The ligand DOTASA was designed and synthesized in the aim of obtaining a kinetically and thermodynamically stable Gd(III) chelate which, through its uncoordinated carboxylate function, will provide an efficient pathway to couple the complex to bio- or macromolecules without affecting the coordination pattern of DOTA. Furthermore, it allows us to study the influence of an extra carboxylate arm on the parameters determining proton relaxivity in comparison to the commercial agent [Gd(DOTA)(H2O)]-. A combined variable-temperature 17O NMR, EPR and nuclear magnetic relaxation dispersion study on the Gd(III) chelate resulted in kex298 = (6.3 +/- 0.2) x 10(6) s-1 for the water exchange rate and tau R298 = 125 +/- 2 ps for the rotational correlation time. The slight increase in both kex298 and tau R298, as compared to those for [Gd(DOTA)(H2O)]-, is attributed to the presence of the extra negative charge. The longer rotational correlation time results in a proton relaxivity of 5.03 mM-1 s-1 for [Gd(DOTASA)(H2O)]2-, which is approximately 30% higher than that for [Gd(DOTA)(H2O)]-. The increased water exchange rate of [Gd(DOTASA)(H2O)]2- has no consequence for proton relaxivity since this latter is exclusively limited by fast rotation for both complexes. However, for slowly rotating macromolecular agents, which contain a covalently coupled DOTASA unit instead of a coupled DOTA, this increased exchange rate will have a significant positive effect.