Photo- and redox-active supramolecular systems containing metal complexes

The aim of this Ph.D. project has been the photophysical and photochemical characterization of new photo- and redox-active supramolecular systems. In particular we studied two different classes of compounds: metal complexes and dendrimers. Two different families of bis-cyclometalated neutral Ir(III) complexes are presented and their photophysical properties are discussed. The first family of complexes contains two 2-phenylpyridyl (ppy) or 2-(4,6-difluorophenyl)pyridyl (F2ppy) cyclometalated ligands and an ancillary ligand constituted by a phenol-oxazoline (phox), which can be substituted in the third position with a fluorine group (Fphox). In the second part of this study, we present another family of bis-cyclometalated Ir(III) complexes in which the ancillary ligand could be a chiral or an achiral bis-oxazoline (box). We report on their structural, electrochemical, photophysical, and photochemical properties. Complexes containing phox and Fphox ancillary ligands show blue luminescence with very high quantum yield, while complexes with box ligands do not show particularly interesting photophysical properties. Surprisingly these complexes give an unexpected photoreaction when irradiated with UV light in presence of dioxygen. This photoreaction originates a stable, strong blue emitting and particularly interesting photoproduct. Three successive generations of a family of polyethyleneglycol (PEG)-coated Pd(II) tetrabenzoporphyrin (PdTBP)-based dendritic nanoprobes are presented, and their ability to sensitize singlet oxygen and inflict cellular photodamage are discussed. It was found that the size of the dendrimer has practically no effect on the singlet oxygen sensitization efficiency, that approximate the unity, in spite of the strong attenuation of the triplet quenching rate with an increase in the dendrimer generation. Nevertheless, when compared against a commonly used singlet oxygen sensitizer, as Photofrin, the phosphorescent probes were found to be non-phototoxic. The lack of phototoxicity is presumably due to the inability of PEGylated probes to associate with cell surfaces and/or penetrate cellular membranes. The results suggest that protected phosphorescent probes can be safely used for oxygen measurements in biological systems in vivo. A new family of two photoswitchable (G0(Azo) and G1(Azo)) dendrimers with an azobenzene core, two cyclam units as coordination sites for metal ions, and luminescent naphthalene units at the periphery have been characterized and their coordination abilities have been studied. Because of their proximity, the various functional groups of the dendrimer may interact, so that the properties of the dendrimers are different from those exhibited by the separated functional units. Both the naphthalene fluorescence and the azobenzene photoisomerization can be observed in the dendrimer, but it has been shown that (i) the fluorescent excited state of the naphthalene units is substantially quenched by excimer and exciplex formation and by energy transfer to the azobenzene units, and (ii) in the latter case the fluorescence quenching is accompanied by the photosensitized isomerization of the trans → cis, and, with higher efficiency, the cis → trans reaction. Complexation of these dendrimers, both trans and cis isomers, with Zn(II) ions shows that complexes of 1:1 and 2:1 metal per dendrimer stoichiometry are formed showing different photophysical and photochemical properties compared to the corresponding free ligands. Practically unitary efficiency of the sensitized isomerization of trans → cis and cis → trans reaction is observed, as well as a slight increase in the naphthalene monomer emission. These results are consistent with the coordination of the cyclam amine units with Zn(II), which prevents exciplex formation. No indication of a concomitant coordination of both cyclam to a single metal ion has been obtained both for trans and cis isomer.

Synthesis and characterization of metal-chalcogenide MQ 2-Nanoparticles (M = Mo, W, Zr; Q = S, O)

