Two DO3A-based ligands appended with the propylphosphonate side arm and their Ln(3+) complexes were investigated. Proton relaxometric in vitro studies at 20 MHz and 60 MHz and 37 degrees C of the Gd3+ complex containing free acid exhibited relative changes of up to 56% in r(1) relaxivity when the pH of the medium was changed from 4 to 7. This change is explained by the decrease in the number of coordinated water molecules from two to one. Temperature-dependent relaxivity and NMRD profiles of Gd3+ complexes showed a fast water exchange and a slightly increased rotational correlation time, which is characteristic of phosphonate-containing compounds. Thermodynamic and kinetic studies of the Gd3+ and Eu3+ complexes were performed by means of potentiometry and luminescence spectroscopy. The results indicate that the thermodynamic stability and kinetic inertness of these complexes are sufficient for their in vivo application. ((C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)