Altering the mobile phase composition to enhance self-disproportionation of enantiomers in achiral chromatography.

The influence of mobile phase composition on the efficiency of enantiomer separation by achiral chromatography (ACh) was investigated. The separation was induced by the phenomenon of self-disproportionation of enantiomers (SDE) triggered by their homo and hetero-chiral interactions in an achiral environment. Typically, SDE occurs in apolar mobile phases of weak elution strength, which causes the separation time to extend and the process productivity to deteriorate. To mitigate that effect, we altered the content of a strong solvent (modifier) in the mobile phase by use of a solvent gradient in which the target enantiomer was separated in the presence of the weak solvent, whereas the unresolved mixture of enantiomers was eluted by increasing the modifier content in the mobile phase. This enabled accelerating the solute elution while preserving the separation selectivity. The approach was examined for the separation of nonracemic mixtures of two structurally different compounds that exhibited the SDE effect in ACh, i.e., metalaxyl (MX) and methyl p-tolyl sulfoxide (MTSO). The target compound of the separation was the more abundant enantiomer in the enantiomeric mixture. The process realization was preceded by the determination of the effect of the modifier content on the separation yield for enantiomeric mixtures of MX and MTSO of different enantiomeric excess (ee). In the case of MX, yield of the pure target enantiomer varied from 2 %, for the maximum concentration of the modifier, to 45 % for the minimum modifier concentration and the largest ee used in the experiments. In the case of MTSO, the yield varied from minimum 40 % to maximum 66 %. To predict the process, we employed a dynamic model, in which underlying thermodynamic dependencies were implemented.

Separation of non-racemic mixtures of enantiomers by achiral chromatography.

The phenomenon of partial separation of enantiomeric mixtures in achiral chromatography (ACh) has already been documented for a wide variety of chiral compounds. It is attributed to the so-called effect of self-disproportionation of enantiomers (SDE). However, quantitative description of the SDE mechanism underlying adsorption of enantiomers on achiral surfaces is still incomplete, which hinders the application of that technique for large-scale separations. In this study, a mechanistic model for description of retention behavior of SDE-phoric compounds in silica-based ACh has been developed along with a procedure for fast determination of the model parameters. The model assumes formation of associates of chiral molecules, which occurs due to homo and hetero-chiral interactions in the adsorbed phase. The ability of the model to reproduce band profiles was verified for enantiomeric mixtures of three structurally different chiral compounds.