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

Abstract

Superoxide anion (O2•−), the first generated reactive oxygen species (ROS), is a critical player in cellular signaling network and redox homeostasis. Imaging of O2•−, 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 O2•−, 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 O2•− in HepG2 cells over L02 cells, as well as in A549 over BEAS-2B cells by β-lapachone (an anticancer agent that generates O2•−), and more importantly, visualized overproduction of O2•− in living mice with liver injury induced by acetaminophen (a well-known analgesic and antipyretic drug).