Time‐Gated Detection of Cystathionine γ‐Lyase Activity and Inhibition with a Selective, Luminogenic Hydrogen Sulfide Sensor. Issue 4 (25th November 2016)

• Record Type: Journal Article
• Authors: Yao, Yao; Kong, Chen; Yin, Liang; Jain, Atul D.; Ratia, Kiira; Thatcher, Gregory R. J.; Moore, Terry W.; Driver, Tom G.; Miller, Lawrence W.
• Is Part Of: Chemistry. Volume 23:Issue 4(2017)
• Page Start: 752
• Page End: 756
• Publication Date: 2016-11-25
• Subjects: high-throughput screening -- hydrogen sulfide -- lanthanides -- luminescence -- sensors; Chemistry -- Periodicals; 540
• DOI: 10.1002/chem.201604786
• Languages: English
• ISSNs: 0947-6539

Abstract

Abstract: Herein, we report the design, synthesis, and characterization of a lanthanide III 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 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 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 Eu III analogue of the sensor showed a low false‐positive rate and high Z′‐factor (>0.7). Abstract : Time‐gated sensing : An emissive lanthanide probe LLPS‐Ln III was developed that gives a strong turn‐on response to hydrogen sulfide. H2 S reduces an aryl azide moiety to trigger an intramolecular cyclization to form a quinolinone that efficiently sensitizes long‐lifetime Tb III or Eu III luminescence (see figure). Time‐gated detection permits sensitive, high‐throughput screening for inhibition of H2 S‐producing cystathionine γ‐lyase.