Here, we present the adaptation and optimization of (i) the solvothermal and (ii) the metal-organic chemical vapor deposition (MOCVD) approach as simple methods for the high-yield synthesis of MQ2 (M=Mo, W, Zr; Q = O, S) nanoparticles. Extensive characterization was carried out using X-ray diffraction (XRD), scanning and transmission electron micros¬copy (SEM/TEM) combined with energy dispersive X-ray analysis (EDXA), Raman spectroscopy, thermal analyses (DTA/TG), small angle X-ray scattering (SAXS) and BET measurements. After a general introduction to the state of the art, a simple route to nanostructured MoS2 based on the decomposition of the cluster-based precursor (NH4)2Mo3S13∙xH2O under solvothermal conditions (toluene, 653 K) is presented. Solvothermal decomposition results in nanostructured material that is distinct from the material obtained by decomposition of the same precursor in sealed quartz tubes at the same temperature. When carried out in the presence of the surfactant cetyltrimethyl¬ammonium bromide (CTAB), the decomposition product exhibits highly disordered MoS2 lamellae with high surface areas. The synthesis of WS2 onion-like nanoparticles by means of a single-step MOCVD process is discussed. Furthermore, the results of the successful transfer of the two-step MO¬CVD based synthesis of MoQ2 nanoparticles (Q = S, Se), comprising the formation of amorphous precursor particles and followed by the formation of fullerene-like particles in a subsequent annealing step to the W-S system, are presented. Based on a study of the temperature dependence of the reactions a set of conditions for the formation of onion-like structures in a one-step reaction could be derived. The MOCVD approach allows a selective synthesis of open and filled fullerene-like chalcogenide nanoparticles. An in situ heating stage transmission electron microscopy (TEM) study was employed to comparatively investigate the growth mechanism of MoS2 and WS2 nanoparticles obtained from MOCVD upon annealing. Round, mainly amorphous particles in the pristine sample trans¬form to hollow onion-like particles upon annealing. A significant difference between both compounds could be demonstrated in their crystallization conduct. Finally, the results of the in situ hea¬ting experiments are compared to those obtained from an ex situ annealing process under Ar. Eventually, a low temperature synthesis of monodisperse ZrO2 nanoparticles with diameters of ~ 8 nm is introduced. Whereas the solvent could be omitted, the synthesis in an autoclave is crucial for gaining nano-sized (n) ZrO2 by thermal decomposition of Zr(C2O4)2. The n-ZrO2 particles exhibits high specific surface areas (up to 385 m2/g) which make them promising candidates as catalysts and catalyst supports. Co-existence of m- and t-ZrO2 nano-particles of 6-9 nm in diameter, i.e. above the critical particle size of 6 nm, demonstrates that the particle size is not the only factor for stabilization of the t-ZrO2 modification at room temperature. In conclusion, synthesis within an autoclave (with and without solvent) and the MOCVD process could be successfully adapted to the synthesis of MoS2, WS2 and ZrO2 nanoparticles. A comparative in situ heating stage TEM study elucidated the growth mechanism of MoS2 and WS2 fullerene-like particles. As the general processes are similar, a transfer of this synthesis approach to other layered transition metal chalcogenide systems is to be expected. Application of the obtained nanomaterials as lubricants (MoS2, WS2) or as dental filling materials (ZrO2) is currently under investigation.

Effects of metal-induced oxidative stress on endothelial cells in vitro

Aseptic loosening of metal implants is mainly attributed to the formation of metal degradation products. These include particulate debris and corrosion products, such as metal ions (anodic half-reaction) and ROS (cathodic half-reaction). While numerous clinical studies describe various adverse effects of metal degradation products, detailed knowledge of metal-induced cellular reactions, which might be important for possible therapeutic intervention, is not comprehensive. Since endothelial cells are involved in inflammation and angiogenesis, two processes which are critical for wound healing and integration of metal implants, the effects of different metal alloys and their degradation products on these cells were investigated. Endothelial cells on Ti6Al4V alloy showed signs of oxidative stress, which was similar to the response of endothelial cells to cathodic partial reaction of corrosion induced directly on Ti6Al4V surfaces. Furthermore, oxidative stress on Ti6Al4V alloy reduced the pro-inflammatory stimulation of endothelial cells by TNF-α and LPS. Oxidative stress and other stress-related responses were observed in endothelial cells in contact with Co28Cr6Mo alloy. Importantly, these features could be reduced by coating Co28Cr6Mo with a TiO2 layer, thus favouring the use of such surface modification in the development of medical devices for orthopaedic surgery. The reaction of endothelial cells to Co28Cr6Mo alloy was partially similar to the effects exerted by Co2+, which is known to be released from metal implants. Co2+ also induced ROS formation and DNA damage in endothelial cells. This correlated with p53 and p21 up-regulation, indicating the possibility of cell cycle arrest. Since CoCl2 is used as an hypoxia-mimicking agent, HIF-1α-dependence of cellular responses to Co2+ was studied in comparison to anoxia-induced effects. Although important HIF-1α-dependent genes were identified, a more detailed analysis of microarray data will be required to provide additional information about the mechanisms of Co2+ action. All these reactions of endothelial cells to metal degradation products might play their role in the complex processes taking place in the body following metal device implantation. In the worst case this can lead to aseptic loosening of the implant and requirement for revision surgery. Knowledge of molecular mechanisms of metal-induced responses will hopefully provide the possibility to interfere with undesirable processes at the implant/tissue interface, thus extending the life-time of the implant and the overall success of metal implant applications.

