Homoadamantane-Fused Tetrahydroquinoxaline as a Robust Electron-Donating Unit for High-Performance Asymmetric NIR Rhodamine Development.

Rhodamines have emerged as a useful class of dye for bioimaging. However, intrinsic issues such as short emission wavelengths and small Stokes shifts limit their widespread applications in living systems. By taking advantage of the homoadamantane-fused tetrahydroquinoxaline (HFT) moiety as an electron donor, we developed a new class of asymmetric NIR rhodamine dyes, NNR1-7. These new dyes retained ideal photophysical properties from the classical rhodamine scaffold and showed large Stokes shifts (>80 nm) with improved chemo/photostability. We found that NNR1-7 specifically target cellular mitochondria with superior photobleaching resistance and improved tolerance for cell fixation compared to commercial mitochondria trackers. Based on NNR4, a novel NIR pH sensor (NNR4M) was also constructed and successfully applied for real-time monitoring of variations in lysosomal pH. We envision this design strategy would find broad applications in the development of highly stable NIR dyes with a large Stokes shift.