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Dramatic relaxation enhancements of L‐lactate resonances have been observed upon formation of ternary adducts with GdIIIcomplexes of heptadentate DO3A and DO3A‐like ligands (DO3A=1,4,7,10‐tetraazaciclododecane‐1,4,7‐triacetic acid). Detailed 1H and 17O NMR relaxometry investigations allow us to obtain structural, dynamic and thermodynamic information on the ternary complexes in which L‐lactate acts as a bidentate ligand replacing two water molecules in the inner coordination sphere of the GdIIIion. It has been found that the exchange rate of the coordinated L‐lactate is modulated by the structural and electronic properties of the parent Gd‐heptacoordinated macrocyclic chelate. In addition to the characterisation of the relaxation behaviour of the 1H methyl resonance of L‐lactate, this study has been extended to its 13C isomer (fully enriched at the three positions) and to the trifluoro‐L‐lactate. The obtained results may be relevant to the development of relaxation agents able to promote the relaxation enhancement of specific substrates detectable by in vivo magnetic resonance spectroscopy.

The 1H and 17O NMR relaxometric properties of two cationic complexes formed by GdIIIwith a macrocyclic heptadentate triamide ligand, L1, and its Nmethylated analogue, L2, have been investigated in aqueous media as a function of pH, temperature and magnetic field strength. The complexes possess two water molecules in their inner coordination sphere for which the rate of exchange has been found to be sensibly faster for the Nmethylated derivative and explained in terms of electronic effects (decrease of the charge density at the metal center) and perturbation of the network of hydrogen‐bonded water molecules in the outer hydration sphere. The proton relaxivity shows a marked dependence from pH and decreases of about six units in the pH range 6.5 to 9.0. This has been accounted for by the displacement of the two water molecules by dissolved carbonate which acts as a chelating anion. The formation of ternary complexes with lactate, malonate, citrate, acetate, fluoride and hydrogenphosphate has been monitored by 1H NMR relaxometric titrations at 20 MHz and pH 6.3 and the value of the affinity constant, K, and of the relaxivity of the adducts could be obtained. Lactate, malonate and citrate interact strongly with the complexes (log K≥3.7) and coordinate in a bidendate mode by displacing both water molecules. Larger affinity constants have been measured for GdL2. Acetate, fluoride and hydrogenphosphate form monoaqua ternary complexes which were investigated in detail with regard to their relaxometric properties. The NMR dispersion (NMRD) profiles indicate a large contribution to the relaxivity of the adducts from water molecules belonging to the second hydration shell of the complexes and hydrogen‐bonded to the anion. A VT 17O NMR study has shown a marked increase of the rate of water exchange upon binding which is explained by coordination of the anion in an equatorial site, thus leaving the water molecule in an apical position, more accessible for interactions with the solvent molecules of the second hydration shell which facilitate the exchange process.

The results reported in this work show that tightly assembled adducts formed by trisubstituted GdIIIcomplexes and a β‐CD multimer (Poly‐β‐CD, d.p. ca. 12) may represent very interesting candidates for novel MRI applications wherein a high number of paramagnetic ions endowed with high relaxivity (per GdIIIion) are necessary. The relaxivities found for the paramagnetic adducts represent a remarkable step forward on the relaxivity scale. However, a detailed investigation of the determinants of the relaxation enhancement in these systems shows that their relaxivities are still limited by a nonoptimal τRand a relatively long exchange lifetime of the coordinated water(s). Moreover, the exchange rate of the water molecule(s) coordinated to the GdIIIion further decreases upon binding to the Poly‐β‐CD. It is suggested that this finding is related to the structural properties of the supramolecule, which brings a high density of hydroxyl groups into the proximity of the “guest” complexes, and this yields an overall reinforcement of the hydrogen‐bonding network involving the coordinated water(s). On the other hand, such a tight arrangement appears responsible for an enhanced contribution to the observed relaxivity arising from water molecules in the second coordination sphere of the metal center.