Nonlinear effects in enantioselective chromatography: prediction of unusual elution profiles of enantiomers in non-racemic mixtures on an achiral stationary phase doped with small amounts of a chiral selector

Nonlinear effects caused by molecular association of enantiomers in non-racemic mixtures can cause unexpected effects in chiroptics, NMR spectroscopy, homogeneous catalysis, and chromatography. Herein we present a theoretical model to simulate and verify unusual elution orders of enantiomers on an achiral stationary phase doped with a small amount of a chiral selector or achiral columns coupled with columns doped with a chiral selector. Scenarios with strong, medium, and weak associations of enantiomers, different separation efficiencies typical for flash chromatography and liquid chromatography, and the influence of the enantioselectivity of the chiral selector on the complex equilibria have been investigated. The findings presented here are of importance for the validation of the determination of enantiomeric ratios in not fully separated elution zones as well as for the preparative separation of non-racemic enantiomeric mixtures on chiral stationary phases bonded to achiral matrices.