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 - Kraus, Werner A1 - Walther, M. A1 - Jung, C. M. A1 - Emmerling, Franziska A1 - Pietzsch, H.-J. T1 - Bromotricarbonyl{15-[2-(methylsulfanyl)ethylsulfanyl]pentadecanoic acid-kappa2S,S'}rhenium(I) N2 - The title compound, [ReBr(C18H36O2S2)(CO)3], was synthesized and characterized as a non-radioactive surrogate of a novel Tc-containing fatty acid derivative prepared according to the tricarbonyl/dithioether design with the objective of developing new Tc-based radiopharmaceuticals for the non-invasive diagnosis of myocardial metabolism. The Re chelate contains the metal in the oxidation state +1 and is attached to the terminal position of a fatty acid. The complex formation was accomplished by a ligand exchange reaction using [NBu4]2[Re(CO)3Br3] as starting material. KW - Fatty acid KW - Tc-compound KW - Radio-pharmaceutical PY - 2006 DO - https://doi.org/10.1107/S1600536806024081 SN - 1600-5368 VL - 62 IS - 7 SP - m1660 EP - m1662 PB - Munksgaard CY - Copenhagen AN - OPUS4-12529 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Tisato, F. A1 - Refosco, F. A1 - Porchia, M. A1 - Bolzati, C. A1 - Bandoli, G. A1 - Dolmella, A. A1 - Duatti, A. A1 - Boschi, A. A1 - Jung, C. M. A1 - Pietzsch, H.-J. A1 - Kraus, Werner T1 - The Crucial Role of the Diphosphine Heteroatom X in the Stereochemistry and Stabilization of the Substitution-Inert [M(N)(PXP)]2+ Metal Fragments (M = Tc, Re; PXP = Diphosphine Ligand) N2 - The nature of the heteroatom X incorporated in the five-membered PXP-diphosphine bridging chain was found to play a primary unit role both in the overall stability and in the stereochemical arrangement of nitrido-containing [M(N)(PXP)]2+ metal fragments (M = Tc, Re). Thus, by mixing PXP ligands with labile [Re(N)Cl4]- and Tc(N)Cl2(PPh3)2 nitrido precursors in CH2Cl2/MeOH mixtures, a series of neutral M(N)Cl2(PXP) complexes (M = Tc, 1-5; M = Re, 8, 9) was collected. In the resulting distorted octahedrons, PXP adopted facial or meridional coordination, and combination with halide co-ligands produced three different stereochemical arrangements, that is, fac,cis, mer,cis, and mer,trans, depending primarily on the nature of the diphosphine heteroatom X. When X = NH, mer,cis-Tc(N)Cl2(PNP1), 1, was the only isomer formed. Alternatively, when a tertiary amine nitrogen (X = NR; R = CH3, CH2CH2OCH3) was introduced in the bridging chain, fac,cis-M(N)Cl2(PN(R)P) complexes (M = Tc, 2, 3; M = Re, 8f) were obtained. Isomerization into the mer,cis-Re(N)Cl2(PN(R)P), 8m, species was observed only in the case of rhenium when the tertiary amine group carried the less encumbering methyl substituent. fac,cis-Tc(N)Cl2(PSP), 4f, was isolated in the solid state when X = S, but a mixture of fac,cis-Tc(N)Cl2(PSP) and mer,trans-Tc(N)Cl2(PSP), 4m, isomers was found in equilibrium in the solution state. A similar equilibrium between fac,cis-M(N)Cl2(POP) (M = Tc, 5f; M = Re, 9f) and mer,trans-M(N)Cl2(POP) (M = Tc, 5m; M = Re, 9m) species was detected in POP-containing complexes. The molecular structure of all of these complexes was assessed by means of conventional physicochemical techniques including multinuclear NMR spectroscopy and X-ray diffraction analysis of representative mer,cis-Tc(N)Cl2(PN(H)P), 1, fac,cis-Tc(N)Cl2(PSP), 4f, and mer,cis-Re(N)Cl2(PN(Me)P), 8m, compounds. PY - 2004 DO - https://doi.org/10.1021/ic049139r SN - 0020-1669 SN - 1520-510X VL - 43 IS - 26 SP - 8617 EP - 8625 PB - American Chemical Society CY - Washington, DC AN - OPUS4-5546 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Walther, M. A1 - Jung, C. M. A1 - Bergmann, R. A1 - Pietzsch, J. A1 - Rode, K. A1 - Fahmy, K. A1 - Mirtschink, P. A1 - Stehr, S. A1 - Heintz, A. A1 - Wunderlich, G. A1 - Kraus, Werner A1 - Pietzsch, H.