Fluorescence imaging is one of the most powerful techniques for visualizing temporal and spatial changes of biological phenomena in living cells, and many fluorescent probes have been developed. In particular, xanthene dyes such as fluorescein and rhodamines have favorable characteristics, such as high water solubility, high fluorescence quantum yield and high molar extinction coefficient, and they have been utilized as fluorescent cores for fluorescent probes working in the green to red wavelength region. Recently, silicon-substituted xanthene dyes such as 2,7-N,N,N′,N′-tetramethyl-9-dimethyl-10-hydro-9-silaanthracene (TMDHS), Si-rhodamines and TokyoMagentas, in which the O atom at the 10-position of xanthene is replaced with a Si atom, have been developed as novel far-red to near-infrared fluorescent cores that retain the key advantages of the parent structures. Fluorescent probes based on them have opened up new possibilities for imaging biological processes in living cells. This minireview covers recent progress in silicon-substituted xanthene dyes, including representative applications for in vivo tumor imaging, triple-color imaging of neuronal activity, and super-resolution microscopy.

The mammalian brain is highly vulnerable to oxygen deprivation, yet the mechanism underlying the brain’s sensitivity to hypoxia is incompletely understood. Hypoxia induces accumulation of hydrogen sulfide, a gas that inhibits mitochondrial respiration. Here, we show that, in mice, rats, and naturally hypoxia-tolerant ground squirrels, the sensitivity of the brain to hypoxia is inversely related to the levels of sulfide:quinone oxidoreductase (SQOR) and the capacity to catabolize sulfide. Silencing SQOR increased the sensitivity of the brain to hypoxia, whereas neuron-specific SQOR expression prevented hypoxia-induced sulfide accumulation, bioenergetic failure, and ischemic brain injury. Excluding SQOR from mitochondria increased sensitivity to hypoxia not only in the brain but also in heart and liver. Pharmacological scavenging of sulfide maintained mitochondrial respiration in hypoxic neurons and made mice resistant to hypoxia. These results illuminate the critical role of sulfide catabolism in energy homeostasis during hypoxia and identify a therapeutic target for ischemic brain injury.