Thermodynamics of Iron-Siderophore Interactions

As mentioned previously, siderophores must selectively bind iron tightly in order to solubilize the metal ion and prevent hydrolysis, as well as effectively compete with other chelators in the system. The following discussion will address in more detail the effect of siderophore structure on the thermodynamics of iron binding, as well as different methods for measuring and comparing iron-siderophore complex stability. The redox potentials of the ferri-siderophore complexes will also be addressed, as ferri-siderophore reduction may be important in the iron uptake process in biological systems. 

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. 

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. 

However, Eqs. (14) and (15) can be combined with the proton independent overall stability constant of the FeL complex to give an overall stability constant for the FeLH complex, /iin. 

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). 

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