SYNTHESIS, STABILITY, AND STRUCTURE OF GADOLINIUM(III) AND YTTRIUM(III) MACROCYCLIC POLY(AMINO CARBOXYLATES)

The ligand protonation constants of three macrocyclic poly(amino carbo xylates), DO3A, HP-DO3A, and DOTA, and stability constants governing f ormation of their Gd(III) and Y(III) complexes have been determined by potentiometric and spectrophotometric methods, respectively, at 25.0 +/- 0.1-degrees-C and at a constant ionic strength of 0.1 M ((TMA)CI). The first protonation constant of the ligands was lowered in the pres ence of Na+ ions, indicating a preferred binding of the ligands to Na. Corroborating this finding, a crystal structure analysis of a comple x of NaBr and of the tetra-tert-butyl ester of DOTA revealed that the Na+ ion was chelated deep in the ligand cage. The thermodynamic stabil ity constants of the Gd(III) and Y(III) complexes followed the order: DOTA > HP-DO3A > DTPA > DO3A > EDTA. Crystal structures of the isostru ctural Gd(III) and Y(III) complexes of HP-DO3A, the [Na(tBu-DOTA)] Br complex, and the H2SO4 salt of DO3A were determined. The nine-coordina ted Gd(III) and Y(III) ions were eight-coordinate by the ligand, with a water molecule occupying the ninth (apical) position. The geometry o f the eight-coordinate binding of Na+ in the DOTA tetraester was simil ar to that in the (Gd/Y)HP-DO3A complexes, except that sodium was appr oximately 0.3 angstrom deeper in the ligand cavity. The metal-free D03 A ligand (protonated on the sec and transannular nitrogens) was preorg anized for metal coordination.