Multiple-Path Dissociation Mechanism for Mono- and Dinuclear Tris(hydroxamato)iron(III) Complexes with Dihydroxamic Acid Ligands in Aqueous Solution

Linear synthetic dihydroxamic acids ([CH₃N(OH)CO)]₂(CH₂)_n; H₂Lⁿ) with short (n = 2) and long (n = 8) hydrocarbon-connecting chains form mono- and dinuclear complexes with Fe(III) in aqueous solution. At conditions where the formation of Fe₂(Lⁿ)₃ is favored, complexes with each of the two ligand systems undergo [H⁺]-induced ligand dissociation processes via multiple sequential and parallel paths, some of which are common and some of which are different for the two ligands. The pH jump induced ligand dissociation proceeds in two major stages (I and II) where each stage is shown to be comprised of multiple components (I_x, where x = 1−3 for L² and L⁸, and II_y, where y = 1−3 for L² and y = 1−4 for L⁸). A reaction scheme consistent with kinetic and independent ESI-MS data is proposed that includes the tris-chelated complexes (coordinated H₂O omitted for clarity) {Fe₂(Lⁿ)₃, Fe₂(L²)₂(L²H)₂, Fe(LⁿH)₃, Fe(L⁸)(L⁸H)}, bis-chelated complexes {Fe₂(Lⁿ)₂²⁺, Fe(LⁿH)₂⁺, Fe(L⁸)⁺}, and monochelated complexes {Fe(LⁿH)²⁺}. Analysis of kinetic data for ligand dissociation from Fe₂(Lⁿ)(LⁿH)³⁺ (n = 2, 4, 6, 8) allows us to estimate the dielectric constant at the reactive dinuclear Fe(III) site. The existence of multiple ligand dissociation paths for the dihydroxamic acid complexes of Fe(III) is a feature that distinguishes these systems from their bidentate monohydroxamic acid and hexadentate trihydroxamic acid counterparts and may be a reason for the biosynthesis of dihydroxamic acid siderophores, despite higher environmental molar concentrations necessary to completely chelate Fe(III).