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.