Hydrophilic and lipophilic iron chelators with the same complexing abilities.
A new series of iron chelators with the same coordination sphere as the water-soluble ligand O-trensox, but featuring a variable hydrophilic-lipophilic balance, have been obtained by grafting oxyethylene chains of variable length on a C-pivot tripodal scaffold. The X-ray structure of a ferric complex exhibiting tris(8-hydroxyquinolinate) coordination and solution thermodynamic properties (pK(a) of the ligands, stability constants of the ferric complexes) have been determined. The complexing ability (pFe(III) values) of the ligands are similar to that of O-trensox. Partition coefficients between water and octanol or chloroform have been measured and transport across a membrane has been mimicked ("shuttle process"). The results of biological assays (iron chelation with free ligands or iron nutrition with ferric complexes) could not be correlated with the partition coefficients. These results call into question the role of distribution coefficients (of the ligands and/or complexes) in the biological activities of iron chelators.
Imbert
Daniel
D
Laboratoire de Chimie Biomimétique, LEDSS, UMR CNRS 5616, Université Joseph Fourier BP 53, 38041 Grenoble Cedex 9, France.
Baret
Paul
P
Gaude
Didier
D
Gautier-Luneau
Isabelle
I
Gellon
Gisèle
G
Thomas
Fabrice
F
Serratrice
Guy
G
Pierre
Jean-Louis
JL
D000465:Algorithms; D002478:Cells, Cultured; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D007501:Iron / Q000378:metabolism; D007502:Iron Chelating Agents / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D008055:Lipids / Q000737:chemistry; D008567:Membranes, Artificial; D008958:Models, Molecular; D059828:Plant Cells; D010944:Plants / Q000187:drug effects / Q000378:metabolism; D011199:Potentiometry; D012995:Solubility; D013056:Spectrophotometry, Ultraviolet; D013816:Thermodynamics
D007502:Iron Chelating Agents; D008055:Lipids; D008567:Membranes, Artificial; D007501:Iron