Using sulfur isotope fractionation to understand the atmospheric oxidation of SO 2

Sulfate aerosol plays an important but uncertain role in cloud formation and radiative forcing of the climate, and is also important for acid deposition and human health. The oxidation of SO2 to sulfate is a key reaction in determining the impact of sulfate in the environment through its effect on aerosol size distribution and composition. This thesis presents a laboratory investigation of sulfur isotope fractionation during SO2 oxidation by the most important gas-phase and heterogeneous pathways occurring in the atmosphere. The fractionation factors are then used to examine the role of sulfate formation in cloud processing of aerosol particles during the HCCT campaign in Thuringia, central Germany. The fractionation factor for the oxidation of SO2 by ·OH radicals was measured by reacting SO2 gas, with a known initial isotopic composition, with ·OH radicals generated from the photolysis of water at -25, 0, 19 and 40°C (Chapter 2). The product sulfate and the residual SO2 were collected as BaSO4 and the sulfur isotopic compositions measured with the Cameca NanoSIMS 50. The measured fractionation factor for 34S/32S during gas phase oxidation is αOH = (1.0089 ± 0.0007) − ((4 ± 5) × 10−5 )T (°C). Fractionation during oxidation by major aqueous pathways was measured by bubbling the SO2 gas through a solution of H2 O2

HCl gas gettering of 3d transition metals for crystalline silicon solar cell concepts

In order to reduce the costs of crystalline silicon solar cells, low-cost silicon materials like upgraded metallurgical grade (UMG) silicon are investigated for the application in the photovoltaic (PV) industry. Conventional high-purity silicon is made by cost-intensive methods, based on the so-called Siemens process, which uses the reaction to form chlorosilanes and subsequent several distillation steps before the deposition of high-purity silicon on slim high-purity silicon rods. UMG silicon in contrast is gained from metallurgical silicon by a rather inexpensive physicochemical purification (e.g., acid leaching and/or segregation). However, this type of silicon usually contains much higher concentrations of impurities, especially 3d transition metals like Ti, Fe, and Cu. These metals are extremely detrimental in the electrically active part of silicon solar cells, as they form recombination centers for charge carriers in the silicon band gap. This is why simple purification techniques like gettering, which can be applied between or during solar cell process steps, will play an important role for such low-cost silicon materials. Gettering in general describes a process, whereby impurities are moved to a place or turned into a state, where they are less detrimental to the solar cell. Hydrogen chloride (HCl) gas gettering in particular is a promising simple and cheap gettering technique, which is based on the reaction of HCl gas with transition metals to form volatile metal chloride species at high temperatures.rnThe aim of this thesis was to find the optimum process parameters for HCl gas gettering of 3d transition metals in low-cost silicon to improve the cell efficiency of solar cells for two different cell concepts, the standard wafer cell concept and the epitaxial wafer equivalent (EpiWE) cell concept. Whereas the former is based on a wafer which is the electrically active part of the solar cell, the latter uses an electrically inactive low-cost silicon substrate with an active layer of epitaxially grown silicon on top. Low-cost silicon materials with different impurity grades were used for HCl gas gettering experiments with the variation of process parameters like the temperature, the gettering time, and the HCl gas concentration. Subsequently, the multicrystalline silicon neighboring wafers with and without gettering were compared by element analysis techniques like neutron activation analysis (NAA). It was demonstrated that HCl gas gettering is an effective purification technique for silicon wafers, which is able to reduce some 3d transition metal concentrations by over 90%. Solar cells were processed for both concepts which could demonstrate a significant increase of the solar cell efficiency by HCl gas gettering. The efficiency of EpiWE cells could be increased by HCl gas gettering by approximately 25% relative to cells without gettering. First process simulations were performed based on a simple model for HCl gas gettering processes, which could be used to make qualitative predictions.

