氧化还原引发乙烯基自缩合制备超支化聚糖和氨基酸类高分子及应用

Glycopolymers (or poly(amino acid)) have been received much more attention due to their potential applications in biosensors, cell-cell interactions and drug controlled release field in a similar fashion to natural material in recent years. An aim of this project is to synthesize the hyperbranched glycopolymers (or hyperbranched poly(amino acid)). The vinyl monomers containing sugar moiety (or amino acid moiety) are prepared firstly. The polymerization will be promoted by redox process where the initiating system is constructed by the reduction groups on the vinyl monomers containing sugar moiety (or amino acid moiety) with supernormal valence transition-metals. The propagation can take place either at the double groups resulting in the linear segments or after the initiation of the reduction groups functionality resulting in the branching point. Since the initiation rate of radical formation is slower than that of linear chain growth, the product has much lower degree of branching indicating the linear architecture. The competition between linear chain growth and the formation of the branching points strongly affect the topological structure of hyperbranched polymers. The key problem in the project is to control the rate of linear chain growth and the formation of branching points. In order to overcome this problem, the synthetic pathways may be listed as follows. By addition of a reversible chain transfer agent (RCTA) in the self-condensing vinyl polymerization system, the concentration of propagating polymer radicals should be suppressed efficiently. So growth rate of linear polymer chains slow down while the rate of forming branching point increase simultaneously, and eventually the hyperbranched polymers are afforded successfully. The polymerization mechanism is basically in agreement with the idea of self-condensing vinyl polymerization combining with the reversible addition-fragmentation chain transfer (RAFT) polymerization technique. The effect of reaction condition on the conversion, molecular parameters, and the degree of branching will be also investigated in detail to examine the best matching condition between the rate of linear chain growth and formation of branching points. The post-polymerization will be performed to study living character of product. The topological structure of the hyperbranched polymers proposed in the project will be tuned through the copolymerization of monomer containing sugar moiety (or amino acid moiety) synthesized in the plan with the mono vinyl monomer. The controlled release behavior of the product, as well as interactions between product and protein, will be explored.

含糖及氨基酸类高分子具有广泛的应用背景。本项目的目标是合成超支化聚糖及聚氨基酸类高分子。合成方法是首先在糖和氨基酸基元上引入烯键，利用超常价态过渡金属氧化剂与糖或氨基酸上的还原性基团构成氧化还原引发体系，进行乙烯基自缩合制备超支化聚糖及聚氨基酸类高分子，支化点由糖和氨基酸类基元构成。由于链增长速率远大于氧化还原产生的自由基速率，导致产物的支化度较低，因此调控链增长速率是本项目拟解决的关键问题。我们将利用RAFT试剂调控链的增长速率，解决该关键问题。本项目将研究RAFT试剂和超常价态过渡金属氧化剂之间匹配问题；反应条件对超支化聚糖及聚氨基酸类高分子的分子量、支化度等的影响；制备的超支化聚糖及聚氨基酸类高分子活性特征；单烯类单体作为线性单元的加入对超支化高分子拓扑结构的影响。本项目还将进行超支化聚糖和氨基酸类高分子与生物蛋白的相互作用以及药物负载等方面的研究。

本项目利用氧化还原体系中还原性基团产生自由基的特点，引发乙烯基自缩合制备超支化聚糖和聚氨基酸类高分子。项目组首先通过硝酸铈铵/羟基（Ce(IV)/OH）氧化还原引发体系制备了超支化聚羟甲基丙烯酰胺和超支化聚6-O-甘露糖，研究结果表明两种单体中羟基的活性不同导致引发机理发生改变。超支化聚羟甲基丙烯酰胺的自由基产生机理为羟基自由基转移至相邻的亚甲基，形成C自由基，最终由C自由基引发聚合。而超支化聚6-O-甘露糖的自由基产生机理则为氧自由基，自由基转移过程并未出现。在支化结构的调控上，研究结果表明，在本项目研究的范围内，超支化聚6-O-甘露糖的相对支化度与硝酸铈铵/6-O-甘露糖呈线性增长关系；超支化聚6-O-甘露糖的分子量与硝酸铈铵的用量呈反比关系；研究中发现在糖环在未保护的条件下，发生氧化还原反应时糖环结构保持完整，氧自由基未发生转移。利用RAFT试剂对链增长速率的抑制作用，项目组以双丙烯酰胺类单体为模型，考察了RAFT的种类和用量对聚合反应的影响，并制备了具有高支化度（90%）和高产率（89%）的超支化聚双丙烯酰胺。然而RAFT试剂在氧化还原制备超支化聚6-O-甘露糖时未取得明显效果。项目组利用Ce(IV)/NH2氧化还原引发体系，制备了超支化聚N-甲基丙烯酰基丝氨酸甲酯。实验结果表明该引发体系可给出支化度的计算方案，其支化度与硝酸铈铵的用量成正比，最高值可达34%。项目组开展了超支化聚糖的功能化研究，在超支化聚糖与刀豆蛋白络合方向，研究结果表明，提高超支化聚糖的分子量有利于提高其与刀豆蛋白的络合能力，增加超支化聚糖的支化度使得其与刀豆蛋白的络合能力下降。利用超支化聚糖良好的水溶性和生物相容性，项目组以其为基材制备了聚糖/姜黄素接枝共聚物，聚糖/荧光素接枝共聚物，结果表明聚糖/姜黄素接枝共聚物、聚糖/荧光素接枝共聚物的水溶性显著提高，且对H2O2和线粒体具有优良的识别能力。