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

Abstract

Two hybrid-type artificial siderophore ligands containing both catecholate and hydroxamate groups as iron-capturing sites, bis(2,3-dihydroxybenzamidepropyl)mono[2-propyl]aminomethane (H 5 L C2H1 ) and mono(2,3-dihydroxybenzamide-propyl)bis[2-propyl]aminomethane (H 4 L C1H2 ), were designed and synthesized. Iron(III) complexes, K 2 [Fe III L C2H1 ] and K[Fe III L 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, K 3 [Fe III L C3 ] and [Fe III L H3 ]. Both K 2 [Fe III L C2H1 ] and K[Fe III L 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 K 2 [Fe III L C2H1 ] and K[Fe III L C1H2 ], respectively, which were intermediate between those of K 3 [Fe III L C3 ] (44.2) and [Fe III L 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 K 2 [Fe III L C2H1 ] and K[Fe III L C1H2 ] generated the corresponding protonated species, [Fe III H n L C2H1 ] (2−n)− and [Fe III H n L 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.

Detection of Microorganisms Using Artificial Siderophore–FeIII Complex-Modified Substrates

“…FeL C3 /Au, FeL C2H1 /Au, FeL C1H2 /Au, and FeL H3 /Au showed irreversible one-electron redox couples at −0.92, −0.85 V, −0.70 V, and −0.67 V vs Ag/AgCl, respectively (Figures S5). As these potentials are close to those of K 3 [ Fe III L C3 ], K 2 [ Fe III L C2H1 ], K­[ Fe III L C1H2 ], and [ Fe III L H3 ] in a homogeneous solution (−0.9 V, −0.88 V, −0.70 V, and −0.65 V vs Ag/AgCl in 0.1 M NaClO 4 aqueous solution at pH 7.4), we assigned these redox couples to Fe II/III of FeL C3 /Au, FeL C2H1 /Au, FeL C1H2 /Au, and FeL H3 /Au, respectively. As expected, the peak currents of K 3 [ Fe III L C3 ], K 2 [ Fe III L C2H1 ], K­[ Fe III L C1H2 ], and [ Fe III L H3 ] dissolved in water showed a linear relation for the square root of the scan rates, whereas for FeL C3 /Au, FeL C2H1 /Au, FeL C1H2 /Au, and FeL H3 /Au, the peak currents increased linearly with an increase in the scan rates (see the inset of Figures S5), indicating that the redox species existed on the surface.…”

“…The schematic structures of the artificial siderophores, L , and their Fe III -complexes, [ Fe III L ] n − , are shown in Figure S1. These siderophores and their iron complexes were synthesized and identified based on our previous study . The stepwise method using activated ester with disulfide is convenient for preparing [ Fe III L ] n − -modified Au ( FeL /Au).…”

“…flavescens recognizes the structure of the artificial siderophore–Fe III complex-modified Au substrate. We have recently shown that the biological activities of four types of [ Fe III L ] n − complexes correlate with the structures of their Fe III ion-coordination units . As the reduction in frequency is supposed to reflect the strength of interaction between FeL /Au and the receptor or binding protein on M.…”

“…The syntheses of artificial siderophores containing catecholate and/or hydroxamate groups ( H 6 L C3 , H 5 L C2H1 , H 4 L C1H2 , and H 3 L H3 ) and their Fe III complexes (K 3 [ Fe III L C3 ], K 2 [ Fe III L C2H1 ], K­[ Fe III L C1H2 ], and [ Fe III L H3 ]) were performed according to previously described procedures …”

“…A technique to selectively immobilize Escherichia coli on cantilevers modified with a natural siderophore, desferrioxamine B, has also been reported . We have also previously studied the synthesis of artificial siderophores, which are model compounds mimicking the structures and functions of natural siderophores, − and their applications in microorganism adsorption. − We have reported a selective microorganism detection method using QCM sensors modified with artificial siderophore–Fe III complexes, tris-hydroxamate type ( FeL H3 /Au) and tris-catecholate type ( FeL C3 /Au) . Furthermore, the artificial siderophore–Fe III complex-modified AuNPs (gold nanoparticles) have shown selective aggregation of microorganisms adsorbed on the QCM sensor .…”