Thiol-maleimide click reaction-driven imprinted polymer for chiral resolution of indoprofen

J Chromatogr A. 2025 Feb 22:1743:465657. doi: 10.1016/j.chroma.2025.465657. Epub 2025 Jan 5.

Abstract

Indoprofen (INP) comprises two enantiomers, R- and S-, whose high pharmacological efficacy is realized only in the case of the separated enantiomers. A newly synthesized poly(acrylonitrile-co-divinylbenzene) (PANB)-based sorbent with selective affinity to the S-enantiomer of INP was applied to separate INP racemate. The synthesis was performed by suspension polymerization with low-crosslinked PANB microparticles and by reaction of the inserted nitriles with 1-amino-1H-pyrrole-2,5‑dione (Ma-NH2). The cationic maleimide-hydrazidine was then attached to the polymer particles, followed by its loading with anionic S-INP. In the post-crosslinking, ethane-1,2-dithiol (ETH) was used as a crosslinker through a thiol-maleimide click reaction, which attached the ETH to the maleimide groups in Ma-P. Acidic elution released S-INP enantiomers through specific receptor sites formed in the imprinted polymer particles, S-INP-P. Characterization of the polymers was done by Fourier transform infrared spectroscopy (FTIR), nuclear magnetic resonance (13C NMR), and X-ray diffraction (XRD) while the surface morphology of the sorbents was investigated by scanning electron microscope (SEM). Optimum conditions for the enantioselective adsorption indicated that at pH 7, 285 mg/g of S-INP can be extracted. The chiral separation of the INP racemate led to an ee of 85% for R-INP in the first run and 97% for S-INP during elution.

Keywords: Indoprofen; Maleic anhydride; Molecular-imprinting; Thiol-maleimide.

MeSH terms

  • Chromatography, High Pressure Liquid / methods
  • Click Chemistry*
  • Maleimides* / chemistry
  • Molecularly Imprinted Polymers / chemistry
  • Polymers / chemistry
  • Stereoisomerism
  • Sulfhydryl Compounds* / chemistry

Substances

  • Maleimides
  • Sulfhydryl Compounds
  • Polymers
  • maleimide
  • Molecularly Imprinted Polymers
  • thiol-maleimide