Kinetics and thermodynamics of complex formation with iron of a new series of dicatecholspermidine siderophore-like ligands

Abstract

This article deals with the kinetics and thermodynamics of complex formation between Fe3+ and a series of four synthetic chelators of the 1,2-dicatecholspermidine family (LA5, LA3, LE5 and LE3). LA5 and LA3 bear a carboxylic moiety linked to the central nitrogen by either a C5 or a C3 chain, whereas LE5 and LE3 bear an ethyl ester moiety. The following data concern LE5, LE3, LA5 and LA3, respectively. Each species undergoes four acid-base dissociations of the hydroxyls of the catechols with, for the two hydroxyls in position 1; average pK2a=7.30, 7.25, 7.45, 7.34 and, for the two hydroxyl in position 2; average pK3a=12.35, 12.65, 12.10, 12.60. The LA5 and LA3 species also undergo proton-dissociations of their carboxylic moieties; pK1a=5.20 and 5.10. The four species form one-to-one iron complexes with, for the 1-hydroxyl; an average pK22a=2.65, 2.25, 2.95, 2.80, for the 2-hydroxyl; pK33a=5.20, 5.40, 6.10, 5.40 and, for the carboxylic moieties; pK11a=3.90 and 4.45. In the vicinity of pH 5, Fe3+ is rapidly exchanged between FeNta and the four ligands. This occurs with direct rate constants: k1=(1.3±0.1)×104, (1.4±0.2)×104, (3.3±0.2)×104, (1.4±0.1)×104M−1s−1, and reverse rate constants: k−1=(7±0.5)×104, (9±1)×104, (1.15±0.15)×105, (7±0.5)×104M−1s−1. The kinetic data, the pKa values of the free ligands, those of the iron complexes and the β value of FeNta allow us to determine the affinity constants of the four ligands for iron: logβ1=33, 34, 33, 34, and pFe=23.3, 24.6, 22.2, 24.3. This implies that these ligands of the dicatecholspermidine family may act as siderophores. They may also be used as drug carriers which can utilize the bacterial iron-acquisition paths.