Iron is one of the most common elements on Earth, but its availability to living organisms is limited because of its extremely low solubility. Siderophores are low-molecularweight iron(iii) chelators that were evolved by microorganisms for the uptake of physiologically essential iron.[1] Among the mechanisms proposed for iron solubilization and transport into cells, [2] the self-assembly of amphiphilic siderophores from marine bacteria observed by Butler et al.[3] is a noteworthy process. Hydrophilic siderophores (marinobactins and aquachelins) with polar peptidic head groups and hydrophobic fatty acid tails are surface-active amphiphiles that form self-assembled structures. We thought that the biologically inspired use of this strategy might allow the resolution of the crucial problem of the hydrophilic/lipophilic balance encountered with abiotic siderophores designed for iron nutrition.[4] Amphiphilic iron chelators may also offer a new approach in iron chelation therapy.Herein, we present a preliminary report on the selfassembly properties of amphiphilic chelators and their iron complexes, and discuss the first results concerning iron nutrition of Erwinia chrysanthemi and some mutants defective in the production of one or both of its siderophores. Three synthetic catechol-based chelators were investigated (Scheme 1).The two monopodal ligands L a and L b were synthesized by reaction of 2,3-dimethoxybenzoyl chloride with dodecylamine and octylamine, respectively, followed by a deprotection step with BBr 3 . The tripodal ligand L T was obtained from our previously described [5] tripodal precursor 2,2,2-tris[3-(2,3-dimethoxybenzamido)propyl]acetic acid (by reaction of the acid chloride with hexadecylamine and then deprotection of the catechol groups). The ligands were characterized by mass spectrometry and 1 H and 13 C NMR spectroscopy (see Supporting Information). The pH-dependent equilibria of the ligand species and their ferric complexes were determined by potentiometric and spectrophotometric titrations to obtain their net charge at physiological pH, which tunes the amphiphilic properties.[ [5] Notably, at pH 9 the spectral parameters (l max = 490 nm, e = 4300 m In water/methanol (95/5, v/v) solution containing 3-(Nmorpholino)propanesulfonic acid (MOPS) buffer at pH 7.4, the free ligands and their iron complexes exhibit tensioactive properties with a critical micelle concentration (CMC) of < 10 À5 m.[10] The low CMC values of the iron-free ligands are in the same range as that for marinobactin.[3a] Dynamic lightscattering studies [11] on solutions (10, and L T in the same medium revealed the presence of spherical particles of diameter 200-250, 100-110, and 130 nm, respectively. In all cases the distribution is rather broad (polydispersity index of 0.2-0.3). The free ligands, which do not scatter light, are probably limited to micellar assembly. Similar observations have been made for the siderophores from marine bacteria.[3a] Cryo-transmission Scheme 1. Chemical formulae of the synthetic amphiphilic ligands.

Iron is one of the most common elements on Earth, but its availability to living organisms is limited because of its extremely low solubility. Siderophores are low-molecularweight iron(iii) chelators that were evolved by microorganisms for the uptake of physiologically essential iron.[1] Among the mechanisms proposed for iron solubilization and transport into cells, [2] the self-assembly of amphiphilic siderophores from marine bacteria observed by Butler et al.[3] is a noteworthy process. Hydrophilic siderophores (marinobactins and aquachelins) with polar peptidic head groups and hydrophobic fatty acid tails are surface-active amphiphiles that form self-assembled structures. We thought that the biologically inspired use of this strategy might allow the resolution of the crucial problem of the hydrophilic/lipophilic balance encountered with abiotic siderophores designed for iron nutrition.[4] Amphiphilic iron chelators may also offer a new approach in iron chelation therapy.Herein, we present a preliminary report on the selfassembly properties of amphiphilic chelators and their iron complexes, and discuss the first results concerning iron nutrition of Erwinia chrysanthemi and some mutants defective in the production of one or both of its siderophores. Three synthetic catechol-based chelators were investigated (Scheme 1).The two monopodal ligands L a and L b were synthesized by reaction of 2,3-dimethoxybenzoyl chloride with dodecylamine and octylamine, respectively, followed by a deprotection step with BBr 3 . The tripodal ligand L T was obtained from our previously described [5] tripodal precursor 2,2,2-tris[3-(2,3-dimethoxybenzamido)propyl]acetic acid (by reaction of the acid chloride with hexadecylamine and then deprotection of the catechol groups). The ligands were characterized by mass spectrometry and 1 H and 13 C NMR spectroscopy (see Supporting Information). The pH-dependent equilibria of the ligand species and their ferric complexes were determined by potentiometric and spectrophotometric titrations to obtain their net charge at physiological pH, which tunes the amphiphilic properties.[ [5] Notably, at pH 9 the spectral parameters (l max = 490 nm, e = 4300 m In water/methanol (95/5, v/v) solution containing 3-(Nmorpholino)propanesulfonic acid (MOPS) buffer at pH 7.4, the free ligands and their iron complexes exhibit tensioactive properties with a critical micelle concentration (CMC) of < 10 À5 m.[10] The low CMC values of the iron-free ligands are in the same range as that for marinobactin.[3a] Dynamic lightscattering studies [11] on solutions (10, and L T in the same medium revealed the presence of spherical particles of diameter 200-250, 100-110, and 130 nm, respectively. In all cases the distribution is rather broad (polydispersity index of 0.2-0.3). The free ligands, which do not scatter light, are probably limited to micellar assembly. Similar observations have been made for the siderophores from marine bacteria.[3a] Cryo-transmission Scheme 1. Chemical formulae of the synthetic amphiphilic ligands.

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