Dissociation Kinetics of (N-Methylacetohydroxamato)iron(III) Complexes: A Model for Probing Electronic and Structural Effects in the Dissociation of Siderophore Complexes

Abstract

The proton-initiated dissociation kinetics and equilibria of the mono, bis, and tris complexes of iron(III) with TV-methylacetohydroxamic acid (NMHA) were studied under conditions of 2.0 M NaC104/HC104 at 25 °C. The proton-dependent rate constants k3, k2, and k¡ for dissociation of the tris, bis, and mono complexes are 8.6 X 103 M"* 1 s"1,1.02 X 102 M"1 s-1, and 3.2 X 10~3 M"1 s-1, respectively. The corresponding equilibrium constants log K3, log K2, and log K\ are 1.06, -0.9, and -2.75, respectively. An acid-independent dissociation pathway is observed in the dissociation of the mono complex with a rate constant k\ =7.1 X 10~3 s_1. The solution NMR spectrum of the ligand shows split methyl peaks indicating hindered rotation about the C-N bond. The equilibrium ratio for the C-N rotation was found to be 3.5 in favor of the Z isomer and the minimum lifetime of the rotation was estimated to be 0.3 s. The rates and mechanism of Fe(NMHA);3"' dissociation are compared to corresponding processes observed for dissociation of (acetohydroxamato)iron(III) complexes and the natural trihydroxamate siderophore ferrioxamine B. Differences in rate and mechanism between the model systems and ferrioxamine B are discussed in terms of solvent effects, electrostatic effects, and C-N bond rotation in the hydroxamate group.

Conformational analysis of a secondary hydroxamic acid in aqueous solution by NOE spectroscopy

“…The hydroxamic acid is a naturally occurring metal ligand with high affinity for ferric iron. The relevance of hydroxamic acids to medicine, microbial iron harvesting, and industrial metal‐binding applications has prompted the development of various model systems . Hydroxamic acids favor two conformations, the so‐called E and Z (antiperiplanar and synperiplanar; Fig.…”

“…The propensity for hydroxamic acids to aggregate in nonpolar media selectively stabilizes the Z form at higher concentrations, which has been used as a basis for assignment [4b,7,9] . Computational studies of differential stabilities of E and Z have also been used to support assignment of major and minor conformations . One report has used NOE studies to assign conformations .…”

Iron(III) Complexation by New Aminocarboxylate Chelators − Thermodynamic and Kinetic Studies

“…The dissociation rate of FeL3 by the [FeOH] 2ϩ pathway (1.6 and 0.42 s Ϫ1 ) is close to that of the (monocatecholato)FeϪTiron (1,2-dihydroxy-3,5-benzenedisulfonate) complex (1.2 s Ϫ1 ) [22] but significantly faster than those of the monohydroxamato complexes (0.08 s Ϫ1 for acetohydroxamic acid and 0.0071 s Ϫ1 for N-methylacetohydroxamic acid). [23,24] A comparison with the last step of the dissociation of hexadentate chelates shows that L3 releases Fe III much faster than the tricatecholate TRENCAMS [25] (0.018 s Ϫ1 ) and than the siderophores pyoverdin [26] (Ͼ 6 10 Ϫ5 s Ϫ1 ) and ferrioxamine B [27,28] (0.0021 s Ϫ1 ).…”

[Pd(en)(H2O)2]2+ and [Pd(pic)(H2O)2]2+ complexation by monohydroxamic acids: A solution equilibrium and solid state approach

“…The values estimated in the present work and listed in Table 3, are in very good agreement (within ±0.05 log units) with the previously reported ones. As it was discussed in several papers [34][35][36], log K HL depends both on the character and position of the substituents on the hydroxamic function. Namely, the electron donating effect of the methyl group in aha À versus the electron withdrawing effect of the phenyl moiety in bha À results in the increased basicity of the hydroxamate group in the former molecule.…”

“…Compared to the R C ones, the electronic effects of the R N substituents can cause more pronounced changes in the acid/base character of the hydroxamic groups. There is a significant increase in the acidity of the hydroxamic acid moiety if the C-N bond is involved in a delocalized ring system [34][35][36].…”