Summary: | 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.
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