Design of Modular Receptors for Ion and Molecule Recognition

描述(由申请人提供)：项目摘要/摘要建议的研究计划的主要主题是设计包含识别元件的模块化有机受体，这些识别元件被优化以结合溶液中的阴离子。这种模块化可以方便地替换固有的荧光有机核心、识别元件、连接物和功能。这项研究将有助于下一代阴离子分子探针、传感器和结合剂的开发。所提出的受体还将有助于从根本上理解阴离子在自组装中所起的结构作用，以及它们与缺电子芳香环的相互作用。这项研究的长期应用包括阴离子的细胞和体外成像。这项研究的具体目标是：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环的相互作用，并设计识别元件来开发这一新兴的阴离子结合基序。建议的设计策略的模块化允许探索各种阴离子识别基序，包括静电吸引、氢键相互作用和与缺电子芳烃的吸引(阴离子-pi、CH-X-氢键和弱sigma络合物)。这种灵活性允许选择性地结合用传统方法难以靶向的阴离子。核心和接头取代提供了另一种通过改变结合口袋的形状和大小来调节受体选择性的方法。受体的功能也可以进行调整，以提供一种途径，使分子可溶于水，甚至可渗透到细胞膜上，因为一旦解决了溶液化学问题，就会在细胞成像中应用。研究新的阴离子识别基序，如阴离子与缺电子芳烃之间的新相互作用，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被转移到用于补救和传感的新材料的设计上，并可能对阴离子与生物底物之间的相互作用提供见解。这项拟议的研究还可能揭示更复杂的生物系统中的自组装过程。因此，如果人们想要阐明阴离子在更复杂的生物过程中的作用，了解分子水平上的阴离子结合是至关重要的。 公共卫生相关性：阴离子是有问题的环境污染物，在自然界的许多过程中都是至关重要的，阴离子结合蛋白和运输通道与许多疾病途径的机制有关。在这项应用中提出的研究将导致新的有机受体选择性地结合和感觉阴离子。这些分子将在传感、成像和/或修复阴离子方面有长期的应用，这将在发现和去除环境污染物以及成像阴离子在生物过程中所起的作用方面影响公众健康。

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. PUBLIC HEALTH RELEVANCE: Anions are problematic environmental contaminants and are vital to many processes in nature, with anion binding proteins and transport channels implicated in the mechanisms of many disease pathways. The research proposed in this application will lead to new organic receptors that selectively bind and sense anions. These molecules will have long-term applications in sensing, imaging and/or remediating anions, which will impact public health in both discovering and removing environmental contaminants and imaging the role anions play in biological processes.