Development of a Mitochondria-Targeted Ruthenium(II)-Based Phosphorescent Probe for Hypochlorite Detection in Acute Inflammatory Model

The uncontrolled acute inflammatory response triggers dysregulation of the immunoinflammatory system, contributing to the development and progression of various acute inflammatory diseases (AIDs). Hypochlorite (ClO^-), as a crucial oxidative mediator in AIDs, accumulates in the inflammatory environment, leading to direct cytotoxicity, secondary injury, and tissue dysfunction. However, achieving rapid detection, accurate tracking, in situ monitoring, and real-time imaging of ClO^- in vivo remains a significant challenge. To address these issues, we developed a mitochondria-targeted phosphorescent probe (RuDM), which introduces a ligand containing a C═N bond as a ClO^- recognition site to precisely identify ClO^- in AIDs. It responds rapidly (6 s) and exhibits long-lived luminescence (471 ns), with a 190-fold luminescence enhancement in monitoring ClO^-. Meanwhile, density functional theory (DFT) indicates that the luminescence enhancement of RuCOOH is attributed to the removal of an electron-withdrawing group (diaminomaleonitrile) from RuDM, which leads to an increase in the intersystem crossing rate and a greater probability of radiative transition from the T₁ state. Finally, RuDM is used to monitor the levels of exogenous and endogenous ClO^- in cells using confocal microscopy imaging and to evaluate its capability for ClO^- detection over time in an acute inflammatory model. The above results suggest that RuDM, as a novel molecular platform to detect ClO^-, has potential as a practical tool for research on the pathogenesis of acute inflammatory diseases.