An Evidence for the Chiral Discrimination of Naproxen Enantiomers: A Combined Experimental and Theoretical Study

Naproxen enantiomers possess strong room temperature phosphorescence (RTP) in β-cyclodextrin (β-CD) system with a small amount of 1,2-dibromoethane (1,2-DBE) under ambient conditions. The effects of pH, concentration of β-CD, and 1,2-DBE on the RTP of naproxen enantiomers have been investigated in detail. Time-resolved RTP spectroscopy shows that both naproxen enantiomers exhibit biexponential decay pattern with lifetimes of τ 1 = 4.79 ± 0.13 and τ 2 = 1.51 ± 0.096 ms for R -naproxen and τ 1 = 6.67 ± 0.15 and τ 2 = 2.13 ± 0.061 ms for S -naproxen. The lifetime differences between these enantiomers are Δτ 1 = 1.88 and Δτ 2 = 0.62 ms, indicating that chiral discrimination of naproxen enantiomers can be achieved in β-CD/1,2-DBE system. Naproxen enantiomers can form stable complexes with β-CD and 1,2-DBE in stoichiometric ratios of 1:1:2 and 1:1:1 (naproxen:β-CD:1,2-DBE), and the association constants are 3.20 × 10 3 M −4 and 2.43 × 10 3 M −3 for the S - and R -enantiomers, respectively. The chiral discrimination of R -naproxen and S -naproxen is realized via their difference in interaction with the chiral cavity of β-CD due to their difference in stereochemical structure. Finally, molecular modeling is performed to determine the chiral recognition on a molecular level, and the results are in good agreement with the experimental data.