Theoretical investigation into the influence of conformational equilibria on the water-exchange process in magnetic resonance imaging contrast agents

The conformational behavior in aqueous solution of four complexes of the Eu(III) ion with bis (R–amide) derivatives (R=H, methyl, ethyl, butyl) of diethylentriamine pentacetate ligands has been characterized at the ab initio level to rationalize the experimentally observed influence of alkyl substituents on the rate of the exchange process of the water molecule coordinated to the ion with the bulk water. Calculations were performed in vacuo and for aqueous solution, the latter by using the polarizable continuum model. Geometry optimizations provide, for each system, four isomers as stable conformations, all presenting a distorted tricapped trigonal prism coordination geometry around the ion. No significant influence of the alkyl substitution on the coordination geometry, nor on the europium–water distance, was observed. Moreover, increasing the length of the alkyl chain had no significant effect on the relative isomer population in solution. Thus, these results lead us to suppose that other effects, like those deriving from lateral chain folding in solution, should be considered to explain the increased rate of the water-exchange process with alkyl chain lengthening.Contribution to the Jacopo Tomasi Honorary Issue