Equilibrium theory-based framework for descripting separation of enantiomers by frontal achiral chromatography

The equilibrium theory-based approach was developed to elucidate and quantify the separation of nonracemic enantiomer mixtures by achiral frontal chromatography. Equilibrium theory (ET) provided an analytical formula and a graphical solution for the prediction of the migration velocity of the adsorption fronts. Two model components were selected for the study, i.e., citalopram and methyl N-acetyl-phenylalaninate, which exhibited the phenomenon of self-disproportionation when eluted from a silica gel column. The solution of ET was coupled with an optimization routine to determine the adsorption isotherm. The isotherm model assumed the formation of homochiral and heterochiral associates on energetically different adsorption sites on the silica surface. The retention times of breakthrough adsorption fronts of enantiomers were measured and used as a basis for the estimation of the isotherm coefficients. For both pairs of the enantiomers, the formation of associates at the high-energy binding sites exerted a dominating influence on the separation selectivity. The effect was dependent on the concentration of enantiomers and the enantiomeric excess in the mixtures. The equilibrium-dispersive model was used to assess the effect of band broadening on the accuracy of the ET solution. It was demonstrated that ET is an effective mathematical tool for rapid prediction of the SDE-driven chromatographic process.