Ferric ion sequestering agents. 20. 2,3-Dihydroxyterephthalamides: highly efficient iron(III)-chelating agents

Abstract

The synthesis and ferric ion complexation of a general series of 2,3-dihydroxyterephthalamides are described. These ligands are more acidic than other catechol ligands and are much more effective sequestering agents at neutral pH. The proton association constants are as follows: 2,3-dihydroxy-N,N'-dimethylterephthalamide log poll = 11.1 (l), log pOl2 = 17.2 ( I ) ; 2,3-dihydroxy-N,N'-diethylterephthalamide log poll = 11.1 (I), log pOl2 = 17.1 (I); 2,3-dihydroxy-N,N'-dipropylterephthalamide log flOll = 11.0 (l), log poiz = 17.0 (1); 2,3-dihydroxy-N,N'-dibutylterephthalamide log poll = 11.0 (1). Formation constants of the ferric complexes were determined by potentiometric and spectrophotometric studies: 2,3-dihydroxy-N,N'-dimethylterephthalamide log @i30 = 41.8 (l), log pi20 = 30.9 (l), log pilo = 16.4 (1); 2,3-dihydroxy-N,N'-diethylterephthalamide log pi30 = 42.2 ( I ) , log plzo = 30.7 (l), log pilo = 16.3 (I); 2,3-dihydroxy-NJV'-dipropylterephthalamide log pilo = 43.1 (l), log p,20 = 31.2 (I). The resultant equilibrium free metal ion concentrations (-log [Fe"] = pM, a direct measure of a ligand's ability to bind a metal at physiological pH; for M total ligand and 10" M total iron(II1)) are as follows: 2,3-dihydroxy-N,N'-dimethylterephthalamide, 21.

A Bidentate Terephthalamide Ligand, TAMmeg, as an Entry into Terephthalamide-Containing Therapeutic Iron Chelating Agents

“…7 The strong iron binding ability of this unit 8,9 makes it a promising candidate for use in therapeutic chelators. An added advantage of terephthalamide is the ease of tailoring the properties of this unit relative to other chelating units (e.g., hydroxypyridinone) used in the development of iron chelators.…”

Model compounds of humic acid and oxovanadium cations. Potentiometric titration and EPR spectroscopy studies

“…Although the molecules chosen as models are not sophisticated ones and do not to reproduce the inherently complex properties a geopolymer might have, as any model would 19 , they have provided information concerning the aqueous equilibria for humic acid models for nitrosalicylic acids -oxovanadium complexes, as well as have shown the possibility of studying them by EPR spectroscopy in aqueous solutions, opening new perspectives in using them as slow-release fertilizers. Vol.…”

Synthesis and Thermodynamic Evaluation of Mixed Hexadentate Linear Iron Chelators Containing Hydroxypyridinone and Terephthalamide Units1

“…Both hydroxypyridinone and terephthalamide units are effective for binding iron at comparable concentrations. However, terephthalamide units are more basic 28 and so are especially effective at higher (physiological) pH. Indeed, the sum of the first three pK a 's (Table 2) can be compared for the three ligands 3,4-LI(Me-3,2-HOPO) 2 (TAMmeg), 3,4-LI(Me-3,2-HOPO)(TAMmeg) 2 , and 3,4-LI(TAMmeg): they are respectively 19.85, 21.03, and 21.56.…”

“…This is consistent with the behavior of 2,3-dihydroxyterephthalamide ligands, which are extremely powerful Fe 3+ chelators and to stabilize this oxidation state of the metal. 28,37 …”