Synthesis of phosphonic analogues of AAZTA and relaxometric evaluation of the corresponding Gd(III) complexes as potential MRI contrast agents

AAZTA was developed in the last decade as an efficient chelating agent for lanthanides and other metal ions of diagnostic and therapeutic interest. Different derivatives of AAZTA were designed and synthesized in order to modulate the physico-chemical properties of the corresponding chelates or to conjugate them to carrier molecules for molecular imaging applications. In this work, three different analogues of AAZTA bearing one or two phosphonic acid residues were synthesized in three step procedures and moderate to good yields. The effects of this isofunctional substitution on the structure and properties of the corresponding Gd(III) complexes were preliminarily investigated by relaxometric techniques. The presence of phosphonic groups progressively reduces the number of coordinated water molecules on the metal center and increases the second-sphere contribution to the relaxivity.