No abstract

Pseudomonas aeruginosa is an opportunistic pathogen, synthesizing two major siderophores, pyoverdine (Pvd) and pyochelin (Pch), to cover its needs in iron(III). If the high affinity and specificity of Pvd toward iron(III) (pFe = 27.0) was well described in the literature, the physicochemical and coordination properties of Pch toward biologically relevant metals (Fe(III), Cu(II) or Zn(II)) have been only scarcely investigated. We report a thorough physico-chemical investigation of Pch (potentiometry, spectrophotometries, ESI/MS) that highlighted its moderate but significantly higher affinity for Fe(3+) (pFe = 16.0 at p[H] 7.4) than reported previously. We also demonstrated that Pch strongly chelates divalent metals such as Zn(II) (pZn = 11.8 at p[H] 7.4) and Cu(II) (pCu = 14.9 at p[H] 7.4) and forms predominantly 1 : 2 (M(2+)/Pch) complexes. Kinetic studies revealed that the formation of the ferric Pch complexes proceeds through a Eigen-Wilkins dissociative ligand interchange mechanism involving two protonated species of Pch and the Fe(OH)(2+) species of Fe(III). Our physico-chemical parameters supports the previous biochemical studies which proposed that siderophores are not only devoted to iron(III) shuttling but most likely display other specific biological role in the subtle metals homeostasis in microorganisms. This work also represents a step toward deciphering the role of siderophores throughout evolution.

We have synthesized the mono, di-, and tri-alpha-fluoro ligands in the tris(2-pyridylmethyl)amine (TPA) series, namely, FTPA, F(2)TPA and F(3)TPA, respectively. Fluorination at the alpha-position of these nitrogen-containing tripods shifts the oxidation potential of the ligand by 45-70 mV per added fluorine atom. The crystal structures of the dichloroiron(II) complexes with FTPA and F(2)TPA reveal that the iron center lies in a distorted octahedral geometry comparable to that already found in TPAFeCl(2). All spectroscopic data indicate that the geometry is retained in solution. These three isostructural complexes all react with molecular dioxygen to yield stable mu-oxodiiron(III) complexes. Crystal structure analyses are reported for each of these three mu-oxo compounds. With TPA, a symmetrical structure is obtained for a dicationic compound with the tripod coordinated in the kappa(4)N coordination mode. With FTPA, the compound is a neutral mu-oxodiiron(III) complex with a kappa(3)N coordination mode of the ligand. Oxygenation of the F(2)TPA complex gave a neutral unsymmetrical compound, the structure of which is reminiscent of that already found with the trifluorinated ligand. On reduction, all mu-oxodiiron(III) complexes revert to the starting iron(II) species. The oxygenation reaction parallels the well-known formation of mu-oxo derivatives from dioxygen in the chemistry of porphyrins reported almost three decades ago. The striking feature of the series of iron(II) precursors is the effect of the ligand on the kinetics of oxygenation of the complexes. Whereas the parent complex undergoes 90 % conversion over 40 h, the monofluorinated ligand provides a complex that has fully reacted after 30 h, whereas the reaction time for the complex with the difluorinated ligand is only 10 h. Analysis of the spectroscopic data reveals that formation of the mu-oxo complexes proceeds in two distinct reversible kinetic steps with k(1) approximately 10 k(2). For TPAFeCl(2) and FTPAFeCl(2) only small variations in the k(1) and k(2) values are observed. By contrast, F(2)TPAFeCl(2) exhibits k(1) and k(2) values that are ten times higher. These differences in kinetics are interpreted in the light of structural and electronic effects, especially the Lewis acidity at the metal center. Our results suggest coordination of dioxygen as an initial step in the process leading to formation of mu-oxodiiron(III) compounds, by contrast with an unlikely outer-sphere reduction of dioxygen, which generally occurs at negative potentials.