Designing Axially Chiral Sensors for Enantioselective Recognition of Chiral Compounds

Georgetown University, Washington DC

Investigators

Abstract

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.