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 l igands containing pendant functionalities attached to the common 1,4,7,10-t etraazacyclododecane macrocyclic ring have been studied by means of potenti ometric and microcalorimetric methods. Stability constants for the 1,4,7,10 -tetra(methylcarbamoylmethyl) ligand (DTMA), and for the new 10-(2-hydroxyp ropyl) 1,4,7-tri(2-hydroxymethylacetic acid) (HPDO3A-3HM) and 1,4,7-tri(2-h ydroxymethylacetic acid) ligand (DO3A-3HM) are reported for the first time, while analogous data for the remaining ligands have been redetermined unde r 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 complex es 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 physiologi cal pH follows the order HPDO3A > DOTA > HPDO3A-3HM > DO3A-3HM > DO3A > DTM A. The thermodynamic resistance of the Gd3+ complexes, at a plasma concentr ation of clinical administrations, toward demetallation in the presence of important components of blood plasma, such as Na+, Ca2+, Cu2+, Zn2+, phosph ate and carbonate, has been evaluated: the results are consistent with the previous trend of binding selectivity. The formation of intermediate comple xed species formed in the first minutes of the complexation reactions has b een studied from a thermodynamic point of view. The crystal structure of [G d(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 t he tetraazamacrocyclic moiety, eight amidic oxygen atoms of the side arms a nd by an oxygen atom of a water molecule.