A series of 20 CuAIAC reactions between eight 4-acylamino substituted pyrazolidine-3-one-1-azomethine imines and four terminal ynones were performed using Cu⁰ as catalyst. The corresponding fluorescent cycloadducts were obtained in very high yields upon simple workup. Thus, Cu-metal turned out to be a better catalyst than Cu^I in terms of yield and ease of isolation. Availability of azomethine imines, mild reaction conditions, and simple workup enable a “click” access to libraries of densely substituted 2,3-dihydro-1H,5H-pyrazolo[1,2-a]pyrazol-1-ones. Reactivity of differently substituted dipoles was evaluated experimentally and by quantum chemical methods (DFT).     

Synthesis and antioxidative/anti-inflammatory activity of novel fullerene–polyamine conjugates

(E)-4-(Fullerenopyrrolidin-1-yl)-3-methylbut-2-enoic acid and its corresponding succinimidyl ester, readily obtained through Prato-type modification of C₆₀, were used for the selective N-acylation of polyamines. The thus obtained conjugates were evaluated for their antioxidative and anti-inflammatory activity and their cytotoxicity was determined. Members of this family of compounds showed interesting anti-lipid peroxidation, anti-lipoxygenase and anti-inflammatory activity and comparable cytocompatibility to spermidine.