The ligand protonation constants of three macrocyclic poly(amino carboxylates), DO3A, HP-DO3A, and DOTA, and stability constants governing formation 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 presence of Na+ ions, indicating a preferred binding of the ligands to Na+. Corroborating this finding, a crystal structure analysis of a complex 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 stability constants of the Gd(III) and Y(III) complexes followed the order : DOTA > HP-DO3A > DTPA > DO3A > EDTA. Crystal structures of the isostructural 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-coordinated Gd(III) and Y(III) ions were eight-coordinate by the ligand, with a water molecule occupying the ninth (apical) position. The geometry of the eight-coordinate binding of Na+ in the DOTA tetraester was similar to that in the (Gd/Y)HP-DO3A complexes, except that sodium was approximately 0.3 angstrom deeper in the ligand cavity. The metal-free D03A ligand (protonated on the sec and transannular nitrogens) was preorganized for metal coordination.