DESIGNING ATROPISOMERIC SENSORS FOR ENANTIOSELECTIVE RECOGNITION OF CHIRAL COMPOUNDS

Georgetown University, Washington DC

Investigators

Abstract

Many biologically active compounds, including pharmaceuticals, agrochemicals, flavors, fragrances, and nutrients, are chiral, and more than 50% of today?s top-selling drugs are sold as single enantiomers. The increasing demand for enantiopure chemicals has been accompanied by significant progress in asymmetric synthesis, and it requires the development of analytical techniques for fast and accurate determination of the stereochemical purity and integrity of chiral compounds. The current bottleneck in drug discovery is to analyze the enantiomeric composition and yield of these reaction mixtures. The Wolf group will therefore develop new sensors that can be used to determine both the enantiomeric purity and the overall concentration of a wide range of compounds, thus providing a new entry to rapid screening of reaction mixtures and libraries of chiral compounds. The unique design of these sensors facilitates differentiation of enantiomers based on ultraviolet and fluorescence spectroscopy or other optical methods. The group will develop and test sensing assays that combine several attractive features: (1) fast determination of both concentration and enantiomeric composition of unknown mixtures; (2) simple optical measurements will provide accurate values with high reproducibility; (3) laborious substrate derivatization will become unnecessary; and (4) the use of cost-effective and sensitive techniques (UV or fluorescence spectroscopy) will greatly reduce the amount of sensor and analyte required. Based on the significance of enantioselective analysis outlined above, it is expected that the fundamental and applied aspects of the proposed research will benefit academic and industrial chemists alike. Several students from groups that are underrepresented in the sciences will participate in this project and receive extensive experience in stereochemistry, synthetic chemistry, stereoselective recognition and chiral resolution. This will provide fertile training grounds for the next generation of chemists working in the pharmaceutical, food and agrochemical industries.