Bisamide DTPA derivatives

The water exchange rate is hardly affected by substituents which do not directly interfere in the inner coordination sphere. Different bisamide DTPA derivatives have similar exchange rates.28-30 Substituents on the carbon backbone of DTPA also have little influence on the water-exchange kinetics.31 38 39... 

We should note that the water exchange rate remains relatively constant on introducing different substituents on the ligand, which do not directly interfere in the inner coordination shell. Similar rates have been reported for the different bisamide DTPA derivatives (57,59,60,68). Even bulky substituents on the carbon backbone of the DTPA had limited influence on the water... 

The inversion of the N-atoms in the diethylenetriamine backbone is precluded. The central N-atom is always chiral, since the ethylene bridges around it have different conformations (<5 and A). Furthermore, the two other N-atoms are chiral as well in the bisamides and chirality of the metal ion should be taken into account. DTPA derivatives with three chiral N-atoms can be wrapped around the Ln3 + ion in 16 different ways (8 diastereomeric pairs, see Fig. 1). In crystal structures of these compounds the Ln3+ coordination polyhedron can generally be best described as a tricapped trigonal prism (TTP). For [Ln(DTPA)]2-A1=A2=A3 = B1=B2, and, consequently, only two enantiomers remain (1/1 ). Analogously, it can be seen that the DTPA-bisamides can have 4 diastereomeric pairs. 

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. 

Linear copolymers of Gd(DTPA-bisamide) or Gd(EGTA-bisamide) units with poly(ethylene-glycol) (PEG) or polyalkyl (-(CH2)n- n = 6,10 and 12) spacers also had water exchange kinetics similar to that of the corresponding monomer chelate [60-62]. An 170 NMR study on the micellar system formed in aqueous solution of the amphiphilic DOTA-derivative [Gd(D0TA-C12)(H20)] also showed that the water exchange is not altered by the micellar structure [63]. 

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