Probing Deep\nHydrogen Polysulfides Fluctuations In\nVivo by Engineering Activatable Fluorescence Reporters with Second\nNear-Infrared Window Emission

Deep and comprehensive understanding of the intricate\nbiochemical\nprocesses mediated by H<sub>2</sub>S<i><sub>n</sub></i> (<i>n</i> ≥ 1), but not H<sub>2</sub>S, is of paramount importance.\nA few fluorescent probes have been developed with the intention of\naddressing this issue. However, there is currently no evidence of\nany activatable NIR-II fluorescent probes for H<sub>2</sub>S<i><sub>n</sub></i>-specific imaging over H<sub>2</sub>S. In this\nstudy, we developed the inaugural H<sub>2</sub>S<i><sub>n</sub></i>-activated NIR-II probe for specific and deep imaging of\nH<sub>2</sub>S<i><sub>n</sub></i> through a series of molecular\nengineering strategies. Strong electron-absorbing moieties enabled\nthe redshift of the emission of the designed reporter, while leaving\ngroups with different dissociation capacities were responsible for\nmodulating the selective and sensitive responsiveness to H<sub>2</sub>S<i><sub>n</sub></i> over H<sub>2</sub>S. By using this\nactivatable specific probe for deep tissue mapping of endogenous H<sub>2</sub>S<i><sub>n</sub></i> fluctuations, accurate identification\nof acute inflammation in animal models was achieved. It is anticipated\nthat the advancement of this activatable NIR-II probe will facilitate\na more profound comprehension of the physiological implications of\nH<sub>2</sub>S<i><sub>n</sub></i>.