Development of Stereodynamic Chemosensors for Chiroptical Analysis

在这个由化学部化学结构、动力学机制B计划资助的项目中，乔治城大学化学系的Christian Wolf教授将开发实用的双模化学传感器，该传感器产生独特的圆二色性（CD）信号，并结合UV或荧光响应，可用于快速测定各种手性化合物的绝对构型、对映选择性和产率。所设想的传感器和电流引线被设计成利用底物识别和手性放大事件进行定量实时分析，并且将解决手性感测的常见缺点，包括响应时间慢和分析前的精细底物衍生化。 强大的手性化学传感检测的引入，预计将提高许多实验室的生产力，提供实用，时间效率和成本效益的筛选工具，简化目前的不对称反应发现和优化协议，同时尽量减少废物的产生和能源消耗。这个跨学科的研究计划将培养下一代科学家，并由研究生，本科生和当地高中学生组成的团队进行。 与默克公司在新泽西州Rahway的工业伙伴关系，以及几个国际合作，解决手性化学传感发展的几个方面将加强当地的研究和教育基础设施。该项目涉及的操作模式，动力学和热力学方面的底物结合事件，底物到传感器的手性印迹过程，并最终chiropical传感器响应的深入分析。在平行的立体动力学探针，基于共价底物结合，立体动力学金属络合物和其他探针设计，将探讨与手性目标化合物的非共价相互作用的基础上操作的发展。这些方向将包括新的分子识别和手性放大基序，并进一步扩展手性传感的一般范围。在这些情况下，系统的传感器开发将与使用NMR（核磁共振）、ESR（电子自旋共振）、MS（质谱）、X射线、UV（紫外线）、CD（圆二色性）、荧光和原位IR（红外线）结合滴定和竞争实验的详细机理研究齐头并进。真实的案例应用的调查，即不对称反应的直接分析，也将继续进行。

In this project funded by the Chemical Structure, Dynamic & Mechanism B Program of the Chemistry Division, Professor Christian Wolf of the Department of Chemistry at Georgetown University will develop practical dual-mode chemosensors that produce distinct circular dichroism (CD) signals combined with either a UV or a fluorescence response that can be used for rapid determination of the absolute configuration, enantioselectivity, and yield of a large variety of chiral compounds. The envisioned sensors and current leads are designed to exploit substrate recognition and chirality amplification events for quantitative real-time analysis, and will address common drawbacks of chirality sensing, including slow response time and elaborate substrate derivatization prior to analysis. The introduction of robust chirality chemosensing assays is expected to increase the productivity of many laboratories by providing practical, time-efficient and cost-effective screening tools that streamline current asymmetric reaction discovery and optimization protocols while minimizing waste production and energy consumption. This interdisciplinary research program will train the next generation of scientists and be conducted by a team of graduate, undergraduate and local high school students. An industrial partnership with Merck in Rahway, NJ, and several international collaborations that address several aspects of the chirality chemosensing development will enhance the local research and education infrastructure.The project involves the in-depth analysis of the operational mode, kinetic and thermodynamic aspects of the substrate binding event, the substrate-to-sensor chirality imprinting process, and the ultimate chiroptical sensor response. In parallel to the development of stereodynamic probes that operate based on covalent substrate binding, stereodynamic metal complexes and other probe designs that incorporate noncovalent interactions with the chiral target compounds will be explored. These directions will include new molecular recognition and chiral amplification motifs and further extend the general scope of chirality sensing. In these cases, systematic sensor developments will go hand in hand with detailed mechanistic studies using NMR (Nuclear Magnetic Resonance), ESR (Electron Spin Resonance), MS (Mass Spectrometry), X-ray, UV (Ultraviolet), CD (Circular Dichroism), fluorescence and in situ IR (Infrared) in combination with titration and competition experiments. The investigation of real case applications, i.e. the direct analysis of asymmetric reactions, will also be pursued.