Transition-metal-mediated uncaging in living human cells—an emerging alternative to photolabile protecting groups

Photolabile protecting groups have been widely used for activation strategies of caged substrates within living cells. However, an alternative uncaging method in which, instead of light, chemical compounds are used as activators (chemical uncaging) is still in its infancy. The recent advances in bioorthogonal reactions mediated by transition metals have shown that bioorthogonal catalysts have the potential to yield such a chemical activator. By now we have seen transition metal compounds that activate caged enzymes, toxigenic prodrugs and other small molecules such as fluorophores within living human cells. In this review we will focus on metal catalysts based on palladium, ruthenium and iron and we will mainly discuss their biocompatibility and catalytic efficiency in uncaging reactions within biological environments.