Stereospecific recognition of S-fluoxetine enabled by HOF-101-based multimodal probe.

BACKGROUND

Given the distinct pharmacological activities and toxicological profiles of fluoxetine enantiomers, highly selective analytical tools are essential to ensure medication safety and advance the accuracy of chiral recognition. The hydrogen-bonded organic framework HOF-101 possesses well defined porous channels, abundant directional hydrogen-bonding sites, and intrinsic fluorescence, and can achieve chiral recognition through differential cavity confinement and stereospecific hydrogen-bonding interactions. Based on this, we have developed a multimodal chiral fluorescent probe based on HOF-101 to identify the enantiomers of fluoxetine.

RESULTS

By leveraging the ordered porous structure and abundant active sites of HOF-101, we effectively identified the enantiomers of fluoxetine using a combination of colorimetric, fluorescent, and electrochemical detection methods. We investigated the probe's performance across three orthogonal detection modalities: visual colorimetry response, fluorescence turn-on (λem blue-shift from 550.0 nm to 450.0 nm; PLQY increase from 7.38% to 87.77%), and electrochemistry response. The limits of detection (LODs) were 0.464 nM (fluorescence) and 0.0303 nM (electrochemistry), respectively, the probe achieved sub-nanomolar sensitivity. The selective recognition mechanism involves competitive hydrogen bonding, wherein S-FLX enters the cavity of HOF-101, inducing a structural collapse that elicits pronounced photophysical and electrochemical responses. In contrast, the R-enantiomer is excluded due to steric incompatibility, resulting in negligible signal changes.

SIGNIFICANCE AND NOVELTY: These results highlight that cross validation across all three modes confirms result reproducibility and eliminates modality specific artifacts. This study provides a new technical solution for the rapid recognition and high sensitivity detection of chiral drugs.