This session was recorded during Pittcon 2013 in Philadelphia, Pennsylvania on Monday, March 18, 2013.
TITLE: Stereochemical Characterization of Drugs: Enantioselective HPLC and Electronic Circular Dichroism as Detection System
AUTHOR: Carlo Bertucci - University of Bologna
ABSTRACT OVERVIEW: The need for analytical methods to determine the enantiomeric excess of chiral drugs and natural compounds increased significantly in the last twenty years, because chirality greatly affects their pharmacological and toxicological properties. Surely enantioselective high-performance liquid chromatography (HPLC) resulted particularly efficient to this aim. However, the stereochemistry of analytes is left unspecified if detection systems not based on the monitoring of chiroptical properties are used for the HPLC analysis. When circular dichroism (CD) detection is employed in enantioselective HPLC, the stereochemistry of a chiral analyte (enantiomeric excess, and assignment of the absolute configuration to the prevailing enantiomer) can be fully determined. The development of increasingly reliable non-empirical methods for the absolute configuration assignment, based on quantum chemical calculations of the theoretical chiroptical properties, has further contributed to the emergence of HPLC-CD method as effective tools for a complete stereochemical characterization of chiral compounds.
The assignment of the absolute stereochemistry of drugs and natural products is essential in order to establish reliable structure--activity relationships. Relevant HPLC applications of electronic circular dichroism detection systems for absolute configuration assignment will be discussed, and the analytical advantages highlighted. The selectivity of CD detection towards chiral molecules enhances the analytical power of enantioselective HPLC, allowing the collection of relevant information about the chirality of drugs and natural products. In particular, the importance of the concentration-independent anisotropy factor (g=Δε⁄ε) will be underlined for determining the enantiomeric composition of non-racemic chiral compounds upon non-chiral stationary phases. This methodology is extremely valuable when dealing with large libraries of chiral compounds and natural extracts.
