Achieving efficient chiral discrimination by a convenient method remains a challenge in pharmaceutical and biotechnology industries. Our aim in this paper was to develop a dual-signaling enantioselective sensing strategy based on the competitive binding assay. A combination of β-cyclodextrin (β-CD) and methylene blue (MB) was used as an enantioselective discrimination probe to develop a straightforward electrochemical chiral sensor using the drug naproxen (R-and S-NaX) as the representative enantiomers. The principle relied on the difference between two enantiomers in the ability to replace a pre-binding redox probe, which in turn resulted in different dual signals for the two enantiomers. The applicability of the optimized procedure was demonstrated by the analysis of NaX enantiomers in the range of 0.4–6.0 μM. Featuring both signal-on and signal-off elements, the electrode presented significantly enhanced electrochemical activity with a low limit of detection (LOD) of 0.07 μM. We expect that our work will inspire interesting engineering strategies for developing novel enantioselective electrochemical sensors.
