Chiral ligand-exchange chromatography with Cinchona alkaloids. Exploring experimental conditions for enantioseparation of α-amino acids

Abstract

The natural Cinchona alkaloid quinidine as chiral selector in chiral ligand-exchange chromatography was systematically studied. Chromatographic conditions for enantioseparation of twentya-amino acidswere first timestudied by changing mobile phase parameters such as pH, concentration of organic solvent, type of salt, ligand to metal ratio and also column temperature. Maximum retention and enantioselectivity factors were observed at the region close to pH = 8, since the tertiary amine (the quinuclidinic nitrogen) of the quinidine is protonated only in a small degree, and therefore is available for the chelate formation. Additionally at this pH value there is no other competing ligand for complex the metallic cation. The thermodynamic transfer parameters of the enantiomers from the mobile to the stationary phase from van't Hoff plots within the range of 10-35 °C were estimated. Thus, the differences in the transfer enthalpy Δ(ΔH), and transfer entropy Δ(ΔS) enabled an investigation of the origin of the differences in interaction energies Δ(ΔG). Finally, the molecular geometry of the formed diastereomeric complexes was modelled and energetic differences between both compounds were calculated by a semi empirical method.