Development of a Small Molecule Probe Capable of Discriminating Cysteine, Homocysteine, and Glutathione with Three Distinct Turn-On Fluorescent Outputs

The simultaneous discrimination of Cys, Hcy, and GSH by a single probe is still an unmet challenge. The design and synthesis of a small molecule probe MeO‐BODIPY‐Cl (BODIPY=boron dipyrromethene) is presented, which can allow Cys, Hcy, and GSH to be simultaneously discriminated on the basis of three distinct fluorescence turn‐on responses. The probe reacts with these thiols to form sulfenyl‐substituted BODIPY, which is followed by intramolecular displacement to yield amino‐substituted BODIPY. The kinetic rate of the intramolecular displacement reaction determines the observed different sensing behavior. Therefore, the probe responds to Cys, Hcy, and GSH with fluorescence turn‐on colors of yellow, yellow and red, and red, respectively. With this promising feature in hand, the probe was successfully used in imaging of Cys, Hcy and GSH in living cells. Three little birds: Simultaneous discrimination of cysteine (Cys), homocystein (Hcy), and glutathione (GSH) by a single probe is still an unmet challenge. A new boron dipyrromethene (BODIPY)‐based small molecule fluorescent probe is reported, which responds to Cys, Hcy, and GSH with three different sets of fluorescent features, thus displaying the detection of Cys, Hcy, and GSH with high selectivity (see figure).