Binding constants siderophores

Iron(III) binding siderophores exhibit some of the highest binding constants known for metal ions, with artificial hosts being just as effective as natural systems. 

Siderophore. Any one of a group of red-brown, iron-transporting biochemicals which have a characteristic absorption band at 420-440 nm and iron binding constants of about 10 . 

Many siderophores are three-armed podands that contain hydroxamates or catechol moieties which bind to the metal ion. Siderophore iron(iii) complexes are high-spin and are highly thermodynamically stable. The highest stability constant for a natural siderophore is for enterobactin (2.43), whose affinity for iron(iii) is 10 M h The iron(iii) ion is totally enveloped by the catechol arms in a six-coordinate geometry (2.43). Artificial, macrobicyclic siderophores have achieved binding constants of up to... 

The identity of the hard donor group and how it is incorporated in a molecular structure has a bearing on the affinity of a siderophore for iron(III). An analysis of siderophore structure and its relationship to iron(III) binding affinity as expressed by the thermodynamic stability constant is useful in understanding structure/function relationships and in the design of siderophore mimics for specific applications. 

This means that the sequestration equilibrium reaction will be pH-dependent. The constant K is known as the conditional equilibrium constant. However, for stability comparisons between complexes of the same denticity, it may be more convenient to compare the equilibrium constant for the proton independent reaction between iron and siderophore. This can also be useful in a theoretical sense, as it allows comparison of complex stability where siderophores have different protonation constants. However, this approach does not account for competition between H+ and Fe3+ for binding, which is always present in a real situation in aqueous solution. 

Stability comparisons between siderophore complexes with different binding stoichiometries are complicated by the fact that the units for the concentration equilibrium constants are different. Also, since the Fe3+ binding moieties have different pKa values competition for binding with H+ differs, which will not be reflected in the pH-independent / mlh values. Therefore, it is important to have a scale for iron-siderophore complex... 

Using linear regression, it is possible to estimate the protonation constants of the Fe(II) complexes of siderophore complexes where the redox potentials have been measured over a range of pH values (59). This also explains the variation in reversibility of reduction as the pH changes, as the stability of the ferro-siderophore complex is much lower than the ferric complex, and the increased lability of ligand exchange and increased binding site competition from H+ may result in dissociation of the complex before the iron center can be reoxidized. 

The schizokinen-mediated Fe " transport in Bacillus megaterium was studied by double labelling with e and (8). At 37°C, uptake of Fe and of are parallel during the first 30 sec, then that of e continues until it levels off after 2 min, while that of [ H]-schizokinen drops to a low constant level. At 0°C, uptake of both labels reaches this low level which is obviously due to the binding of the ferri-siderophore to the cell surface. At 37°C, transport into the cell, release of iron, and re-export of the ligand follow. Apparently a shuttle mechanism takes place, cf. the experimental results obtained with parabactin (Sect. 3.2) indicative of a taxi mechanism. 

The siderophore enterobactin (enterochelin) (64) is a cyclic lactone of three N-(2,3-dihydroxybenzoyl) L-serine moieties produced by E. coli under iron stress. Enterobactin (64) was first isolated from iron-limited cultures of Salmonella typhimur-ium [83], E. coli [84], and Aerobacter aerogenes [84]. Structural analysis has confirmed that 64 chelates iron as a hexadentate ligand via the two hydroxyl groups on each catechol moiety (see Fig. 13) [85]. Of all the siderophores characterized to date, 64 has been shown to have the highest affinity for ferric iron, with a stability constant of 1052 M 1 [86, 87], which is remarkable, considering the affinity of EDTA for iron is 27 orders of magnitude lower. In mammals, serum albumin [88] and siderocalin [89, 90] bind the hydrophobic 64 which impedes siderophore-mediated transfer of iron to bacteria. Consequently, bacteria such as E. coli and... 

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