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

Hydrogen sulfide (H2S) plays an important role in various pathophysiological processes, and its concentration is associated with various diseases. As such, the development of new H2S probes for the early detection of these diseases is of great significance. To date, a variety of probes have been developed for H2S 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-3NO2 and TF-4NO2) were synthesized to detection of H2S in biological systems. Among them, TF-3NO2 exhibited a more specific fluorescent response to H2S compared to TF-4NO2. Upon treatment with H2S, 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 H2S in cells and mice, and enabled to distinguish changes in the H2S concentration in the brains of APP/PS1 transgenic and wild-type mice. The above results indicate that TF-3NO2 can penetrate the mouse blood brain barrier, and is expected to be a powerful molecular tool for detecting H2S in living systems within basic and biomedical research fields.