Reaktion von Übergangsmetallhydrid-Komplexen mit Tetrylenen und Ein-Elektronen-Reduktion von Halogentetranen

Das Stannylen SnHyp2 (Hyp = Si(SiMe3)3) reagiert mit den Übergangsmetallhydrid-Komplexen Cp2MH2 (Cp = C5H5, M = Mo, W) in einer alpha-Additionsreaktion zu Cp2MSn(H)Hyp2. Ferner bilden sich unter Abspaltung von HSi(SiMe3)3 auch vierkernige Verbindungen der Form [Cp2MSn(H)Hyp]2, welche für M = Mo röntgendiffraktometrisch nachgewiesen wurden. Erhöht man den sterischen Anspruch der Silylreste des Stannylens, so nimmt die Tendenz der Adduktbildung ab, so dass nur die vierkernigen Komplexe nachweisbar sind. Im Fall für SnSit2 (Sit = Si(SiMe3)2SiMe2tBu) konnten sogar Stereoisomere der vierkernigen Verbindungen [Cp2MoSn(H)Sit]2 nachgewiesen werden. Im Gegensatz dazu reagiert das Plumbylen PbHyp2 mit Cp2MoH2 in einer Substitutionsreaktion zu dem nachgewiesenen Cp2Mo(H)Hyp. Bei größer werdendem Silylrest werden andere Reaktionsabläufe bevorzugt. Auf dem Forschungsgebiet der Ein-Elektronen-Reduktion von Halogenstannanen und -plumbanen XER2R´ (X = Halogen; E = Sn, Pb; R = Silylrest; R = Aryl- / Alkylrest) mit dem 19-Elektronen-Komplex Decamethylcobaltocen CoCp*2 (Cp* = C5Me5) konnten Unterschiede zwischen den Verbindungen des Zinns und des Bleis festgestellt werden: Bei der Reduktion von Halogenstannanen fallen die erwarteten Decamethylcobaltocenium-Halogenide [CoCp*2]X aus und ESR-Messungen bestätigen die Anwesenheit von Stannylradikalen, während bei der Reduktion von hypersilylierten Halogenplumbanen unterschiedliche Folgeprodukte entstehen und Plumbylradikale via ESR-Spektroskopie nicht feststellbar sind. Bei alkylhaltigen Halogenplumbanen XPbHyp2R (R = Alkyl) findet eine Spaltung der Pb-C-Bindung statt und es bilden sich Plumbate der Form [CoCp*2][PbHyp2X], während die Reduktion von einem arylhaltigen Halogenplumban IPbHyp2Ph (Ph = Phenyl) das erwartete Decamethylcobaltocenium-Salze ergibt.

Methodenentwicklung zur Charakterisierung von metallischen Nanopartikeln und deren potentieller Einsatz bei der Analyse von Biomolekülen mittels ICP-MS Kopplungstechniken

