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)] · xH2O (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 (R1 and R2) 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)(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 (R1 and R2) 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-β-cyclodextrin (HP-β-CD) solutions.

A new series of DTPA-bis(amides) (1a–1l) significantly enhance thermodynamic stabilities of the corresponding Gd(III) complexes as compared with related DTPA-BMA. Yet, the relaxivities (R1 and R2) drop significantly in an aqueous solution, whereas they increase by 6–10 fold in aqueous hydroxypropyl-β-cyclodextrin solutions.Figure optionsDownload as PowerPoint slide