Some new DTPA- N, N″-bis(amides) functionalized by alkyl carboxylates: Synthesis, complexation and stability properties

Abstract

A new series of DTPA- N, N″-bis(amide) ligands functionalized by alkyl carboxylates on the amide side-arms ( 1a– 1l) and their Gd(III) complexes of the type [Gd( 1)(H 2O)] · xH 2O ( 2a– 2l) were synthesized and characterized by analytical and spectroscopic techniques. Potentiality of 2a– 2l as contrast agent for magnetic resonance imaging (MRI CA) was investigated by measuring some relevant physicochemical properties such as (i) the protonation constants of 1a– 1l, (ii) thermodynamic and conditional stability constants of 2a– 2l, (iii) the selectivity (pGd) of 1a– 1l for the Gd(III) ion over the endogenous metal ions such as Zn(II), Ca(II), and Cu(II), and (iv) the relaxivities ( R 1 and R 2) of 2a– 2l in aqueous and aqueous HP-β-CD solutions. Comparative studies reveal that most of new Gd(III) complexes show enhanced thermodynamic stability and selectivity as compared with those of [Gd(DTPA-BMA)(H 2O)] (DTPA-BMA = N, N″-di(methylcarbamoylmethyl)diethylenetriamine- N, N′, N″-triacetate). Also enhanced with 1a– 1l (except 1f and 1h) is affinity for Gd(III) as compared with [DTPA-BMA] 3− under physiological conditions. The relaxivities ( R 1 and R 2) of aqueous solutions of 2a– 2l, on the other hand, drop significantly as compared with [Gd(DTPA-BMA)(H 2O)] although they increase dramatically (6–10 fold) in aqueous hydroxypropyl-β-cyclodextrin (HP-β-CD) solutions.