Design of an amino-functionalized molecularly imprinted polymer via thiol–maleimide click chemistry for chiral separation of ketoprofen

Abstract

A molecularly imprinted polymer was developed to selectively adsorb S-ketoprofen (S-KP) and chirally separate it from a racemic mixture. Synthesis involves condensation polymerization of 4-mercaptophenol and 4-nitrophenol with formaldehyde to obtain a thiolated/nitro-functionalized polymer that was further reduced to an amino-functionalized polymer (HS-P-NH₂) using sodium dithionite. Finally, the S-imprinted polymer (S-KP-P) was prepared by imprinting S-KP onto HS-P-NH₂, followed by post-crosslinking with bis(maleimido)ethane through thiol–maleimide click reaction. Confirmation of the successful functionalization and crosslinking was done via structural characterization techniques. Kinetic studies showed that the crosslinking reaction followed second-order kinetics, with thermodynamic analysis indicating a spontaneous, exothermic process. In the adsorption experiments, S-KP-P manifested better enantioselectivity in the maximum capacity of adsorptions of 422 mg g⁻¹ for S-KP versus 243 mg g⁻¹ for R-KP. The Langmuir model provided the best fit to the isotherm data, confirming monolayer adsorption on homogeneous binding sites. Chiral separation experiments using column chromatography demonstrated the ability of S-KP-P to resolve (±)-KP, yielding 97% enantiomeric excess (ee) for R-KP in the first elution and 94% ee for S-KP in the second. In contrast, the non-imprinted polymer showed no enantioselectivity. The results confirm the potential of S-KP-P for efficient enantioselective separation in pharmaceutical applications. © 2025 Society of Chemical Industry.