Cation-selective luminescent indicators offer the possibility of tracking metal accumulation patterns at the (sub)cellular level, enabling detailed mechanistic studies of the connection between metal imbalance and disease. Despite much progress in the field, however, the development of cation-selective indicators that enable quantification of the target metals remains a challenge. Taking advantage of metal-mediated modulation of internal charge transfer in donor-acceptor fluorophores, we have developed a new series of small molecule luminescent indicators for wavelength-ratiometric detection and quantification of Mg2+ with high selectivity over Ca2+. We have demonstrated the application of the new quinoline-based indicators in the study of alterations in cellular Mg2+ distribution and mobilization in liver diseases, using a combination of microscopy and flow cytometry techniques. Finally, we will discuss how metal-mediated modulation of charge distribution in small molecules can be used in the design of cation indicators for other spectroscopies and imaging modalities, beyond conventional, single photon fluorescence microscopy.

New tools for imaging biometals: Shining light on cellular magnesium and more

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ACS Spring 2023

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