2022 Annual Meeting

Reticular Synthesis of Homochiral Metal-Organic Frameworks for Enhanced Enantioselectivity of Chiral Drugs

More than half of all drugs are chiral; among those, 90% are marketed as racemates, a 50:50 mixture of their non-superimposable mirrored stereoisomers, otherwise known as enantiomers. In some cases, these enantiomers may differ in their pharmacokinetics and toxicity profile. Separation of enantiomers is performed either during stereoselective synthesis or through challenging separation techniques, thus, the process of delivering an enantiopure drug to the market is an essential, yet timely and expensive feat. Porous chiral adsorbents have been employed to resolve racemic solutions and collect enantiopure materials. Metal-organic frameworks (MOFs) are examples of such adsorbents that can offer designability to introduce chiral recognition sites in the frameworks and organic linkers of varying sizes to selectively separate chiral molecules based on their size.

In this work, a rigid, 1-D homochiral MOF is synthesized using cobalt linked to glycyl-L-glutamic acid dipeptide. To study the influence of pore aperture size on enantioselective separation, these frameworks are systematically spaced with increasing-length bipyridyl linkers. Five novel isostructural MOFs, denoted as Co-L-GG(R), are structurally characterized and compared for enantioselective separation capacity by diffusing racemic D/L Penicillamine solution through the adsorbent. Enantiomeric excess of the resultant solution is determined through a Beer's Law calibration curve obtained from circular dichroism. It was found that enantioselectivity of Co-L-GG(R) to L-Penicillamine is optimal at a specific pore size, although the total adsorption of Penicillamine generally increased with larger-spaced linkers. Allowing the racemate to diffuse through a packed MOF column showed higher enantiomeric excess compared to letting the MOF sit overnight in the solution. This study reports a method of enantioselective separation of D/L Penicillamine through chiral MOFs, and by increasing the linker size through reticular synthesis, this work can be further employed to larger pharmaceutical drugs.