Turn-on quinoline probe for selective sensing of hypochlorite in live cells

Hypochlorite is a highly reactive oxygen species (ROS) implicated in diverse physiological and pathological processes. Elevated hypochlorite levels cause oxidative stress, leading to structural and functional disruptions in biomacromolecules and contributing to the onset and progression of disease. Despite significant progress, many reported hypochlorite probes suffer from relatively high molecular weights and often depend on emission shifts, which complicate sensitivity and quantitative analysis. To overcome these limitations, we developed a low-molecular-weight quinoline-derived probe 5 that, to our knowledge, represents the first example of a quinoline-phenothiazine-based hypochlorite sensor that is non-fluorescent in its basal state yet undergoes a selective oxidative transformation to yield a robust emission at 523 nm. The probe exhibits exceptional temporal resolution, with fluorescence activation observed within 10 s in cell-free assays and generates a visible signal that scales directly with ROS concentration. Importantly, the probe maintains performance in live-cell studies, where activation occurs in a concentration-dependent manner. Altogether, these results establish 5 as a rapid, sensitive, and biologically compatible tool for monitoring hypochlorite dynamics in real time, advancing the design of next-generation ROS probes by combining low molecular weight, rapid response time, and straightforward readout.