Die qualitative und quantitative Analyse von Biomolekülen hat in den letzten Jahren und Jahrzehnten immer mehr an Bedeutung gewonnen. Durch das Aufkommen und die kontinuierliche Weiterentwicklung neuer Separations- und Detektionsmethoden und deren Verbindung miteinander zu leistungsfähigen Einheiten, erlangte man Schritt für Schritt neue Erkenntnisse bei ihrer Untersuchung. Die Elementmassenspektrometrie als nachweisstarke Detektionsmethode wird von vielen wissenschaftlichen Arbeitsgruppen bei der Trennung und Quantifizierung von Proteinen und Metalloproteinen mittels Detektion der in den Biomolekülen vorkommenden Metalle und Heteroatome angewendet. Heteroatome (z.B. Schwefel, Phosphor) haben im Plasma des ICP-MS (inductively coupled plasma - mass spectrometer) schlechte Ionisationseigenschaften und dementsprechend deutlich höhere Nachweisgrenzen als Metalle. Ein Ansatz, schlecht oder nicht detektierbare Verbindungen (also solche, die keine Metalle oder Heteroatome enthalten) mit dem ICP-MS sichtbar zu machen, ist die Markierung der selbigen mit Metallionen oder -cluster. rnIn dieser Arbeit ist es gelungen, der Analyse ganz unterschiedlicher Substanzklassen, zum einen metallische Nanopartikel und zum anderen Proteine, neue Impulse zu geben und zukünftiges Potential bei der Anwendung gekoppelter Techniken zur Separation und Detektion aufzuzeigen. Durch die Verwendung einer alten, aber neu konzipierten Trenntechnik, der Gelelektrophorese (GE), und deren Kopplung an einen modernen Detektor, dem ICP-MS, kann die für die Proteinanalytik weit verbreitete Gelelektrophorese ihr enormes Potential bei der Trennung verschiedenster Verbindungsklassen mit der exzellenten Nachweisstärke und Elementspezifität des ICP-MS verbinden und dadurch mit deutlich weniger Arbeitsaufwand als bisher qualitative und auch quantitative Ergebnisse produzieren. Bisher war dies nur mit großem präparativem Aufwand unter Verwendung der laser ablation möglich. Bei der Analyse von Nanopartikeln konnte aufgezeigt werden, dass durch die GE-ICP-MS-Kopplung aufgrund der guten Trenneigenschaften der GE vorhandene Spezies bzw. Fraktionen voneinander separiert werden und mit Hilfe des ICP-MS Informationen auf atomarem Niveau gewonnen werden können. Es war möglich, das atomare Verhältnis der Metallatome im Kern und der Schwefelatome in der Ligandenhülle eines Nanopartikels zu bestimmen und damit die Größe des Partikels abzuschätzen. Auch konnte die Anzahl der Goldatome in einem dem Schmid-Cluster ähnlichen Nanopartikel bestimmt werden, was vorher nur mit Hilfe von MALDI-TOF möglich war. Bei der Analyse von Biomolekülen konnte auf einfache Weise der Phosphorylierungsgrad verschiedener Proteine bestimmt werden. Auch bei kleinen Molekülen erzielt die Gelelektrophorese ausgezeichnete Trennergebnisse, wie z. B. bei der Analyse verschiedener Brom- und Iodspezies.rnDie stöchiometrische Kopplung eines Proteins an einen Nanopartikel, ohne eine der beiden Verbindungen in einem größeren Maße zu verändern, stellte jedoch eine Herausforderung dar, die im Rahmen dieser Arbeit nicht vollständig gelöst werden konnte. Verschiedene Ansätze zur Kopplung der beiden Substanzen wurden erprobt, jedoch führte keine zu dem gewünschten Ergebnis einer stöchiometrisch vollständigen und spezifischen Modifikation eines Proteins mit einem Nanopartikel. Durch das Potential der GE-ICP-MS-Kopplung bei der Analyse beider Substanz-klassen und dem Beweis der Praktikabilität und Zuverlässigkeit der Methode ist jedoch der Grundstein für weitere Forschungen auf diesem Gebiet gelegt worden. Ist eine geeignete chemische Kopplung der beiden Substanzklassen gefunden und beherrscht, steht auf analytischer Seite eine leistungsstarke Kombination aus Trennung und Detektion zur Verfügung, um die Quantifizierung von Proteinen entscheidend zu verbessern.rn

