Abstract
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 ^17^O‐nucleus of H~2~O gave values for the water‐residence time (τ~M~) of 86–143 ns at 310 K, values that are not limiting the proton relaxivity at body temperature. ^1^H‐NMRD (nuclear magnetic‐relaxation dispersion) Profiles showed that the relaxivity of 1–4 (r~1~=4.3–5.1 s^−1^ mM^−1^ at 20 MHz and 310 K) is higher than for the GdDTPA parent compound 5. Transmetallation assessment demonstrated that all substituted compounds, except for (S)‐2, are more stable than 5. The highest stability towards Zn^2+^‐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.