An evaluation of the enantiomeric recognition of amino acid based polymeric surfactants and cyclodextrins using spectroscopic and chromatographic methods.

摘要

The scope of this dissertation is to explore the enantiomeric recognition properties of amino acid based polymeric surfactants using a combination of analytical techniques including chromatographic and spectroscopic methods. Chapter 1 includes an introduction to chirality and chiral separations using capillary electrophoresis. Using cyclodextrin modified micellar electrokinetic chromatography (CD-MEKC), the enantioseparation of three binaphthyl derivatives using native beta- and gamma-cyclodextrins in combination with various diastereomers of chiral polymeric surfactants (PS) was examined. A reversal of enantiomeric order was observed with the enantiomers of (+/-)1,1'-binaphthyl-2,2'-diamine (BNA) and (+/-)1,1'-binaphthyl (BOH) due to a competition between the two chiral selectors for the same enantiomer. Overall trends observed for the analytes were discussed in terms of selectivity and resolution values for each possible combination of CD and PS. In a subsequent study, the dipeptide micelle polymer, poly (sodium N-undecanoyl-L-leucylvalinate) p-(L-SULV), was used as the sole chiral discriminator in an extensive chiral screening program for the separation of 75 racemic drug compounds. P-(L-SULV) was developed in our lab based on information gleaned from previous studies and our understanding of chiral separation mechanisms. A total of 58 out of 75 compounds were resolved using p-(L-SULV) thereby establishing the dipeptide as a broadly applicable chiral selector for micellar electrokinetic chromatography (MEKC). Complementary analytical methods (MEKC, nuclear magnetic resonance (NMR), and steady-state fluorescence anisotropy) were used to elucidate the chiral separation mechanisms involving the dipeptide p-(L-SULV). An MEKC technique developed by our group was used to determine the primary site of interaction which leads to the enantioseparation of a select group of analytes. Subsequently, NOESY NMR used as a validation tool in certain instances where MEKC results were inconclusive. For example, while MEKC results were ambiguous regarding the primary site of interaction, NOESY NMR results strongly suggested that the analyte Troger's Base interacted primarily with the valine chiral center. In addition, the alpha vs. beta relationship, first introduced by our group, was validated using p-(L-SULV) as the chiral selector. The fluorescence studies revealed a correlation between the chromatographic parameter, selectivity (alpha) and the spectroscopic parameter, beta.