Modellkomplexe zur Sauerstoffaktivierung auf Basis des 1,3,4-Thiadiazols

Das Ziel der vorliegenden Arbeit waren die Synthese und Untersuchung von Modellverbindungen zur Sauerstoffaktivierung auf der Basis neuer Ligandensysteme des 1,3,4-Thiadiazols unter Ausarbeitung einer Synthesestrategie zur Derivatisierung der heteroaromatischen 1,3,4-Thiadiazol-Liganden, deren Koordinationsverhalten in Abhängigkeit ihres 2,5-Substitutionsmusters untersucht wurde, sowie die fortführende Bearbeitung bereits bekannter Ligandensysteme zur Erzeugung von homo- und heterovalenten Übergangsmetallkomplexverbindungen.rnDie unter der Verwendung der modifizierten Liganden TPDE, H1TPDP und H1BPMP resultierenden dinuklearen Komplexverbindungen zeigen unterschiedlich starke antiferromagnetische Wechselwirkungen in Abhängigkeit der vorhandenen Brückenliganden. In der Verbindung [Fe6O2(OH)(L´)2(OOCMe3)9(OEt)2] trat eine Fragmentierung des Liganden H1TPDP auf. Das cisoide Ligandensubstitutionsmuster der entstandenen sechskernigen Verbindung ist verantwortlich für die interessanten magnetischen Eigenschaften des Komplexes. rnNeue Perspektiven zur Erzeugung von Modellverbindungen zur Sauerstoffaktivierung wurden mit dem Mono-Chelatliganden H1ETHP und den Bis-Chelatliganden HL2H, H2L2H und H2BATP aufgezeigt. Die Umsetzung von H1ETHP mit verschiedenen Übergangsmetallsalzen resultierte für die Metalle Cr(III), Fe(III), Co(III) und Ni(II) in mononuklearen Verbindungen des Typs [M(ETHP)2]X (X = ClO4, FeCl4, OMe, Cl, Br) sowie in zwei tetranuklearen Verbindungen mit Mn(II) und Cu(II). [Mn4(ETHP)6] besitzt ein propellerförmiges, planares [Mn4O6]2+-System mit einen Spingrundzustand von S = 5. In allen Verbindungen von H1ETHP konnte eine mono-κN-Koordination des 1,3,4-Thiadiazol-Rückgrates über eines seiner beiden endozyklischen Stickstoffdonoratome beobachtet werden. rnAus Umsetzungen der Bis-Chelatliganden wurden fast ausschließlich polynukleare Übergangsmetallkomplexe erhalten. Insbesondere der Ligand H2L2H zeigt eine ausgeprägte Tendenz zur Ausbildung trinuklearer, linearer Komplexe, welche auf Grund ihrer ungeraden Anzahl von Übergangsmetallionen einen Spingrundzustand S ≠ 0 aufweisen.rn Die mit dem Liganden HL2H erhaltenen Verbindungen unterstreichen die hohe Flexibilität dieser Systeme hinsichtlich der Erzeugung polynuklearer und heterovalenter Komplexverbindungen. So konnten in Abhängigkeit vom verwendeten Übergangsmetallsalz trinukleare, pentanukleare, aber auch hepta- und oktanukleare Verbindungen synthetisiert werden. Insbesondere die Komplexe des Mangans und des Cobalts zeigen ein heterovalentes [MnIIMnIII4]- bzw. [CoII2CoIII3]-Motiv, was sich in Spingrundzuständen von S ≠ 0 äußert. Der diamagnetische, achtkernige Fe8-Cluster besitzt eine pseudo C3-symmetrische Anordnung der Metall-Zentren, während für die heptanukleare Cu7-Kette durch ihre stark unterschiedlichen Kupfer-Koordinationsgeometrien interessante magnetische Austauschwechselwirkungen beobachtet werden konnten. Der dreikernige µ3-oxo-verbrückte Komplex des Liganden H2BATP zeigt als interessante strukturelle Eigenschaft ein ein µ3-Verbrückungsmuster des eingesetzten Sulfat-Anions. rnIn allen Komplexen der Bis-Chelatliganden HL2H, H2L2H und H2BATP konnte ein µ2-κN,κN-Koordiantionsmodus des 1,3,4-Thiadiazols und somit eine Abhängigkeit der Verbrückung vom Ligandensubstitutionsmuster beobachtet werden.rn

Modellkomplexe oligonuklearer Metalloproteine auf Basis von Salen-Liganden und Spin-Crossover-Verbindungen als Chemosensoren

