Short- and Long-Range Structural Complexity from Ortho-arylene Foldamers

在化学系大分子、超分子和纳米化学项目的支持下，C。迈阿密大学的斯科特·哈特利将研究控制非生物分子折叠的方法。生物化学系统利用的分子既大又结构复杂。这种结合对于生物化学系统的显著复杂性和功能是必要的。构建可比较的非生物分子目前超出了合成化学的能力。大自然产生结构复杂性的策略是将长链分子折叠成特定形状。这个研究项目旨在增加我们对长链分子折叠的因素的理解。控制分子折叠成复杂3D结构的能力对于分子识别和催化的高级应用是重要的。 这项工作将涉及研究生和本科生，他们将接受合成和物理有机化学方面的培训。其他更广泛的影响包括开发一个新的教学实验室活动，与分子折叠相关的吸引力相互作用，并与俄亥俄州大学联盟的一个项目合作，支持来自代表性不足背景的学生。该项目旨在研究一类称为“foldamer”的非生物分子的折叠，并开发两种控制其折叠成3D结构的策略。 更具体地说，本项目将集中研究邻亚芳基折叠体。邻亚苯基是一类简单的芳香族折叠体，具有两个非常有用的性质：它们的折叠结构可以在溶液中使用核磁共振（NMR）光谱和计算化学非常精确地确定，并且它们的折叠倾向足够弱，很容易被扰动。这些特性使它们非常适合从二级结构发展到三级结构，这是折叠体研究目前面临的挑战。在第一种策略中，将研究在单个分子内混合吸引和排斥相互作用的链的折叠。 通过将吡嗪-2，3-二基单元并入序列中来编程折叠，将获得用于构建三级结构所需的卷曲片段的复杂结构。在第二种策略中，笼状结构纳入多个邻亚苯基单元将作为简单的三级结构的例子进行研究。重点将放在理解如何折叠的邻苯响应笼的几何形状和包括客体分子。 这项研究有可能提供访问和理解从根本上新的分子折叠系统，以建立复杂的非生物结构，具有结合小分子分析物的巨大潜力，并有可能提供一个新的分子支架催化。该奖项反映了NSF的法定使命，并已被认为是值得通过使用基金会的智力价值和更广泛的影响审查标准进行评估的支持。

With the support of the Macromolecular, Supramolecular and Nanochemistry Program in the Division of Chemistry, Professor C. Scott Hartley of Miami University will investigate methods by which the folding of non-biological molecules can be controlled. Biochemical systems make use of molecules that are both large and structurally complex. This combination is necessary for the remarkable sophistication, and thus function, of biochemical systems. Constructing comparable non-biological molecules is currently beyond the capabilities of synthetic chemistry. Nature’s strategy for generating structural complexity is by folding a long chain molecule into a specific shape. This research project aims to increase our understanding of the factors that govern the folding of long chain molecules. The ability to control molecular folding into complex 3D structures is important for advanced applications in molecular recognition and catalysis. The work will involve graduate students and undergraduates, who will be trained in synthetic and physical organic chemistry. Additional broader impacts include the development of a new teaching laboratory activity on attractive interactions relevant to molecular folding and work with a program from a consortium of Ohio universities supporting students from underrepresented backgrounds.This project aims to study the folding of a class of non-biological molecules called “foldamers” and to develop two strategies for controlling their folding into 3D structures. More specifically, this project will focus on studying ortho-arylene foldamers. ortho-Phenylenes are a simple class of aromatic foldamers that exhibit two very useful properties: their folded structures can be determined in solution with great precision using nuclear magnetic resonance (NMR) spectroscopy and computational chemistry, and their folding propensities are weak enough to be easily perturbed. These properties make them well suited to progressing from secondary to tertiary structure, a current challenge for foldamers research. In the first strategy, the folding of chains that mix attractive and repulsive interactions within a single molecule will be studied. By programming folding through the incorporation of pyrazine-2,3-diyl units into the sequence, complex structures will be obtained that are to be used to construct the coil segments necessary for tertiary structure. In the second strategy, cage structures incorporating multiple o-phenylene units will be investigated as simple examples of tertiary structure. Emphasis will be placed on understanding how the folding of the o-phenylenes responds to cage geometry and the inclusion of guest molecules. This research has the potential to provide access to and understanding of fundamentally new molecular folder systems to build complex non-biological structures with great potential for binding small molecule analytes and the potential for providing a new molecular scaffold for catalysis.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.