Chiroptical Sensing with Stereodynamic Probes

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 is developing molecular probes for quantitative analysis of the amount, absolute configuration and enantiomeric composition of chiral compounds in complex samples. Many pharmaceuticals are chiral compounds and their effective analysis is clearly important in developing new medicines. This project could lead to new analysis methods that are compatible with modern workflow platforms, that can minimize waste production and operational costs, and that are applicable to automated parallel analysis of small scale reactions or biomarker sensing. The project is highly collaborative, involving industrial and academic partners. It provides multiple training opportunities for graduate, undergraduate and high school students, including those from underrepresented groups. The specific goals are to introduce and test several molecular probes that are designed to capture a chiral target either by covalent bond formation or noncovalent interactions and to then translate the molecular recognition event via spontaneous substrate-controlled chirality amplification across the stereodynamic receptor scaffold into a distinct chiroptical response. The prospects of this research are multifaceted and include important applications such as direct asymmetric reaction analysis or quantification of medicinally relevant biomarkers. Comprehensive optical sensing (determination of absolute configuration, enantiomeric purity and concentration of chiral substrates) is to be achieved using conceptually new molecular recognition and chiral amplification strategies. These strategies utilize stereodynamic cup-shaped architectures, foldamers, axially chiral reporter units, molecular propellers, multicomponent assemblies, dynamic covalent chemistry, organocatalysis, frustrated Lewis pairs, and tropos ligand derived metal complexes. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.