title: Synthesis and Structure of a New Macrocyclic Polyhydroxylated Gadolinium Chelate Used as a Contrast Agent for Magnetic Resonance Imaging.
abstract: Three approaches to the synthesis of a new ligand 1,4,7-tris(carboxymethyl)-10-(1-(hydroxymethyl)-2,3-dihydroxypropyl)-1,4,7,10-tetraazacyclododecane (6) are described. This ligand forms the both thermodynamically and kinetically very stable gadolinium chelate Gadobutrol (1), which is a neutral and highly hydrophilic compound that is used for magnetic resonance imaging in the clinic. According to the crystal structure the Gd(III) ion in 1 is nine coordinated. The ligand provides eight coordination sites whereas the ninth coordination partner surprisingly is a carboxylate oxygen of a neighboring centrosymmetrically-related complex molecule. Ligand 6 was also utilized to prepare the calcium complex 12 which is used as an additive in the pharmaceutical formulation of 1. For the calcium complex 12, two complex molecules adopting almost identical conformations are present in the crystal.
authors.affiliation: Research Laboratories of Schering AG, D-13342 Berlin, Germany, and Freie Universität Berlin, Institute for Crystallography, D-14195 Berlin, Germany.
authors.forename: J.
authors.initials: J
authors.lastname: Platzek
authors.forename: P.
authors.initials: P
authors.lastname: Blaszkiewicz
authors.forename: H.
authors.initials: H
authors.lastname: Gries
authors.forename: P.
authors.initials: P
authors.lastname: Luger
authors.forename: G.
authors.initials: G
authors.lastname: Michl
authors.forename: A.
authors.initials: A
authors.lastname: Müller-Fahrnow
authors.forename: B.
authors.initials: B
authors.lastname: Radüchel
authors.forename: D.
authors.initials: D
authors.lastname: Sülzle