Biologically active thiosemicarbazone Fe chelators and their reactions with ferrioxamine B and ferric EDTA; a kinetic study

Abstract

The Fe III abstraction from Fe III /DFO and Fe III /EDTA complex systems by thiosemicarbazone ligands derived from 2-acetylpyridine has been studied from a kinetico-mechanistic perspective at relevant pH conditions and at varying temperatures and buffer solutions. The reactions have been found to be extremely dependent on the dominant E/Z isomeric form of the TSC ligands present in the reaction medium. Consequently the isomerisation processes occurring on the free ligands have also been monitored under equivalent conditions. The isomerisation process is found to be acid dependent, despite the absence of protonation under the conditions used, and presumably proceeds via an azo-type tautomer of the ligand. In all cases the existence of outer-sphere interaction processes has been established, both promoting the reactions and producing dead-end complexes. has also been conducted with significant differences in the kinetic features that implicate keystone outer-sphere interactions which dominate reactivity, even with isomeric forms that are not the best suited for direct complexation.

A comparative study of α- N -pyridyl thiosemicarbazones: Spectroscopic properties, solution stability and copper(II) complexation

“…The isomerization pattern for AcPTSC is more complicated in the DMSO-d 6 /H 2 O mixture ( Fig. 3) and in D 2 O as it was expected based on the literature data obtained in pure DMSO-d 6 [42,44] and CDCl 3 [46]. The isomer ratios were reevaluated in the latter two solvents as well, and our data are in a good agreement with literature.…”

“…TSCs are known to be able to appear as E and Z isomers about the C@N double bond and they exhibit thione-thiol tautomerism. Numerous papers reported on the identification and characterization of such isomers of particular TSCs, where the isomer patterns were usually determined on the basis of 1 H NMR spectroscopic studies and DFT calculations [23,[42][43][44][45][46][47][48][49]. The dominant formation of the E isomer was reported for FTSC in pure DMSO by several authors [45,49].…”

“…The isomers are in a slow interconversion processes with regard to the NMR time scale (t 1/2(obs) > $1 ms) and the integrated signals of the different ligand protons belonging to the E and Z isomers could be converted to molar fractions. The identification of the isomers was mainly based on the chemical shifts of the NH proton of the hydrazinic moiety (in the cases of pure DMSO-d 6 and CDCl 3 samples), that is highly sensitive to the formation of the hydrogen bonding in the Z form, and those of N@CH and N@CACH 3 protons, and/or by comparison to literature data [42,44,47]. Distribution data are collected in Table 2.…”

Kineticomechanistic Study of the Redox pH Cycling Processes Occurring on a Robust Water-Soluble Cyanido-Bridged Mixed-Valence {CoIII/FeII}2 Square

“…[47][48][49] Nevertheless, when the fully protonated H 2 {Co III /Fe II } 2 species is considered (pH = 0) the trend is maintained with equivalent (if not larger) values of K OS , thus implying that the outer-sphere solvent-assisted complexation should occur on the non-protonated nitrile units; even simultaneous hydrogen-bonding between a molecule of water with the non-protonated and protonated nitrile units can explain these facts (Scheme 4 and S2). [50,51] As for the kinetic and activation parameters at pH >2.0 (see Table 1), there is a dramatic change on going from the single (pH =1.5-2.0) to the doubly protonated mixed-valence square complex (pH = 0).…”

Synthesis and biological evaluation of (acyl)hydrazones and thiosemicarbazones obtained via in situ condensation of iminium salts with nitrogen-containing nucleophiles

“…2). Indeed, acylhydrazones [10] and thiosemicarbazones [11] are known metal chelators with a broad repertoire of coordination prop- erties. In the past, chelation therapy was used in clinical toxicology for the most common forms of heavy metal intoxication (e.g., lead, arsenic, mercury).…”