【作者】 洪海燕；

【导师】 颜德岳； 周永丰；

【作者基本信息】 上海交通大学 ， 高分子化学与物理， 2008， 博士

【摘要】 超支化聚合物是一类具有准球形结构的高度支化大分子,在其不规则的分子结构中含有大量内部空穴和末端官能团。由于超支化聚合物独特的结构和性能特点,目前它已成为高分子领域的研究热点。经过近20年的发展和探索,人们在超支化聚合物的合成、结构表征、功能化改性等方面已经取得了重要进展,尤其是超支化聚合物的合成方法已经趋于全面和成熟,这为超支化聚合物的应用开发奠定了坚实的基础。但是,在超支化聚合物的研究中还有许多问题亟待解决,如基础理论的完善、未知性能的挖掘、新颖现象的解释、应用领域的拓展等等。本文在综述前人有关超支化聚合物工作的基础上,在超支化聚合物的功能化及自组装方面做了一些新的探索和研究。将具有环境响应性的聚合物链段通过活性聚合的方法引入超支化聚醚表面,设计合成了两类功能性的基于超支化聚醚的多臂共聚物,并且研究了其环境响应性和自组装行为,进一步开展了应用的研究。研究工作中,通过活性聚合的方法制备得到了两类不同臂链段的响应性两亲超支化多臂共聚物HBPO-g-PDMAEMA和HBPO-g-PDEAEMA;前者可在水中直接自组装形成大胶束,且具有良好的温度响应性,将其作为药物载体实现了温度响应的药物释放;后者在二氧六环/水混合溶剂中组装时,随水含量的变化而产生了一系列的形貌转变,并在溶剂挥发诱导作用下发生了多种形貌变化,并且具有良好的pH值响应性,将其组装液同时作为稳定剂和还原剂,分别在水相和油相中制备得到了具有胶体金纳米粒子分散液。主要研究内容和结论概括如下:1.HBPO-g-PDMAEMA的可控合成及水中直接自组装行为研究;采用原子转移自由基聚合法,成功在HBPO表面接枝PDMAEMA链段,合成了一系列不同臂长的超支化多臂共聚物HBPO-g-PDMAEMA。多臂共聚物的臂长可通过调节单体DMAEMA的加入量来很好地控制。臂平均聚合度为5到77的HBPO-g-PDMAEMA均可在水中经直接溶解法组装成10 nm的球形小胶束和100 nm的球形大胶束。且大胶束的尺寸随着多臂共聚物中PDMAEMA臂聚合度的增加而减小,小的单分子胶束基本保持不变。核磁表征证明所形成的胶束为核-壳结构,在水中溶解性良好的PDMAEMA伸展为壳,而溶解性不好的HBPO卷曲成核。透射电镜的直观证据证明大的多胶束聚集体由很多5 nm左右的小基元构成。在此基础上,提出了单分子胶束经PDMAEMA链段间的疏水相互作用聚集形成多分子胶束聚集体的多胶束聚集机理(MMA机理)。该机理的提出,为高度支化聚合物形成大球形胶束的体系提供了理论参考。2. HBPO-g-PDMAEMA的环境响应性研究及其在药物释放方面的应用;HBPO-g-PDMAEMA在纯水中具有离子响应性和pH值响应性。动态光散射测试表明,在其水溶液中加入氯化钠至一定浓度时,组装体发生聚集形成微米级的聚集体;随着水溶液pH值的增加,逐渐聚集形成大的聚集体。尼罗红为荧光探针的临界胶束浓度(CMC)测试表明,随着pH值的增加,共聚物的CMC增大。HBPO-g-PDMAEMA同时也具有温度敏感性,且发现其分子量分布对温敏性能有较大影响。分子量单分散的HBPO-g-PDMAEMA具有可逆的温敏特性,在高于LCST的温度下很快达到热力学稳定。动态光散射和变温核磁分析表明,随着温度的升高,首先发生壳层PDMAEMA链段的脱水,塌缩在多胶束聚集体表面,使组装体尺寸小幅下降,接着组装体间由于壳层PDMAEMA链段间疏水相互作用增加而发生进一步聚集,多胶束聚集体的尺寸增加。在此基础上,提出了分子量单分散的HBPO-g-PDMAEMA温敏响应组装的机理。而分子量分布宽的HBPO-g-PDMAEMA在温度高于LCST时,达到热力学稳定需非常长的时间。这也导致其在加热-冷却循环下的温度响应行为受热历史的影响。作者认为分子量分布宽的HBPO-g-PDMAEMA中PDMAEMA长链和短链的选择性排列是造成这种现象的原因。药物释放的探索性研究表明:HBPO-g-PDMAEMA对药物吲哚美辛有较好的包裹特性,包裹效率可达68%,在pH值为7.4的磷酸盐缓冲溶液中体外释放实验发现,温度对药物的释放有一定影响。3. HBPO-g-PDEAEMA的可控合成及溶液中自组装行为研究;同样采用原子转移自由基聚合法成功制备得到臂聚合度可控的HBPO-g-PDEAEMA共聚物。HBPO-g-PDEAEMA在诸多混合溶剂如二氧六环/水、乙醇/水、丙酮/水、四氢呋喃/水、DMF/水中均可发生聚集。聚合物在各混合溶剂中发生聚集的临界聚集水浓度与有机溶剂的溶解度参数有关。冷冻透射电镜分析表明,臂平均聚合度为11的POPE3在二氧六环/水混合溶剂中随着水含量的变化而发生了一系列的形貌转变:囊泡——单分子胶束和囊泡共存——多分子聚集体胶束和囊泡共存——多分子聚集体——空心球——空心球聚集体。核磁分析表明这种多阶段的形貌变化由PDEAEMA臂多阶段的溶解性变化引起。第一阶段中,由于PDEAEMA臂溶解性上升,导致囊泡中部分分子解离出来形成单分子胶束;第二阶段中,由于PDEAEMA臂溶解性的下降,导致单分子胶束聚集形成多胶束聚集体;第三阶段中,PDEAEMA臂溶解性继续下降,导致PDEAEMA分子塌缩,多胶束聚集体结构向外围收缩,形成中空球结构;第四阶段,PDEAEMA臂溶解性继续下降,导致臂塌缩程度增加,空心球壁厚下降,而后PDEAEMA间的疏水相互作用增加,导致空心球间聚集,形成较大的聚集体。另外,丹磺酰氯标记的HBPO-g-PDEAEMA的荧光分析可以很好地反应体系中其所处微环境的变化,从而为组装形貌的转变提供了另一强有力的证据。4. HBPO-g-PDEAEMA响应性研究及其在还原稳定纳米金方面应用;HBPO-g-PDEAEMA具有一定的pH值响应性。随着pH值的升高发生了聚集。NMR、DLS、冷冻透射电镜等分析表明:在低pH值下,形成了具有核壳结构的粒径较小的单分子胶束及多胶束聚集体;随着pH值的增加,发生形貌转变,形成囊泡结构;而pH值进一步升高导致组装体沉积。以HBPO-g-PDEAEMA为还原剂和稳定剂,可分别在水相和油相中成功制备纳米金胶体粒子。在水相中制备纳米金粒子时,溶液pH值对金纳米粒子的制备有很大影响,pH较小的溶液中不能实现金纳米粒子的有效还原,制备稳定纳米金分散溶液的条件为pH大于6.15以及N/Au高于10。且在低pH下制备时所得金颗粒为球形颗粒和棒状颗粒的混合物,而高pH时为球形颗粒。在油相中制备纳米金粒子时,通过改变溶剂中二氧六环和水的配比可控制生成的纳米金颗粒的大小和形貌。