Der erste Teil der hier vorgestellten Arbeit verfolgt die Synthese potentieller Modellverbindungen oligonuklearer Metalloproteine auf Basis von Salen-Liganden. Dazu wurden zwei Ligandensysteme mit unterschiedlich raumerfüllenden Alkyl-Substituenten modifiziert und auf ihre koordinativen Eigenschaften hin untersucht. Für das Ligandensystem auf Basis des Bis-(salicylidenamino)-propan-2-ols konnten fünf Derivate (H3L1, H3L2A,H3L2B, H3L3, H3L4), für das zweite verwendete Ligandensystem auf Basis des 1H-3,5-Bis-(salicylidenaminomethyl)-pyrazols konnten zwei weitere Derivate (H3L5A, H3L5B) dargestellt und zu Koordinationsverbindungen umgesetzt werden.rnFür den hier verwendeten Bis-(salicylidenamino)-propan-2-ol Liganden H3L1, welcher die geringsten sterischen Anforderungen stellt, konnten mono-, tri- und tetranukleare Koordinationsverbindungen synthetisiert werden. Dabei gelingt es dem Liganden, sich sowohl in planarer als auch in unterschiedlich stark gewinkelter Konformation um ein oder mehrere Metallzentren anzuordnen, wobei der Ligand ein N2O2- seines N2O3-Donorsets zur Koordination nutzt. Die Verbindung {[Ni7(HL1)2(L1)2(OBz)4(OMe)(H2O)]}n zeigt, dass eine Verkettung der so gestalteten dreikernigen Einheiten über das freie Propanol-Sauerstoffatomdes Ligandenrückgrats möglich ist. Mit zunehmendem sterischen Anspruch der angefügten Alkylsubstituenten nimmt die geometrische Flexibilität und somit das Potential des Liganden zur Ausbildung höhernuklearer Strukturen ab. So ist für Liganden mit mittlerem sterischen Anspruch neben mononuklearen Komplexen noch die Gestaltung dinuklearer Systeme möglich. Erhöht man den sterischen Anspruch des Liganden weiter, findet nur noch eine Reaktion zu mononuklearen Verbindungen statt.rnMit den Pyrazol-basierten Ligandensystemen H3L5A und H3L5B konnten dinukleare Kupfer- und Nickelverbindungen synthetisiert werden.rnDer zweite Teil dieser Arbeit befasst sich mit der Gestaltung von Spin-Crossover Systemen (SCO). Dazu soll ein Spinübergang innerhalb des gestalteten schaltbaren Systems an die Anwesenheit eines Signalstoffs gekoppelt werden, so dass diese SCO-Verbindung als Sensor für den Signalstoff eingesetzt werden kann. Dazu wurden zwei unterschiedliche Ansätze entwickelt und untersucht.rnDie erste Methode beruht auf der Kombination eines zum Spin-Crossover befähigten Metallzentrums, eines Capping-Liganden, eines zur Signalstofferkennung funktionalisierten Co-Liganden sowie eines entsprechenden Signalstoffs. Als Capping-Liganden wurden tetra- und pentadentateLigandensysteme eingesetzt und mit unterschiedlich Picolyl-substituierten Monoaza-[12]-krone-4-Derivaten umgesetzt, wobei die Monoazakrone zur Komplexierung des Signalstoffs,hier in Form eines Alkalimetallions, zur Verfügung steht. Nach dieser ersten Methode konnten im Zeitraum dieser Arbeit noch keine zufriedenstellenden Ergebnisse erzielt werden.rnEine vielversprechende zweite Möglichkeit beruht auf der Verwendung eines mehrzähnigen, etablierten Spin-Crossover Liganden,welcher in seiner Peripherie mit einer Bindungstasche zur Aufnahme des Signalstoffmodifiziert wird.Mit Hilfe des so gestalteten Liganden 4'-(4'''-Benzo-[15]-krone-5)-methyloxy-2,2':6',2''-terpyridin ([b15c5]-tpy) gelang die Umsetzung zu entsprechenden Eisen(II)- und Kobalt(II)komplexen der Zusammensetzung [M([b15c5]-tpy)2]2+. Alle synthetisierten Eisen(II)-Komplexe liegen aufgrund der hohen Ligandenfeldstärke des Terpyridins über einen Temperaturbereich von 300 – 400 K in ihrer diamagnetischen Low Spin Form vor. Die entsprechenden Kobalt(II)-Komplexe zeigen über einen Temperaturbereich von 2 – 350 K ein kontinuierliches, aber unvollständiges Spin-Crossover Verhalten.rnDer Einfluss von Signalstoffen auf das Spin-Crossover Verhalten der Kobalt(II)-Systeme wurde in einem ersten Versuch unter der Verwendung von Natriumionen als Signalstoff untersucht. Dabei stellte sich heraus, dass Natriumionen für dieses System zwar nicht als Auslöser eines SCO verwendet werden können, sie aber dennoch eine starke Auswirkung auf den Verlauf des Spin-Crossovers haben.

