Descriptor ΔGC‐O Enables the Quantitative Design of Spontaneously Blinking Rhodamines for Live‐Cell Super‐Resolution Imaging.

Herein, we reported a simple, fast, and quantitative theoretical descriptor ΔGC‐O that allows accurate predictions of a wide range of spontaneously blinking rhodamines. ΔGC‐O denotes the Gibbs free energy differences between the closed and open forms of rhodamines and has a good linear relationship with experimental pKcycl 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 ΔGC‐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 ΔGC‐O will greatly facilitate the efficient creations of spontaneously blinking fluorophores and aid the advancements of super‐resolution bioimaging techniques. [ABSTRACT FROM AUTHOR]