TY - JOUR A1 - Comba, P. A1 - Emmerling, Franziska A1 - Jakob, M. A1 - Kraus, Werner A1 - Kubeil, M. A1 - Morgen, M. A1 - Pietzsch, J. A1 - Stephan, H. T1 - Copper(II) chemistry of the functionalized macrocycle cyclam tetrapropionic acid N2 - 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. KW - Copper(II) KW - Chemistry PY - 2013 DO - https://doi.org/10.1039/c2dt32356g SN - 1477-9226 SN - 1477-9234 SN - 1364-5447 VL - 42 IS - 17 SP - 6142 EP - 6148 PB - RSC CY - Cambridge AN - OPUS4-28075 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Stephan, H. A1 - Kubeil, M. A1 - Emmerling, Franziska A1 - Müller, C.E. T1 - Polyoxometalates as versatile enzyme inhibitors N2 - Polyoxometalates (POMs) are inorganic cluster compounds that have been shown to possess a number of pharmacological properties, including antidiabetic, antibacterial, antiprotozoal, antiviral and anticancer activities. Their molecular mechanism of action is largely unknown. However, several studies indicate that many of their activities may be due to the inhibition of enzymes, in particular, of those enzymes that are accessible from the extracellular space and do not require the penetration of cell membranes. In this review, we describe the recent progress in the preparation and optimization of POMs, and an evaluation of their use as inhibitors of different families of enzymes. The next important steps in this area of research will be to gain a better understanding of the interactions of POMs with enzymes on a structural level through an X-ray crystallographic study of enzyme–POM complexes and the analysis of structure–activity relationships. Furthermore, POMs with increased stability and in vivo half-lives have to be prepared. Surface modification may allow the targeting of POM drugs at their sites of action. KW - Cluster compounds KW - Poly­oxometalates KW - Metalloprotein mimics KW - Enzymes KW - Inhibitors KW - Bioinorganic chemistry PY - 2013 DO - https://doi.org/10.1002/ejic.201201224 SN - 1434-1948 SN - 1099-0682 VL - 2013 IS - 10-11 SP - 1585 EP - 1594 PB - Wiley-VCH Verl. CY - Weinheim AN - OPUS4-28076 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Kubeil, M. A1 - Zarschler, K. A1 - Pietzsch, J. A1 - Kraus, Werner A1 - Comba, P. A1 - Stephan, H. T1 - Copper(II) cyclam complexes with N-propionic acid pendant arms N2 - 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 64Cu–TETA (TETA = 1,4,8,11-tetraazacyclotetradecane-1,4,8,11-tetraacetic acid). KW - Copper KW - Chelates KW - Macrocyclic ligands KW - Radiopharmaceuticals KW - Diagnostic and therapy KW - Copper complexes PY - 2015 DO - https://doi.org/10.1002/ejic.201500510 SN - 1434-1948 SN - 1099-0682 IS - 24 SP - 4013 EP - 4023 PB - Wiley-VCH Verl. CY - Weinheim AN - OPUS4-33993 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER -