Inorganic Chemistry, Vol.34, No.6, 1408-1412, 1995
Amide Functional-Group Contribution to the Stability of Gadolinium(III) Complexes - DTPA Derivatives
The Gd3+ complexes of diethylenetriaminepentaacetic acid (DTPA) and several closely related ligands are in use, or being developed, as contrast agents for magnetic resonance imaging (MRI). The bis(amide) derivatives of DTPA are, like the parent DTPA ligand, octadentate : complexing agents of gadolinium, replacing two carboxylate coordinating groups with coordinating amide oxygens. Remarkably, this maintains a significant portion of the stability of the gadolinium complex and an increase in the relative selectivity fur Gd3+ vs Ca2+. The magnitude of the contribution of the amide functional groups to this stability is investigated. A diethylenetriaminetricarboxylic acid bis(amide) derivative in which the two terminal amide groups are replaced by methyl groups (bis(methyl)-diethylenetriaminetriacetic acid, DTTA-BM) is found to have a metal ion affinity at pH 7.4 that is 6.75 log units smaller than the effective stability of the bis-amide DTPA derivatives, corresponding to an average contribution of 3.38 log units to the stability of the complex from each amide functional group. The effective stability of the DTTA-BM Ca2+ complex relative to the bis(amide) ligands does not change as much. Hence the amide functional groups contribute significant stability for gadolinium complexation but little or no enhancement of calcium complexation, explaining the relative selectivity of bis(amide) ligands as gadolinium(III) complexing agents.
Keywords:AGENTS