Toward the development of prochelators as fluorescent probes of copper-mediated oxidative stress.
Journal Article (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 2010
Published In
Start / End Page
- 568 - 576
PubMed ID
- 20023995
Pubmed Central ID
- 20023995
Electronic International Standard Serial Number (EISSN)
- 1477-9234
International Standard Serial Number (ISSN)
- 1477-9226
Digital Object Identifier (DOI)
- 10.1039/b914568k
Language
- eng