Chiral separations and chiroptical spectroscopic studies

Abstract

Chiral chromatography is a convenient method to obtain the pure enantiomers of a racemate and is also the most widely-used analytical technique to determine enantiomeric purity in the pharmaceutical industry. Seventeen new L-proline based chiral stationary phases (CSPs) for HPLC have been designed, prepared and evaluated. The influence of structural components of these CSPs, including support, linker, number of L-proline units and end group, and mobile phase system on the enatio-selectivity and versatility of CSPs have been investigated. Separation ability of the best CSP (Fmoc-Pro-Pro-Pro-Pro-N(Me)-Ahx-APS) has also been compared with those of three popular commercial CSPs. The enantio-selectivity and versatility of this CSP are comparable with commercial ones. Chiroptical spectroscopic techniques play important roles in determination of the configuration and conformation of chiral molecules. In this work, optical rotation, ECD (electronic circular dichroism) and VCD (vibrational circular dichroism) techniques have been used for conformational analysis of chiral molecules. To understand the separation mechanism of a decaproline chiral column, multiple chiroptical techniques and infrared (IR) spectroscopy have been used to study the conformation of the decaproline oligomer in isopropanol(IPA)/dichloromethane(DCM) mixtures. The combined use of VCD, IR, and optical rotation techniques with DFT calculation has been adopted to study the conformational change of dialkyl tartrates in different solvents. The interaction between guest and host molecules in dialkyl tartrate-cyclodextrin complexes has also been investigated by VCD, IR and optical rotation techniques. A film-making method with cyclodextrin matrix has been developed for the measurement of VCD spectra of amino acids in the mid-IR region. Validity of van’t Hoff’s principle of optical superposition has also been investigated with carefully designed experiments.