TY - JOUR A1 - Hoyer, Jan A1 - Schatzschneider, Ulrich A1 - Schulz-Siegmund, Michaela A1 - Neundorf, Ines T1 - Dimerization of a cell-penetrating peptide leads to enhanced cellular uptake and drug delivery JF - Beilstein Journal of Organic Chemistry N2 - Over the past 20 years, cell-penetrating peptides (CPPs) have gained tremendous interest due to their ability to deliver a variety of therapeutically active molecules that would otherwise be unable to cross the cellular membrane due to their size or hydrophilicity. Recently, we reported on the identification of a novel CPP, sC18, which is derived from the C-terminus of the 18 kDa cationic antimicrobial protein. Furthermore, we demonstrated successful application of sC18 for the delivery of functionalized cyclopentadienyl manganese tricarbonyl (cymantrene) complexes to tumor cell lines, inducing high cellular toxicity. In order to increase the potential of the organometallic complexes to kill tumor cells, we were looking for a way to enhance cellular uptake. Therefore, we designed a branched dimeric variant of sC18, (sC18)\(_2\), which was shown to have a dramatically improved capacity to internalize into various cell lines, even primary cells, using flow cytometry and fluorescence microscopy. Cell viability assays indicated increased cytotoxicity of the dimer presumably caused by membrane leakage; however, this effect turned out to be dependent on the specific cell type. Finally, we could show that conjugation of a functionalized cymantrene with (sC18)\(_2\) leads to significant reduction of its IC\(_{50}\) value in tumor cells compared to the respective sC18 conjugate, proving that dimerization is a useful method to increase the drug-delivery potential of a cell-penetrating peptide. KW - peptides KW - internalization studies KW - drug delivery KW - cell-penetrating peptides KW - anti-tumor agents KW - organometallic complexes Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-133933 VL - 8 ER - TY - JOUR A1 - Hartung, Andreas A1 - Seufert, Florian A1 - Berges, Carsten A1 - Gessner, Viktoria H. A1 - Holzgrabe, Ulrike T1 - One-Pot Ugi/Aza-Michael Synthesis of Highly Substituted 2,5-Diketopiperazines with Anti-Proliferative Properties JF - Molecules N2 - The well-known Ugi reaction of aldehydes with amines, carboxylic acids and isocyanides leads to the formation of acyclic alpha-acylaminocarboxamides. Replacement of the carboxylic acid derivatives with beta-acyl substituted acrylic acids gives access to highly substituted 2,5-diketopiperazines in one single reaction-step without additives or complex reaction procedures. The obtained diketopiperazines show anti-proliferative effects on activated T cells and represent therefore potential candidates for targeting unwanted T cell-mediated immune responses. KW - multicomponent Ugi-type reaction KW - intramolecular Michael addition KW - strategy KW - derivates KW - diketopiperazines KW - chemistry KW - T cell KW - 2,5-diketopiperazines KW - anti-proliferative effects Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-130423 VL - 17 IS - 12 ER - TY - JOUR A1 - Arnold, Nicole A1 - Braunschweig, Holger A1 - Damme, Alexander T1 - Bis(μ-diisopropyl-phosphanido-\(κ^2\)P:P)bis-[hydrido(triisopropyl-phosphane-κP)platinum(II)] JF - Acta crystallographica. Section E, Structure reports online N2 - In the centrosymmetric molecular structure of the title compound \([Pt_2(C_6H_{14}P)_2H_2)(C_9H_{21}P)_2]\), each \(Pt^{II}\) atom is bound on one side to a phosphane ligand \((PiPr_3)\) and a hydrido ligand. On the other side, it is bound to two phosphanide ligands \((μ-PiPr_2)\), which engage a bridging position between the two \(Pt^{II}\) atoms, forming a distorted square-planar structure motif. The PtPt distance is 3.6755(2)Å. A comparable molecular structure was observed for bis-(μ-di-tert-butyl-phosphanido)bis-[hydrido(triethyl-phosphane)platinum(II)] [Itazaki et al. (2004 ). Organometallics, 23, 1610-1621]. KW - data-to-parameter ratio = 22.3 KW - mean σ(C–C) = 0.004 Å KW - single-crystal X-ray study KW - T = 100 K KW - R factor = 0.018 KW - wR factor = 0.038 Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-123723 VL - E68 ER - TY - JOUR A1 - Gessner, Viktoria H. T1 - Diphenyl[2-(phenyl-sulfon-yl)propan-2-yl]-\(\lambda^5\)-phosphanethione JF - Acta crystallographica. Section E, Structure reports online N2 - The title compound, \(C_{21}H_{21}O_2PS_2\), was obtained from the corresponding dilithio methandiide by treatment with iodo-methane. The bond lengths and angles deviate considerably from those in the dimetallated compound. These differences are most pronounced in the PCS backbone. While the title compound features C-P and C-S distances of 1.9082(17) and 1.8348(17)Å, respectively, the dianion showed \(C-P_{av}\) distances shortened by 11% [1.710(4)Å] and C-S distances shortened by 12% [1.614(3)Å]. Additionally, the P-C-S angle experiences a contraction by methyl-ation of the dianion from 121.4(2) to 111.96(9)° in the title compound. KW - wR factor = 0.068 KW - mean σ(C–C) = 0.003 Å KW - T = 173 K KW - single-crystal X-ray study KW - R factor = 0.025 KW - data-to-parameter ratio = 14.6 Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-123635 VL - E68 IS - o1045 ER - TY - THES A1 - Hu, Wanning T1 - Organometal half-sandwich complexes and their bioconjugates: Biological activity on cancer cells and potential applications in biolabelling T1 - Organometall-Halbsandwich Komplexe und ihre Biokonjugate: Die biologischen Eigenschaften auf Krebszellen und die potenziellen Anwendungen in Biolabelling N2 - In summary, structure-activity relationships in peptide and dendrimer carriers modified with different organometal complexes were studied on a human breast cancer cell line. Variation of the organometal cargo and carrier can significantly influence their biological properties and might open the way to new approaches in chemotherapy. Furthermore, the incorporation of complexes with different C≡O vibrational signatures in a model peptide was explored to examine information encoding in biomolecules in a barcoding strategy for potential imaging applications. In particular for the latter, additional stable metal-carbonyl markers need to be prepared in future work to expand the pool of vibrational labels available. N2 - In der vorliegenden Arbeit konnten also Struktur-Wirkungs-Beziehungen für Organometall-Peptid- und Dendrimer-Konjugate mit unterschiedlichen funktionellen Gruppen an einer humanen Brustkrebs-Zelllinie untersucht werden. Die Variation der Organometall-Gruppen und des Trägermoleküls führen zu signifikanten Unterschieden in ihrer biologischen Aktivität. Zusätzlich wurden Modell-Peptide mit verschiedenen Metallcarbonyl-basierten IR-Markern versehen um diese in einer Barcoding-Strategie zu labeln. In Zukunft soll das Spektrum der verfügbaren, nicht-überlappenden Schwingungsmarker noch deutlich erweitert werden. KW - Konjugate KW - Sandwich-Verbindungen KW - Metallorganische Verbindungen KW - bioconjugate KW - CPP-peptide KW - dendrimer KW - biolabelling KW - organometal complexes KW - cymantrene KW - Biokonjugate KW - CPP Peptide KW - Dendrimer KW - Biolabelling KW - Organometall-Komplexe KW - Cymantren Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-87899 ER - TY - THES A1 - Würtemberger, Max T1 - Untersuchungen zur Synthese und Reaktivität NHC-substituierter Ruthenium- und Eisen-Komplexe T1 - Investigations of the synthesis and reactivity of NHC substituted ruthenium and iron complexes N2 - Diese Arbeit beschäftigt sich mit Untersuchungen zur Synthese und Reaktivität von Ruthenium(II)- und Eisen(II)-Komplexen welche durch Alkyl-subsituierte N-Heterozyklische-Carben Liganden stabilisiert werden. Ein besonderes Augenmerk liegt hierbei auf dem synthetischen Zugang von Rutheniumverbindungen jenseits der Metathese-Katalysatoren. N2 - This Work is concerned with the inverstigations of the synthesis and reactivity of ruthenium(II) and iron(II) complexes which are sabilised by alkyl-substituted N-heterocyclic carbenes ligands. Particular attention is paid to the synthetic approach towards ruthenium compounds beyond metathesis catalysts. KW - Rutheniumkomplexe KW - Eisenkomplexe KW - Heterocyclische Carbene <-N> KW - Carbenkomplexe KW - Ruthenium KW - Eisen KW - Carben-Komplexe KW - NHC-Komplexe KW - Ruthenium KW - Iron KW - carbene complexes KW - NHC complexes Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-72032 ER - TY - THES A1 - Rybak, Jens-Christoph