Enantioselective Fluorescent Analysis of Amino Acids

University Of Virginia Main Campus, Charlottesville VA

Investigators

Abstract

With the support of the Chemical Structure, Dynamics, and Mechanisms B (CSDM-B) Program in the Division of Chemistry, Professor Lin Pu of University of Virginia is studying fluorescent sensors that can distinguish the enantiomers of chiral amino acids. A chiral amino acid can exist in L- and D-enantiomeric forms whose molecular structures are mirror images of each other, but not superimposable. L-Amino acids are the essential molecular building blocks of proteins in living systems on earth. D-Amino acids are less common in nature but are still found to play important roles in biological systems. Both L- and D-amino acids are very useful in the synthesis of diverse organic compounds including those of pharmaceutical importance. Because of the significance of L- and D-amino acids in biology and synthesis, it is important to analyze their chiral configuration and enantiomeric composition. Among the methods that have been developed to analyze the enantiomers of amino acids, using enantioselective fluorescent sensors has advantages such as readily available instrumentation, high sensitivity, real-time measurement, multiple sensing modes, non-invasive imaging, continuous online monitoring, parallel analysis, etc. Professor Pu will develop new enantioselective fluorescent sensors for amino acids to facilitate the deployment of these sensors for the rapid screening of catalysts being investigated for the asymmetric synthesis of amino acids and related compounds. The researchers engaged in this project will also conduct outreach activities to provide science education for local K-12 students of diverse background. In this project, a 1,1’-binaphthyl-coumarin-based fluorescent probe will be further developed for application in the rapid analysis of chiral amino acids obtained from asymmetric reactions. The pseudo-enantiomer of this probe will be prepared and the resulting pseudo-enantiomeric sensor pair will be applied to simultaneously determine the concentration and enantiomeric composition of an amino acid sample by one fluorescence measurement. This strategy also allows the identification of the absolute configuration of the amino acid. A systematic structural modification of this probe will be conducted to improve its enantioselectivity and expand the accessible substrate scope of the method. In order to minimize the interference of other components in an amino acid sample on the fluorescence measurement, a perfluoro alkyl group or an amphiphilic polymer chain will be incorporated into the fluorescent probes. These fluorous phase-based or polymer-supported fluorescent probes will be able to transport the sensor-substrate interaction away from the original sample phase for more accurate fluorescence measurements. The proposed fluorescent sensors will be used in the screening of chiral catalysts for the asymmetric alkyne addition to imines and for asymmetric Akabori-like reactions. These studies should facilitate the search of efficient and environmentally friendly chiral catalysts for asymmetric syntheses. The enantioselective fluorescent probes developed in this project also have potential to be used much more broadly in asymmetric synthesis, including in automated systems for high throughput catalyst screening. 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.