Two new macrocyclic ligands, 6,6'-((1,4,7,10-tetraazacyclododecane-1,7-diyl)bis(methylene))dipicolini c acid (H(2)DODPA) and 6,6'-((4,10-dimethyl-1,4,7,10-tetraazacyclododecane-1,7-diyl)bis(methyle ne))dipicolinic acid (H2Me-DODPA), designed for complexation of lanthanide ions in aqueous solution, have been synthesized and studied. The X-ray crystal structure of [Yb(DODPA)](PF6)center dot H2O shows that the metal ion is directly bound to the eight donor atoms of the ligand, which results in a square-antiprismatic coordination around the metal ion. The hydration numbers (q) obtained from luminescence lifetime measurements in aqueous solution of the Eu-III and Tb-III complexes indicate that the DODPA complexes contain one inner-sphere water molecule, while those of the methylated analogue H2Me-DODPA are q = 0. The structure of the complexes in solution has been investigated by H-1 and C-13 NMR spectroscopy, as well as by theoretical calculations performed at the density functional theory (DFT; mPWB95) level. The minimum energy conformation calculated for the Yb-III complex [Lambda(lambda lambda lambda lambda)] is in good agreement with the experimental structure in solution, as demonstrated by the analysis of the Yb-III-induced paramagnetic H-1 shifts. The nuclear magnetic relaxation dispersion (NMRD) profiles recorded for [Gd(Me-DODPA)](+) are typical of a complex with q = 0, where the observed relaxivity can be accounted for by the outer-sphere mechanism. However, [Gd(DODPA)](+) shows NMRD profiles consistent with the presence of both inner- and outer-sphere contributions to relaxivity. A simultaneous fitting of the NMRD profiles and variable temperature O-17 NMR chemical shifts and transversal relaxation rates provided the parameters governing the relaxivity in [Gd(DODPA)](+). The results show that this system is endowed with a relatively fast water exchange rate k(ex)(298) = 58 x 10(6) s(-1).