Ternary Gd(III)L-HSA adducts: evidence for the replacement of inner-spherewater molecules by coordinating groups of the protein. Implications for the design of contrast agents for MRI

Two novel gadolinium(III) chelates based on the structure of the heptadenta te macrocyclic 1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid (DO3A) l igand have been synthesized and their relaxometric and luminescent properti es thoroughly investigated. They contain two water molecules in the inner c oordination sphere in fast exchange with the bulk solvent and bear either a p-bromobenzyl or a p-phosphonatomethylbenzanilido substituent for promotin g further interaction with macromolecular substrates. Upon interaction with human serum albumin the expected relaxation enhancement is not observed ow ing to displacement of the two inner-sphere water molecules of the complexe s by a donor atom (likely from a carboxylate group) on the protein and poss ibly the phosphate anion of the buffered solution, respectively. We modeled the observed behavior by measuring the decrease of the relaxation rate of the water protons upon addition of malonate anion to aqueous solutions of t he complexes. Conversely, no change in the hydratation state of the Gd(III) center for both complexes has been observed when the substrate for the for mation of the macromolecular adduct is represented by poly-beta-cyclodextri n.