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.