-J. A1 - Kropp, J. A1 - Deussen, A. A1 - Spies, H. T1 - Synthesis and Biological Evaluation of a New Type of 99mTechnetium-Labeled Fatty Acid for Myocardial Metabolism Imaging PY - 2007 SN - 1043-1802 SN - 1520-4812 VL - 18 SP - 216 EP - 230 CY - Washington, DC AN - OPUS4-14514 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Walther, M. A1 - Matterna, M. A1 - Juran, S. A1 - Fähnemann, S. A1 - Stephan, H. A1 - Kraus, Werner A1 - Emmerling, Franziska T1 - Imidazole-containing bispidine ligands: synthesis, structure and Cu(II) complexation N2 - The preparation and characterization of tris-pyridyl bispidine (3,7-diazabicyclo[3.3.1]nonane) derivatives with benzimidazole and imidazole donor groups at the N-3 position of the bispidine Skeleton and their copper(II) complexes are reported. The impact of the hetaryl substituents on the configurational isomerism of piperidones and their corresponding bispidones has been studied by NMR spectroscopy, revealing the exclusive appearance in the enol form for the piperidones in solution and the trans-configuration regarding the two pyridyl substituents, as well as the sole formation of the unsymmetric exo-endo isomers for the corresponding bispidones. Thus, the bispidones are preorganized ligands for building pentacoordinated complexes, confirmed by the preparation and characterization of the corresponding Cu(II) complexes. Of the di-pyridyl piperidones with benzimidazole and imidazole substituents, and of the Cu(II) complex of the benzimidazole-containing bispidone, Crystals have become available for the analysis by X-ray diffraction, showing that the piperidones form the enol tautomers also in the solid state. KW - Piperidone KW - Bispidine KW - Copper(II) KW - Configuration isomerism PY - 2011 SN - 0932-0776 SN - 0340-5087 SN - 0044-3174 VL - 66b SP - 721 EP - 728 PB - Verl. d. Zeitschrift für Naturforschung CY - Tübingen AN - OPUS4-24091 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Weber, K. A1 - Weber, M. A1 - Menneken, M. A1 - Kral, A. G. A1 - Mertz-Kraus, R. A1 - Geisler, T. A1 - Vogl, Jochen A1 - Tütken, T. T1 - Diagenetic stability of non-traditional stable isotope systems (Ca, Sr, Mg, Zn) in teeth – An in-vitro alteration experiment of biogenic apatite in isotopically enriched tracer solution N2 - Stable isotope ratios and trace element concentrations of fossil bones and teeth are important geochemical proxies for the reconstruction of diet and past environment in archaeology and palaeontology. However, since diagenesis can significantly alter primary diet-related isotope signatures and elemental compositions, it is important to understand and quantify alteration processes. Here, we present the results of in-vitro Alteration experiments of dental tissues from a modern African elephant molar reacted in aqueous solutions at 30 °C and 90 °C for 4 to 63 days. Dental cubes with ≈ 3 mm edge length, comprising both enamel and dentin, were placed into 2 mL of acidic aqueous solution enriched in different isotopes (25Mg, 44Ca, 67Zn, 86Sr, initial pH 1). Element and isotope distribution profiles across the reacted cubes were measured with LA-(MC-)ICP-MS and EMPA, while potential effects on the bioapatite crystal structure were characterised by Raman spectroscopy. In all experiments isotope ratios measured by LA-(MC-)ICP-MS revealed an alteration of the enamel in the outer ≈ 200–300 μm. In contrast, dentin was fully altered (≈ 1.4 mm) after one week at 90 °C while the alteration did not exceed a depth of 150–200 μm during the 30 °C experiments. Then, the tracer solution started also to penetrate through the enamel-dentin junction into the innermost enamel, however, leaving the central part of the enamel unaltered, even after three months. The Raman spectra suggest an initial demineralisation in the acidic environment while organic matter (i.e. collagen) is still preserved. In the 90 °C experiment, Raman spectra of the v1 PO4) band of the dentin shift over time towards synthetic hydroxylapatite patterns and the Ca (and Sr) concentrations in the respective solutions decrease. This indicates precipitation of newly formed apatite. Isotope and element concentration profiles across the dental tissues reveal different exchange mechanisms for different isotope systems. Magnesium is leached from enamel and dentin, while Zn is incorporated into the apatite crystal structure. However, the distribution of both elements is not affected in the innermost enamel where their concentrations do not change over the whole duration of the experiments. We found no correlation of reaction depth in the cubes and experimental duration, which might be caused by natural variability of the dental material already at the beginning of the experiment. Our alteration experiments in a closed system at high temperatures ≤90 °C and low initial pH demonstrate that at least the central part of mm-thick mammalian enamel apatite seems to be resistant against alteration preserving its pristine bioapatite mineral structure as well as its in-vivo elemental and isotopic composition. The experiments assess diagenetic alteration in a novel multi-proxy approach using in-situ analyses in high spatial resolution. It is demonstrated that the isotopes of Ca, Sr, Zn and Mg in the dentin are prone for diagenetic alteration, while enamel is more resistant against alteration and could be used for dietary and physiological reconstructions in fossil teeth. KW - Bioapatite KW - Isotopes KW - Raman spectroscopy KW - Diagenesis KW - LA-(MC-)ICP-MS KW - EPMA PY - 2021 DO - https://doi.org/10.1016/j.chemgeo.2021.120196 VL - 572 SP - 120196 PB - Elsevier B.V. CY - Amsterdam AN - OPUS4-52447 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Grote, M. A1 - Noll, S. A1 - Noll, B. A1 - Johannsen, B. A1 - Kraus, Werner T1 - Syntheses of novel modified acyclic purine and pyrimidine nucleosides as potential substrates of herpes simplex virus type-1 thymidine kinase for monitoring gene expression N2 - Suicide gene therapy with the herpes simplex virus type-1 thymidine kinase gene (HSV-1 tk) is considered to be a promising approach to the treatment of cancer. Making use of the lower specificity of the viral enzyme compared to human thymidine kinase, the therapy involves the administration of antiviral agents (e.g., ganciclovir) as prodrugs to induce enzymatic cell death in those cells that express the transferred gene. 18F-labelled derivatives have been described for monitoring location, duration, and magnitude of the viral kinase enzyme activity by positron emission tomography (PET). Since an optimal radiotracer has not been developed, novel substances were synthesized for monitoring gene expression. A group of 13 nucleoside analogues were synthesized, among them N1-methyl-9-[(1,3-dihydroxy-2-propoxy)methyl]guanine (5) and N1-methyl-9-[(4-hydroxy)-3-hydroxymethylbutyl]guanine (7) as methyl analogues of ganciclovir and penciclovir and their related fluoro compounds (6, 8). Further novel derivatives include N6-methyl-9-[(1,3-dihydroxy-2-propoxy)methyl]-, N6-methyl-9-[(4-hydroxy)-3-hydroxymethylbutyl]adenine (9, 10), as well as the uracil derivatives 5-hydroxy-1-[(1,3-dihydroxy-2-propoxy)methyl]uracil (11), 6-methyl-1-[(1,3-dihydroxy-2-propoxy)-methyl]uracil (12), and its 3-fluoro-derivative (13). KW - Fluorinated nucleoside analogues KW - Gene therapy KW - PET KW - Thymidine kinase PY - 2004 DO - https://doi.org/10.1139/v04-005 SN - 0008-4042 SN - 1480-3291 VL - 82 SP - 513 EP - 523 PB - National Research Council of Canada CY - Ottawa, Ont. AN - OPUS4-3490 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - GEN A1 - Jung, C. M. A1 - Heintz, A. A1 - Kraus, Werner A1 - Wunderlich, G. A1 - Leibnitz, Peter A1 - Pietzsch, H.-J. A1 - Kropp, J. A1 - Deussen, A. A1 - Spies, H. ED - Marino, N. T1 - Technetium- and Rhenium-Labelled Fatty Acids as Model Compounds for Myocardial Metabolism Imaging N2 - In an attempt to develop new technetium-based radiopharmaceuticals for the non-invasive diagnosis of oxidative myocardial metabolism, rhenium model compounds according to the ‚3+1' mixed ligand approach as well as the organometallic tricarbonyl-design were synthesized. The geometrical impact of different chelates on the integrity of the fatty acid head structure was determined by single crystal X-ray analyses. To evaluate the diagnostic potential of the analogous Technetium-99m compounds, fatty acid complexes of the ‚3+1' mixed ligand type were prepared on n.c.a.-level and studied in the isolated constant-flow-perfused guinea pig heart model; compared to established [123I]Iodine-labelled fatty acid radiotracers, the tested Technetium-99m derivatives showed a specific, however significantly lower myocardial extraction rate. T2 - 6th International Symposium on Technetium in Chemistry and Nuclear Medicine CY - Bressanone, Italy DA - 2002-09-04 KW - Fatty acids KW - Metabolism KW - Myocardial Imaging KW - Rhenium KW - Technetium-99m PY - 2002 UR - http://www.fzd.de/db/!Publications?pSelYear=2002&pLang=en&pNid=0&pSelWithSubmitted=0&pSelSort=TITEL&pSelPublForm=4&pSelPage=2 SN - 88-86281-73-0 N1 - Serientitel: Technetium, rhenium and other metals in chemistry and nuclear medicine – Series title: Technetium, rhenium and other metals in chemistry and nuclear medicine VL - 6 IS - 6 SP - 443 EP - 445 PB - SGEditoriali CY - Padova AN - OPUS4-1999 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Jung, C. M. A1 - Kraus, Werner A1 - Leibnitz, Peter A1 - Pietzsch, H.