Siderophore formation

G. L. Boyer, Iron uptake and siderophore formation in the actinorhizal symbiont Frankia Biochemistry of Metal Micronutrients in the Rhizosphere (J. A. Manthey, D. E. Crowley, and D. G. Luster, eds.). CRC Press, Boca Raton, Florida, USA London, England, UK, 1994, pp. 41-54. 

There are other mechanisms by which Fe3+ siderophores induce the formation of their cognate transport systems. The reader is referred to recent reviews (Crosa, 1997 Vasil and Ochsner, 1999 Venturi et ah, 1995). 

Siderophore binding sites for iron(III) are for the most part negatively charged and therefore, in aqueous solution there is a competition between H+ and Fe3+ binding. Consequently, the equilibrium expression for the formation of the iron-siderophore complex must take into account proton participation in the reaction. 

Complexes formed by tetradentate siderophores involve stepwise complex formation and therefore, have somewhat different equilibria from their hexadentate analogs. Initial chelation will occur with a tetracoordinate FeL complex forming. A subsequent equilibrium then occurs, where the FeL complexes will react in a 2 1 stoichiometry with free ligands in solution to form a single Fe2L3 complex (coordinated water and charges not shown for clarity). 

As mentioned previously, in many siderophore complexes, a decrease in pH will result in protonation and dissociation of a donor group. This decrease in effective denticity of the chelator will lead to a corresponding decrease in complex stability and the opening of available coordination sites for the formation of ternary complexes, and/or exchange with other chelators. However, in the case of catecholamide donor group siderophores, such... 

The kinetics and mechanism of iron-siderophore complex formation are influenced by the oxidation state and composition of the first coordination shell of iron. The iron sequestration... 

While studying the formation kinetics of complexes gives useful mechanistic information about the reactivity of the iron center when bound to a particular siderophore, it is not necessarily a good model for how environmental iron will react in the siderophore system of interest. In biological systems,... 

A series of model siderophore molecular recognition studies coupled with host-guest carrier facilitated model membrane transport studies was reported (198-202). Three approaches were taken which incorporate (i) second coordination shell host-guest complexation, (ii) ternary complex formation, and (iii) a combination of ternary complex - second coordination shell host-guest complex formation. Examples of these approaches are described below. 

Siderophore-ionophore supramolecular assembly formation via host-guest complexation of the pendant protonated amine arm of ferrioxamine B has been confirmed by X-ray crystallography (Fig. 28) (203). The stability and selectivity of this interaction as a function of ionophore structure, metal ion identity, and counter anion identity were determined by liquid-liquid extraction, isothermal calorimetry, and MS (204 -211). Second-sphere host-guest complexation constants fall in the range 103— 106M-1 in CHC13 and methanol depending on ionophore structure. 

Staphyloferrin B (59, Fig. 17) is produced together with staphyloferrin A (see below Sect. 4.4) by Staphylococcus hyicus and other staphylococci 94, 131), by Ralstonia eutropha 250) (= Cupriavidus metallidurans 90a)). Comparison of its CD spectrum with those of model compounds suggests the (S)-configuration of the central citric acid C-atom. Mass spectral investigations show a 1 1 Fe V to-ligand ratio, and NMR studies of the Ga " complex confirm the participation of the two ot-hydroxy- and of the a-amino acid functions in complex formation. Uptake studies with Fe " showed that staphyloferrin B acts as a siderophore, but it is less efficient than staphyloferrin A. 

From iron-deficient cultures of Pseudomonas fluorescens, 8-hydroxy-4-methoxy-monothioquinaldic acid (thioquinolobactin) together with the corresponding quinaldic acid (quinolobactin) (Fig. 26, 74 and 75), could be isolated (258). Quinolobactin can act as an alternative siderophore of Pseudomonas fluorescens (245), although it is the hydrolysis product of the thioacid (220). Its synthesis and complex formation as (Fe )Lig2 was described (9S). 

Pseudomonine (Fig. 27, 76) is produced by Pseudomonas fluorescens strains (7, 228) and by P. entomophila, where it can act as a secondary siderophore (209). The substituents on C-4 and C-5 of the isoxazolinone ring are in trans positions (333). The complex formation has not been studied. In vitro enzyme-catalyzed synthesis studies (333,388) showed that initially the intermediate pre-pseudomonine (Fig. 24, 79) is formed, which non-enzymatically rearranges to pseudomonine. 

Anderegg G, Raber M (1990) Metal Complex Formation of a New Siderophore Desferrithi-ocin and of Three Related Ligands. J Chem Soc Chem Commun 1194... 

Table 3 lists stability constants for complex formation from Fe + and a range of common ligands, all values being from one investigation. Further information on stabilities of iron complexes may be found in several later sections, especially Sections 5.4.5.5 and 5.4.5.6 on hydroxypyri-dinones and siderophores. 

Kinetic and equilibrium data are available for complex formation between iron(III) and 4-Me0C6H4C(S)N(0 )H, a system studied in relation to the possibility that some natural siderophores may bind iron through a thiohydroxamate moiety. The Fe " " complex of this... 

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