Controllable Cleavage of C-N Bond-Based Fluorescent and Photoacoustic Dual-Modal Probes for the Detection of H 2 S in Living Mice.

Hydrogen sulfide (H ₂ S) has been recognized to influence a wide range of physiological and pathological processes. Its underlying molecular events, however, are still poorly understood. An activatable H ₂ S probe for photoacoustic (PA) imaging is desirable to further explore the role of H ₂ S in vivo. Nevertheless, only a few activatable PA probes for H ₂ S detection have been reported. In particular, examples of dual-modal H ₂ S probes with the combined advantages of fluorescence (high sensitivity and resolution) and PA imaging (deep penetration) are very rare. Herein the controllable cleavage of the C-N bond in nitrobenzoxadiazole (NBD) amine derivatives by H ₂ S is presented for the first time. The cleavage reactivity was found to be accelerated by the introduction of an electron-withdrawing group. Through this strategy, a series of fluorescent and PA dual-modal probes ( 1 - 3 ) were developed for H ₂ S detection. Among them, probe 3 shows a high fluorescence on-off response rate ( k ₂ = 4.04 M ^-1 s ^-1 ) and excellent selectivity for H ₂ S over other biothiols. Moreover, probe 3 can also work as an activatable PA H ₂ S probe because of the significant shift of its absorption peak from 468 to 532 nm in the H ₂ S reaction. Importantly, probe 3 demonstrates its capability for fluorescence and PA imaging of H ₂ S in living cells and mice. These results indicate that the controllable cleavage of the C-N bond can serve as an efficient strategy for designing fluorescent and PA dual-modal H ₂ S probes.