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Dalton Transactions

The international journal for inorganic, organometallic and bioinorganic chemistry



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Dalton Trans., 2010, 39, 568 - 576, DOI: 10.1039/b914568k

Toward the development of prochelators as fluorescent probes of copper-mediated oxidative stress

Lynne M. Hyman, Clifton J. Stephenson, Marina G. Dickens, Ken D. Shimizu and Katherine J. Franz

A fluorescent sensor prochelator, FlamB (fluorescein hydrizido 2-imidophenylboronic ester), has been developed that selectively probes for copper under conditions of oxidative stress. High levels of hydrogen peroxide trigger the release of a boronic ester masking group from the prochelator to unveil a metal chelator, FlamS (fluorescein hydrizido 2-imidophenol), that provides a modest fluorescence increase in response to Cu2+ but not other metal ions. X-Ray crystal structures of FlamB, FlamS, and Cu-bound FlamS are all reported. The fluorescence turn-on results from opening of a fluorescein spirolactam ring upon Cu2+ binding to FlamS in aqueous solution. Oxidation of the aryl boronic ester of FlamB to the metal-binding phenol of FlamS proceeds in organic solvents. However, in aqueous solution a competing mechanism occurs due to hydrolytic instability of the masked prochelator. Hydrolysis of FlamB leads to formation of fluorescein hydrazide, which interacts with copper or H2O2 to produce fluorescein and a significant fluorescence increase.

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