Development of Stereodynamic Chemosensors for Chiroptical Analysis

Georgetown University, Washington DC

Investigators

Abstract

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.