水含量较低的二氧六环和水混合溶剂中不能实现金粒子的有效还原,使用水含量为32.4wt%的POPE3组装液作为还原剂时,在N/Au为20和10的条件下均可获得稳定性良好的胶体球形金颗粒分散液;使用水含量为42.8 wt%的POPE3组装液作为还原剂时,在N/Au为20的条件下可获的稳定的粒径为22 nm金颗粒分散液,该条件下获得的金颗粒形貌丰富而将N/Au由20降至10后,所得金颗粒粒径较大,沉积在容器底部。5. HBPO-g-PDEAEMA溶剂诱导组装行为研究——囊泡的不对称分裂、薄壁空心球的粘连及网络状结构的形成;首先发现在溶剂挥发过程诱导下,囊泡内外溶剂渗透压的驱动下,HBPO-g-PDEAEMA囊泡发生由双分子层母囊泡分裂为单分子层子囊泡的不对称分裂。整个过程中HBPO-g-PDEAEMA的超支化特性为单分子层子囊泡的稳定提供了可能,这也是成功分裂的关键。另外,溶剂的挥发还会导致组装体间粘连、缔合的发生。不同挥发时间下的冷冻透射电镜表明,水含量为10 wt%的二氧六环/水混合溶剂中形成的囊泡间在溶剂挥发的驱动下发生粘连,而水含量为50 wt%的二氧六环/水混合溶剂中形成的薄壁空心球在溶剂挥发的驱动下,经PDEAEMA链间的疏水相互作用发生空心球的缔合。而对于水含量更高的混合溶剂中形成的空心球,其间的疏水相互作用因PDEAEMA溶解性的下降而表现的更为明显,即使在无溶剂挥发的驱动下,仍能形成大的缔合体。而后发现空心结构的组装体可作为模板制备得到网络状结构。用液氮冷冻的方法,将较高水含量下形成的薄壁空心球状组装体固定,经真空干燥,可获得纳米孔径的微观网络状结构。另外低水含量下的组装体在溶剂挥发作用下发生聚集,待溶剂挥发后形成介观网络状结构。更多还原

【Abstract】 Hyperbranched polymers are a novel kind of three dimensional torispherical irregular macromolecules possessing highly branched architectures, many inner cavities and a large amount of terminal functional groups. Due to their unique molecular structures and properties, hyperbranched polymers have become the hot topics in many research fields. Up to now, great progresses have been made in the synthesis, characterization, modification, and application of hyperbranched polymers. However, many problems still need to be resolved, such as the exploration of the unknown features, the explanation of new phenomena and the spread of the application fields. In this dissertation, based on the summarization of previous research works of hyperbranched polymers, some creative investigations are conducted in the modification and self-assembly of hyperbranched polymers. Two novel kinds of functional star copolymers based on hyperbranched polyethers with stimuli responsibilities were synthesized successfully, their stimuli responsibilities and self-assembly behaviors in solution were investigated detailedly, their potential use in drug delivery and the stabilization of gold nanoparticles were explored. The detailed main results are shown as follows.1. The controll synthesis and self-assembly of HBPO-g-PDMAEMA in water;The PDMAEMA chains were grafted to HBPO surface by graft-from method, through atom transfer radical polymerization. By altering the amount of DMAEMA monomer, the DParm of HBPO-g-PDMAEMA can be controlled easily. And HBPO-g-PDMAEMAs with DParm varied from 5 to 77 were synthesized successfully. The HBPO-g-PDMAEMAs can form aggregates in water as confirmed by pyrene and Nile Red probe fluorescence spectrometry, and the CMC value of HBPO-g-PDMAEMAs rises with the increase of PDMAEMA arm length (DParm values). These star copolymers can self-assembly into small unimolecular micelles with particle size of approximately 10 nm and large spherical micelles with particle size of approximately 100 nm simultaneously. With the increase of the PDMAEMA chain length, the dimension of the large spherical micelles decreased, but the size of the