【作者】 殷俊；

【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】 微凝胶/纳米凝胶是一类交联的聚合物粒子,这类物质具有高的水含量、生物相容性及可调节的化学、物理等性质,如果其中包含水溶性或水可溶胀性的聚合物链亦可称之为水凝胶。其具有的独特性质,使得微凝胶在药物传输(DDS)、生物分离等领域有着极为重要而广泛的应用价值,且长期以来一直是科研领域研究的热点。当前和今后对于微凝胶应用领域的研究,主要集中在如何很好的控制这些性质上,主要包括生物医药上的官能化、粒子尺寸的控制、降解性质及药物的持续可控释放及残留物的移除。这篇论文主要集中研究环境(温度、pH等)响应型微凝胶在外界刺激改变时的相转变动力学及其特征弛豫时间与微凝胶初始粒径之间的标度关系,以及功能化的微凝胶在重金属离子检测方面的应用。具体来说,本论文的工作包括以下几个方面：1.利用自由基乳液聚合法,制备环境(pH、温度等)响应型的聚(2-乙烯基吡啶)(P2VP)和聚(N-异丙基丙烯酰胺)(PNIPAM)微凝胶。通过停流光谱仪的快速混合装置实现pH值或温度跃变,并结合光散射和荧光分辨技术,检测输出信号随时间变化的动力学曲线,分析微凝胶的相转变行为及其溶胀/收缩的重要动力学过程,选择合适的拟合手段,得出每个过程对应的特征弛豫时间,并揭示微凝胶尺寸与相转变特征时间之间的标度关系。2.在研究微凝胶相转变动力学的基础上,进一步对影响相转变行为的因素进行了探讨。首先合成了含有对光敏感弱键单元(2-硝基苄酯)的PNIPAM微凝胶,这种弱键在紫外光照下可以断裂并产生亲水性的官能团,通过控制光照时间及共聚单元的比例,可以很好的实现在不同温度下对微凝胶相转变行为(体积变化)的调控,并可以通过荧光共振能量转移(FRET)体系对该过程进行监控；另外,合成了含有能够选择性络合离子的冠醚单元的PNIPAM微凝胶,通过主客体分子识别,一旦配合上相应的离子(K+)后,也能大大改善其亲水性,同样可以实现在不同温度下对微凝胶相转变行为(体积变化)的调控,并可以通过FRET对该过程及其动力学进行监控。3.基于聚(N-异丙基丙烯酰胺)(PNIPAM)的温度响应性质,制备了含有特定检测基元的微凝胶基化学传感器,实现了对水溶液中特定重金属离子高效、高选择性检测,检测性能可以通过温度进行调控。该课题首次合成了含有吡啶单元,在溶液中可以高效、高选择性的捕捉金属二价铜离子(Cu2+)的配体单体,并将该单体与具有荧光性质的丹磺酰单体通过自由基乳液聚合,无规共聚入轻度交联的温度响应性PNIPAM微凝胶中。该传感器在不同温度时,呈溶胀或收缩状态,共聚的吡啶单体可以高效、高选择性的捕捉溶液中的Cu2+,形成的Cu2+-吡啶配合物可以有效的淬灭临近丹磺酰分子的荧光,通过检测丹磺酰荧光强度的变化,从而达到检测溶液中Cu2+的目的。4.结合原子转移自由基聚合(ATRP)与“点击”化学(Click Chemistry)技术,合成了两亲性的Poly(PMMA-alt-PNIPAM)交替共聚物,并研究了该种聚合物在水溶液中的自组装行为,可以形成以PMMA为核、PNIPAM为壳层的球形胶束,利用TEM、LLS、DSC等测试手段对胶束的结构和性质进行了详细研究。更多还原

【Abstract】 Microgels or nanogels are cross-linked polymeric particles. Most of them possess high water content, biocompatibility, and desirable mechanical properties. They offer unique advantages for polymer-based drug delivery systems (DDS) and chemical separation. Present and future microgel applications require a high degree of control over properties, including novel functionality for further bioconjugation, controlled particle size with uniform diameter, biodegradability, and sustained release of drugs for a desired period of time and facile removal of empty devices. In this dissertation, kinetics of volume phase transition (deswelling or swelling) of pH-and thermo-responsive microgels, uptake and controlled release of small molecules, polymers, and proteins into and out of microgels, and functionalized microgels/polymers for the detection of heavy metal ion were detailedly investigated. The dissertation includes the following six parts:1. Near-monodisperse and cross-linked poly(N-isopropylacrylamide) (PNIPAM) microgels and poly(2-vinylpyridine) (P2VP) microgels were synthesized using free radical emulsion polymerization, which exhibit completely reversible pH-and thermo-responsive deswelling and swelling behavior in aqueous solution. Kinetics of deswelling was studied using a stopped-flow apparatus equipped with a newly developed millisecond pH-jump and a temperature jump (mT-jump) accessory, the correlation between the characteristic initial microgel deswelling time and the square of the microgel radius, R2, was established.2. We further studied the effects of light and crown ether-ions complex