【作者】 刘昊；

【导师】 刘世勇；

【作者基本信息】 中国科学技术大学 ， 高分子化学与物理， 2010， 博士

【摘要】 超分子自组装体由于在催化化学、材料制备、生物医药等多方面存在着极为重要而广泛的应用价值,已经成为21世纪最重要的研究课题之一。在本论文中,我们结合可控/活性自由基聚合和点击化学等先进合成技术,制备了多种结构明确具有特定功能的全亲水性聚合物,包括多温敏全亲水性三嵌段聚合物、可以用来构筑多重响应性超分子全亲水性嵌段聚合物的端基官能化聚合物以及结合有反应型检测基元的温度敏感全亲水性两嵌段聚合物,并利用它们成功构筑了各种功能性聚合物自组装体。另外还实现了对聚合物自组装体的表面修饰。具体来说,本论文的工作包括以下四个方面：1.基于温敏性大分子引发剂,通过原子转移自由基聚合(ATRP)合成了两种多温敏全亲水性ABC三嵌段聚合物,它们分别含有两个和三个LCST不同的温度敏感性嵌段。首先对聚环氧丙烷单丁醚(PPO42-OH)进行端基改性,制备了氯端基的PPO大分子引发剂(PPO-Cl),随后通过连续投料的方法依次聚合N-异丙基丙烯酰胺(NIPAM)与N,N-二甲基丙烯酰胺(DMA),制备了含有两种温度敏感性嵌段的双温敏全亲水性ABC三嵌段聚合物PPO-b-PNIPAM-b-PDMA,其在水溶液中会表现出两阶的温度敏感胶束化行为；另外,利用PPO大分子引发剂聚合二甘醇单甲醚甲基丙烯酸酯(MEO2MA)得到聚环氧丙烷-6-聚二甘醇单甲醚甲基丙烯酸酯(PPO-b-PMEO2MA),再以其为大分子引发剂聚合三甘醇单甲醚甲基丙烯酸酯(MEO3MA),制备了含有三种温度敏感性嵌段且完全生物相容的三温敏全亲水性ABC嵌段聚合物PPO-b-PMEO2MA-b-PMEO3MA,其在水溶液中也会表现出多阶的温度敏感聚集行为。我们通过紫外-可见(UV-vis)光谱、核磁氢谱(1H NMR)以及光散射(LLS)等多种手段细致研究了它们的温度诱导多阶自组装过程,并揭示了每个阶段中的相转变。2.基于β-环糊精(β-CD)与金刚烷(Ad)之间的包结络合作用,结合多重刺激响应性全亲水聚合物与超分子聚合物概念,构筑了两种多重响应性的超分子全亲水性共聚物,它们分别具有嵌段共聚物与接枝共聚物的拓扑结构。首先,利用点击化学与ATRP,制备了端基β-CD官能化的温度敏感聚合物(β-CD-PNIPAM)与pH敏感的端基Ad官能化的聚(N,N-二乙基氨乙基甲基丙烯酸酯)(Ad-PDEAEMA);在水溶液中通过包结络合作用,两种聚合物可以形成在很宽的pH与温度范围内稳定的超分子嵌段共聚物,并表现出多重响应性自组装行为；通过调节溶液的温度与pH值,这种超分子嵌段聚合物可以实现胶束-囊泡的可逆结构转化。3.使用苯甲醛衍生的ATRP引发剂,通过连续投料的方法依次聚合寡聚乙二醇单甲醚甲基丙烯酸酯(OEGMA)、N,N-二甲基氨乙基甲基丙烯酸酯(DMAEMA)和DEAEMA,合成了端基醛基官能化的全亲水性三嵌段聚合物Ald-POEGMA-b-PDMAEMA-b-PDEAEMA;在碱性条件下,该嵌段聚合物可以自组装得到以pH敏感的PDEAEMA为内核、可交联的PDMAEMA为壳层、生物相容的POEGMA为亲水性外层的“洋葱型”多层胶束,并可以通过1,2-双(2-碘代乙氧基)乙烷与PDMAEMA壳层的季铵化反应很方便的实现壳交联；进一步利用壳交联胶束表面的醛基官能团可以实现其与溶菌酶的生物偶联。4.最后,将反应型小分子探针的设计理念融入环境响应聚合物的设计与功能化中,制备了基于嵌段聚合物胶束组装体的多功能(巯基、温度等)环境响应聚合物基化学传感器。基于香豆素设计了一种带有羟基官能团的巯基检测探针,这种探针可以与巯基发生加成反应而发出荧光；从PEG大分子链转移剂出发,通过可逆加成-断裂链转移(RAFT)聚合得到一种温度敏感全亲水性两嵌段聚合物,其中温敏嵌段中共聚有侧链带有羧基的单体；通过羚基与羟基的缩合反应可以将巯基检测基元共价引入温敏全亲水性聚合物中,利用这种聚合物可以在水溶液中选择性定量检测含有巯基的生物分子,同时由于聚合物具有温度响应性,改变温度会影响荧光强度,通过监测荧光强度的变化就可以实现对温度的检测。更多还原

【Abstract】 Supramolecular assemblies have attracted considerable interests in the past decedes due to their promising applications in diverse fields, such as catalysis, material preparation, and biomedicine, which renders this interdisciplinary research subject as one of the promising scientific issues in the 21st century. This dissertation mainly focuses on the fabrication and functionalization of supramolecular assemblies from stimuli-responsive double hydrophilic block copolymers. A series of well-defined specific functionalized polymers with varying chemical architectures were prepared in the combination of controlled/living radical polymerizations and click chemistry, include multiple thermo-responsive double hydrophilic triblock copolymers, end-functionalized polymers which can be used to construct multi-responsive supramolecular double hydrophilic block copolymers, and thermo-responsive double hydrophilic diblock copolymers functionalized by fluorescent turn-on probes. Besides the construction of the assemblies, novel approache in the surface