DNA与聚合物胶束之间的精确自组装及其应用

Precise self-assembly of macromolecules is still a difficult problem in the field of macromolecular self-assembly. Our preliminary study reveals that the self-assembly of monodisperse DNA and core-positive-charged polymeric micelles has the characteristic of precise macromolecular self-assembly when conditions for the assembly are deliberately controlled. During the self-assembly, the monodisperse beads-on-a-string structure, which is proved theoretically to be the structure of global minimum in energy, forms firstly. Then, different assembles with the beads-on-a-string structure evolve in a similar manner synchronically, finally into monodisperse core-shell structured nanofibers (nanorings). It is important that, in each of the resultant monodisperse nanofibers of a certain length, a DNA chain with a certain length and a known sequence distribution wraps the core precisely, adopting a left-handed solenoid conformation. As result, there is a 2 nm (the width of DNA chains) width solenoid district on the core surface where each point is modified with a specific base pair due to the wrapping by the DNA . We are going to prove with theoretical calculations that the formation of the globally optimal structure mainly results from the relatively big energy gap between the energy of the globally optimized structure and the metastable structures; the precise interactions in the globally optimized structure is responsible for the monodispersity and precise structure of the assembles. We will take efforts to find unique applications of such precisely structured assemblies, construct highly complex but highly regular structures and functionalize the assembles by fully taking advantage of the precise structure.

大分子的精确自组装是大分子自组装领域的难题。我们初步的研究结果表明，在单分散DNA与聚合物胶束的自组装体系中，通过控制自组装条件，可使得该自组装具有精确自组装的特征。该组装过程中，在理论上被认为是能量最优化的单分散串珠状结构首先形成，并同步演化，最后形成单分散核壳结构纳米线（环）。重要的是，在已知长度的不同单分散纳米线的表面上，长度及序列已知的DNA链以左手螺线管状精确缠绕，使得纳米线表面被缠绕区域上的每一个特定的点都相当于被DNA修饰上一个特定的碱基对，即纳米线表面的部分区域具有精确结构，该自组装具有精确自组装的特征。我们将用计算证明：该体系中，能量最优化结构形成的原因是由于最优化结构与亚稳态结构之间的能量差较大；精确结构的形成与最优化结构中的精确作用方式有关。我们将充分利用该组装体的特点开展应用研究，并基于组装体上的精确结构开展复杂结构的精确构筑，尝试建立在精确结构基础上的功能组装。

在本重点项目的资助下，利用DNA/聚合物之间的精确自组装，获得了表面具有近似于基团水平精确性的线性聚合物组装体，证明了DNA链螺旋缠绕于组装体表面。该精确自组装的原理和途径可总结为预组织加上能量最优化导向的单向结构演化。运用该原理和方法，成功地将溶液中A-b-B-b-C三嵌段共聚物无规线团转化成ABC三嵌段粒子，以及在“伴侣分子“的作用下将A-b-B无规线团转化为AB两嵌段粒子，实现了单链粒子高度排它性的类似于蛋白质结晶的自组装。.实现了环状DNA/聚合物的精确自组装以及聚合物核壳结构纳米环的可控制备。进一步地，实现了尺寸及形态高度均一的高度纯净的纳米线和纳米环的高效、规模化制备。研究了纳米线/环在溶液中的刚性、纳米环与球在介观尺度下的“主客体“相互作用以及由此形成的环状各向异性粒子在溶液中的精确组装、纳米线间的“交联”与“缠结”行为等。构建了纳米线的三维交联结构材料以及具有极低渗滤阈值的二维缠结网络，展示了其重要的应用性能。.总体上，我们实现了本项目申请书中包括核心目标在内的大部分研究目标，另外还发展了可用于规模化制备组装体的新的DNA/聚合物自组装机制，总结出DNA/聚合物间精确组装的原理和途径并将其拓展至多种具有复杂但高度精确结构的大分子组装体的构筑。基于本项目研究所取得的结果在J. Am. Chem. Soc., Angew. Chem. Int. Ed., ACS Macro Lett., Macromolecules, Biomaterials, Chem. Commun., Langmuir, Soft Matter等期刊上发表论文25篇，尚有部分重要结果仍在完善及整理发表的过程中；申请专利8项（其中三项获得授权）；培养硕士、博士、博士后共23人。