SEPARATIONS OF DERIVATIZED AMINO-ACID ENANTIOMERS BY CYCLODEXTRIN-MODIFIED CAPILLARY ELECTROPHORESIS - MECHANISTIC AND MOLECULAR MODELING STUDIES

The enantiomers of 5-dimethylamino-1-naphthalene sulfonyl (DNS)-deriva tives of selected amino acids were successfully separated using capill ary electrophoresis (CE) employing cyclodextrins (CD) as enantio-selec tive running buffer additives. A previously described model for retent ion and chiral recognition in CD-modified CE is shown to adapt well in this application. Resolution of the isomers is strongly influenced by the type and concentration of cyclodextrin employed, as predicted by the model. Although data indicates differences in the electrophoretic mobilities for some of the completely complexed enantiomer pairs, sele ctivity generally requires exploiting differences in the amino acid-CD complexation constants for enantiomer pairs. In this work, the D-enan tiomers exhibit larger formation constants and are complexed to a grea ter degree (elute first) at moderate CD concentration. When mixtures o f amino acids are analyzed, the effects of separation conditions on ge neral elution behavior must be considered or separated enantiomer pair s will co-elute with other enantiomers. Preliminary results aimed at p redicting the strength of DNS-amino acid enantiomer-CD interactions ba sed on molecular modeling studies are presented. A statistical mechani cal approach to treating computationally derived enantiomer-CD interac tion energies is shown to provide reasonable correlation with separati on performance.