An electronic equilibrium strategy to drive the design of reversible fluorescent probes for sulfur dioxide and formaldehyde

Probes based on Michael addition reactions remain underexploited due to a lack of understanding of the mechanisms governing the reversibility of the reaction, resulting in a lack of theoretical guidance for the targeted design of reversible probes for SO₂ and formaldehyde (FA). Herein, we propose an electronic equilibrium strategy (EES) to guide the design of reversible fluorescent probes for SO₂ and FA. To deepen this concept, we further introduce the “reaction electrostatic potential disequilibrium driving force (ESPD) ΔD_r” descriptor to quantify the reaction driving force arising from electrostatic potential disequilibrium. From kinetic and thermodynamic perspectives, modulating the electronic equilibrium state of the probes (adjusting the ΔD_r value) enables a transition from nearly irreversible to moderately reversible and finally to fully reversible behavior. Moreover, as the electronic distribution of the RE probes progressively shifts toward equilibrium, the fluorescence recovery rates reach 10%, 56%, 91%, and 100%, respectively. Among these, RE-D was used for the reversible imaging of SO₂ and FA in live cells and mice, as well as for detecting SO₂ residues in Chinese herbal medicines and FA in cosmetic products. Importantly, encryption ink based on the irreversible nature of RE-A and the reversible characteristics of RE-D enables advanced anti-counterfeiting applications. Overall, this study not only establishes a pioneering design strategy for the rational design of reversible fluorescent probes, but also expands their applications in bioimaging, analytical detection, and smart materials.