Enantioselective extraction of ibuprofen enantiomers using quinine-terminated tetra-arm PEGs as a recyclable chiral selector

Abstract

A novel chiral quinine-terminated tetra-arm PEGs (Quin@4-arm PEGs) was synthesized from tetra-arm PEGs and natural quinine, demonstrating significant chiral recognition of ibuprofen enantiomers, as confirmed by NMR analysis. We have developed a biphasic chiral extraction system to separate the two enantiomers of ibuprofen using the as-prepared Quin@4-arm PEGs as the chiral selector. We explored several extraction parameters, including pH, chiral selector concentration, initial ibuprofen concentration, and temperature, to evaluate their influence on the enantiomeric excess and distribution behavior of the two enantiomers. The optimal conditions for the enantioselective extraction of ibuprofen enantiomers were determined using response surface methodology. The results showed that a single chiral extraction could achieve an enantiomeric excess of up to 54 % and a yield exceeding 80 % for S-ibuprofen at the initial ibuprofen concentration of 0.09 mg⋅mL⁻¹, with 2.22 % Quin@4-arm PEGs, a pH of 7.6 and a temperature of 18.0 °C. In addition, back-extraction experiments demonstrated the effective recycling of the chiral selector in this chiral extraction system, achieving similar enantioselective extraction results over seven cycles. This work provides an effective method for separating ibuprofen enantiomers using quinine-terminated tetra-arm PEGs as a recyclable chiral selector.