Time-Gated Detection of Cystathionine γ-Lyase Activity and Inhibition with a Selective, Luminogenic Hydrogen Sulfide Sensor

Chemistry. 2017 Jan 18;23(4):752-756. doi: 10.1002/chem.201604786. Epub 2016 Nov 25.

Abstract

Herein, we report the design, synthesis, and characterization of a lanthanideIII complex-based probe for the time-gated luminescence detection of hydrogen sulfide (H2 S) 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 TbIII or EuIII 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 H2 S generated by cystathionine γ-lyase (CSE), one of the main producers of H2 S in mammalian cells. In a 240-compound screen to identify potential CSE inhibitors, the EuIII analogue of the sensor showed a low false-positive rate and high Z'-factor (>0.7).

Keywords: high-throughput screening; hydrogen sulfide; lanthanides; luminescence; sensors.

MeSH terms

  • Cystathionine gamma-Lyase / antagonists & inhibitors
  • Cystathionine gamma-Lyase / metabolism*
  • Europium / chemistry
  • High-Throughput Screening Assays
  • Hydrogen Sulfide / analysis*
  • Hydrogen Sulfide / chemistry
  • Lanthanoid Series Elements / chemistry
  • Luminescent Agents / chemical synthesis
  • Luminescent Agents / chemistry
  • Luminescent Measurements*
  • Magnetic Resonance Spectroscopy

Substances

  • Lanthanoid Series Elements
  • Luminescent Agents
  • Europium
  • Cystathionine gamma-Lyase
  • Hydrogen Sulfide