A rational approach to tuning the pK(a) values of rhodamines for living cell fluorescence imaging

A novel strategy to systematically tune the pK(a) values of rhodamines is described. This strategy was applied to rationally develop compound 1e with a pK(a) of 6.5, the highest among rhodamine amide derivatives, and it could be employed to detect acidic pH variations in living cells with a turn-on signal.