W. Luo, Yongcui Ma, Peter J. Quinn
Apr 1, 2004
Citations
0
Influential Citations
20
Citations
Journal
Journal of Pharmacy and Pharmacology
Abstract
Bidentate chelators such as hydroxypyridinones and hydroxypyranones are highly iron selective. The synthesis of two novel fluorescent probes N‐[2‐(3‐hydroxy‐2‐methyl‐4‐oxopyridin‐1(4H)‐yl)ethyl]‐2‐(7‐methoxy‐2‐oxo‐2H‐chromen‐4‐yl)acetamide (CP600) and N‐[(3‐hydroxy‐6‐methyl‐4‐oxo‐4H‐pyran‐2‐yl)methyl]‐2‐(7‐methoxy‐2‐oxo‐2H‐chromen‐4‐yl)acetamide (CP610) is reported. The method involves coupling the bidentate ligands, 3‐hydroxypyridin‐4‐one and 3‐hydroxypyran‐4‐one, with the well‐characterised fluorescent probe methoxycoumarin. Fluorescence emission of both probes at 380 nm is readily quenched by Fe3+. The fluorescence was quenched to a greater extent by Fe3+ than by Mn2+, Co2+, Zn2+, Ca2+, Mg2+, Na+ and K+ and to approximately the same extent as Cu2+. Comparison of the fluorescence‐quenching ability by a range of metal ions on CP600 and CP610 and the hexadentate chelator, calcein, under in‐vitro conditions, demonstrated advantages of the two novel fluorescent probes with respect to both iron(III) sensitivity and selectivity. Chelation of iron(III) by CP600 and CP610 leads to the formation of a complex with a metal‐to‐ligand ratio of 1:3. Fluorescence is quenched on formation of such complexes. These probes possess a molecular weight less than 400 and thus they are predicted to permeate biological membranes by passive diffusion, and have potential for reporting intracellular organelle labile iron levels.