DTPA-amide derivatives

In the case of DTPA derivative complexes, both proton- and metal-assisted (Zn2+ or Cu2+) pathways are important for the dissociation (143). For the DTPA-amide derivatives, the proton-assisted dissociation is much faster, while the metal-assisted pathway is slower (147,148), with a dependency of the... 

The rate of proton-assisted dissociation of Gd(DTPA-BMEA), studied by Rothermel et al., does not differ considerably from that of Gd(DTPA-BMA) (Table 2), indicating that the kinetic stabilities of the complexes of the different DTPA-bis(amide) derivatives are similar [42]. 

Other non-cyclic ligands can be used to bind Gd3+ with most based on the diethylenetriaminepentaacetic acid (DTPA) skeleton. These include GdDTPA, or Magnevist [31], and a di(methyl)amide derivative GdDTPA-BMA, or Omniscan [32], illustrated in Fig. 6.13. 

Dotarem) have been widely used these meet most of the above criteria. Both neutral and charged complexes are used, the former having less osmotic effect and the latter being more hydrophilic, so that amide derivatives hke [Gd(DTPA-BMA)(H20)] (gadodiamide Omniscan) have advantages. 

The structure found in salts like Na2[Gd(dtpa)(H20)] is thought to represent the species found in solution - data from a number of measurements on solutions containing [Ln(dtpa)(H20) ] species, such as luminescence spectra of the Eu and Tb analogues, indicate that one water molecule is coordinated. A wide variety of complexes of amide derivatives of DTPA have also been synthesised, in order to create neutral species. Using [Gd(DTPA)(H20)] it has been shown that these complexes get absorbed by the DNA of the cell they have been used to locate and that they could act as an agent for neutron capture cancer therapy. 

Five bis(amid derivatives of DTPA form neutral Gd complexes with similar relaxivity to [Gd(dtpa)(H20)] The structure of a gadolinium complex of a bis(amide) of DTPA (21), a potential contrast agent, has been determined. ... 

Complexes with diethylenetriamine-N,N,N, N, N"-pentaacetate (dtpa ) and amide derivatives of dtpa ... 

In the crystal structures of the La3+ and Eu3+ complexes of Ln( 18-DTPA-dien) oligomerization was observed [20]. The coordination of the Ln3+ ion by each DTPA unit, however, was similar to that in the linear bisamides. Vapor pressure osmometry indicated that oligomerization in solution does not occur under the conditions applied (0.2-0.5 M). Because of the constraints imposed by linking the two amide functions in the macrocycle, the isomers 1,1 and 3,3 depicted in Fig. 1 are sterically very unfavorable. In line with this, resonances for only two pairs of enantiomers were observed in the 11 spectra of the Ln( 18-DTPA-dien) complexes. The dynamic behavior showed that one pair was rather static, whereas the other was rapidly interconverting. The AG for the interconversion (65 kj mol-1) was about the same as those observed for the SS AA isomerization in other DTPA-derivatives. In the Ln( 18-DTPA-dien) complex such an isomerization is only possible between mirror images 2 and 2. All other isomerizations require decoordination and, therefore, are much slower. 

Relaxivity and other studies on other Gd DTPAbis(amide) complexes have been reported Dissociation kinetics of Ce and Gd complexes of bis(amide) ligands derived from DTPA have been studied. Complexes of a new octadentate ligand H5BOPTA (23) similar to DTPA have been made. 

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