Synthesis of Water-Soluble Far-Red-Emitting Amphiphilic BODIPY Dyes

We report the synthesis of two water-soluble BODIPY dyes with far-red absorption and near-infrared fluorescence following cell membrane insertion. Introduction of dicationic or dianionic groups imparts water solubility and prevents translocation of the dye through the plasma membrane for highly effective labeling. The dicationic form is particularly well localized to the plasma membrane and resists quenching even after >8 min of continuous light exposure. The dyes are almost completely nonemissive in water and other highly polar solvents, but display high-fluorescence yields in chloroform and upon insertion into the extracellular leaflet.