【作者】 李欣；

【导师】 洪春雁； 潘才元；

【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】 聚合物的结构与其性能是密切相关的。阐明聚合物结构与性能的关系对于高分子化学的意义在于：根据对性能的要求,设计不同结构的分子,使其具有预定的性能。因此,运用已知的可控活性聚合反应原理,合成出各种新型结构聚合物,对于探索聚合物的链结构与性能的关系,设计具有预定性能的分子结构,有着非常重要的意义。超支化聚合物是一类具有高度支化三维结构的大分子,与线形聚合物相比,它们有很多独特的物理和化学性质,如低粘度,高流动性,良好的溶解性和大量的端基等。超支化聚合物的合成方法主要可分为两种：(一)多官能团单体的缩聚反应, (二)自缩合乙烯基聚合反应。利用这些聚合方法,研究者们成功制备了包括超支化聚酯,聚酰胺,聚碳酸酯和聚氨酯等一系列的超支化聚合物。超支化聚合物已在医药载体、非线性光学、能量存储和传递、纳米材料和催化剂等诸多领域获得广泛应用。嵌段共聚物具有特殊的物理化学性质,作为热塑性弹性体、表面活性剂、表面修饰剂、分散剂和聚合物共混的增溶剂等有着广泛的用途,受到了学术界和工业界的广泛关注。活性自由基聚合技术的发展,为嵌段聚合物的合成提供了更多的手段,很多新型的结构规整、分子量可控和分子量分布窄的嵌段聚合物不断被合成出来。由于具有高度有序的结构,比表面积大,孔道内部容积高,孔径分布窄,介孔硅纳米粒子(MSNs)被认为是一种理想的无机纳米载体。大量的文献报道了介孔硅材料广泛地应用于生物催化,骨组织工程和药物控制释放等生物医学领域。通过介孔硅纳米粒子与聚合物的复合,研究者可以控制有机无机纳米杂化体系的结构和性质。利用表面引发的可控自由基聚合(SI-CRP)可以方便地制备聚合物接枝介孔硅纳米粒子。在前人工作的基础上,本论文在高分子可控合成和材料改性方向上进行了有意义的探索：结合Sonogashira反应和自缩合原子转移自由基乙烯基聚合(SCATRVP)反应,合成了带有超支化侧链的共轭聚合物；应用活性自由基聚合和自缩合乙烯基聚合反应等,制备了不同拓扑结构聚合物修饰的介孔硅纳米粒子,赋予介孔硅纳米粒子以良好的分散性能和特定的功能；以叔丁基过氧化氢-抗坏血酸为引发剂,在室温水相中合成了多种嵌段聚合物并对其性能进行研究。具体研究结果简述如下：1)为了提高聚对苯撑乙炔(PPE)的溶解性,同时降低聚对苯撑乙炔分子链间的相互作用,我们通过SCATRVP反应制备了一种新型的具有超支化聚合物侧链的共轭聚合物PPE-g-HPBBEA。PPE-g-HPBBEA的分子量随着BBEA与PPE-Br投料比的增加而增加。聚合物主链上接枝有超支化聚合物,由于超支化侧链降低了PPE主链的π-π相互作用和PPE主链的堆积,因此PPE-g-HPBBEA在有机溶剂中有着良好的溶解性。相较于PPE-OH, PPE-g-HPBBEA的量子产率有了明显提高,同时随着侧链超支化聚合物分子量的增大,PPE-g-HPBBEA的荧光量子产率也逐渐增加。2)为了提高介孔硅纳米粒子的分散性和稳定性,我们以表面带有ATRP引发基团的介孔硅纳米粒子(MSN-Br)为引发剂,进行自引发单体BBEA的SCATRVP,得到了表面接枝有超支化聚合物的介孔硅纳米粒子(MSN-g-HPBBEA)。随着BBEA与MSN-Br投料重量比的不断增大,表面接枝的超支化聚合物的分子量逐渐增大。我们利用所制备的MSN-g-HPBBEA表面的众多ATRP引发基团,继续引发DMAEMA的ATRP反应,制得了具有pH响应性的介孔硅纳米粒子,这种杂化纳米粒子在药物传输和生物显像等领域有广泛的应用前景。3)我们以MSN-Br为ATRP引发剂,聚合两种带有不同氧化乙烯侧链的单体(MEO2MA和OEGMA),得到了具有核壳结构的新型杂化粒子MSN-g-PMO,同时MSN的介孔结构仍然得以保留。我们通过调整MEO2MA和OEGMA的投料摩尔比,得到了具有不同LCST的MSN-g-PMO。FITC模型分子可以在室温下负载到MSN中,并通过温度的改变来进行FlTC的控制释放。通过内吞作用,MSN-g-PMO可以将FITC分子携带进入细胞并在一定温度下在细胞内释放。MSN-g-PMO具有良好的生物相容性和非常低的细胞毒性,在生物标记,生物传感器和药物控制释放领域都有广泛的应用前景。4)为了实现MEO2MA和OEGMA在水相中的RAFT聚合反应,我们以抗坏血酸-叔丁基过氧化氢为引发剂,CMP为RAFT试剂,在室温下水相中成功合成了PDMAa。利用PDMAa大分子RAFT试剂增加MEO2MA在水中的溶解性,同时控制MEO2MA和OEGMA的聚合,在水中制备了A-B-A三嵌段聚合物PDMAa-PMO-PDMAa。该三嵌段聚合物具有温敏性,其LCST随着OEGMA单元在共聚物中的含量增加而升高。该氧化还原引发体系生物相容性良好,在生物医用材料制备领域有着特殊价值。研究发现所合成的嵌段共聚物在不同的温度下可以形成胶束结构,一些难溶于水的物质可以进入胶束的内核,并可以在一定温度下通过胶束的解离而释放出来。这些性质都使得PDMAa-PMO-PDMAa在药物缓释领域有广泛的应用前景。5)我们利用RAFT聚合方法,在水相中室温下合成了PEO-b-PDMAEMA两嵌段共聚物有,并与MAH-β-CD反应,最终得到了PEO-b-PDMAEMA-(MAH-β-CD)共聚物。该聚合物生物相容性优良,细胞毒性小,是一种优秀的基因转染试剂。通过细胞转染实验,我们证实了该共聚物可以作为基因传递材料进入细胞并将负载的GFP基因成功表达。同时经过实验,我们发现PEO-b-PDMAEMA-(MAH-β-CD)共聚物可以引起细胞的自噬行为,这些优异的性质使得PEO-b-PDMAEMA-(MAH-β-CD)共聚物有望成为一种潜在的基因治疗材料在医治肿瘤方面有着广泛用途。更多还原

【Abstract】 It is well known that the properties of polymers are strongly influenced by their chain architecture. The design of macromolecules is important for obtaining the polymer materials with predetermined properties. Controlling polymer properties through design and synthesis of copolymers and macromolecular architectures is a challenging theme for polymer chemistry. For studying the relationship between the architecture and properties of polymers, and further designing the polymers with predetermined properties, it is necessary to apply known controlled living polymerization mechanism to synthesize different kinds of polymer with special architecture.Hyperbranched polymers are highly branched macromolecules with