Descriptor ΔG_C-O Enables the Quantitative Design of Spontaneously Blinking Rhodamines for Live-Cell Super-Resolution...

Herein, we reported a simple, fast, and quantitative theoretical descriptor ΔG_C-O that allows accurate predictions of a wide range of spontaneously blinking rhodamines. ΔG_C-O denotes the Gibbs free energy differences between the closed and open forms of rhodamines and has a good linear relationship with experimental pK_cycl values. This correlation affords an effective guide for the quantitative designs of spontaneously blinking rhodamines and eliminates trial-and-error. We have validated the predictive power of ΔG_C-O via the development of two spontaneously blinking rhodamines of different colors and enhanced brightness. We also demonstrated their super-resolution imaging utilities in dynamic live-cell imaging. We expect that ΔG_C-O will greatly facilitate the efficient creations of spontaneously blinking fluorophores and aid the advancements of super-resolution bioimaging techniques.