Structures and Dynamics of Lanthanide(III) Complexes of Sugar-Based DTPA-bis(amides) in Aqueous Solution:  A Multinuclear NMR Study

The structure and dynamics of the lanthanide(III) complexes of DTPA-BGLUCA^3- (DTPA-bis(glucamide)), DTPA-BENGALAA^3- (DTPA-bis(ethylenegalactamine−amide)), DTPA-BEA^3- (DTPA-bis(ethanolamide)), and DTPA-BPDA^3- (DTPA-bis(propanediolamide)) in water have been investigated. These complexes are of relevance as potential MRI contrast agents. ¹³C relaxation times of the Nd(III) complexes show octadentate binding of the organic ligand via the three amines, the three carboxylates, and the two amide oxygens. ¹⁷O NMR measurements indicate that the coordination sphere is completed by one water ligand. Eight diastereomeric pairs of isomers are observed for the DTPA-bis(sugaramides). Data sets obtained from variable-temperature and -pressure ¹⁷O NMR at 9.4 T and variable-temperature ¹H nuclear magnetic relaxation dispersion (NMRD) on the Gd(III) complexes were fitted simultaneously to give insight into the parameters governing the water ¹H relaxivity. The water exchange rates, k_ex²⁹⁸, on [Gd(DTPA-BPDA)(H₂O)], [Gd(DTPA-BGLUCA)(H₂O)] and [Gd(DTPA-BENGALAA)(H₂O)] are 3.6 ± 0.3, 3.8 ± 0.2, and 2.2 ± 0.1 × 10⁵ s^-1, and the activation volumes are +6.7, +6.8, and +5.6 cm³ mol^-1 (±0.2 cm³ mol^-1), respectively, indicating a strongly dissociatively activated mechanism. The sugar moieties have no significant influence on the coordination of the Gd(III) ion and on the parameters governing the relaxivity, apart from the expected increase in the rotational correlation time. The relaxivity under the usual MRI conditions is limited by the water exchange rate and the electronic relaxation. The data obtained are used to explain the relaxivity of conjugates of polysaccharides and Gd(DTPA).