Side-chain-fixed homoadamantane-fused tetrahydroquinoxaline coumarin: A robust platform for highly photostable HClO probe development

To elucidate the in-depth chemical biology of HClO that involved in various physiological or pathological events, fluorescent probes with the ability to continuously track or monitor the fluctuations in endogenous HClO levels over the long term are highly desirable. Unfortunately, most of the currently reported HClO probes have not answered this call due to their unsatisfactory photostability. Herein, a series of photostable fluorescent dyes termed side-chain-fixed homoadamantane-fused tetrahydroquinoxaline coumarins (SFHTC1–5), were judiciously designed and synthesized. Among these dyes, SFHTC3 was particularly attractive, which absorbance can be preserved over 93 % after 60 min of continuous irradiation under a 1 W 515 nm laser source, far outperforming rhodamine 6 G, a commercially available fluorescent dye known for its good photostability. Based on this robust platform, a highly photostable ratiometric HClO probe, SFHTC3-SO, was rationally constructed. Significantly, the use of SFHTC3-SO for long-term continuous imaging of HClO fluctuations in both HeLa cells and the rheumatoid arthritis mouse model was successfully realized, highlighting the utility of this probe for potential biological investigations.