Designing Axially Chiral Sensors for Enantioselective Recognition of Chiral Compounds

基于化学结构、动力学和机制项目的资助，乔治城大学化学系的Christian Wolf教授小组将开发分子探针，用于区分手性胺、醇、氨基酸和其他重要化合物的对映体。这些分子提供了独特的机会，为时间有效的对映选择性传感的微小样品量。该项目将探索手性识别事件和不对称感应过程，传感器来源于轴向手性1,8-二异芳基萘N，N'-二氧化物，1,8-双酚萘和固有立体动力学聚芳基乙炔。这三类传感器的设计目的是：(a)将与手性化合物的相互作用紧密嵌入到高度立体选择性的环境中；(b)在立体动力学受体分子中对底物控制的轴向手性诱导产生强烈的手性响应；(c)利用荧光、紫外和圆二色光谱定量测量手性识别和诱导事件。许多生物活性化合物，包括药品、农用化学品、香精和营养物，都是手性的（“左手或右手”），今天大多数最畅销的药物都是以单对映体的形式销售的。手性化学物质对映体组成的分析在药物发现过程和不对称反应的优化过程中起着不可或缺的作用。实时对映体选择分析与精心设计的传感器，将手性识别事件转化为强紫外线，荧光或圆二色信号具有重要的前景，有效地补充了自动化平行合成和组合方法的进步，可以在一夜之间产生大量的样品。预计该研究的基础和应用方面将使学术和工业化学家受益，并提供高通量筛选方法，允许对大量样品进行快速对映选择分析，同时最大限度地减少废物产生和能源消耗。

Based on funding from the Chemical Structure, Dynamics and Mechanism Program, Prof. Christian Wolf's group at the Department of Chemistry at Georgetown University will develop molecular probes that differentiate between the enantiomers of chiral amines, alcohols, amino acids and other important classes of compounds. These molecules provide unique opportunities for time-efficient enantioselective sensing of minute samples amounts. This program will explore chiral recognition events and asymmetric induction processes with sensors derived from axially chiral 1,8-diheteroarylnaphthalene N,N'-dioxides, 1,8-bisphenolnaphthalenes, and intrinsically stereodynamic polyarylacetylenes. These three classes of sensors are designed (a) to closely embed interactions with chiral compounds into a highly stereoselective environment (b) to generate a strong chiroptical response to substrate-controlled induction of axial chirality in stereodynamic receptor molecules, and (c) to utilize fluorescence, UV and circular dichroism spectroscopy to quantitatively measure chiral recognition and induction events. Many biologically active compounds, including pharmaceuticals, agrochemicals, flavors, and nutrients, are chiral ("left- or right-handed"), and the majority of today's top-selling drugs are marketed as single enantiomers. The analysis of the enantiomeric composition of chiral chemicals plays an integral role in the drug discovery process and during optimization of asymmetric reactions. Real-time enantioselective analysis with carefully designed sensors that translate a chiral recognition event into a strong UV, fluorescence or circular dichroism signal holds significant promise to effectively complement the advance in automated parallel synthesis and combinatorial methods that can generate large numbers of samples overnight. It is expected that the fundamental and applied aspects of the proposed research will benefit academic and industrial chemists alike and provide high-throughput screening methods that allow rapid enantioselective analysis of large numbers of samples while minimizing waste production and energy consumption.