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

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 P0-pH-SO2 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 P0-pH-SO2 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.