T1 - Funktionale Koordinationspolymere und MOFs aus Reaktionen der Lanthanide und des Bariums mit Azol-Liganden – Synthese und Charakterisierung mit dem Fokus der Strukturbestimmung anhand von Röntgenpulverbeugungsdaten T1 - Functional Coordination Polymers and MOFs from Reactions of the Lanthanides and Barium with Azole Ligands – Synthesis and Characterization with a Focus on Structure Determination from X-ray Powder Diffraction Data N2 - Die hier vorliegende Arbeit behandelt die Darstellung und Charakterisierung von Koordinationspolymeren und MOFs der Lanthanide und des Bariums mit verschiedenen, azolischen, N-Heterozyklen. Es können insgesamt 18 neue organisch-anorganische Hybridmaterialien sowie eine Reihe von co-dotierten Verbindungen präsentiert werden. Neben der strukturellen Charakterisierung dieser Materialien anhand von Röntgenpulverbeugungsdaten steht die Betrachtung der thermischen und photolumineszenzspektroskopischen Eigenschaften im Fokus. Die Lanthanide von La bis Lu, mit den Ausnahmen Eu und Pm ergeben durch Reaktion mit 1H-1,2,3-Triazol die Reihe der isotypen dichten 3D-MOFs 3{infinite}[Ln(Tz*)3]. Die photolumineszenzspektroskopische Untersuchung dieser Verbindungen offenbart eine große Bandbreite verschiedener Lumineszenzphänomene inklusive eines so erstmals beobachteten intrinsischen inner-filter-Effektes der Ln3+-Ionen. Die Strukturen dieser isotypen Reihe von Verbindungen wurden anhand von Röntgenpulverbeugungsdaten gelöst und verfeinert. Ein 2D-Polymorph dieser Verbindungen, 2{infinite}[Ln(Tz*)3], wird für Ln = Sm, Tb beschrieben und anhand von Einkristallbeugungsdaten charakterisiert. Die Reaktion von Eu mit 1H-Benzotriazol ergibt das 1D-Koodinationspolymer 1{infinite}[Eu(Btz)2(BtzH)2], welches das erste Beispiel eines zweiwertigen Seltenerdbenzotriazolats darstellt. Die Analyse der thermischen Eigenschaften dieser Verbindung weist auf die Umwandlung in das 3D-MOF 3{infinite}[Eu(Btz)2] hin, dessen Struktur ebenfalls aus Röntgenpulverbeugungsdaten bestimmt wurde. Die Untersuchung der Photolumineszenzeigenschaften der Verbindungen der Mischkristallreihe 3{infinite}[Ba1-xEux(Im)2], welche aus Reaktionen der salzartigen Hydride BaH2 und EuH2 mit Imidazol dargestellt wurden, zeigen, dass die Synthese lumineszenter MOFs durch Co-Dotierung nicht lumineszenter Netzwerke mit geeigneten Lumineszenzzentren möglich ist. Die Struktur dieser Materialien wurde anhand der undotierten Verbindung 3{infinite}[BaEu(Im)2] aus Röntgenpulverbeugungsdaten bestimmt. Die strukturelle Charakterisierung von Materialien anhand von Röntgenpulverbeugungsdaten nimmt einen besonderen Stellenwert innerhalb dieser Arbeit an. Es wird ein Verfahren präsentiert, das über Indizierung des Diffraktogramms, Intensitätsextraktion und Strukturlösung über charge-flipping-Methoden eine Möglichkeit darstellt ab initio die Struktur eines unbekannten Materials ausschließlich anhand von Röntgenpulverbeugungsdaten zu bestimmten. Des Weiteren wird aufgezeigt, wie die Strukturen dieser Materialien, mit einem hohen Anteil schwach streuender Leichtatome, durch die Verwendung von rigid body constraints verfeinert werden können. Die Strukturlösungen von 3{infinite}[Ga(Tz)2], 3{infinite}[Sr(Im)2]:Ce und 3{infinite}[Yb(Im)3]ImH aus Röntgenpulverbeugungsdaten stellen weitere Beispiele für die erfolgreiche Anwendung der im Rahmen dieser Arbeit präsentierten Methode dar. N2 - This thesis deals with the synthesis and characterization of coordination polymers and MOFs of the lanthanides and barium with different azolic N-heterocycles. A total of 18 new organic-inorganic hybrid materials, as well as a series of co-doped compounds is presented. Besides the structural characterization of these materials from X-ray diffraction powder data, the focus of the investigations is on the thermal and photoluminescence spectroscopic properties. The lanthanides La – Lu, except Eu and Pm, can be reacted with 1H-1,2,3-triazole to give the series of the isotypic dense 3D-MOFs 3{infinite}[Ln(Tz*)3]. Investigation of the photoluminescence properties of these compounds reveals a broad range of different luminescence phenomena, including the first observation of an intrinsic inner-filter effect of the Ln3+-ions. The structure