[Gd(AAZTA)]- derivatives with n-alkyl acid side chains show improved properties for their application as MRI contrast agents.

Herein the synthesis and an extensive characterization of two novel Gd(AAZTA) derivatives functionalized with short (C2 and C4 ) n -alkyl acid function are reported. The carboxylate functionality is the site for further conjugations for the design of more specific contrast agents (CAs). Interestingly it has been found that the synthetized complexes display enhanced properties for their use as MRI contrast agents by their own. The 1H-NMR spectra of the complexes with EuIII and YbIII displayed a set of signals consistent with half the number of methylene protons present on each ligand. The number of resonances resulted invariant over a large range of temperature to suggest the occurrence of a fast interconversion between structural isomers. The relaxivity values (298K, 20MHz) were consistent with q =2 being equal to 8.8 mM-1s-1 for the C2 derivative and 9.4 mM-1 s-1 for the C4 one, i.e sensibly higher than the one reported for Gd(AAZTA) (7.1 mM-1s-1 ). VT- T2 17O-NMR measurements showed, for both complexes, the presence of two populations of coordinated water molecules, one in fast and one in slow exchange with the bulk water. The analysis of the 17O NMR VT- T2 profiles vs. temperature allowed to establish their relative molar fraction being 35% for the isomer with the fast exchanging water and 65% for the isomer with the water molecules in slower exchange. Finally, 1H NMRD profiles over an extended range of applied magnetic field strengths have been satisfactory fitted on the basis of the occurrence of the two interconverting species.