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‐NH 2 ) using sodium dithionite. Finally, the S ‐imprinted polymer (S‐KP‐P) was prepared by imprinting S‐KP onto HS‐P‐NH 2 , 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.