Kinetics and mechanism of iron exchange in hydroxamate siderophores: Catalysis of the iron(III) transfer from ferrioxamine B to ethylenediaminetetraacetic acid

Abstract

The oxalate catalyzed iron(III) transfer from a trihydroxamate siderophore ferrioxamine B, [Fe(Hdfb) +], to ethylenediaminetetraacetic acid (H 4edta) has been studied spectro-photometrically in weakly acidic aqueous solutions at 298 K and a constant 2.0 M ionic strength maintained by NaClO 4. The results reveal that oxalate is a more efficient catalyst than the so far studied synthetic monohydroxamic acids. Any role of reduction of Fe(Hdfb) + by oxalate in the catalysis has been rejected by the experimentally observed preservation of the oxalate concentration during the reaction time. Therefore, catalysis has been proposed to be a substitution based process. Under our experimental conditions Fe(Hdfb) + is hexacoordinated and addition of oxalate results in the formation of Fe(H 2dfb)(C 2O 4), Fe(H 3dfb)(C 2O 4) − 2 and Fe(C 2O 4) 3− 3. Therefore, catalysis was proposed to be accomplished by the intermediate formation of the ternary and tris(oxalato) complexes. All three complexes react with H 2edta 2− to form thermodynamically stable Fe(edta) − as a final reaction product. Whereas the formation of the ternary complexes is fast enough to feature a pre-equilibrium process to the iron exchange reaction, the formation of Fe(C 2O 4) 3− 3 is slow and is directly involved in the rate determining step of the Fe(edta) − formation. Nonlinear dependencies of the rate constant on the oxalate and the proton concentrations have been observed and a four parallel path mechanism is proposed for the exchange reaction. The rate and equilibrium constants for the various reaction paths were determined from the kinetic and equilibrium study involving the desferrioxamine B- (H 4dfb +), oxalate- and proton-concentration variations. The observed proton catalysis was attributed to the fast monoprotonation of ferrioxamine B as well as of the oxalate ligand. The observed catalysis of iron dissociation from the siderophore has been discussed in view of its significance with respect to in vivo microbial iron transport.