A near-infrared fluorescent probe for visualizing transformation pathway of Cys/Hcy and H2 S and its applications in living system

Sulfydryl-contained (-SH) substances including hydrogen sulfide (H2 S), cysteine (Cys), homocysteine (Hcy) and glutathione (GSH) play crucial roles in living systems, and their variations are closely associated with various diseases. Herein, we developed a near-infrared intramolecular charge transfer (ICT) based fluorescent probe Y-NBD , achieving detection of Cys/Hcy and H2 S with different fluorescent signals (green-red for Cys/Hcy, red for H2 S), large Stokes shifts ( similar to 100/105 nm or 191 nm) and high signal-background-ratio, but not responding to GSH. Y-NBD was successfully applied to image exogenous/endogenous Cys/Hcy and H2 S in various living cancer cells (HeLa, A549, and HepG2) and in zebrafish. It not only visualized the transformation pathway of several thiols in HepG2 cells but also verified that the intestine is the main site for the activation and metabolism of Y-NBD in zebrafish, as well as realized to evaluate the degree of drug-induced liver injury. This work provides a promising tool for imaging Cys/Hcy and H2 S in living systems and shows great potency in evaluating drug-induced liver injury and its treatment. (c) 2024 Published by Elsevier B.V. on behalf of Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences.