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

Journal Article

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 Cu(2+) 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 Cu(2+) 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 H(2)O(2) to produce fluorescein and a significant fluorescence increase.

Full Text

Duke Authors

Cited Authors

  • Hyman, LM; Stephenson, CJ; Dickens, MG; Shimizu, KD; Franz, KJ

Published Date

  • January 14, 2010

Published In

Start / End Page

  • 568 - 576

PubMed ID

  • 20023995

Electronic International Standard Serial Number (EISSN)

  • 1477-9234

Digital Object Identifier (DOI)

  • 10.1039/b914568k

Language

  • eng

Conference Location

  • England