Filtern
Dokumenttyp
Sprache
- Englisch (4)
Referierte Publikation
- ja (4)
Schlagworte
- Chelates (2)
- Bispidines (1)
- Chemistry (1)
- Copper (1)
- Copper complexes (1)
- Copper(II) (1)
- Diagnostic and therapy (1)
- Imaging agents (1)
- Lanthanides (1)
- Macrocyclic ligands (1)
Four cyclam (1,4,8,11-tetraazacyclotetradecane) ligands with different numbers of N-substituted propionic acid groups lead to pentacoordinate copper(II) complexes that adopt trans-I configurations (4+1 geometry), that is, the complexes have a dx2-y2 ground state with significant rhombic distortion. From the structural data (X-ray diffraction analysis and electron paramagnetic resonance, UV/Vis and IR spectroscopy), as the number of secondary amine groups of the macrocyclic ring substituted with propionic acid groups increases, the distortion from square pyramidal to trigonal bipyramidal increases, and this is expected to lead to relatively low complex stabilities. This is confirmed by in vitro studies with superoxide dismutase (SOD) and human serum challenge experiments as well as by biodistribution data with the 64Cu-labelled complexes. The 64Cu-labelled complexes with cyclam monopropionic and dipropionic acid show high in vitro and in vivo stabilities, and the latter provides a comparable biodistribution profile to that of 64CuTETA (TETA = 1,4,8,11-tetraazacyclotetradecane-1,4,8,11-tetraacetic acid).
Bispidines for dual imaging
(2014)
The efficient transformation of the hexadentate bispidinol 1 into carbamate derivatives yields functional bispidines enabling convenient functionalization for targeted imaging. The BODIPY-substituted bispidine 3 combines a coordination site for metal ions, such as radioactive 64CuII, with a fluorescent unit. Product 3 was thoroughly characterized by standard analytical methods, single crystal X-ray diffraction, radiolabeling, and photophysical analysis. The luminescence of ligand 3 was found to be strongly dependent on metal ion coordination: CuII quenches the BODIPY fluorescence, whereas NiII and ZnII ions do not affect it. It follows that, in imaging applications with the positron emitter 64CuII, residues of its origin from enriched 64Ni and the decay products 64NiII and 64ZnII, efficiently restore the fluorescence of the ligand. This allows for monitoring of the emitted radiation as well as the fluorescence signal. The stability of the 64CuII–3 complex is investigated by transmetalation experiments with ZnII and NiII, using fluorescence and radioactivity detection, and the results confirm the high stability of 64CuII–3. In addition, metal complexes of ligand 3 with the lanthanide ions TbIII, EuIII, and NdIII are shown to exhibit emission of the BODIPY ligand and the lanthanide ion, thus enabling dual emission detection.
The CuII complex of H4TETP (H4TETP = 1,4,8,11-tetraazatetradecane-1,4,8,11-tetrapropionic acid) is five-coordinate with a distorted square-pyramidal structure (τ = 0.45; i.e. the geometry is nearly half-way between square-pyramidal and trigonal-bipyramidal) and a relatively long Cu–N and a short Cu–O bond; the comparison between powder and solution electronic spectroscopy, the frozen solution EPR spectrum and ligand-field-based calculations (angular overlap model, AOM) indicate that the solution and solid state structures are very similar, i.e. the complex has a relatively low 'in-plane' and a significant axial ligand field with a dx²-y² ground state. The ligand-enforced structure is therefore shown to lead to a partially quenched Jahn–Teller distortion and to a relatively low complex stability, lower than with the corresponding acetate-derived ligand H4TETA. This is confirmed by potentiometric titration and by the biodistribution with 64Cu-labeled ligands which show that the uptake in the liver is significantly increased with the H4TETP-based system.