DOTA-derived ligands

Kinetic Stabilities of Gd3+ Complexes of DOTA and DOTA Derivative Ligands... 

Aime, S., Anelli, P.L., Botta, M., Fedeli, F., Grandi, M., Paoli, P., and Uggeri, F. (1992) Synthesis, characterization, and 1/T1 NMRD profiles of gadolinium (III) complexes of monoamide derivatives of DOTA-like ligands. X-ray structure of the 10-[2-[[2-hydroxy-l-(hydroxyl-methyl)ethyl]amino]-l-[phenylmethoxy)methyl]-2-oxo-ethyl]-l,4,7,10-tetraaza-cyclododecane-l,4,7-triacetic acid-gadolinium (III) complex. Inorg. Chem. 31, 2422-2428. 

Gadolinium(III) complexes containing phosphonate groups can be targeted to bone. Examples are the DOTA derivatives (325, 326) and complexes of aminophosphonate ligands (327). 

The ligand tetracarboxyethyl DOTA derivative (TCE-DOTA) was synthesized as a mixture of the six stereoisomers defined by the absolute configuration of the four chiral carbons, RRRR/SSSS pair, RSSS/SRRR pair, RSRS and RRSS, which were separated, crystallized and their crystal structures determined [78,79]. The crystal structures of the Eu3+, Gd3+ and Tb3+ complexes of the TCE-DOTA... 

The complexation properties of the macrocyclic, spider-like tetraaza-tetraace-tate ligand DOTA were found by Desreux to be very unique [45]. The stability constants of the complexes Ln(DOTA)- are very high and both the formation and dissociation rates are unusually low. The behavior of the DOTA- analogous ligands containing at least three acetate and three or four methylene-phospho-nate or methylene-phosphinate groups is very similar, and a number of new derivatives have been synthesized and investigated in order to develop new CAs. 

Fig. 46. Chemical structure of various DOTA-like tetramide derivative ligands.

The isomer possibilities in DOTA derivatives can increase dramatically. For example, introducing a chiral center by substitution at Ca, of the acetate arms of DOTA can gives rise to six ligand isomers defined by the absolute configuration at the carbon (SSSS), RSSS (SRRR), and the achiral... 

Complex stability constants are most often determined by pH-potentiometric titration of the ligand in the presence and absence of the metal ion.100 This method works well when equilibrium is reached rapidly (within a few minutes), which is usually the case for linear ligands. For macrocyclic compounds, such as DOTA and its derivatives, complex formation is very slow, especially for low pH values where the formation is not complete, therefore a batch method is... 

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