Design of Modular Receptors for Ion and Molecule Recognition

描述（由申请人提供）：项目摘要/摘要所提出的研究计划的首要主题是设计模块化有机受体含有识别元素，优化结合溶液中的阴离子。模块化允许容易地取代固有荧光有机核、识别元件、连接体和功能性。这项研究将有助于开发下一代分子探针、传感器和阴离子结合剂。所提出的受体也将有助于提供一个基本的理解的结构作用阴离子在自组装和它们的相互作用与缺电子芳环。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）合成和研究一系列的阴离子受体，从建议的模块化设计策略，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，和3）研究阴离子与缺电子芳环的相互作用和设计识别元件，以利用这种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各种识别图案的阴离子，包括静电吸引力，氢键相互作用和吸引力与缺电子芳烃（阴离子π，CH-X-氢键和弱σ复合物）。这种灵活性允许选择性结合传统方法难以靶向的阴离子的可能性。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。受体的功能也可以被调整，以提供一种途径，使分子水溶性或甚至渗透细胞膜，在细胞成像中的应用，一旦解决了化学。 研究阴离子的新识别基序，例如阴离子和缺电子芳烃之间的新兴相互作用，需要了解操纵这些新的理论结合基序的基础科学，以设计新的受体。这项研究的应用有可能被转移到新材料的修复和传感的设计，并可能提供对阴离子和生物基质之间的相互作用的见解。这项研究还可能揭示更复杂生物系统中的自组装过程。因此，如果人们希望阐明阴离子在更为复杂的生物过程中的作用，那么在分子水平上理解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，并且对自然界中的许多过程至关重要，其中阴离子结合蛋白和转运通道涉及许多疾病途径的机制。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知阴离子。这些分子将在传感、成像和/或修复阴离子方面具有长期应用，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.