1510-04-9Relevant articles and documents
Relaxivity and transmetallation stability of new benzyl-substituted derivatives of gadolinium-DTPA complexes
Laurent, Sophie,Botteman, Francois,Vander Elst, Luce,Muller, Robert N.
, p. 1077 - 1089 (2007/10/03)
In our efforts of finding new specific contrast agents of higher relaxivity and selectivity, we have prepared the two new benzyl-functionalized DTPA ('diethylenetriamine pentaacetate') gadolinium complexes (S)-3 and (R,S)-4, and compared their properties with those of the known regioisomers (S)-2 and (S)-1. The theoretical fitting of the reduced transverse relaxation rates of the 17O-nucleus of H2O gave values for the water-residence time (τM) of 86-143 ns at 310 K, values that are not limiting the proton relaxivity at body temperature. 1H-NMRD (nuclear magnetic-relaxation dispersion) Profiles showed that the relaxivity of 1-4 (r1=4.3-5.1 s-1 mM-1 at 20 MHz and 310 K) is higher than for the Gd-DTPA parent compound 5. Transmetallation assessment demonstrated that all substituted compounds, except for (S)-2, are more stable than 5. The highest stability towards Zn2+-induced transmetallation was achieved with complexes 3, 1, and 4 (in decreasing order). Apparently, the steric hindrance of the benzyl substituents in positions 5, 4, and 2, respectively, favorably reduces the accessibility of Zn ions. From a synthetic point of view, 4-substituted DTPA complexes of type 1 are more readily accessible than 5-substituted compounds of type 3. Therefore, the former seem to be superior for linking substituted DTPA complexes to macromolecules or specific vectors.
