NOVEL CONTRAST AGENTS FOR MAGNETIC-RESONANCE-IMAGING - SYNTHESIS AND CHARACTERIZATION OF THE LIGAND BOPTA AND ITS LN(III) COMPLEXES (LN=GD, LA, LU) - X-RAY STRUCTURE OF DISODIUM (TPS-9-145337286-C-S)-[4-CARBOXY-5,8,11-TRIS(CARBOXYMETHYL)-1-PHENYL-2-OXA-5,8,11-TRIAZATRIDECAN-13-OATO(5-)]GADOLINATE(2-) IN A MIXTURE WITH ITS ENANTIOMER

The syntheses of the ligand BOPTA, (4-carboxy-5,8,11-tris(carboxymethyl)-1-phenyl-2-oxa-5,8,11-triazatridecan-13-oic acid; benic acid) and its Gd(III), La(III), and Lu(III) complexes are reported. Protonation constants for BOPTA have been determined by potentiometry, and the microscopic protonation sequence has been investigated by H-1 NMR. The results obtained together with the value of the Gd-BOPTA(2-) stability constant (log K-ML = 22.59) show that the complexing properties of the ligand, in comparison with DTPA, are little affected by the presence of the benzyloxymethyl residue in the structure. The solid state:structure of Gd-BDPTA disodium salt [C22H26N3O11(H2O)Gd]Na-2(3)/2H2O was determined in a single-crystal X-ray diffraction study; The structure consists of [C22H26N3O11(H2O)Gd](2-) anions, sodium cations, and water molecules; the space group is P (1) over bar (Z = 2), with a = 9.083(6) Angstrom, b = 9.469(2) Angstrom, c = 16.698(6) Angstrom, alpha = 102.22(3)degrees, beta = 92.48(4)degrees, gamma = 102.26(3)degrees, V = 1366(1) Angstrom(3), d = 1.84 g/mL. The gadolinium ion adopts a nine-coordinate geometry, which is best described as a distorted tricapped trigonal prism: Eight coordinating sites are occupied by the ligand (three nitrogen atoms and five carboxylate oxygens), and the ninth site is occupied by the oxygen atom of a water molecule. Relaxation studies have shown that in solution also Gd-BOPTA(2-) has one water molecule directly coordinated to the metal ion; La-139 MMR studies on the La-BOPTA(2-) complex have further supported the view that such-complexes maintain in solution the same kind of coordination as found in the solid state for Gd-BOPTA disodium salt. C-13 NMR spectra of the diamagnetic La- and Lu-BOPTA(2-) complexes at various temperatures are consistent with the presence of two couples of isomers interconverting through a dynamic process. Such a process has previously been reported for the parent Ln-DTPA(2-) complexes.