Multiple-chemical equilibria in chiral partition systems

• Main Author: Koska, Jurgen
• Language: English
• Published: 2009
• Online Access: http://hdl.handle.net/2429/10119

Enantiomers are molecules with nearly identical physical properties. The separation of such molecules presents one of the most difficult separation problems in chemical industries. In particular, pharmaceutical companies are challenged with the design of new enantioseparation methods and equipment to meet stricter regulations required for the approval of optically active drugs. Ligand-exchange systems utilize the unique configuration of transition-metal complexes with a chiral ligand for the separation of enantiomers. Equilibrium ternary aminoacid- enantiomer complexes are formed via copper(II) ions and a chiral selector. These ternary complexes have distinct equilibrium binding constants, which depend on the enantiomer type and optical configuration, as well as on solvation effects. The chemical equilibria in ligand-exchange separation systems are governed by a large number of complexation reactions. In this work, a comprehensive model, based on multiple-chemical-equilibria, was developed which is capable of completely describing ligand-exchange separation systems. Equilibrium formation constants were measured experimentally by potentiometric titrations in the aqueous phase and by partition experiments in the organic phase. The work shows that solvent molecules significantly affect the enantioselectivity of the ligand. By solubilizing a water insoluble analogue of the chiral selector in an n-octanol phase, the enantioselectivity increased by nearly an order of magnitude for some enantiomers. Molecular mechanics calculations support experimental findings that water molecules significantly affect ligand selectivity and the highest enantioselectivities were predicted in non-aqueous environments, which agreed with experimental measurements performed in organic solvents. Due to low ligand enantioselectivities, the multiple-chemical-equilibria model was extended to multi-staged extraction systems. Experimentally, a hollow-fibre membrane two-phase extraction system was designed to test the model. The system consisted of a chiral selector that was solubilized in an organic phase flowing in counter-current direction to an aqueous stream containing the racemates. The enantiomer-concentration profiles predicted at different conditions were in good agreement with experiments. The work showed that ligand-exchange separations are difficult to operate due to the large number of complexation reactions. In particular, the enantioseparation performance is very sensitive to solution conditions. The developed models are useful in the prediction of chiral separation performances as a function of operating conditions and for system optimization. Furthermore, the models are applicable to any separation schemes that are governed by multiple-chemical equilibrium.