small unimolecular micelles changes slightly. The solution-state NMR studies show that the aggegates hold a core-shell structure, the hydrophobic HBPOs aggregate together to form the solid-like core while the hydrophilic PDMAEMA arms form the shell. TEM measurements have provided direct evidence that the large micelles are multimolecular aggregates with the basic building units of unimolecular micelles. Then a self-assembly mechanism named as multimicellar aggregates was presented, it is the first demonstration of the self-assembly mechanism for the large multimolecular micelles generated from the solution self-assembly of hyperbranched copolymers.2. The stimuli-responsibilities of HBPO-g-PDMAEMA copolymer and potential use in drug delivery;Aqueous HBPO-g-PDMAEMA solution is sensitive to ionic strength, pH value and temperature. The DLS studies for HBPO-g-PDMAEMA solution with different amount of NaCl shows that large aggregates can be formed when the amount of NaCl is large enough. The DLS and CMC stuides for HBPO-g-PDMAEMA solution with different pH value shows that the aggregate behavior happened with the increase of pH value, and the CMC at pH 1.97 water is larger than that at neutral water. HBPO-g-PDMAEMA copolymers with narrow molecular weight distribution have reverse temperature responsibilities. The quantitative variable temperature NMR studies show that the PDMAEMA arms dehydrated by heating, so the MMAs aggregate together to form large aggregates as detected by the DLS analysis, driving by the increased hydrophobic interactions between PDMAEMA shells. Based on these studies, a proposed mechanism of heating-induced aggregation was presented. But the thermosensitivity of copolymers with broad molecular weight distribution are quite different from the above ones. Several heating experiments including transmttance and DLS mesurements show that they need more time to achieve the stable thermodynamics state. It is supposed that the broad molecular weight distribution plays an important role in the heating-history-influenced thermosensitivities. The selective arrangements of the longer and the shorter PDMAEMA chains are thought to be the main reason. The drug loading and temperature-dependent release properties of HBPO-g-PDMAEMA micelles were also investigated by using indomethacin as a model drug. The indomethacin-loaded micelles display a rapid drug release at temperature around LCST.3. The controllable synthesis of HBPO-g-PDEAEMA star copolymers and the self-assembly behavior in mixture of dioxane and water;The HBPO-g-PDEAEMAs with different length of PDEAEMA arms were also synthesized successfully by ATRP methods. The transmittance vs water content studies show that POPE3 sample with DParm of 11 can aggregate in various mixture of solvent, such as dioxane/water, THF/water, DMF/water, acetone/water