CAREER: Supramolecular Polycondensation of Polymer Brushes via DNA Hybridization

生物非常擅长利用纳米级物体，如蛋白质，作为构建模块来创造它们需要的材料。事实上，蛋白质之间的相互作用是所有细胞的基础，因为它们具有高度的方向性、特异性和可逆性；这些都是合成化学家尚未完全模仿的特征。该项目的目标是通过提取这种组装的要求来模拟天然蛋白质所表现出的一些精确组装能力，并以现代聚合物和有机化学可获得的新形式重新创造它们。为了实现这一目标，PI的团队将设计类似于瓶刷的合成聚合物（长聚合物分子有短附属物，就像瓶刷的刷毛一样），并将它们与短链DNA连接起来。由于互补链的DNA识别是明确的，原则上可以精确地设计刷状聚合物彼此之间的互连性。通过这种方法，有可能创造出一类新的“超聚合物”，即聚合物的构建块是纳米级的聚合物物体。PI将探索可以形成的超聚合物的种类，并确定控制它们形成的规则。由于DNA识别的特异性，具有各种特性（如大小、电导率或生物相互作用）的聚合物构建块可以以序列特异性和空间定义的方式连接在一起，以创建以前难以或不可能获得的功能材料。这种合成技术还具有由细胞内先天核酸介导的潜力，因此在医学上具有重要意义。这些研究活动将与教育项目交织在一起，为研究生/本科生（包括来自缺乏研究能力机构的本科生）提供实验室培训，并促进高中学生和STEM教师对科学相关职业的学习和意识。技术概述纳米级物体，如大分子和胶体纳米粒子，在存在引力的情况下可以形成有序结构。由于球形颗粒在其表面均匀地相互作用，因此定向组装以形成1D或2D结构是一个重大挑战。在这个由材料研究部聚合物和生物材料项目共同资助的项目中，PI将利用DNA识别作为一个功能群，相当于编程自下而上的按顺序组装聚合物构建块，这些构建块只能在指定的方向上相互作用。这些有限价构建块将用于研究拓扑调节的超分子聚合。提出的自组装策略包括合成三嵌段刷状聚合物作为“大单体”，它将与核酸偶联。核酸链之间的杂交允许单体从头到尾自组装，将它们线性或分支连接起来，形成更高阶的组装。通过系统地研究具有不同侧链长度，DNA双工和反应块长度的刷聚合物库，将获得关于刷构建块线性组装的机制见解。此外，将研究使用多单体体系（例如AA+BB）的超高聚物序列控制，为创建多组分功能材料奠定基础。定义小分子聚合的缩聚反应概念将在利用单价和多价大单体的超高聚物合成中进行测试，这些大单体有望提供对结构、平均聚合度和链端功能的控制。从这个项目中获得的能力将打开一个广泛的设计材料的范围，这些材料的顺序和拓扑特征在纳米尺度上是明确的，并将为聚合物科学带来新的知识，并为研究未知的特性创造机会。

NON-TECHNICAL SUMMARYLiving organisms are very proficient at utilizing nanoscopic objects, such as proteins, as building blocks to create materials that they need. Indeed, protein-protein interactions are the foundation of all cells because they are highly directional, specific, and reversible; these are characteristics that synthetic chemists have yet to fully emulate. The goal of this project is to emulate some of the precision-assembly ability that natural proteins exhibit by extracting the requirements for such assembly, and recreating them in new forms accessible to modern polymer and organic chemistry. Towards this goal, the PI's team will design bottlebrush-like synthetic polymers (where long polymer molecules have short appendages across them like the bristles in a bottlebrush) and connect them with short strands of DNA. Because DNA recognition of a complementary strand is well defined, one can in principle design the interconnectivity of the brush polymers with one another accurately. With this approach, it is possible to create a new class of "superpolymers", i.e. polymers whose building blocks are nanoscale-sized polymeric objects. The PI will explore the kinds of superpolymers that can be formed, and identify rules governing their formation. Because of the specificity of DNA recognition, polymer building blocks with various properties, such as size, electrical conductivity, or biological interactions, can be linked together in a sequence-specific and spatially defined manner, to create functional materials previously difficult or impossible to access. This synthetic technique also has the potential to be mediated by innate nucleic acids in cells, and therefore has important implications in medicine. These research activities will intertwine with educational programs to provide laboratory training to graduate/undergraduate students (including undergraduates from institutions lacking research capabilities) and to promote learning and awareness in science-related careers among high school students and STEM teachers.TECHNICAL SUMMARYNanoscopic objects such as macromolecules and colloidal nanoparticles can form ordered structures when there exist attractive forces. Because sphere-like particles uniformly interact across their surfaces, directional assembly to form 1D or 2D structures represents a significant challenge. In this project, co-funded by the Polymers and Biomaterials Programs in the Division of Materials Research, the PI will utilize DNA recognition as a functional group-equivalent to program the bottom-up assembly of made-to-order polymeric building blocks that can interact with each other only in defined directions. These limited-valency building blocks will be used to study topologically regulated supramolecular polymerizations. The proposed self-assembly strategy involves the synthesis of triblock brush polymers as "macromonomers", which will be conjugated with nucleic acids. The hybridization between the nucleic acid strands allows the monomers to self-assemble head-to-tail, connecting them either linearly or with branching, to form higher order assemblies. By systematically studying a library of brush polymers with different side-chain length, DNA duplex, and reactive block length, mechanistic insights about linear assembly of the brush building blocks will be obtained. In addition, superpolymer sequence control will be studied using multiple monomer systems (e.g. AA+BB), paving the ground for creating multi-component functional materials. Concepts from polycondensation reactions that define small-molecule polymerization will be tested against superpolymer synthesis, utilizing mono- and multi-valency macromonomers, which are expected to provide control over architecture, average degree of polymerization, and chain-end functionality. The capabilities gained from this project will open a wide spectrum of designer materials whose sequential and topological characteristics are well-defined on the nanoscopic scale, and will bring about new knowledge in polymer science and create opportunities to study yet unknown properties.