Construction of Single Molecule Nanostructures by Self-Assembly and Fixation

1982年首次描述了DNA链自发组装成分枝纳米结构的可能性；然而，尽管在其间的30年里，基于DNA的制造取得了非凡的进步，但得到的结构相对较弱，降低了其作为纳米级制造方法的多功能性。此外，构建高度复杂的结构需要多个顺序的制造步骤，需要不完整结构的周期性稳定。该奖项支持对单分子纳米结构制造的研究，单分子纳米结构是由小分子组成逐步建立起来的，以产生具有优异的热稳定性、化学稳定性和机械稳定性的复杂的多维纳米结构。该项目将提供制造自我组装的纳米级设备的能力，这些设备在恶劣的环境中保持稳定，在恶劣的环境中，较弱的结构将失效。由于这个项目的多学科性质，学生参与者将接受培训，以识别有机化学和聚合物化学以及反应动力学和热力学中的问题，并设计和进行回答这些问题所需的实验。这些学生将拥有处理新兴研究领域的广泛技能，并将有效地与来自不同学科的研究人员进行沟通。此外，该项目将通过扩大代表性不足的人口统计数字，帮助招募、教育和发展下一代科学家，扩大研究人才库。在这项研究中，可逆、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。在一种模拟通常在互补DNA链中观察到的自组装的方法中，将进行利用固相合成制备的类肽和杂化类肽/肽动态共价低聚物的互补链的组装，并将表征双链组件的杂交选择性。固定反应，结合在正交反应条件下二聚的碱基对，允许在不破坏新出现的纳米结构的情况下执行多个组装步骤。最后，通过仔细考虑它们的残基序列，将展示低聚物在动态共价介导下组装成支化纳米结构的过程。这项工作的成功完成将带来利用动态共价介导的组装来制造任意、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.