Novel flavone-based near-infrared fluorescent probe for the detection of H2S in vitro and in vivo

Hydrogen sulfide (H 2 S) plays an important role in various pathophysiological processes, and its concentration is associated with various diseases. As such, the development of new H 2 S probes for the early detection of these diseases is of great significance. To date, a variety of probes have been developed for H 2 S detection, however, most probes exhibit response to other sulfur-containing compounds, resulting in a lack of specificity and weaker anti-interference performance. In this paper, a new flavone-based near-infrared (NIR) fluorophore was synthesized by introducing a 5-[4-(dimethylamino) phenyl] thiophene group at the 2-position of the chromone structure. Moreover, using nitrobenzoate as recognition group, two novel probes (TF-3NO 2 and TF-4NO 2 ) were synthesized to detection of H 2 S in biological systems. Among them, TF-3NO 2 exhibited a more specific fluorescent response to H 2 S compared to TF-4NO 2 . Upon treatment with H 2 S, the fluorescence intensity showed a significant increase, showcasing the high specificity, strong anti-interference capability, near-infrared emission (690 nm), and large Stokes shift (∆λ = 223 nm) of the probe. Moreover, the probe was successfully applied for imaging both exogenous and endogenous H 2 S in cells and mice, and enabled to distinguish changes in the H 2 S concentration in the brains of APP/PS1 transgenic and wild-type mice. The above results indicate that TF-3NO 2 can penetrate the mouse blood brain barrier, and is expected to be a powerful molecular tool for detecting H 2 S in living systems within basic and biomedical research fields.