Synthesis and physicochemical characterisation of new amphiphilic gadolinium DO3A complexes as contrast agents for MRI

Two approaches were employed in the syntheses of four 1,4,7-tris(carboxymet hyl)-10-(2-hydroxyalkyl)-1,4,7,10-tetraazacyclododecanes (4) with alkyl cha in lengths from 4 to 16 carbons. Physicochemical properties, such as critic al micelle concentration (CMC), micelle size, partition coefficient (P) bet ween water and octan-1-ol and T-1 relaxivity (r(1)), were investigated for the corresponding gadolinium (Gd) complexes. The Gd complexes containing th e shortest alkyl chains (5a and 5b) showed properties typical of water-solu ble Gd complexes. On the other hand, the long-chained chelates (5c and 5d) were found to possess amphiphilic properties and to form micelles. The rela xivities of these amphiphilic complexes were found to be concentration depe ndent, consistent with the formation of micelles. An unexpectedly high rela xivity was measured for compound 5d below its CMC. This feature is probably caused by cluster formation due to low solubility in water.