Synthesis, Characterization, and 1 /T₁ NMRD Profiles of Gadolinium(III) Complexes of Monoamide Derivatives of DOTA-Like Ligands. X-ray Structure of the 10-[2-[[2-Hydroxy-1-(Hydroxymethyl)Ethyl]amino]-1-[(Phenylmethoxy)Methyl]-2-Oxoethyl]-1, 4, 7, 10-Tetraazacyclododecane-1, 4, 7-Triacetic Acid-Gadolinium(III) Complex

The synthesis of two novel DOTA-like ligands (5a, b) containing a polyhydroxy(benzyloxy)propionamide substituent and their Gd(III) complexes (6a, b) is reported. Debenzylation by hydrogenolysis of the latter complexes in the presence of Pd/C leads to the corresponding derivatives (7a, b) with a primary alcoholic function. Water proton relaxation rates of aqueous solutions of 6a, b and 7a, b strongly suggest that these complexes contain only one water molecule in their inner coordination sphere, as was previously found for the parent DOTA complex. The high formation constants measured for complexes 6a, b (log K_ML = 25.9 and 26.4, respectively) support the hypothesis of a direct involvement of the amide functionality in the coordination cage. This was shown by the determination of the solid-state structure of 6a, which was accomplished in a single-crystal X-ray diffraction study. The structure consists of a Gd(C₂₇H₄₀N₅O₁₀)(H₂O) unit and three water molecules; space group P2₁/c (Z = 4) with a = 17.378 (4) Å, b = 8.283 (7) Å, c = 22.813 (5) Å, β = 100.33 (2)°, V = 3230 (3) ų, d = 1.590 g/mL. The coordination polyhedron around the gadolinium ion is best described by a distorted-square antiprism capped by the coordinated water oxygen. All Gd-O distances (ranging from 2.34 to 2.43 Å) are very similar and this unambiguously proves the coordination of the carboxamide oxygen to the gadolinium ion. The 1 /T₁ NMRD profiles of aqueous solutions of 6a, b and 7a, b reveal that at the higher frequencies, the solvent proton relaxation rates are dominated by the molecular reorientational time t_R; i.e., the observed relaxivities are linearly related to the molecular size. However, the main effect associated with the transformation of carboxylate to carboxamide is the drastic reduction of the electronic relaxation time So, which is responsible for a decrease in relaxivity at the low fields.