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Metal ions are involved in various biological processes, and their essential roles and pathological involvement have facilitated the development of new synthetic chemical tools for the detection and monitoring of metal ions in cells and living organisms. For example, fluorescent and other optical probes have been used to study metal homeostasis and alterations with spatial and temporal resolution. They are categorized into chelation-based and activity-based probes based on their detection mechanism. Chelation-based probes have been used since the 1980s and operate through the complexation of a metal ion with a chelator tethered to a fluorophore, which is detected as a change in fluorescence intensity and/or wavelength. On the other hand, activity-based sensing has only been developed in the last decade for the selective detection of metal ions that are difficult to detect using chelation-based probes. These activity-based probes provide new possibilities in the detection of biological metals because they can avoid the disadvantages of chelation-based probes, including the fluorescence-quenching effect of d-unsaturated metal ions and metal-ion depletions. In this chapter, specific examples of activity-based probes for metal-ion detection are introduced, and their sensing mechanisms and features are discussed.

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