modification of self-assembled micelles was also investigated. The dissertation includes the following four parts:1. Well-defined double thermo-responsive triblock copolymer poly(propylene glycol)-b-poly(N-isopropylacrylamide)-b-poly(N,N-dimethylacrylamide), PPO-b-PNIPAM-b-PDMA, was synthesized via sequential atom transfer radical polymerization (ATRP) technique using a PPO-based macroinitiator. The double thermo-responsive ABC triblock copolymer contains PDMA as one permanently hydrophilic block, with PPO and PNIPAM as two different thermo-responsive blocks.Thermo-responsive micellization behavior of the PPO-b-PNIPAM-b-PDMA triblock copolymer was then investigated by a combination of spectroscopic techniques and dynamic light scattering (DSL). A thermally induced two-step association is observed when heating beyond the first and second cloud points of the thermo-responsive blocks. The critical micellization temperature (CMT) and critical micellization concentration (CMC) values at different temperatures of the PPO-b-PNIPAM-b-PDMA triblock copolymer were determined. Moreover, a triply thermo-responsive biocompatible ABC triblock copolymer poly(propylene glycol)-b-poly(di(ethylene glycol) methyl ether methacrylate)-b-poly(tri(ethylene glycol) methyl ether methacrylate), PPO-b- PMEO2MA-b-PMEO3MA, was also synthesized via sequential ATRP. The thermo-responsive characteristics of the aqueous solution of the triblock copolymer have been studied in comparison with the corresponding mono-and diblocks by spectroscopic techniques and DSL. The hydrophilicity of the blocks influences each other, rendering each block a phase transition temperature different from that of the corresponding homopolymers. The cloud points of the three steps of the phase separations were determined to be 10,41, and 49℃for steps one to three, respectively, while heating the aqueous solution of the triblock copolymer.2. Supramolecular double hydrophilic block copolymer (DHBC) with multi-responsive self-assembling behavior was fabricated fromβ-CD-terminated PNIPAM (β-CD-PNIPAM) and adamantyl-terminated poly(2-(diethylamino)ethyl methacrylate) (Ad-PDEAEMA). Two alternate strategies, direct ATRP of NIPAM usingβ-CD-based initiator (β-CD-Br) and click reaction of mono-6-deoxy-6-azido-β-cyclodextrin (β-CD-N3) with alkynyl-terminated PNIPAM, were employed for the preparation ofβ-CD-PNIPAM. The latter strategy afforded well-definedβ-CD-PNIPAM with narrow polydispersity. Ad-PDEAEMA was synthesized via ATRP technique using adamantane-based initiator. Host-guest inclusion complexation betweenβ-CD and adamantyl moieties spontaneously drives the formation of supramolecular DHBC fromβ-CD-PNIPAM and Ad-PDEAEMA. Possessing well-known thermoresponsive PNIPAM and pH-responsive PDEAEMA sequences, the obtained supramolecular PNIPAM-b-PDEAEMA