Iron(III) Complexes with Hybrid-Type Artificial Siderophores Containing Catecholate and Hydroxamate Sites

Two hybrid-type artificial siderophore ligands containing both catecholate and hydroxamate groups as iron-capturing sites, bis(2,3-dihydroxybenzamidepropyl)mono[2-propyl]aminomethane (H5LC2H1) and mono(2,3-dihydroxybenzamide-propyl)-bis[2-propyl]aminomethane (H4LC1H2), were designed and synthesized. Iron(III) complexes, K-2[(FeLC2H1)-L-III] and K[(FeLC1H2)-L-III], were prepared and characterized spectroscopically, potentiometrically, and electrochemically. The results were compared with those previously reported for iron complexes with non-hybridized siderophores containing either catecholate or hydroxamate groups, K-3[(FeLC3)-L-III] and [(FeLH3)-L-III]. Both K-2[(FeLC2H1)-L-III] and K[(FeLC1H2)-L-III] formed six-coordinate octahedral iron(III) complexes. Evaluation of the thermodynamic properties of the complexes in an aqueous solution indicated high log ss values of 37.3 and 32.3 for K-2[(FeLC2H1)-L-III] and K[(FeLC1H2)-L-III], respectively, which were intermediate between those of K-3[(FeLC3)-L-III] (44.2) and [(FeLH3)-L-III] (31). Evaluation of the ultraviolet-visible and Fourier transform infrared spectra of the two hybrid siderophore-iron complexes under different pH or pD (potential of dueterium) conditions showed that the protonation of K-2[(FeLC2H1)-L-III] and K[(FeLC1H2)-L-III] generated the corresponding protonated species, [(FeHnLC2H1)-H-III]((2-n)-) and [(FeHnLC1H2)-H-III]((1-n)-), accompanied by a significant change in the coordination mode. The protonated hybrid-type siderophore-iron complexes showed high reduction potentials, which were well within the range of those of biological reductants. The results suggest that the hybrid-type siderophore easily releases an iron(III) ion at low pH. The biological activity of the four artificial siderophore-iron complexes against Microbacterium flavescens and Escherichia coli clearly depends on the structural differences between the complexes. This finding demonstrates that the changes in the coordination sites of the siderophores enable close control of the interactions between the siderophores and receptors in the cell membrane.

Automated summary

Two hybrid-type artificial siderophore ligands containing both catecholate and hydroxamate groups were designed and synthesized. Iron(III) complexes of these ligands were prepared and characterized using spectroscopic, potentiometric, and electrochemical methods. The protonation of the complexes at low pH resulted in the release of iron ions and a change in the coordination mode, allowing for precise control of interactions with bacterial membrane receptors. The structural differences between the complexes also played a crucial role in their biological activity against Microbacterium flavescens and Escherichia coli.