and ethanol/water. The Cryo-TEM results show that the self-assembly behavior of POPE3 in dioxane/water mixture is very complicated. Solvent-induced multistage morphology transitions were observed. As the increase of water content, the morphology of the aggregates changed from vesicles to unimolecular micelles and vesicles, then to MMAs and vesicles, then to MMAs, then to hollow spheres, the wall of the hollow spheres narrowed and then they aggregated together to form large objects as the further increase of water content. Moreover, the solution state NMR studies show that this morphology transitions are induced by the multistage change of the solubility of PDEAEMA arms. In addition, the fluorescence studies on DNS-labelled HBPO-g-PDEAEMA with DParm of 11 also provided strong evidence for the morphology transition.4. The stimuli-responsibilities of HBPO-g-PDEAEMA and their use in autoreduction and stablization of gold nanoparticles;HBPO-g-PDEAEMAs have certain pH responsibility. As the increase of the pH value of solution, aggregation happen. At low pH, core-shell micelles including unimolecular micelles and large micelles are formed. As the increase of pH value, the aggregates transfered into vesicles., and further increase of pH value induced the precipitation of the aggregates. By using HBPO-g-PDEAEMA as the dioxidizer and stablizer, stable gold naopaticles were synthesized successfully in water and organic solvent. When using HBPO-g-PDEAEMA aqueous solution, pH value is the main parameter which has big influences on the synthesis of gold nanoparticles. At low pH, the dioxide of AuCl4- can not be achieved. Effective preparations were carried out at pH value larger than 6.15, N/Au molar ratio larger than 10. And when using HBPO-g-PDEAEMA solution in dioxane-riched dioxane/water mixture, gold nanoparticles can also be synthesied successfully. The N/Au molar ratio and water content in dioxane/water mixture are parameters which give effects on the resultant gold nanoparticles.5. The solvent-evaporation induced behavior of the aggregates formed by HBPO-g-PDEAEMA in dioxane/water mixture.Firstly, an asymmetrical budding and fission transition of single-component HBPO-g-PDEAEMA vesicle induced by the solvent evaporation, and a very special bilayer-to-monolayer molecular movement was found in the process. Secondly, the adhesion behaviors of the hollow structures were investigated by TEM and cryo-TEM. At last, by using the hollow spheres as the templet, irreglar porous networks with pores of 170 nm and walls of 15 nm were prepared by the cryo-fix of hollow spheres and the in-situ evaporation of enwrapped solvents. And large irreglar porous networks with porous of 800 nm and walls of 280 nm were prepared by the spontaneous aggregation of the self-assembly objects induced by natural solvent evaporation.更多还原