Diels-Alder post-crosslinked sulfonic acid-functionalized polymer for high-performance chiral separation of fluoxetine enantiomers

Abstract

Selective isolation and determination of chiral drugs remain among the biggest hurdles in the pharmaceutical and analytical domains. In this research, a sulfonic acid-functionalized phenolic resin (P-SO₃H) was synthesized as a high-capacity adsorbent for S-fluoxetine (S-FX) utilizing electrostatic interaction and hydrogen bonding for the enhancement of adsorption. For introduction of enantioselectivity and stabilization of binding sites, imprinting was performed through Diels-Alder (DA) post-crosslinking with bis(maleimido)ethane (BMO), resulting in the S-FX-imprinted polymer (S-FX-P). Batch adsorption experiments revealed maximum adsorption in the pH range of 6–7 where S-FX-P expressed a 12 times stronger affinity towards S-FX than R-FX, indicating the presence of well-defined molecular recognition sites. Isotherm analysis indicated that adsorption was according to the Langmuir model with >490 mg/g maximum adsorption capacity. Column-based enantioseparation led to 97 % enantiomeric excess (ee) of R-FX in the initial eluate and 91 % ee of S-FX in the recovered fraction. In contrast, the non-imprinted polymer (NIP) was enantioselective-free. These results attest to the competence of post-crosslinked sulfonated MIPs in high-performance chiral separation with prospect application in the purification of drugs and enantiomeric drug analysis.