Polysiloxane-Based Molecular Logic Gate for Dual-Channel Visualizing Mitochondrial pH and Sulphite Changes during...

Intracellular Cu-induced regulated cell death, characterized by the aggregation of lipidizing mitochondrial enzymes, is called cuproptosis. Mitochondria play a vital role in the metabolic regulation of cell injury and stressful immune responses. The pH levels and sulfur dioxide (SO₂) content in mitochondria have important indicative roles in the regulation of cuproptosis. However, fluorescent probes that simultaneously detect changes in pH and SO₂ in mitochondria during cuprotosis have not been reported. To fill this blank, in this study, we dexterously used functional polysiloxane as a fluorescent platform to propose a molecular logic gate probe P-pH-SO for detecting changes in intramitochondrial pH and SO₂ content through a dual-channel mode. In addition, we defined a new function to reflect the cellular state of the elesclomol-induced cuproptosis process based on the input and output of the relevant logic relationship. This new fluorescent molecular logic gate probe P-pH-SO can be rapidly activated by mitochondrial sulfites to induce green fluorescence, while the red fluorescence is quenched with the proton in the mitochondria. Overall, this study developed a novel logic-gated molecular probe that provided a versatile strategy for monitoring the role played by intramitochondrial sulfites and H⁺ in cuproptosis. This work will open the way to broaden the applications of molecular logic gates and fluorescent polysiloxanes.