MECHANISTIC STUDIES ON THE DISSOCIATION OF MONOMETALLIC AND BIMETALLIC 1/1-FERRIC DIHYDROXAMATE COMPLEXES - PROBING STRUCTURAL EFFECTS IN SIDEROPHORE DISSOCIATION REACTIONS

A PH-jump kinetic technique was used to monitor the dissociation of a series of iron(III) complexes with dihydroxamic acids [CH3N(OH)C(O)](2)(CH2)(n) having a 1:1 metal-to-ligand ratio; For the initial step involving dissociation of one hydroxamate group from each iron, the complexes with n > 6 exhibit a first-order dependence on proton. However, the same step exhibits second-order proton-dependent kinetics when n < 6. When n = 6, two kinetically resolvable reactions are observed, one with first-order and one with second-order dependence on proton. In every case, the spectroscopic change is consistent with a bis(hydroxamato)iron(III) complex dissociating to give a mono(hydroxamato)iron(III) complex. To explain the kinetic data, a mechanism is proposed for the initial step in the dissociation reaction, which involves a dimeric complex (Fe(2)L(2)(2+)) with a 1:1 metal-to-ligand ratio when n less than or equal to 6 and a monomeric complex (FeL(+)) with a 1:1 metal-to-ligand ratio when n greater than or equal to 6. When n = 6, more complicated kinetic behavior is observed which suggests that both the monomeric and dimeric forms exist simultaneously. The dissociation rate constant for the dimeric complex (Fe(2)L(2)(2+)) depends on n, with k(3) = 23, 17, and 1.6 M(-1) s(-1) for n = 6, 4, and 2, respectively. The rate-limiting dissociation rate constants ks for the initial step in the dissociation of the monomeric complex (FeL(+)) are 0.13 and 0.38 s(-1) for n = 8 and 7, respectively. The dissociation of the monomeric complex is kinetically and mechanistically consistent with the dissociation of a tetradentate form of the natural siderophore complex ferrioxamine B. The final dissociation step, involving removal of the last hydroxamate group, was found to involve a dual-path mechanism having parallel acid-dependent and acid-independent pathways. The dissociation rate constants for the final dissociation step do not vary significantly with n, though substitution of a proton for methyl on the hydroxamate nitrogen does increase the overall dissociation rate. Several significant free energy correlations exist for the dissociation of the last hydroxamate group from the iron center in (dihydroxamato)iron(III) complexes, model (monohydroxamato)iron(III) complex, and ferrioxamine B. The free energy correlations are used to elucidate the intimate mechanism for the final dissociation reaction. The overall dissociation mechanism is discussed in terms of electrostatic effects in the dimeric complexes. The dissociation mechanisms for the monomeric complexes are discussed in terms of analogous processes occurring in the ferrioxamine B system.