Thermodynamic and structural properties of Gd3+ complexes with functionalized macrocyclic ligands based upon 1,4,7,10-tetraazacyclododecane

The co-ordination properties toward Na+, Ca2+, Zn2+, Cu2+ and Gd3+ of six ligands containing pendant functionalities attached to the common 1,4,7,10-tetraazacyclododecane macrocyclic ring have been studied by means of potentiometric and microcalorimetric methods. Stability constants for the 1,4,7,10-tetra(methylcarbamoylmethyl) ligand (DTMA), and for the new 10-(2-hydroxypropyl) 1,4,7-tri(2-hydroxymethylacetic acid) (HPDO3A-3HM) and 1,4,7-tri(2-hydroxymethylacetic acid) ligand (DO3A-3HM) are reported for the first time, while analogous data for the remaining ligands have been redetermined under the same experimental conditions (0.1 mol dm(-3) NMe4Cl, 298.1 +/- 0.1 K). The synthesis of DTMA is also described. The stability of the GdL complexes follows the order DOTA (1,4,7,10-tetraacetic acid) approximate to HPDO3A [10-(2-hydroxypropyl) 1,4,7-triacetic acid] > DO3A (1,4,7-triacetic acid) > HPDO3A-3HM > DO3A-3HM > DTMA, although considering both complex formation and ligand basicity the binding selectivity of these ligands at physiological pH follows the order HPDO3A > DOTA > HPDO3A-3HM > DO3A-3HM > DO3A > DTMA. The thermodynamic resistance of the Gd3+ complexes, at a plasma concentration of clinical administrations, toward demetallation in the presence of important components of blood plasma, such as Na+, Ca2+, Cu2+, Zn2+, phosphate and carbonate, has been evaluated: the results are consistent with the previous trend of binding selectivity. The formation of intermediate complexed species formed in the first minutes of the complexation reactions has been studied from a thermodynamic point of view. The crystal structure of [Gd(DTMA)(H2O)][ClO4](3). NaClO4. 3H(2)O, solved by X-ray analysis, displays the Gd3+ ion in a 9-co-ordinated environment defined by four nitrogens of the tetraazamacrocyclic moiety, eight amidic oxygen atoms of the side arms and by an oxygen atom of a water molecule.