Experimental-computational investigation of chiral separations with amino acid-based surfactants

Abstract

This thesis research investigates the use of amino acid-based micelles to separate enantiomeric compounds. These are investigated using both, experimental and computational methods. The experimental portion of my thesis research investigates the effect of counterions on the chiral recognition of 1,1′-Binaphthyl-2,2′-diamine (BNA) and 1,1′-Binaphthyl-2,2′-diyl hydrogen phosphate (BNP) enantiomers when using an amino acid-based surfactant as the chiral pseudo stationary phase in capillary electrophoresis. The effects of sodium counterions on the chiral recognition of binaphthyl derivatives were compared to that of using pH-dependent Lysine counterions at varying pH conditions. The enantiomeric separation of BNP and BNA enantiomers via capillary electrophoresis, using L-Undecyl-Leucine (und-Leu) as the chiral recognition medium, significantly improved the enantiomeric resolution in capillary electrophoresis at pH 7 when using Lysine counterions as compared to using sodium counterions. Therefore, this experimental project provides insight into the advantages of using cationic, pH-dependent counterions such as Lysine to significantly improve the chiral recognition of binaphthyl derivatives in capillary electrophoresis studies. The computational portion of my thesis research focused on developing computational methodology to study the binding interactions between amino acid-based molecular micelles and chiral enantiomers. The computational method development plays a crucial role in helping the research advance towards the development of a predictive database. After developing a set of protocols for the computational research, the methods were then used to study the chiral separation mechanisms of Dansyl amino acids, including Dansyl-Leucine, Dansyl-Norleucine, Dansyl- Tryptophan and Dansyl-Phenylalanine binding to poly-sodium N-undecanoyl-(L)-Leucylvalinate, poly(SULV). This study reveals that the computationally-calculated binding free energy values for Dansyl enantiomers binding to poly(SULV) are in agreement with the enantiomeric order produced in experimental MEKC studies. Furthermore, hydrogen bonding analyses was used to investigate and elucidate the molecular interactions that govern chiral recognition in these molecular systems.