Symmetry-breaking charge-transfer enables turn-on fluorescence sensing in the shortwave infrared spectral region for in vivo vasculature redox homeostasis

Functional in vivo imaging in the short-wavelength infrared spectral region (SWIR) has broad potential in disease diagnosis, fluorescence guided surgery and in vivo pharmacology. In recent years, dyes absorbing in the SWIR region started to emerge. Yet, probe design based on these SWIR dyes remains difficult due to scarcity of efficient fluorescence quenching mechanism. Here, we propose that symmetry breaking charge transfer is a viable approach to develop off-on type probes with SWIR fluorophores. We synthesized the first V-shaped asymmetric cyanine dimer (VAD1080) and verified that its fluorescence was efficiently quenched. The subsequent treatment with highly oxidative species including ONOO^- could be employed to inhibit this photophysical quenching mechanism and restore the fluorescence. Its fluorescence sensing capability of oxidative stress in vivo was exemplified. We discovered that overdose of APAP induced a rapid rise of oxidative stress in the vasculature prior to a prior in the liver. This yields insights over the toxicology of APAP and suggested that clearance of reactive species in blood vessels is be a viable approach as a therapeutic measure of acute APAP toxicity.