The Gd(iii)-complexes of three novel HP-DO3A-like ligands have been investigated to assess the relationship between relaxometry and intramolecular catalysis of the proton exchange. The structures of these ligands differ from the parent HP-DO3A because the methyl group of the hydroxy-propyl arm has been replaced by -Ph-OH, -Ph-NH2 and -Ph-COOH, respectively. The phenol, amine and carboxylate functionalities display an intramolecular H-bonding with the coordinated hydroxyl moiety that affects either the pK values of the involved functionalities and the rate of the proton exchange process.

An efficient and scalable preparation of the thyroid hormone analogue O-[3-iodo-4-(sulfooxy)phenyl]-3,5-diiodo-l-tyrosine sodium salt (T3-sulfate, 1) is reported. The synthesis involved monoiodination of O-(4-hydroxyphenyl)-3,5-diiodo-l-tyrosine to give liothyronine (2) which was sulfated with chlorosulfonic acid in N,N-dimethylacetamide. Crude T3-sulfate was initially purified by chromatography on polystyrene resin Amberlite XAD 1600 and then crystallized with ethanol. This strategy was scaled-up to give a process suitable for the production of kilogram quantities of API, needed to support preclinical and clinical studies.