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

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)(H2O)]center dot xH(2)O (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-beta-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)(H2O)] (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)(H2O)] although they increase dramatically (6-10 fold) in aqueous hydroxypropyl-beta-cyclodextrin (HP-beta-CD) solutions. (c) 2007 Elsevier Ltd. All rights reserved.