An Activatable Chemiluminescent Self-Reporting Sulfur Dioxide Donor for Inflammatory Response and Regulation of Gaseous Vasodilation.

Sulfur dioxide (SO2), being a novel gaseous signaling molecule, exhibits significant potential for application in the field of cardiovascular diseases. SO2 donors serve as crucial tools for the transportation and regulation of SO2 in vivo, facilitating the investigation of physiological roles associated with this molecule. However, the current therapeutic SO2 donors lack the capability to monitor the real-time release of SO2, thereby hindering accurate assessment of their therapeutic efficacy and target localization. Herein, we present an activatable chemiluminescent self-reporting SO2 donor (CL-SO2D) that can be selectively activated by peroxynitrite (ONOO-) to release SO2 and enable real-time visualization of the extent of release through chemiluminescent imaging. In vitro and cellular experiments demonstrate that CL-SO2D exhibits high selectivity and signal-to-noise ratio toward ONOO- and effectively facilitates the SO2 release process. Finally, CL-SO2D successfully achieved the response to the mouse inflammatory model and relieved vasoconstriction in zebrafish by releasing SO2 stimulated by ONOO-. The findings suggest that CL-SO2D exhibits impressive attributes in the diagnosis and treatment of SO2-related diseases, opening the gateway for developing low-background and high-sensitivity self-reporting SO2 donors.