A novel borondifluoro indolenine-functionalized red-shift ratiometric fluorescent probe for detection of hypochlorous acid in drug-induced liver injury.

The diagnosis of drug-induced liver injury (DILI) remains a significant clinical challenge due to the lack of reliable tools for visualizing related biomarkers in vivo. Hypochlorous acid (HClO), a key indicator of oxidative stress, has been demonstrated to be closely linked to the onset and progression of DILI. Herein, to address the limitations of conventional HClO/ClO- detection, we developed a D-π-A architecture probe BFI-Naph through rational molecular engineering of a borondifluoro indolenine (BFI) core and a naphthol group. The probe exhibits a rapid (∼30 s), sensitive (LOD = 120 nM), large emission red-shifted (134 nm) and highly selective ratiometric fluorescence. The probe BFI-Naph was constructed based on the ClO-induced chlorination and concomitant pKa decreased mechanism. This structural and electronic adjustment enables a red shift in the fluorescence emission wavelength-from the red region toward the NIR region-upon recognition, thereby improving the accuracy of ratiometric signals in vivo. We successfully employed BFI-Naph to image endogenous HClO upregulation during APAP-induced hepatotoxicity in live cells. Most importantly, the probe enabled the clear visualization of elevated HClO levels in DILI and OA models. This study not only provides a powerful optical tool for the diagnosis and mechanistic investigation of DILI but also offers a versatile design strategy for developing precision biosensors.