on the volume phase transition behavior of microgels. Firstly, we synthesized thermo-responsive PNIPAM microgels covalently incorporated with fluorescence resonance energy transfer (FRET) donors,4-(2-acryloyloxy-ethylamino)-7-nitro-2,1,3-benzoxadiazole (NBDAE), FRET acceptors, N-(9-(2-((2-(acryloyloxy)ethoxy)carbonyl)phenyl)-6-(diethylamino)-3H-xanthn-3-ylidene)-N-ethylethanaminium (RhBEA), and certain photoactivable monomer,5-(2-(dimethylamino)ethoxy)-2-nitrobenzyl acrylate (DMENBAA) using free radical emulsion polymerization. Upon photoirradiation at 365 nm under UV irradiation at elevated temperature, the 2-nitrobenzyl ester group in the photolabile monomer covalently attached within the microgels would be cleaved, resulting in the formation of a negatively charged carboxylate group and reswell of microgels. Similarly, PNIPAM microgels covalently incorporated with NBDAE, RhBEA, and certain alkali metal ions captures, 4-acrylamidobenzo-18-crown-6 (B18C6Am), were also synthesized. The shift of LCST for volume phase transition of the synthesized microgels in response to K+ at varied concentrations were studied, and the property, such as hydrophilicity, of microgel contains B18C6Am, changes when B18C6Am bind special guest chemicals (K+).3. Cu2+-sensing thermoresponsive poly(N-isopropylacrylamide) (PNIPAM) microgels labeled with metal-chelating acceptor and fluorescent reporter moieties were synthesized. Cu2+ detection sensitivity can be considerably enhanced via thermo-induced collapse of the sensing matrix, which can facilely optimize the relative spatial distribution of Cu2+-binding sites and fluorescence read-out functionalities. A novel picolinamine-containing monomer with Cu2+-binding capability, N-(2-(2-oxo-2-(pyridine-2-yl-methylamino)-ethylamino)ethyl)acrylamide (PyAM), and fluorescent dansylaminoethyl acrylamide (DAEAM) monomers were synthesized at first. At low temperature, as-synthesized samples in their swollen state can selectively bind Cu2+ over other metal ions, leading to prominent quenching of fluorescence emission intensity. Above the volume phase transition temperature, microgels exhibit increased fluorescence intensity. It was observed that Cu2+ detection sensitivity could be dramatically enhanced via thermo-induced microgel collapse at elevated temperatures. The underlying mechanism for this novel type of sensors with thermo-tunable detection sensitivity was tentatively proposed.4. Well-defined amphiphilic copolymer brushes possessing alternating poly(methyl methacrylate) and poly(N-isopropylacrylamide) grafts, poly(PMMA-alt-PNIPAM), via a combination of atom transfer radical polymerization (ATRP) and click reaction were obtained. Poly(PMMA-alt-PNIPAM) supramolecularly self-assembles into spherical micelles consisting of PMMA cores and thermoresponsive PNIPAM coronas in aqueous solution, the properties of micelle solution were characterized via a combination of temperature-dependent optical transmittance, micro-DSC, LLS, and TEM.更多还原