Hydroxyl-bridged lanthanide amino acid clusters and hexatantalum and hexatungsten chloride clusters: synthesis, characterization, and relevance to biomedical imaging

The synthesis and characterization of polynuclear lanthanide complexes and tungsten chloride clusters are detailed. The relevance of these complexes to MRI contrast agents, physiological parameter reporting MRI contrast agents, and X-ray computed tomography contrast agents is discussed. Polylanthanides, in particular polygadolinium and polyeuropium(II) complexes, represent a paradigm shift in contrast agent design. Base hydrolysis of aqueous Ln(ClO4)3 in the presence of L-histidine and alkali metal halide anions (Cl, Br, and I) yields the pentadecalanthanide(III) complexes [Ln15(μ5-X)(μ3-OH)20(his )10(his )5(OH)7] 12+ (X = Cl or Br; his = zwitterionic histidine, his = histidinate) and [Ln15(μ5-OH)(I)2(μ3-OH)20(his )10(his )5(OH)7] 10+ for Ln = Y, Eu, Gd, Tb, Nd, and La (abbreviated Ln15–his X). Base hydrolysis of Ln(ClO4)3 in the presence of L-histidine without added halide yields the complex [Ln15(μ5-OH)(μ3-OH)20(his )10(his )5(OH)7] 12+ (Ln15-his OH) for Ln = Eu and Tb. These latter complexes represent the first halide-free complexes of this structure type. Solution studies revealed the latter complex’s ability to capture halides (Cl, Br, and I) to generate the corresponding Ln15-his X complexes described above. All new complexes were characterized by single-crystal X-ray diffraction. Polyeruopium(III) complexes were studied by electrochemistry and spectrofluorimetry. Diffusion coefficients of Eu15-his X complexes were determined to be between 2.0 x10 and 1.2 x10 cm/s. From fluorescence studies, approximately 22 waters were found to coordinate to the inner sphere of the Eu(III) ions in Eu15-his X. Fluorescence data supported the coordination of strong-field ligands, such as carboxylates and hydroxides. It was also found that the hydrogens of μ3-OH ligands are capable of exchanging with bulk D2O. Electrospray ionization mass spectroscopy (ESIMS) on the Eu(III)-based clusters showed mass-to-charge peaks representative of the intact cluster core minus several counter ions and ligands.