Visualizing changes in mitochondrial Mg²⁺ during apoptosis with organelle-targeted triazole-based ratiometric fluorescent sensors

Magnesium is one of the most abundant metals in cells and is essential for a wide range of cellular processes. Magnesium imbalance has been linked to a variety of diseases, but the scarcity of sensors suitable for detection of Mg²⁺ with subcellular resolution has hampered the study of compartmentalization and mobilization of this ion in the context of physiological and pathological processes. We report herein a family of fluorescent probes for targeted detection of free Mg²⁺ in specific intracellular organelles, and its application in the study of programmed cell death. The new sensors feature a triazole unit that plays both structural and electronic roles by serving as an attachment group for targeting moieties, and modulating a possible internal charge transfer process for ratiometric ion sensing. A probe decorated with an alkylphosphonium group was employed for the detection of mitochondrial Mg²⁺ in live HeLa cells, providing the first direct observation of an increase in free Mg²⁺ levels in this organelle in the early stages of Staurosporine-induced apoptosis.