-J. A1 - Kropp, J. A1 - Spies, H. T1 - Synthesis and First Crystal Structure of Rhenium Complexes derived from omega-Functionalized Fatty Acids as Model Compounds of Technetium Tracers for Myocardial Metabolism Imaging N2 - In an attempt to develop new technetium-based radiopharmaceuticals for the noninvasive diagnosis of myocardial metabolism, we have synthesized three examples of novel metal-containing fatty acid derivatives according to the 3+1 mixed-ligand and the Schiff base/tricarbonyl design. The chelates contain the metal core in the oxidation states +5 and +1, respectively, and are attached to the end-position of a fatty acid chain. The complex formation was accomplished by ligand-exchange reactions with three different rhenium precursors, whereas the inactive rhenium metal was utilized as a surrogate of the technetium radionuclide. The molecular structures of the fatty acid complexes 7, 10 and 14 were determined by single-crystal X-ray diffraction analyses and impressively show a general problem in technetium tracer research, namely the significant structural alterations of bioactive molecules by coordination even to small metal chelates. KW - Rhenium KW - Technetium KW - Fatty acids KW - Drug research KW - Radiopharmaceuticals PY - 2002 DO - https://doi.org/10.1002/1099-0682(200205)2002:5<1219::AID-EJIC1219>3.0.CO;2-N SN - 1434-1948 SN - 1099-0682 VL - 2002 IS - 5 SP - 1219 EP - 1225 PB - Wiley-VCH Verl. CY - Weinheim AN - OPUS4-1552 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Heimbold, I. A1 - Drews, A. A1 - Kretzschmar, M. A1 - Varnäs, K. A1 - Hall, H. A1 - Halldin, C. A1 - Syhre, R. A1 - Kraus, Werner A1 - Pietzsch, H.-J. T1 - Synthesis, Biological and Autoradiographic Evaluation of a Novel Tc-99m Radioligand derived from WAY 100635 with High Affinity for the 5-HT1A Receptor and the alpha1-Adrenergic Receptor N2 - This paper reports the synthesis, biological evaluation, in vitro and ex vivo autoradiography of the first Tc-99m ligand with subnanomolar affinity for the 5-HT1A receptor and a remarkably high affinity for the alpha1-adrenergic receptor. The neutral “3+1” mixed-ligand complex combines 4-(6-mercaptohexyl)-1-(2-methoxyphenyl)piperazine as monodentate and 3-(N-methyl)azapentane-1,5-dithiol as tridentate unit with oxotechnetium(V). The analogous rhenium complex was synthesized for complete structural characterization and used in receptor binding assays. In competition experiments both complexes display subnanomolar affinity for the 5-HT1A receptor (IC500.24 nM for Re, 0.13 nM for Tc) but also very high affinities for the alpha1-adrenergic receptor (IC50 0.05 nM for Re, 0.03 nM for Tc). Biodistribution studies show a brain uptake in rat of 0.22% ID five minutes post injection. In vitro autoradiographic studies in rat brain and postmortem human brain indicate accumulation of the Tc-99m complex in brain areas which are rich in 5-HT1A receptors or in alpha1-adrenergic receptors. This in vitro enrichment can be blocked respectively by the 5-HT1A receptor agonist 8-OH-DPAT or by prazosin hydrochloride, an alpha1-adrenergic receptor antagonist. Ex vivo autoradiographic studies in rats show a slight accumulation of the Tc-99m complex in 5-HT1A receptor-rich areas of the brain, which could not be blocked, as well as in regions rich in alpha1-adrenergic receptors, which could be blocked by prazosin hydrochloride. KW - Serotonin-5-HT1A receptor KW - Tc-99m receptor ligand KW - WAY100635 analogue KW - Ligand synthesis KW - In vitro and ex vivo autoradiography KW - Receptor binding assay PY - 2002 DO - https://doi.org/10.1016/S0969-8051(01)00313-4 SN - 0883-2897 VL - 29 SP - 375 EP - 387 PB - Elsevier Science Inc. CY - New York, NY AN - OPUS4-1554 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER -