Construction of Single Molecule Nanostructures by Self-Assembly and Fixation

DNA链自发组装成分支纳米结构的潜力在1982年首次被描述；然而，尽管基于dna的制造在过去三十年中取得了非凡的进步，但所得到的结构相对较弱，这降低了其作为纳米级制造方法的通用性。此外，高度复杂结构的建造需要多个连续的制造步骤，需要对不完整的结构进行周期性稳定。该奖项支持对单分子纳米结构制造的研究，这些单分子纳米结构是由小分子组分逐步构建而成的，具有优异的热、化学和机械稳定性的复杂、多维纳米结构。该项目将提供制造自组装的纳米级设备的能力，这些设备在较弱的结构可能会失效的恶劣环境下保持稳定。由于该项目的多学科性质，学生参与者将被训练识别有机和聚合物化学，反应动力学和热力学中的问题，并设计和开展必要的实验来回答这些问题。学生将具备处理新兴研究领域的广泛技能，并能有效地与来自不同学科的研究人员进行沟通。此外，该项目将通过接触代表性不足的人口统计数据，帮助下一代科学家的招聘、教育和发展，扩大研究人员的人才库。在本研究中，可逆的、pH和温度敏感的反应，特别是胺/醛缩合反应和呋喃/马来酰亚胺Diels-Alder环加成反应，将被用作动态共价“碱基对”。在一种模拟互补DNA链中常见的自组装的方法中，将使用固相合成技术制备基于肽类和杂化肽类/肽的动态共价低聚物的互补链进行组装，并对双链组装的杂交选择性进行表征。固定反应，结合在正交反应条件下二聚化的碱基对，将被采用，允许多个组装步骤在不破坏新兴纳米结构的情况下进行。最后，通过仔细考虑它们的残基序列，将展示低聚物通过共价介导的动态组装成支链纳米结构。这项工作的成功完成将产生利用动态共价介导组装制造任意、坚固的纳米结构的理解和能力，这是纳米制造的一个重要的新方向。

The potential for strands of DNA to spontaneously assemble into branched nanostructures was first described in 1982; however, although DNA-based fabrication has seen extraordinary advances over the intervening thirty years, the resultant structures are relatively weak, reducing its versatility as a nanoscale manufacturing approach. Additionally, the construction of highly complex structures requires multiple, sequential fabrication steps, requiring periodic stabilization of the incomplete structure. This award supports an investigation into the fabrication of single molecule nanostructures that are progressively built up from small molecular components to generate complex, multi-dimensional nanostructures with excellent thermal, chemical, and mechanical stability. This project will provide the capability to fabricate self-assembled, nanoscale devices that remain stable under harsh environments where weaker structures would fail. Owing to the multi-disciplinary nature of this project, the student participants will be trained to identify questions in organic and polymer chemistry, and in reaction kinetics and thermodynamics, and design and carry out the experiments necessary to answer those questions. The students will have a broad skill set for tackling emerging research areas and will be effective at communicating with researchers from different disciplines. Additionally, this project will assist the recruitment, education, and development of the next generation of scientists through outreach to under-represented demographics, widening the pool of researcher talent. In this research, reversible, pH- and temperature-sensitive reactions, specifically amine/aldehyde condensation and furan/maleimide Diels-Alder cycloaddition reactions, will be employed as dynamic covalent "base pairs". In an approach mimicking the self-assembly commonly observed in complementary DNA strands, the assembly of complementary strands of peptoid- and hybrid peptoid/peptide-based dynamic covalent oligomers, fabricated using solid phase synthesis, will be performed and the hybridization selectivity of the double-stranded assemblies will be characterized. Fixation reactions, in conjunction with the base pairs that dimerize under orthogonal reaction conditions, will be employed, allowing for multiple assembly steps to be performed without disruption of the emergent nanostructure. Finally, through careful consideration of their residue sequence, the dynamic covalent-mediated assembly of oligomers into branched nanostructures will be demonstrated. The successful completion of this work will yield both the understanding and capability to fabricate arbitrary, robust nanostructures using dynamic covalent-mediated assembly, an important new direction in nanomanufacturing.