活性聚合联用制备梳状功能大分子及其单分子自组装行为

Functional proteins serve as superior units in constructing life and their special property are dependent upon multi-level structure. In the view of macromolecules, proteins are aggregates with complex functions constructed by several peptide chains and their functions are closely related with the sequence distribution of limit amino acids and the self-assembly arising from amino acids' sequence. Considering the structural advantage of comb-like macromolecule with multi long branches and the method advantage of combination of different living polymerizations, well-defined comb-like functional macromolecules are prepared via combination of ring-opening metathesis polymerization (ROMP) and reversible addition-fragment chain transfer (RAFT) living polymerization in which back-bones are tailored and generated by ROMP and long-branched chains are designed and grafted by RAFT living polymerization. The sequence distribution of amino acids in peptide chains, multi peptide chains and multi molecule self-assembly in constructing space structure of protein are respectively substituted with the sequence distribution of segments, branch chains and single molecule self-assembly of comb-like macromolecules. Then the senior space structures are constructed by single molecule self-assembly of functional macromolecules. The relationship between chain structure and senior space structure will be extensively studied. Finally, the aggregate of single molecule with multi-functions is constructed through endowing the function of storing Fe3+ and releasing Fe2+ similar to ferritin to different locations of comb-like macromolecule.

功能蛋白作为构筑生物体的高级单元，其多级结构决定了其特定功能。在分子水平上研究和模拟功能蛋白的构效关系，为合成功能大分子提供了思路和借鉴。从大分子的角度看，蛋白质为多肽链参与构筑的具有复杂功能体系的空间结构体，其功能依赖于有限氨基酸种类的侧基序列排布及其基础上的自组装形态。鉴于多长支链梳状大分子的结构优势和活性聚合联用的方法优势，本研究拟采取开环易位聚合（ROMP）、（可逆加成断裂链转移）RAFT活性聚合联用的方法制备多长支链梳状大分子，以链段序列对应肽链的氨基酸侧基序列，多支链对应构筑蛋白空间结构的多肽链，梳状大分子的单分子自组装对应肽链的多分子自组装，分别通过ROMP和RAFT聚合设计生成主链和支链，制备一系列链结构可调的功能大分子并进行自组装，研究链结构对其单分子自组装的影响，并以储铁蛋白氧化储Fe3+、还原释Fe2+功能为模板，赋予组装体功能性，构筑多功能单分子组装体。

本项目主要采用多种活性聚合联用的方法，设计合成结构明确的大分子，研究大分子微结构对组装体形态的影响，探索其特性及潜在应用。为了制备结构明确的梳状大分子并研究其组装行为及功能特性，首先合成了降冰片烯基功能单体，研究了官能团对活性ROMP的影响；进而采用graft to 途径，RAFT多元活性共聚的方法制备了梳状大分子。依据官能团对ROMP的影响，分别采用功能单体直接共聚和先聚合后改性两种手段对ROMP聚合物接枝和功能化。在多元RAFT活性共聚调控支链微结构过程中，对比了两步法和半连续聚合的优缺点，着重研究了细乳液聚合中多位点链转移剂的接枝效率和链段组成对大分子凝聚态和单分子组装体尺寸及形态的影响，并研究了含硫端基的液相催化热解脱除工艺。以大分子药物为应用背景，研究了大分子微结构对性能的影响。结果表明，链段序列结构对小分子药物的负载量和缓释周期产生较大影响。当大分子同时赋予还原和络合特性时，大分子能够附着于癌细胞膜表面，构筑Fe3+向细胞内的传质障碍，有效降低细胞内的Fe3+含量，从而抑制癌细胞的增殖；当大分子赋予氧化催化性能时，Fe2+的氧化反应级数由二级提高为三级，其催化活性优于生物体内的铜蓝蛋白。最后，大分子通过功能单体进行交联能够获得同时具有离子源、离子传导区和膜支撑区的自支撑聚合物电解质膜，该膜具有良好的离子传导率和热稳定性。通过本项目的实施，建立了梳状大分子的合成方法，为梳状大分子的应用开发奠定了理论基础。