Disrupted homeostasis of magnesium has been associated with numerous pathologies including diabetes, neurodegeneration, immunodeficiency and cancer. Cation-selective luminescent indicators offer the possibility of tracking metal trafficking and accumulation patterns at the (sub)cellular level, enabling detailed mechanistic studies of the connection between metal imbalance and such diseases. Magnesium-selective indicators, however, remain scarce. We have developed small molecule luminescent indicators for intensity-based and wavelength ratiometric detection of Mg2+ with high selectivity over Ca2+, and have demonstrated their application in the study of cellular Mg2+ distribution and mobilization. We describe new approaches that take advantage of the formation of ternary complexes for the study of cellular magnesium speciation, and present strategies for targeting small-molecule indicators to various intracellular organelles to enable the study of metal compartmentalization for magnesium and other understudied metals. Applications of these tools in the study of metabolic and liver disease will be discussed.

Shining light on biometals: A look at cellular magnesium and beyond

ACS Spring Meeting 2021

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