O-TRENSOX, a New Tripodal Iron Chelator Based on 8-Hydroxyquinoline Subunits:  Thermodynamic and Kinetic Studies

Abstract

The thermodynamic stability of Fe(III) complexes with a new hexadentate tripodal ligand (O-TRENSOX) incorporating three 8-hydroxyquinoline ("oxine") subunits, linked to a tetraamine ("TREN") via an amide connection, has been investigated by the use of UV-vis spectrophotometry and potentiometric methods. O-TRENSOX has been found to form, at pH < 1, a protonated complex FeLH 5 2+ (orange color) which deprotonates, over the pH range 1-2, to a green complex FeLH 2through a four-proton process. The first protonation constant of ferric O-TRENSOX has been determined to be 5.60. The stability constant log β 110 has been determined to be 30.9. A pFe (pFe ) -log [Fe 3+ ]) value of 29.5 has been calculated at pH ) 7.4, [ligand] tot ) 10 µΜ, and [Fe 3+ ] tot ) 1 µM, indicating that O-TRENSOX is one of the most powerful among the iron synthetic chelators. Cyclic voltammetry experiments have shown that the system Fe III -O-TRENSOX/Fe II -O-TRENSOX is quasi reversible, with a redox potential of 0.087 V vs NHE. This value is related to the high complexing ability of O-TRENSOX for both the ferric and ferrous iron redox states, making it relevant for biological uses. The kinetics of formation and acid hydrolysis of the ferric O-TRENSOX complex have been investigated in acidic medium using the diode array stopped-flow spectrophotometry technique in 2.0 M NaClO 4 /HClO 4 at 25 °C. The determining step for the complex formation involves the reaction of FeOH 2+ with the LH 7 + ligand species, with a rate constant of 789 ( 17 M -1 s -1 . The acid hydrolysis of the FeLH 2complex in 0.02-1.0 M HClO 4 and ionic strength 2.0 M NaClO 4 /HClO 4 leads to the FeLH 5 2+ complex, indicating that O-TRENSOX is a very strong chelating agent for Fe(III) in acidic medium. The kinetic data have been interpreted by a stepwise mechanism related to the successive protonation of four binding sites. The spectroscopic change is consistent with removal of one arm of the ligand followed by a shift from a bis(oxinate) to a bis(salicylate) mode of coordination.

A Novel Strategy for the Design of 8‐Hydroxyquinolinate‐Based Lanthanide Bioprobes That Emit in the Near Infrared Range

“…On the other hand, the addition of one equivalent of diethylenetriaminopentaacetic acid (DTPA) (pEu = 19.6 computed from known stability constants [17] ) results in a large dissociation of the Eu III tripodal chelate. Therefore, we estimate that the pEu value for the T2soxMe chelate is between 15 and 19, and the corresponding values for the other lanthanide ions studied here should be similar, referring to the range of values obtained for TsoxMe (15)(16).…”

“…The three lowest pK a values are attributed to the pyridinium nitrogen atoms by comparison with the pK a values of OTrensox (1.83, 2.55, and 3.01), [16] a tripodal ligand based on sulfonated 7-carboxy-8-hydroxyquinoline, and with the value of 3.92 published for 5-sulfo-8-hydroxyquinoline. [17] .…”

New Trends in the Chemistry of Iron(III) Citrate Complexes: Correlations between X‐ray Structures and Solution Species Probed by Electrospray Mass Spectrometry and Kinetics of Iron Uptake from Citrate by Iron Chelators

“…[16,17] At these wavelengths, Fe citrate solutions do not absorb to any significant extent. Two sets of measurements of iron removal rates were obtained: 1) the first set was collected by varying the ligand concentration (2.0 10 À4 mol dm À3 -1.8 10 À3 mol dm À3 ) for each of the three values of the Fe:cit ratio, 1:5, 1:20, and 1:80; 2) the second set of measurements was realized by varying the Fe:cit molar ratio from 1:10 to 1:80 with the ligand concentration fixed at 4 10 À4 m in order to determine the dependence of the rate constants on the citrate concentration.…”

“…Two kinds of solutions were analyzed by ESI-MS: 1) the final solutions, from which different compounds had been crystallized, to compare the species obtained in the solid state with those present in solution; 2) a series of solutions at different Fe:cit ratios and pH to monitor the evolution of the speciation. Furthermore, we describe a series of kinetic measurements of the iron uptake from citrate complexes at physiological pH 7.4 by two tripodal chelators: the tris(8-hydroxyquinolinate) ligand O-TRENSOX [16] and the tris(catecholate) ligand TRENCAMS. [17] These kinetic measurements were used to provide insight into the speciation between mononuclear and polynuclear Fe citrate species in relation to the Fe:cit ratio.…”

Quantitative 2D EXSY and Dynamic19F-NMR Studies of the Dynamic Behaviour of the Bidentate Chelate Complex Ga(fox)3 (fox = 5-fluoro-8-hydroxyquinoline)

“…[13] Previously, we studied a new tripodal iron chelator, OTrensox, based on 8-hydroxyquinoline. [14] Subsquently, we studied, as a model, the coordination chemistry of Ga(III) [the diamagnetic analogue of Fe(III)] with a fluorine-labelled sub-unit, the 5-fluoro-8-hydroxy-quinoline (fox). [15] The presence of only one fluorine atom per ligand leads to simplified 19 F-NMR studies.…”