Using Ligand-Accelerated Catalysis to Repurpose Fluorogenic Reactions for Platinum or Copper

The development of a fluorescent probe for a specific metal has required exquisite design, synthesis, and optimization of fluorogenic molecules endowed with chelating moieties with heteroatoms. These probes are generally chelation- or reactivity-based. Catalysis-based fluorescent probes have the potential to be more sensitive; however, catalytic methods with a biocompatible fluorescence turn-on switch are rare. Here, we have exploited ligand-accelerated metal catalysis to repurpose known fluorescent probes for different metals, a new approach in probe development. We used the cleavage of allylic and propargylic ethers as platforms that were previously designed for palladium. After a single experiment that combinatorially examined >800 reactions with two variables (metal and ligand) for each ether, we discovered a platinum- or copper-selective method with the ligand effect of specific phosphines. Both metal-ligand systems were previously unknown and afforded strong signals owing to catalytic turnover. The fluorometric technologies were applied to geological, pharmaceutical, serum, and live cell samples and were used to discover that platinum accumulates in lysosomes in cisplatin-resistant cells in a manner that appears to be independent of copper distribution. The use of ligand-accelerated catalysis may present a new blueprint for engineering metal selectivity in probe development.