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

Naproxen enantioners possess strong room temperature phosphorescence (RTP) in beta-cyclodextrin (beta-CD) system with a small amount of 1,2-dibromoethane (1,2-DEB) under ambient conditions. The effects of pH, concentration of beta-CD, and 1,2-DEB on the RTP of naproxen enantiomers have been investigated in detail. Time-resolved RTP spectoscopy shows that both naproxen enantiomers exhibit biexponentioal decay patters with lifetimes of tau(1) = 4.79 +/- 0.013 and tau(2) = 1.51 +/- 0.096 ms for R-naproxen and tau(1) = 6.67 +/- 0.15 tau(2) =2.13 +/- 0.061 ms for S-naproxen. The lifetime differences between these enantiomers are Delta tau(1) = 1.88 and Delta tau(2) = 0.62ms, indicating that chiral discrimination of naproxen enantiomers can be achieved in beta-CD/1,2-DEB system. Naproxen enantiomrs can form stable complexes with beta-CD and 1,2-DEB in stoichiometric ratios of 1:1:2 and 1:1:1 (naproxen:beta.CD:1,2-DEB), and the association constants are 3.20 x 10(3) M-4 and 2.43 x 10(3) M-3 for the S- and R-enantiomers, respectively. The chiral discrimination of R-naproxen and S-naproxen is realized via their differencee in interaction with the chiral cavity of beta-CD due to their difference in sterochemical 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.