Imaging and evaluation of sulfane sulfur in acute brain ischemia using a mitochondria-targeted near-infrared fluorescent probe.

Ischemia is a pathological condition owing to the deficiency of blood supply to a limited area of tissue. Ischemia can induce burst production of reactive oxygen species and lead to oxidative damage. As a family member of reactive sulfur species, sulfane sulfur plays important physiological roles in many biological events including synthesis of cofactors, modulation of enzyme activities, sulfuration of tRNA, and especially regulation of the intracellular redox state. We hypothesize that the endogenous level of sulfane sulfur will be adjusted to deal with ischemia-induced oxidative damage. Therefore, the bioimaging of sulfane sulfur real-time changes during ischemia is important for better understanding its physiological processes. Herein, we describe the development of a mitochondria-targeted fluorescent probe Mito-SH that allowed for selective and sensitive detection of sulfane sulfur. Mito-SH is designed on the basis of the tautomerization of sulfane sulfur to thiosulfoxide, which ensures its high selectivity and sensitivity. A lipophilic triphenylphosphonium cation is selected as the mitochondria-targeted moiety, which can precisely navigate Mito-SH into mitochondria. The emission profile of azo-BODIPY fluorophore locates at the near-infrared region, which deeply penetrates tissue and effectively avoids the interference of biological background. Mito-SH exhibits the desirable combination of selectivity, sensitivity and excellent fluorescence response upon reaction with sulfane sulfur in cells. By employing Mito-SH, we evaluate the real-time sulfane sulfur dynamic changes under oxygen-glucose deprivation. Finally, Mito-SH has been successfully used for imaging sulfane sulfur changes caused by acute ischemia in mice.