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 (H₅L_C2H1) and mono(2,3-dihydroxybenzamide-propyl)bis[2-propyl]aminomethane (H₄L_C1H2), were designed and synthesized. Iron(III) complexes, K₂[Fe^IIIL_C2H1] and K[Fe^IIIL_C1H2], 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, K₃[Fe^IIIL_C3] and [Fe^IIIL_H3]. Both K₂[Fe^IIIL_C2H1] and K[Fe^IIIL_C1H2] formed six-coordinate octahedral iron(III) complexes. Evaluation of the thermodynamic properties of the complexes in an aqueous solution indicated high log β values of 37.3 and 32.3 for K₂[Fe^IIIL_C2H1] and K[Fe^IIIL_C1H2], respectively, which were intermediate between those of K₃[Fe^IIIL_C3] (44.2) and [Fe^IIIL_H3] (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 K₂[Fe^IIIL_C2H1] and K[Fe^IIIL_C1H2] generated the corresponding protonated species, [Fe^IIIH_nL_C2H1]^(2-n)- and [Fe^IIIH_nL_C1H2]^(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.