Simulated moving bed enantioseparation of amino acids employing memory effect-constrained chromatography columns

Abstract

Teicoplanin aglycone-based chromatography columns (Chirobiotic TAG) enable amino acid enantioseparation with aqueous mobile phases, which perfectly accommodates the distinct hydrophilicity of most amino acids. Therefore, this stationary phase constitutes a promising option in particular for preparative-scale separations that require high feed concentrations for economic operation. However, detailed studies revealed a solute-related memory effect when this column is subjected to high loadings of amino acids, conditions that prevail in SMB operation. High loadings yield an activation of the column as indicated by increased retention times when comparing finite injection chromatograms obtained before and after the column had been subjected to a concentrated amino acid feed. This effect can be slowly reversed by flushing the column with solvent devoid of amino acid. Obviously, the activation of the stationary phase needs to be accounted for in the determination of adsorption isotherms that are used for SMB design. In this work we introduce a perturbation method adapted specifically to capture the stationary phase behaviour at SMB-like conditions. The adsorption isotherms obtained from this method indeed allowed for accurate SMB design of a methionine enantioseparation as judged by the very good agreement of experimentally obtained and model-predicted purities. Furthermore, SMB operation over 3 days with constant purities (besides deviations originating from a dip in temperature) was accomplished indicating that the adsorption behaviour in the activated state is indeed time invariant and stable long-term SMB operation with these columns is principally feasible.