Arylthiazoline Unit as a Ferric Ion Chelating Moiety in Siderophores: The Coordination Chemistry of Anguibactin and Its Analogs.

The 2-(2-hydroxyphenyl)- and 2-(2,3-dihydroxyphenyl)thiazoline motifs appear repeatedly across microbial siderophores, yet the thermodynamic properties of their Fe(III) complexes remain fragmentarily described. Herein we present the Fe(III) coordination chemistry of anguibactin (Ang), the siderophore of Vibrio anguillarum, together with four designed analogs (L1-L4) that pair a phenol- or catechol-thiazoline core with an auxiliary donor group, either carboxylate or hydroxamate, analyzing the contribution of each functional group against a common scaffold. Using physicochemical analyses in MeOH/H2O (80:20, w/w), we determined the protonation equilibria, complex stoichiometries, pH-dependent speciation, and Fe(III) affinities. At physiological pH all ligands form bis-ligand complexes in which iron is bound through the phenolate-thiazoline unit and the auxiliary donor rather than a catecholate sphere. Replacing the carboxylate by a hydroxamate unit substantially increases Fe(III) affinity. Of importance, Ang retains the highest affinity of the series (pFe = 28.2), exceeding that of closely related desferrithiocin and being close to other efficient siderophores, like tris(hydroxamate) ferrioxamines or pyoverdine, a peptide-based siderophore comprising dihydroxyquinoline, hydroxamate, and catecholate motifs. As Ang has been proposed as a thermally stable counterpart to acinetobactin - a siderophore from the multidrug-resistant pathogen Acinetobacter baumannii, the structure-property relationships can support the future design of arylthiazoline-based "Trojan horse" siderophore-antibiotic conjugates.