Design of Modular Receptors for Ion and Molecule Recognition

项目概述/摘要本研究计划的总体主题是设计模块化有机受体，该受体包含识别元件，可优化结合溶液中的阴离子。模块化可以方便地替换固有的荧光有机核心、识别元素、连接器和功能。这项研究将有助于下一代分子探针、传感器和阴离子结合剂的开发。所提出的受体也将有助于对阴离子在自组装中的结构作用及其与缺电子芳香环的相互作用提供基本的理解。这项研究的长期应用包括阴离子的细胞和体外成像。本研究的具体目标是：1)合成和研究由所提出的模块化设计策略产生的一系列阴离子受体；2)研究模块化受体作为荧光分子探针在化学生物学中的应用；3)研究阴离子与缺电子芳香环的相互作用并设计识别元件以利用这一新兴的阴离子结合基序。所提出的设计策略的模块化允许探索阴离子的各种识别基序，包括静电吸引，氢键相互作用和与缺电子芳烃（阴离子pi， CH- X-氢键和弱sigma配合物）的吸引。这种灵活性允许选择性结合阴离子的可能性，这是传统方法难以达到的目标。核和连接体替代提供了另一种通过改变结合袋的形状和大小来调节受体选择性的方法。受体的功能也可以调整，以提供一种使分子水溶性甚至可渗透到细胞膜的途径，一旦解决了溶液的化学性质，就可以在细胞成像中应用。研究阴离子的新识别基序，如阴离子与缺电子芳烃之间的相互作用，需要了解操纵这些新的理论结合基序的基础科学，以便设计新的受体。这项研究的应用有可能转移到用于修复和传感的新材料的设计中，并可能为阴离子与生物基质之间的相互作用提供见解。提出的研究也可能揭示在更复杂的生物系统的自组装过程。因此，如果人们希望阐明阴离子在更复杂的生物过程中的作用，从分子水平上理解阴离子结合是至关重要的。

DESCRIPTION (provided by applicant): Project Summary/Abstract The overarching theme of the proposed research program is to design modular organic receptors containing recognition elements that are optimized to bind anions in solution. The modularity allows for facile substitution of inherently fluorescent organic cores, recognition elements, linkers and functionality. This research will aid in the development of the next generation of molecular probes, sensors and binding agents for anions. The proposed receptors will also help provide a fundamental understanding of the structural role anions play in self-assembly and their interactions with electron- deficient aromatic rings. Long-term applications of this research include cellular and in vitro imaging of anions. The specific aims of the proposed research are: 1) to synthesize and to study a series of receptors for anions resulting from the proposed modular design strategy, 2) to study the modular receptors as fluorescent molecular probes for applications in chemical biology, and 3) to study the interaction of anions with electron-deficient aromatic rings and design recognition elements to exploit this emerging anion-binding motif. The modularity of the proposed design strategy allows for exploration of a variety of recognition motifs for anions, including electrostatic attractions, hydrogen bond interactions and attractions with electron-deficient arenes (anion-pi, CH---X- hydrogen bonds and weak-sigma complexes). This flexibility allows for the possibility of selectively binding anions that are challenging to target with traditional approaches. Core and linker substitution provides another approach to tuning the selectivity of the receptors by changing the shape and size of the binding pocket. The functionality of the receptors can also be adjusted to provide a route to make the molecules water-soluble or even permeable to cell membranes, as applications in cellular imaging are pursued once the solution chemistries are worked out. Studying new recognition motifs for anions, such as the emerging interaction between anions and electron-deficient arenes, requires understanding the basic science of manipulating these new theoretical binding motifs in order to design novel receptors. Applications from this research have the potential to be transferred to the design of new materials for remediation and sensing and may provide insights on the interaction between anions and biological substrates. The proposed research may also shed light on self-assembly processes in more complex biological systems. Therefore understanding anion binding on a molecular level is of paramount importance if one wishes to elucidate the roles of anions in the much more complicated biological processes.