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)-l-phenyl-2-oxa-5,8,11-triazatridecan-13-oic acid; benie 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 ¹H NMR. The results obtained together with the value of the Gd-BOPTA²⁻ 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-BOPTA disodium salt [C₂₂H₂₆N₃O₁₁(H₂O)Gd]Na₂ 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 P1 (Z = 2), with a = 9.083(6) Å, b = 9.469(2) Å, c = 16.698(6) Å, a = 102.22(3)°, ß = 92.48(4)°, γ = 102.26(3)°, V = 1366(1) ų, and 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-BOPTA²⁻ has one water molecule directly coordinated to the metal ion. ¹³⁹La NMR studies on the La-BOPTA²⁻ 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. ¹³C NMR spectra of the diamagnetic La- and Lu-BOPTA²⁻ 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-DTPA²⁻ complexes.