Preparation, crystallographic and theoretical study on a bifunctional Gd-AAZTA derivative as potential MRI contrast agent precursor

• A bifunctional Gd(H2O)-AAZTA-C2H4COOBn derivative was obtained.
• The (αR,6R) structure was determined by X-ray, while that of (αR,6S) was theoretically predicted.
• The MD model of (αR,6R) has the Gd(III) nona-coordinated, as in its crystal structure.
• In the MD model of (αR,6S) the Gd(III) remains octa-coordinated.
• The hindrance of the chain disfavours the water access to the Gd(III) coordination sphere.

The crystal structure of the complex (αR,6R)-Na[Gd(H2O)-AAZTA-C2H4COOBn]·3H2O·EtOH was determined by single crystal X-ray diffraction; the complex represents a bifunctional derivative of Gd-AAZTA, previously reported as original scaffold for the development of efficient contrast agents for MRI. The Gd(III) ion is nine coordinated with three nitrogens, five carboxylate oxygens and one water oxygen in a monocapped distorted square antiprism coordination polyhedron. Three of the five carboxylic groups are monodentate while a fourth is bidentate bridging an adjacent Gd ion with the formation of a polymeric structure. The influence on the overall structure of the propionate side arm introduced for conjugation purposes was discussed, and a computational approach to predict the structure of its (αR,6S) isomer is presented and compared with the X-ray structure of the (αR,6R) epimer.

Preparation, crystallographic and theoretical study on a bifunctional Gd-AAZTA derivative as potential MRI contrast agent precursor. The crystal structure of Na[Gd(H2O)-AAZTA-C2H4COOBn]·3H2O·EtOH was determined and showed the Gd(III) ion nine coordinated. The structure of its (αR,6S)-isomer was predicted by means of theoretical calculations. The comparison between the two isomers pointed out the influence of the lateral chain orientation on the water access to the Gd(III) coordination sphere.Figure optionsDownload as PowerPoint slide