of this isotypic series of compounds was solved and refined from X-ray powder diffraction data. A 2D-polymorph of these compounds 2{infinite}[Ln(Tz*)3], is observed for Ln = Sm, Tb and was characterized by single crystal data. The reaction of Eu with 1H-benzotriazole yields the 1D-coordination polymer 1{infinite}[Eu(Btz)2(BtzH)2], which is the first example of a divalent rare earth benzotriazolate. Analysis of the thermal properties reveals the transformation to the 3D-MOF 3{infinite}[Eu(Btz)2] at higher temperatures. The structure of this material was also solved from X-ray powder diffraction data. Investigation of the photoluminescence properties of the co-doped compounds 3{infinite}[Ba1-xEux(Im)2], which were obtained from reaction of the salt-like hydrides BaH2 and EuH2 with imidazole, show that the synthesis of luminescent MOF materials by co-doping of non-luminescent networks with luminescence centers is possible. The structure of these materials was solved from X-ray powder diffraction data of the undoped compound 3{infinite}[BaEu(Im)2]. Structural characterization of materials from X-ray powder diffraction data is an important aspect of this thesis. A method is presented, which allows, by indexing a diffractogram, intensity extraction and structure solution by charge flipping, to solve the structure of a material, ab initio, from X-ray powder diffraction data exclusively. Moreover it is shown how to refine structures with a high amount of weakly scattering atoms, using rigid body constraints. The structure solutions of 3{infinite}[Ga(Tz)2], 3{infinite}[Sr(Im)2]:Ce and 3{infinite}[Yb(Im)3]ImH from X-ray powder diffraction data are further examples for the suc¬cessful application of the method presented within this thesis. KW - Lanthanoide KW - Metallorganisches Netzwerk KW - Barium KW - Pulvermethode KW - Azolate KW - Koordinationspolymere KW - Lanthanides KW - Azolates KW - Coordination Polymers KW - MOFs KW - X-Ray Powder Diffraction Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-77679 ER - TY - THES A1 - Beringer, Reiner Ernst T1 - Synthese von Dextran-umhüllten Eisenoxid-Nanopartikeln als Kontrastmittel für die MR-Tomographie T1 - Synthesis of dextran-coated iron oxide nanoparticles as contrast agent for MRI N2 - Durch Fällung von Eisen(II)- und Eisen(III)-salzen wurden Dextran-umhüllte Eisenoxid-Nanopartikel (SPIOs) und durch anschließende Umsetzung mit Epichlorhydrin und Ammoniak CLIOs gewonnen. An diesen Kolloiden wurden niedermolekulare Moleküle wie Diamine oder Bernsteinsäureanhydrid als Linker angebracht. Ein weiterer Aspekt dieser Arbeit stellt die Anbindung von Fluoreszenzmarkern und Antikörpern an der Partikeloberfläche sowie deren spektroskopische Untersuchung dar. N2 - By precipitation of iron (II) - and iron (III) salts dextran-coated iron oxide were nanoparticles (SPIOs) synthesized and CLIOs were generated by reaction with epichlorohydrin and ammonia. At these colloids low molecular weight molecules such as diamines or succinic anhydride were placed as a linker. Another aspect of this work is the integration of fluorescent markers and antibodies on the particle surface and spectroscopic investigation of these colloids. KW - Eisenoxide KW - Magnetische Resonanz KW - NMR-Tomographie KW - Nanopartikel KW - Dextrane KW - Kontrastmittel KW - Eisenoxid-Nanopartikel KW - SPIO KW - CLIO KW - Kontrastmittel KW - iron oxide nanoparticles KW - MR contrast agent KW - SPIO KW - CLIO Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-77218 ER - TY - JOUR A1 - Finze, Maik A1 - Reiss, Guido J. A1 - Frohn, Hermann-Josef T1 - 2,3,5,6-Tetrafluoro-1,4-bis(trimethylsilyl)benzene N2 - no abstract available KW - Chemie KW - single-crystal X-ray study KW - T = 199 K KW - R factor = 0.027 KW - wR factor = 0.068 KW - data-to-parameter ratio = 14.0. Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-75401 ER - TY - JOUR A1 - Finze, Maik A1 - Reiss, Guido J. T1 - Trimethyl­sulfonium 1-amino-6-fluoro-2,3,4,5,7,8,9,10,11,12-decaiodo-1-carba-closo-dodeca­borate N2 - no abstract available KW - Chemie KW - single-crystal X-ray study KW - T = 100 K KW - wR factor = 0.052 KW - data-to-parameter ratio = 20.8 Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-75397 ER -