three-dimensional dentritic architecture, and they have many special physical and chemical properties, such as low viscosity, high fluidity, good solubility and a large number of terminal groups in comparison of linear polymers. The synthesis of hyperbranched polymers can be classified by two main strategies:(i) step-growth polycondensation of ABX monomers and (ii) self-condensing vinyl polymerization. Utilizing these polymerization strategies, a wide variety of hyperbranched architectures have been synthesized successfully, including hyperbranched polyesters, polyamides, polycarbonates and polyurethanes. Hyperbranched polymers have been utilized in various fields such as medicine carriers, nonlinear optics, nanometer materials and catalysis.Recently, block copolymers have attracted considerable attention because of their unique behaviors and potential applications, such as thermoplastics, surfactants, modifiers, dispersants, and tackifier, etc. With the development of living radical polymerizations, such as SFRP, ATRP and RAFT, a large number of novel well-defined block copolymers with controlled molecular weights and narrow molecular weight distributions were prepared.The nanoscale coupling of organic and inorganic materials has proven to be a very efficient way to create smart hybrid materials. Due to their highly ordered structure associated with large specific surface area, high internal volume, and narrow pore size distribution, mesoporous silica nanoparticles (MSNs) are ideal inorganic nanocarriers. The increasing interest in these materials is strongly evidenced by their biomedical applications devoted for instance to biocatalysis, bone tissue engineering, or to the creation of stimuli-responsive nanovalves for controlled drug delivery. Such hybrid organic-inorganic nanosystems can be advantageously created by coupling MSNs with polymers of controlled architecture and precise properties. As a facile method to synthesize polymer grafted MSNs, surface-initiated controlled free radical polymerization (SI-CRP) provides polymer brushes grafted MSNs.Based on the researches of the precursors, this dissertation described several outspread works in the synthesis of topologically structured polymers and the modification of mesoporous silica nanoparticles. All these facts are the origin and impetus of this thesis. The main results obtained in this thesis are as follows:1) To enhance the solubility of PPE and decreaseπ-πinteractions of PPE main chains, a facile synthetic strategy for preparation of a novel conjugated polymer with hyperbranched polymer side chains-PPE-g-HPBBEA has been developed through SCATRVP in one-pot. The molecular weight of PPE-g-HPBBEA increased with increasing feed ratio of BBEA to PPE-Br. The conjugated PPE backbones are wrapped with the HPBBEA, and this structure restrains the stacking of conjugated PPE chains because hyperbranched side chains decrease theπ-πinteractions of PPE main chains. Thus, the PPE-g-HPBBEA has good solubility in normal organic solvents such as THF and chloroform. The quantum yields of PPE-g-HPBBEAs increased significantly in comparison with their precursor, PPE-OH, and the quantum yields increased with the increase