Self-Immolative Thiocarbamates Provide Access to Triggered H2S Donors and Analyte Replacement Fluorescent Probes

J Am Chem Soc. 2016 Jun 15;138(23):7256-9. doi: 10.1021/jacs.6b03780. Epub 2016 Jun 3.

Abstract

Hydrogen sulfide (H2S) is an important biological signaling molecule, and chemical tools for H2S delivery and detection have emerged as important investigative methods. Key challenges in these fields include developing donors that are triggered to release H2S in response to stimuli and developing probes that do not irreversibly consume H2S. Here we report a new strategy for H2S donation based on self-immolation of benzyl thiocarbamates to release carbonyl sulfide, which is rapidly converted to H2S by carbonic anhydrase. We leverage this chemistry to develop easily modifiable donors that can be triggered to release H2S. We also demonstrate that this approach can be coupled with common H2S-sensing motifs to generate scaffolds which, upon reaction with H2S, generate a fluorescence response and also release caged H2S, thus addressing challenges of analyte homeostasis in reaction-based probes.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Biosensing Techniques*
  • Carbonic Anhydrases / chemistry*
  • Catalysis
  • Fluorescent Dyes / chemistry*
  • Hydrogen Sulfide / analysis*
  • Hydrogen Sulfide / blood
  • Male
  • Mice
  • Sulfur Oxides / analysis*
  • Sulfur Oxides / blood
  • Thiocarbamates / chemical synthesis
  • Thiocarbamates / chemistry*

Substances

  • Fluorescent Dyes
  • Sulfur Oxides
  • Thiocarbamates
  • carbonyl sulfide
  • Carbonic Anhydrases
  • Hydrogen Sulfide