Relaxivity and Transmetallation Stability of New Benzyl-Substituted Derivatives of Gadolinium-DTPA Complexes

摘要

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)-l.The theoretical fitting of the reduced transverse relaxation rates of the ~(17)O-nucleus of H_2O gave values for the water-residence time(tau_M)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(r_1=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 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.