Mechanism and Kinetics of Ligand Exchange between Ferric Citrate and Desferrioxamine B

Abstract

The kinetics of ligand exchange between ferric citrate and desferrioxamine B (DFB) was investigated at pH 8.0 and high citrate/Fe molar ratios (500-5000) with particular attention given to understanding the precise mechanism of ligand exchange. Ferric citrate complexes present in a test solution and therefore involved in the reaction with the incoming ligand (DFB) were initially examined by evaluating ferric citrate speciation on the basis of published thermodynamic constants. The speciation analysis indicated that mononuclear (mono- and dicitrate) ferric complexes are the major species responsible for the ligand exchange with DFB under the conditions examined in the present work. Given the tendency of DFB to adjunctively associate with the ferric citrate complexes, we propose a kinetic model containing the following three mechanisms: (i) direct association of DFB to the ferric dicitrate complex prior to any dissociation of citrate molecules from the Fe center, (ii) adjunctive association of DFB toward ferric monocitrate complex following dissociation of one molecule of citrate from the parent complex, and (iii) complexation of hydrated Fe by DFB after sequential dissociation of two molecules of citrate from the Fe center. Overall rates for the ligand exchange were determined by spectrophotometrically monitoring the formation of ferrioxamine B. Further analysis in quantifying the rate of each mechanism by use of published and determined rate constants of relevant elemental reactions suggested that the first and second mechanisms were significant under our experimental conditions where [Cit] ≫ [DFB] with the relative importance of these two pathways depending on citrate concentration.

Effect of ionic strength on ligand exchange kinetics between a mononuclear ferric citrate complex and siderophore desferrioxamine B

“…Whereas polymeric complexes and precipitated solids dominate at low citrate/Fe ratios because of the presence of insufficient citrate to maintain Fe in the mononuclear complex form, polynuclear complex formation or polymerization can be suppressed at citrate/Fe ratios greater than 20, where monomeric complexes dominate, even at circumneutral pH (Spiro et al, 1967). Our previous work (Ito et al, 2011) was, therefore, conducted under high citrate/Fe conditions (500-5000) with fixed pH (8.0 buffered by 2 mM bicarbonate) and ionic strength (I = 0.5 M in NaCl), allowing us to develop a kinetic model that reasonably described the results obtained under these specific conditions. According to the thermodynamic calculations using the reported stability constants for ferric citrate (Table 1), almost the entire ferric citrate complex obtained under these conditions was found to be in the form of ferric dicitrate (FeCit 2 ).…”

“…Any proton or hydroxyl ions that may be incorporated into the molecules were omitted in previously published models (Ito et al, 2011) and have also been omitted in the model described in this section. Thus, the chemical species described here represent the sum of individual protonated and hydroxylated species (e.g., ½FeCit ¼ P i ½FeCitH þi i ).…”

“…In the case of siderophore-mediated processes, Fe-siderophore complexes can be formed via ligand exchange reactions between siderophores and biologically unavailable Fe(III) such as Fe(III) bound to heterogeneous natural organic matter and oxyhydroxides (Ito et al, 2011). In the ligand exchange reaction between a siderophore and organically complexed Fe(III) (hereafter, referred to as incoming ligand and initial FeL complex, respectively), the Fe-siderophore formation proceeds as a second-order reaction with respect to the concentrations of these two molecules (Ito et al, 2011).…”

“…In the ligand exchange reaction between a siderophore and organically complexed Fe(III) (hereafter, referred to as incoming ligand and initial FeL complex, respectively), the Fe-siderophore formation proceeds as a second-order reaction with respect to the concentrations of these two molecules (Ito et al, 2011). In this process, two major pathways have been proposed to occur concurrently: (i) the adjunctive pathway, in which an incoming ligand directly associates with the FeL complex, followed by dissociation of the initial ligand (L) from the metal center via intermediate ternary complex formation and (ii) the disjunctive pathway in which unchelated Fe(III) forms via thermal dissociation of the FeL complex then reacts with an incoming ligand (Hering and Morel, 1990;Schuman, 1992;Celo et al, 2001).…”

“…Recently, a detailed kinetic model considering both the disjunctive and adjunctive pathways has been developed ( Fig. 1) and validated under specific conditions (i.e., in a 0.5 M NaCl solution at pH 8 and 25°C) (Ito et al, 2011). The model generally suggests that the adjunctive pathway is more significant than the disjunctive pathway under the conditions examined.…”