Time-gated detection of cystathionine γ-lyase activity and inhibition with a selective luminogenic hydrogen sulfide sensor

摘要

Herein, we report the design, synthesis and characterization of a lanthanide^III complex-based probe for the time-gated luminescence detection of hydrogen sulfide (H2S) in aqueous media. The probe’s unique sensing mechanism relies on the selective reduction of azide to amine by sulfide, followed by intramolecular cyclization to form a quinolinone. The quinolinone is a sensitizer that absorbs near-UV light and transfers excitation energy to coordinated Tb^III or Eu^III ions to trigger a strong “turn-on” luminescence response with ms-scale lifetimes characteristic of lanthanide complexes. Using this probe, we developed a robust, high throughput screening (HTS) assay for detecting H2S generated by cystathionine γ-lyase (CSE), one of the main producers of H2S in mammalian cells. In a 240-compound screen to identify potential CSE inhibitors, the Eu^III analog of the sensor showed a low false positive rate and high Z′-factor (> 0.7).