Applications of brush-type chiral stationary phases in new chromatographic techniques

Chromatographic enantioseparations are an important class of resolutions by which a chiral stationary phase (CSP) is utilized to affect the separation of a mixture of enantiomers to provide, as the end result, the single enantiomers of the mixture. In the studies described within, three areas involved in chiral discrimination are investigated. Capillary electrochromatography, a hybrid of capillary electrophoresis and high-performance liquid chromatography has been used to study the enantioseparations of hydantoins and thiohydantoins. Thiohydantoins are a class of compounds that typically result from the Edman degradation of peptides. The Edman degradation provides information about the primary structure of peptides, but it does not give any information about the chirality (or absolute configuration) of the original amino acid component of the peptide. The work described in Chapter 2 focuses on this reaction and thiohydantoin analytes to develop a new isothiocyanate derivatizing reagent, 4-acenaphthylisothiocyanate, which greatly improves the enantioseparation of the racemic analytes. Capillary electrochromatography was also utilized to determine the factors that enhance chiral discrimination within the 5-aryl hydantoin family of compounds. Addition of increased pi-basic aryl groups at the chiral center along with alkylation of the imide and amide nitrogens provides improved enantioseparation of the racemic compounds. The development of a means of fast enantioseparations utilizing traditional CSPs with the novel monolithic silica solid support are investigated and compared against traditional particulate silica supports. Enantioseparations can be completed quite easily in less than 3 min on the new chiral monolithic silica phase with benefits seen for high throughput screening. Finally, this thesis describes the development and synthesis of a novel CSP derived from alpha-acenaphthylglycine. This pi-acidic, pi-basic CSP shows wide applicability in reciprocity studies. The synthesis of this CSP reduces the number of stereoisomers that are encountered in other successful CSPs to possibly allow the synthesis and utilization of a novel CSP for use in both reverse and normal phase liquid chromatography.