Rational Design of a Ratiometric Fluorescent Probe Based on Arene-Metal-Ion Contact for Endogenous Hydrogen Sulfide Detection in Living Cells

We report the design and development of a fluorescent Cd^II ion complex that is capable of the ratiometric detection of H₂S in living cells. This probe exploits the metal-ion-induced emission red shift resulting from direct contact between the aromatic ring of a fluorophore and a metal ion (i.e., arene-metal-ion or "AM" contact). The Cd^II complex displays a large emission blue shift upon interaction with H₂S as the Cd^II-free ligand is released by the formation of cadmium sulfide. Screening of potential ligands and fluorophores led to the discovery of a pyronine-type probe, 6Cd^II, that generated a sensitive and rapid ratio value change upon interaction with H₂S, without interference from the glutathione that is abundant in the cell. The membrane-impermeable 6Cd^II was successfully translocated into live cells by using an oligo-arginine peptide and pyrenebutylate as carriers. As such, 6Cd^II was successfully applied to the ratiometric detection of both exogenous and endogenous H₂S produced by the enzymes in living cells, thus demonstrating the utility of 6Cd^II in biological fluorescence analysis.