Gd(III) complexes of poly(hydroxymethyl)substituted derivatives of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid

Gd(III) complexes of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid bearing two and four hydroxymethyl moieties on the cyclen ring were prepared to be studied as low toxicity MRI contrast agents. The key intermediates in the syntheses of the two ligands are the corresponding bis and tetrasubstituted cyclen derivatives. Bis(hydroxymetyl)cyclen was obtained according the so-called ‘crab-like’ cyclization procedure. Photoelectron transfer-induced tetramerization of (R)-2-(benzyloxymethyl)-N-(benzyl)aziridine stereoselectively led to homochiral tetra(hydroxymethyl)cyclen. The X-ray crystal structure of the latter compound unambiguously proved the alike stereochemical configuration of the four stereogenic carbon atoms in the cyclen ring. Carboxymethylation of the cyclen derivatives followed by complexation with either GdCl3 or Gd(OAc)3 afforded the target complexes.