Oxinobactin and Sulfoxinobactin, Abiotic Siderophore Analogues to Enterobactin Involving 8‑Hydroxyquinoline Subunits: Thermodynamic and Structural Studies

The synthesis of two new iron chelators built on the tris-l-serine trilactone scaffold of enterobactin and bearing a 8-hydroxyquinoline (oxinobactin) or 8-hydroxyquinoline-5-sulfonate (sulfoxinobactin) unit has been described. The X-ray structure of the ferric oxinobactin has been determined, exhibiting a slightly distorted octahedral environment for Fe­(III) and a Δ configuration. The Fe­(III) chelating properties have been examined by potentiometric and spectrophotometric titrations in methanol–water 80/20% w/w solvent for oxinobactin and in water for sulfoxinobactin. They reveal the extraordinarily complexing ability (pFe^III values) of oxinobactin over the p­[H] range 2–9, the pFe value at p­[H] 7.4 being 32.8. This was supported by spectrophotometric competition showing that oxinobactin removes Fe­(III) from ferric enterobactin at p­[H] 7.4. In contrast, the Fe­(III) affinity of sulfoxinobactin was largely lower as compared to oxinobactin but similar to that of the ligand O-TRENSOX having a TREN backbone. These results are discussed in relation to the predisposition by the trilactone scaffold of the chelating units. Some comparisons are also made with other quinoline-based ligands and hydroxypyridinonate ligand (hopobactin).