Fine-tuning water exchange on GdIIIpolyamino carboxylates by modulation of steric crowdingElectronic supplementary information (ESI) available: Tables of the variable temperature 17O NMR, EPR and NMRD data. Figures of 17O NMR experimental data and fitted curves for GdDO3A-NpropH2O−, and 17O NMR, EPR and NMRD experimental data and fitted curves for GdEPTPA-BBAH2O. Outline of the Solomon–Bloembergen–Morgan theory used for the analysis of 17O NMR, EPR and NMRD data. See http://dx.doi.org/10.1039b506702b

In the objective of optimizing water exchange rate on stable, nine-coordinate, monohydrated GdIIIpolyamino carboxylate complexes, we have prepared monopropionate derivatives of DOTA4−DO3A-Nprop4− and DTPA5−DTTA-Nprop5−. A novel ligand, EPTPA-BAA3−, the bisamylamide derivative of ethylenepropylenetriamine-pentaacetate EPTPA5− was also synthesized. A variable temperature 17O NMR study has been performed on their GdIIIcomplexes, which, for GdDTTA-NpropH2O2−and GdEPTPA-BAAH2O has been combined with multiple field EPR and NMRD measurements. The water exchange rates, kex298, are 8.0 × 107s−1, 6.1 × 107s−1and 5.7 × 107s−1for GdDTTA-NpropH2O2−, GdDO3A-NpropH2O−and GdEPTPA-BAAH2O, respectively, all in the narrow optimal range to attain maximum proton relaxivities, provided the other parameters electronic relaxation and rotation are also optimized. The substitution of an acetate with a propionate arm in DTPA5−or DOTA4−induces increased steric compression around the water binding site and thus leads to an accelerated water exchange on the GdIIIcomplex. The kexvalues on the propionate complexes are, however, lower than those obtained for GdEPTPAH2O2−and GdTRITAH2O−which contain one additional CH2unit in the amine backbone as compared to the parent GdDTPAH2O2−and GdDOTAH2O−. In addition to their optimal water exchange rate, GdDTTA-NpropH2O2−has, and GdDO3A-NpropH2O−is expected to have sufficient thermodynamic stability. These properties together make them prime candidates for the development of high relaxivity, macromolecular MRI contrast agents.