Kinetics and Mechanism of the Stepwise Dissociation of Iron(III) from Ferrioxamine B in Aqueous Acid
Deferriferrioxamine B (H3DFB) is a linear trihydroxamic acid siderophore with molecular formula NH2(CH2)5[N(OH)C(O)(CH2)2C(O)NH(CH2)5]2N(OH)C(O)CH3. In aqueous solution at pH 5, the siderophore forms a hexadentate chelate with iron(III), ferrioxamine B (Fe(HDFB)+), in which the terminal amine group is protonated. The aquation reaction of ferrioxamine B has been investigated over the [H+] range 0.03–1.0 M at 25.0 °C and ionic strength 2.0 (NaClO4/HClO4). The dissociation reaction, which may be represented as Fe(HDFB)+ + 3Haq+ ⇌ Feaq3+ + H4DFB+, is observed to proceed in four kinetically distinguishable stages. The microscopic rate constants for the first three steps are 2.9 × 102 s−1, 1.4 × 101 s−1, and 1.8 × 10−1 s−1. The final dissociation step proceeds by parallel [H+]-dependent and [H+]-independent paths, with rate constants of 1.9 × 10−3 M−1 s−1 and 2.1 × 10−3 s−1, respectively. Equilibrium quotients have also been determined for various stages of the reaction. Ferrioxamine B formation rate constants are computed to be 2 × 10−1 M−1 s−1 and 2 × 102 M−1s−1 for the reactions of H4DFB+ with Fe(H2O)63+ and Fe(H2O)5OH2+, respectively. Five intermediate species between fully coordinated reactant and completely dissociated products are detectable by spectral and/or kinetic techniques. A mechanism is proposed whereby the intermediates correspond to the stepwise unwrapping of deferriferrioxamine B from iron(III), starting with the N-O oxygen atom at the protonated amine end of the linear trihydroxamic acid ligand. Careful analysis of the aquation reaction suggests that the detailed mechanism for mono(hydroxamato)iron(III) dissociation is applicable to the dissociation of each hydroxamate group of deferriferrioxamine B, including the important role of coordinated H2O cis to the dissociating hydroxamate group, acid dependencies, and the role of the hydroxamate group in the transition state of the dissociating complex. The importance of mechanistic information for iron release from ferrioxamine B in understanding siderophore-mediated iron transport is discussed. © 1982, American Chemical Society. All rights reserved.
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