Chiral Separations using Semipermeable Ultrafiltration Membranes

Jonathan Romero and Andrew Zydney
University of Delaware
Colburn Laboratory,   Academy Street
Newark, DE   19716
romero@che.udel.edu
(302) 831-6344

Many pharmaceuticals and agricultural products occur as stereoisomers, with only one isomer possessing the desired biological activity.  Recent studies have demonstrated the feasibility of using affinity membrane systems with a stereospecific/binding agent in free solution to separate chiral mixtures.  However, there is currently no fundamental understanding of the key factors that determine the effectiveness of this type of chiral separation or the key principles governing process design.  Experiments were performed using a model system of bovine serum albumin as a stereospecific binding agent for optical resolution of the amino acid tryptophan. Batch ultrafiltration data showed strong stereospecific binding of L-tryptophan with a filtrate purification factor of 11 at relatively low feed amino acid concentrations. Data obtained over a range of concentrations were used to determine the equilibrium binding constants at pH 8.5: KL= 39,000 M-1 and KD =510 M-1.  Actual separations were performed using a constant volume diafiltration system to wash the less strongly bound isomer through the membrane.  The L-tryptophan was recovered in the retentate with a final purity of 97% and greater than 50% yield. Model calculations developed using the equilibrium binding constants were in good agreement with the experimental results.  Simulations were performed to examine the effects of protein and amino acid concentration on the separation performance.  These results provide an appropriate framework for analyzing and designing membrane systems for the separation of chiral molecules using ultrafiltration with a stereoselective binding agent.