Developing a ratiometric two-photon probe with baseline resolved emissions by through band energy transfer strategy: Tracking mitochondrial SO2 during neuroinflammation

Sulfur dioxide (SO2) with the largest quantity and widest distribution in the atmosphere is closely related to many nervous system diseases via mitochondria respiration. It is of great significance to monitor this gaseous molecule during various physiological and pathological processes, but currently the task still remains challenging due to the lack of reliable tools. Through-bond energy transfer (TBET) is a relatively new strategy to fabricate ratiometric fluorescent probes, which does not need spectral overlap between the energy donor and acceptor while provides high energy-transfer efficiency. It offers strong dual fluorescence emission peaks as well as large wavelength differences between the two peaks, which increases the bioimaging resolution and reliability. Herein, we developed a TBET-based ratiometric probe (TBET-SO2) with a series of superior properties for in vivo SO2 imaging. Excited by near-infrared pulsed laser (810 nm), the probe undergoes TBET and produces far-red emission (611 nm). It achieved significant energy-transfer efficiency (90.5%) and large spectral gap between two peaks (△λ = 118 nm). Upon reacting with SO2, TBET-SO2 showed ~30-fold enhancement of ratiometric signal contributed by the baseline resolved emissions. A detection limit of as low as 0.09 μM was obtained. Furthermore, TBET-SO2 was successfully applied for visualizing the mitochondrial SO2 in living cells and mice brain tissue during the neuroinflammation process induced by SO2 pollution.