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Relaxivity and Transmetallation Stability of New Benzyl‐Substituted Derivatives of GadoliniumDTPA Complexes
Author(s) -
Laurent Sophie,
Botteman François,
Elst Luce Vander,
Muller Robert N.
Publication year - 2004
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/hlca.200490098
Subject(s) - transmetalation , chemistry , gadolinium , steric effects , macromolecule , relaxation (psychology) , selectivity , crystallography , medicinal chemistry , stereochemistry , organic chemistry , catalysis , psychology , social psychology , biochemistry
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 m M −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.