Developing a novel benzothiazole-based red-emitting probe for intravital imaging of superoxide anion.

Superoxide anion (O), the first generated reactive oxygen species (ROS), is a critical player in cellular signaling network and redox homeostasis. Imaging of O, particularly in vivo, is of concern for further understanding its roles in pathophysiological and pharmacological events. Herein, we designed a novel probe, (E)-4-(5-(2-(benzo[d]thiazol-2-yl)-2-cyanovinyl)furan-2-yl)phenyl trifluoromethane-sulfonate (BFTF), by modifying hydroxyphenyl benzothiazole (a widely used dye scaffold) which includes insertion of both an acrylonitrile unit and a furan ring to extend the total π-conjugation system and to enhance push-pull intramolecular charge transfer process, and utilization of trifluoromethanesulfonate as the response unit. Toward O, the probe features near-infrared fluorescent emission (685 nm), large Stokes shift (135 nm), and deep tissue penetration (300 μm). With its help, we successfully mapped preferential generation of O in HepG2 cells over L02 cells, as well as in A549 over BEAS-2B cells by β-lapachone (an anticancer agent that generates O), and more importantly, visualized overproduction of O in living mice with liver injury induced by acetaminophen (a well-known analgesic and antipyretic drug).