of molecular weight of the HPBBEA on the PPE backbones.2) Core-shell nanostructure with a mesoporous silica nanoparticle core and a hyperbranched polymer shell has been prepared by the surface-initiated SCATRVP of BBEA using MSN with bromoisobutyryl groups as initiator. The molecular weight of HPBBEA grafted increased with the increasing ratio of inimer BBEA to MSN-Br. Hybrid nanoparticles showed better dispersibility in organic solvents than the precursor MSNs. Utilizing MSN-g-HPBBEA as macroinitiator, PDMAEMA was successfully grafted onto the hyperbranched polymer shell of MSN-g-HPBBEA. The resultant nanoparticles, MSN-g-HPBBEA-g-PDMAEMA showed pH-responsive property, which will have potential applications in biomedicine and biotechnology.3) MSN-g-PMO core-shell nanoparticles were successfully synthesized through surface-initiating ATRP technique, and the inner channels of MSNs remained. The LCST of MSN-g-PMO could be adjusted by changing the feed molar ratio of MEO2MA and OEGMA. FITC as a model guest molecule could be encapsulated in the mesopores of MSNs above LCST, and released from the mesopores in MSN when the temperature was below LCST. Through an endocytic mechanism, MSN-g-PMO could easily carry FITC into cells. The MSN-g-PMO showed good biocompatibility and very low cytotoxicity, which make it a promising material for applications in biomarkers, biosensors and controlled drug delivery systems.4) In order to achieve RAFT polymerization of MEO2MA and OEGMA in the aqueous phase, at first, we synthesized macroRAFT agent PDMAa by utilizing ascorbic acid/tert-butyl hydrogen peroxide redox initiator and CMP as the RAFT agent, in aqueous solution at room temperature. The polymers obtained were characterized by GPC. MacroRAFT agent PDMAa could enhance solubility of MEO2MA in water, while control RAFT copolymerization of MEO2MA and OEGMA in water. The obtained ABA triblock polymer-PDMAa-PMO-PDMAa exhibit thermo-sensitivity and the LCSTs rise with the increase of OEGMA content in the PDMAa-PMO-PDMAa. The initiators in polymerization exhibit better biocompatibility, which has a special value in the field of biological materials. The triblock copolymers can form micelle in different temperature, and some insoluble molecules could enter into the core of micelles. The guest molecules in core of micelle could be released through dissociation of micelle in predetermined temperature. These properties make PDMAa-PMO-PDMAa be widely used in the field of drug delivery.5) We synthesized the PEO-b-PDMAEMA diblock copolymer by RAFT polymerization in aqueous solution at room temperature, and obtained the PEO-b-PDMAEMA-(MAH-p-CD) copolymer by the reaction of PEO-b-PDMAEMA and MAH-P-CD. The copolymers have excellent biocompatibility and low cell toxicity. We confirmed that the PEO-b-PDMAEMA-(MAH-β-CD) copolymer can transfect gene into the cell and successfully expressed the GFP gene. Through the cell experiment, we found that PEO-b-PDMAEMA-(MAH-β-CD) copolymer can cause cell autophagic behavior. These outstanding properties make PEO-b-PDMAEMA-(MAH-P-CD) copolymer be potential gene treatment materials which have a wide range of applications in the treatment of cancer.更多还原