Separation of Racemic Penicillamine on Chiral Gold Nanoparticles

Penicillamine is a chiral active pharmaceutical ingredient. The D-enantiomer of penicillamine, sold under the trade name Cuprimine, is used to treat Wilson’s disease and rheumatoid arthritis. The L-enantiomer of penicillamine, however, is toxic. The enantiomers of racemic penicillamine must therefore be separated and purified before D-penicillamine can be put into a dosage form. The current method for enantiomeric separation used in the pharmaceutical industry is chiral column chromatography, which can be expensive and cumbersome. To avoid this cumbersome method, this work presents an innovative method for enantiomeric separation of racemic penicillamine using chiral gold nanoparticles. Spherical gold nanoparticles of diameter 4 nm are chemically synthesized. The gold nanoparticles are then coated in either L-cysteine or D-cysteine to render them chiral. The enantioselective interactions of these nanoparticles are then inspected using optical rotation measurements. Results demonstrate that when racemic penicillamine is added to gold nanoparticles coated in either D or L-cysteine, one enantiomer of penicillamine is selectively adsorbed onto the gold nanoparticles, leaving an excess of the other enantiomer in solution. Gold nanoparticles coated in D-cysteine adsorb D-penicillamine, leaving an excess of L-penicillamine in the solution phase. D-cysteine on gold nanoparticles has an initially positive optical rotation. As the amount of L-penicillamine (negative optical rotation) in the solution phase increases with subsequent additions of racemic penicillamine, the optical rotation decreases. Conversely, gold nanoparticles coated in L-cysteine adsorb L-penicillamine, leaving an excess of D-penicillamine in the solution phase. L-cysteine on gold nanoparticles has an initially negative optical rotation. As the amount of D-penicillamine (positive optical rotation) increases with subsequent additions of racemic penicillamine, the optical rotation increases. Control experiments indicate that D-cysteine and L-cysteine in solution show no net separation of racemic penicillamine, demonstrating that the gold nanoparticles are necessary for the enantiospecific selection to occur.