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

Abstract

Two approaches were employed in the syntheses of four 1,4,7-tris(carboxymethyl)-10-(2-hydroxyalkyl)-1,4,7,10-tetraazacyclododecanes (4) with alkyl chain lengths from 4 to 16 carbons. Physicochemical properties, such as critical micelle concentration (CMC), micelle size, partition coefficient (P) between water and octan-1-ol and T₁ relaxivity (r₁), were investigated for the corresponding gadolinium (Gd) complexes. The Gd complexes containing the shortest alkyl chains (5a and 5b) showed properties typical of water-soluble Gd complexes. On the other hand, the long-chained chelates (5c and 5d) were found to possess amphiphilic properties and to form micelles. The relaxivities of these amphiphilic complexes were found to be concentration dependent, consistent with the formation of micelles. An unexpectedly high relaxivity was measured for compound 5d below its CMC. This feature is probably caused by cluster formation due to low solubility in water.