The solution structure and dynamics of metal-bound water exchange have been investigated in a series of lanthanide complexes of primary, secondary, and tertiary tetraamide derivatives of 1,4,7,10-tetraazacyclododecane. In the gadolinium complexes at ambient pH, water exchange lifetimes (τm) determined by 17O NMR were sufficiently long (19 μs for [Gd·2]3+, 298 K, 17 μs for [Gd·3]3+, and 8 μs for [Gd·4]3+) to limit the measured relaxivity. Direct 1H NMR observation of the bound water resonance is possible for the corresponding Eu complexes at low temperature in CD3CN, and the rate of water proton exchange is about 50 times faster in the twisted square antiprismatic isomer (m) than in the isomeric square antiprismatic (M) complex. The ratio of these two isomers in solution is sensitive to the steric demand of the amide substituent, with m/M = 2 for [Eu·4]3+, but 0.25 for [Eu·2]3+. The slowness of coordinated water exchange has allowed the rate of prototropic exchange to be studied:  in basic media deprotonation of the bound water molecule or of proximate ligand amide NH protons leads to relaxivity enhancements, whereas in acidic media, hydration around the strongly ion-paired complexes is perturbed, facilitating water exchange. The X-ray crystal structure of ligand 3 reveals a hydrogen-bonded structure with two pairs of ring N-substituents related in a trans arrangement, contrasting with the structure of diprotonated DOTA in which the ligand is predisposed to bind metal ions. In the dysprosium complex [Dy·3·OH2](PF6)3, the metal ion adopts a regular monocapped square antiprismatic coordination geometry, with a water Dy−O bond length of 2.427(3) Å, and a PF6 counterion is strongly hydrogen-bonded to this bound water molecule.

Reversible anion binding in aqueous media at chiral Eu III and Tb III centers has been characterized by 1 H NMR and by changes in the emission intensity and circular polarization following direct or sensitized (365 nm) excitation via an alkylphenanthridinium chromophore. Using a series of heptadentate tri-amide or polycarboxylate ligands, the affinity for CO 3 2-/HCO 3 -, phosphate, lactate, citrate, acetate, and malonate at pH 7.4 was found to decrease as a function of the overall negative charge on the complex: citrate and malonate bound most strongly, and lactate and hydrogen carbonate also formed chelated ternary complexes in which displacement of both of the metal-bound water molecules occurred, which was confirmed by VT 17-O NMR measurements of the corresponding Gd complexes. The binding of carbonate was studied in particular, and 1 H NMR and CPL data were obtained that were consistent with the formation of a complex with a reduced helical twist about the metal center. Monohydrogen phosphate was bound in a monodentate manner, giving a monoaqua adduct. The binding of carbonate to cationic Eu complexes in the presence of a simulated extra-cellular anionic background at pH 7.4 was monitored by variation in the emission intensity, ratio of intensities (615/ 594 nm), and dissymmetry factors as a function of added total carbonate.