Dual-Selector Biphasic Recognition Chiral Extraction for Naproxen Enantiomers: Experimental Evaluation and Molecular-Level Mechanism

Single-selector screening first identified HE-β-CD as the preferred aqueous selector for <i>S</i>-naproxen and L-DTTA as a complementary organic selector for <i>R</i>-naproxen.

After optimization of selector concentrations, feed concentration, pH and temperature, the single-stage enantioselectivity yields 2.10, with an enantiomeric excess of 31.93%. Quantum chemical calculations and molecular dynamics simulations were then used to interpret the experimentally verified selectivity trends. The results indicate that HE-β-CD preferentially stabilizes <i>S</i>-naproxen through cavity-size matching and a directional hydrogen-bonding network near the modified cavity entrance, whereas L-DTTA favors <i>R</i>-naproxen through steric complementarity and extensive van der Waals contacts.