diblock copolymer exhibits intriguing multi-responsive and reversible micelle-to-vesicle transition behavior in aqueous solution by dually playing with solution pH and temperatures.3. Two approaches were attempted for the syntheses of a-aldehyde terminally functionalized double hydrophilic diblock or triblock copolymers of 2-(dimethyl-amino)ethyl methacrylate (DMAEMA), DEAEMA, and oligo(ethylene glycol) methyl ether methacrylate (OEGMA) via ATRP. The first approach employed 2-(2,2-dimethoxyethoxy)ethyl a-bromoisobutyrate as the ATRP initiator for the sequential polymerization of DMAEMA and DEAEMA monomers. However, after deprotection of the terminal acetal into aldehyde groups, the obtained Ald-PDMAEMA-b-PDEAEMA diblock copolymer was prone to aldol condensation at alkaline pH, leading to the extensive formation of dimmers. Directly using 4-aldehydephenyl a-bromoisobutyrate as the ATRP initiator, the sequential polymerization of OEGMA, DMAEMA, and DEAEMA resulted in the successful preparation of a-aldehyde terminally functionalized triblock copolymer, Ald-POEGMA-b-PDMAEMA-b-PDEAEMA. This triblock copolymer molecularly dissolves in acidic media, and self-assembles into three-layer "onion-like" micelles consisting of PDEAEMA cores, PDMAEMA inner shells, and POEGMA outer coronas at alkaline pH. Selective cross-linking of the PDMAEMA inner shell with 2-bis(2-iodoethoxy)ethane leads to structurally stabilized shell cross-linked (SCL) micelles surface functionalized with aldehyde groups. Possessing the PDEAEMA cores, the obtained SCL micelles exhibit reversible pH-responsive swelling/deswelling behavior, as revealed by LLS. The surface aldehyde groups enable the facile conjugation of SCL micelles with a model protein, lysozyme, via the formation of Schiff base.4. Novel DHBC-based multifunctional chemosensor to thiol and temperature was designed and synthesized. A new coumarin-based fluorescent thiol probe was constructed on the basis of the conjugate 1,4-addition of thiols toα,β-unsaturated ketones. Well-defined DHBC bearing the thiol-reactive moieties in the thermo-responsive block were synthesized by chemical modification of poly(ethylene glycol)-b-poly(di(ethylene glycol) methyl ether methacrylate-co-oligo(ethylene glycol) methyl ether methacrylate-co-2-succinyloxyethyl methacrylate) (PEG-b-P(MEO2MA-co-OEGMA-co-SEMA)), which was obtained via reversible addition-fragmentation chain transfer (RAFT) polymerization. The nonfluorescent probe moieties are subjected to selective Michael addition reaction upon addition of thiol, producing highly fluorescent species, and there is a linear relationship between temperatures and the fluorescence intensity. Thus, the thermo-responsive DHBC can serve as water-soluble multifunctional and efficient fluorescent chemosensors to thiol and temperature.更多还原