Comparison of monomeric and polymeric amino acid based surfactants for chiral separations

Abstract

To better understand chiral recognition with polymeric amino acid based surfactants, the chromatographic performance of 18 monomeric and polymeric surfactants were compared for chiral analytes with various charge states and hydrophobicities. In this study, four amino acids (glycine, l-alanine, l-valine, and l-leucine) were chosen, and all possible combinations of the chiral single amino acid and dipeptide surfactants were synthesized. The results indicate that polymeric surfactants usually provide better chiral resolution for enantiomers of lorazepam, temazepam, 1,1′-bi-2-naphthol, and propranolol as compared to monomeric surfactants. In contrast, monomers perform better for chiral recognition of the 1,1′-bi-2-naphthyl-2,2′-diyl hydrogenphosphate enantiomers.

Introduction

Micelles are aggregates of surfactant molecules that assemble above a certain concentration referred to as the critical micelle concentration (CMC). Normal micelles are aggregates with a dynamic equilibrium existing between the micelles and the surfactant monomers [1], [2]. In addition, complexation of micelles with a given solute is also a dynamic interaction [3], [4], which can be altered by the equilibrium that exists between micelle and the surfactant monomer. Thus, the dynamic micellar system may have a negative influence on the efficiency of the chiral interaction.

Exposure of aqueous solutions of micelles, which contain a terminal double bond at the end of the hydrophobic chain, to γ-radiation, results in formation of covalently linked polymeric surfactants [5], [6], [7], [8], [9], [10]. Polymerization eliminates the dynamic equilibrium between the monomer and the micelle [1], [2], [3], [4], [5], [6], [7], [8], [9], [10]. This, in turn, may result in increased mass transfer of the solute with the chiral pseudostationary phases (CPSPs). In addition, covalent stabilization in polymeric surfactants results in a more structured phase with greater constraints than the unpolymerized micelle. It should be mentioned that in conventional micelles, surfactant molecules open up and reorganize themselves to provide hydrophobic pockets for the solute. Polymerized micelles, on the other hand, have a rigid structure. This rigidity may diminish the ability of the polymer to create proper hydrophobic pockets for organic compounds [8].

Although several papers, which investigate the potential of polymeric surfactants in chiral recognition, have been published [10], [11], [12], [13], [14], [15], [16], [17], [18], [19], [20], [21], [22], not much work has been done comparing the performance of monomeric and polymeric chiral surfactants. Wang and Warner demonstrated several advantages of polymeric amino acid based chiral surfactants as compared to monomeric chiral surfactants in 1994 [10]. In that study, the authors discussed the enantioselectivity of sodium N-undecanoyl l-valinate (SUV). It was shown that polymeric surfactants of SUV separated the enantiomers of 1-1′-binaphthyl-2,2′-diol better than its corresponding monomer. Later, Dobashi et al. used a similar polymer to separate the enantiomers of 3,5-dinitrobenzoyl amino acid isopropyl ester [22], [23].

Billiot et al. have examined the performance of a series of dipeptide surfactants [14]. The monomeric sodium N-undecanoyl (L,L) valyl-leucinate provided resolution of the enantiomers of 1,1′-bi-2-naphthyl-2,2′-diyl hydrogenphosphate (BNP), while the polymer of this surfactant exhibited no enantioselectivity. In contrast, polymeric sodium N-undecanoyl (L,L) leucyl-valinate separated enantiomers of BNP better than its corresponding monomer. In the study presented here, a comparison is made of the performance of a variety of monomeric and polymeric amino acid based surfactants in chiral separations.