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(π₅-X)(π₃-OH)₂₀(his+/-)₁₀(his-)₅(OH)₇]¹²⁺ (X = Cl- or Br-; his+/- = zwitterionic histidine, his- = histidinate) and [Ln₁₅(π₅-OH)(I)₂(π₃-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(π₅-OH)(π₃-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 x10-7 and 1.2 x10-6 cm²/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 π₃-OH ligands are capable of exchanging with bulk D₂O. Electrospray ionization mass spectroscopy (ESI-MS) on the Eu(III)-based clusters showed mass-to-charge peaks representative of the intact cluster core minus several counter ions and ligands. Yttrium analogues were prepared for ¹³C and ⁸⁹Y NMR spectroscopy studies. The ¹³C NMR spectra exhibited two sets of resonances for histidine. One set matches that of free-histidine in aqueous solution, and the other most likely represents yttrium-coordinated histidine. ⁸⁹Y NMR spectra exhibited two resonances and correlate with the solid-state structure. Solution-state studies of the Ln₁₅-his X complexes suggest that the Ln₁₅-his X clusters maintain the observed solid-state structure in solution. Inner-ligand-substituted hexanuclear tantalum and tungsten chloride clusters were also investigated. Substitution of inner chlorines by metathesis of the robust cluster cores in solution proved to be challenging. Solid-state synthesis to obtain mixed oxygen-chlorine hexatantalum clusters resulted in ampoule explosions because of side reactions between the reactants and the quartz ampoule. Solid-state routes towards tungsten clusters with mixed inner ligands yielded the (H₃O)₂[α/β-W₆(π₂-O)₆(π₂-Cl)₆Cl₆]*X(H₂O) (X_α = 4; X_β = 6) complexes.