Molecular Optimization of a Near-Infrared Fluorogenic Probe for Hydrogen Polysulfide Imaging in Acute Liver Injury

Hydrogen polysulfides (H 2 S n ), a key reactive sulfur species, play pivotal roles in cellular signaling, antioxidative stress, and cell death regulation. Revealing the dynamic changes of H 2 S n levels in vivo is crucial for elucidating its physiological functions. However, real-time detection of H 2 S n in vivo faces significant challenges due to its inherent instability. In this study, we screened a near-infrared fluorogenic (NIRF) probe DCICl-H 2 S n for the detection of H 2 S n in cells and mice models. This probe employed a dicyanoisophorone scaffold functionalized with ortho-NO 2 substituted phenyl sulfonate groups, which endowed it with exceptional photophysical properties and high specificity toward H 2 S n . Upon reaction with H 2 S n, DCICl-H 2 S n emitted a fluorescent “turn-on” signal at 675 nm. Benefiting from its excellent optical properties, DCICl-H 2 S n enabled monitoring of both exogenous and endogenous H 2 S n level changes in live cells. Leveraging DCICl-H 2 S n, we explored the role of H 2 S n in APAP or CCl 4 -induced acute liver injury (ALI) mice models. The results revealed a negative correlation between H 2 S n levels and the severity of liver injury, suggesting that H 2 S n could be used as a potential biomarker for assessing the severity of ALI. Moreover, oral administration of silybin (SLB) significantly reduced liver injury and up-regulated H 2 S n levels. The present probe DCICl-H 2 S n proved to be an effective tool for investigating the dynamic changes of H 2 S n, which could help to uncover the molecular mechanisms of liver injury.