Heavy metal cations permeate the TRPV6 epithelial cation channel

TRPV6 belongs to the vanilloid family of the transient receptor potential channel (TRP) superfamily. This calcium-selective channel is highly expressed in the duodenum and the placenta, being responsible for calcium absorption in the body and fetus. Previous observations have suggested that TRPV6 is not only permeable to calcium but also to other divalent cations in epithelial tissues. In this study, we tested whether TRPV6 is indeed also permeable to cations such as zinc and cadmium. We found that the basal intracellular calcium concentration was higher in HEK293 cells transfected with hTRPV6 than in non-transfected cells, and that this difference almost disappeared in nominally calcium-free solution. Live cell imaging experiments with Fura-2 and NewPort Green DCF showed that overexpression of human TRPV6 increased the permeability for Ca(2+), Ba(2+), Sr(2+), Mn(2+), Zn(2+), Cd(2+), and interestingly also for La(3+) and Gd(3+). These results were confirmed using the patch clamp technique. (45)Ca uptake experiments showed that cadmium, lanthanum and gadolinium were also highly efficient inhibitors of TRPV6-mediated calcium influx at higher micromolar concentrations. Our results suggest that TRPV6 is not only involved in calcium transport but also in the transport of other divalent cations, including heavy metal ions, which may have toxicological implications.

The Exploitation of Versatile Building Blocks for the Self-Assembly of Novel Molecular Magnets

Using molecular building blocks to self-assemble lattices supporting long-range magnetic order is currently an active area of solid-state chemistry. Consequently, it is the realm of supramolecular chemistry that synthetic chemists are turning to in order to develop techniques for the synthesis of structurally well-defined supramolecular materials. In recent years we have investigated the versatility and usefulness of two classes of molecular building blocks, namely, tris-oxalato transition-metal (M. Pilkington and S. Decurtins, in “Magnetoscience—From Molecules to Materials,” Wiley–VCH, 2000), and octacyanometalate complexes (Pilkington and Decurtins, Chimia 54, 593 (2001)), for applications in the field of molecule-based magnets. Anionic, tris-chelated oxalato building blocks are able to build up two-dimensional honeycomb-layered structural motifs as well as three-dimensional decagon frameworks. The discrimination between the crystallization of the two- or three-dimensional structures relies on the choice of the templating counterions (Decurtins, Chimia 52, 539 (1998); Decurtins et al. Mol. Cryst. Liq. Cryst. 273, 167 (1995); New J. Chem. 117 (1998)). These structural types display a range of ferro, ferri, and antiferromagnetic properties (Pilkington and Decurtins, in “Magnetoscience—From Molecules to Materials”). Octacyanometalate building blocks self-assemble to afford two new classes of cyano-bridged compounds namely, molecular clusters and extended three dimensional networks (J. Larionova et al., Angew. Chem. Int. Ed. 39, 1605 (2000); Pilkington et al., in preparation). The molecular cluster with a MnII9MoV6 core has the highest ground state spin value, S=51/2, reported to-date (Larionova et al., Angew. Chem. Int. Ed. 39, 1605 (2000)). In the high-temperature regime, the magnetic properties are characterized by ferromagnetic intracluster coupling. In the magnetic range below 44 K, the magnetic cluster signature is lost as possibly a bulk behavior starts to emerge. The three-dimensional networks exhibit both paramagnetic and ferromagnetic behavior, since the magnetic properties of these materials directly reflect the electronic configuration of the metal ion incorporated into the octacyanometalate building blocks (Pilkington et al., in preparation). For both the oxalate- and cyanide-bridged materials, we are able to manipulate the magnetic properties of the supramolecular assemblies by tuning the electronic configurations of the metal ions incorporated into the appropriate molecular building blocks (Pilkington and Decurtins, in “Magnetoscience—From Molecules to Materials,” Chimia 54, 593 (2000)).

Molecular-Based Magnetism in High-Spin Molecular Clusters and Three-Dimensional Networks Based on Cyanometalate Building Blocks

The field of molecule-based magnets is a relatively new branch of chemistry, which involves the design and study of molecular compounds that exhibit a spontaneous magnetic ordering below a critical temperature, Tc. One major goal involves the design of materials with tuneable Tc's for specific applications in memory storage devices. Molecule-based magnets with high magnetic ordering temperatures have recently been obtained from bimetallic and mixed-valence transition metal μ-cyanide complexes of the Prussian blue family. Since the μ-cyanide linkages permit an interaction between paramagnetic metal ions, cyanometalate building blocks have found useful applications in the field of molecule-based magnets. Our work involves the use of octacyanometalate building blocks for the self-assembly of two new classes of magnetic materials namely, high-spin molecular clusters which exhibit both ferromagnetic intra- and intercluster coupling, and specific extended network topologies which show long-range ferromagnetic ordering.

Discovery and characterization of a novel non-competitive inhibitor of the divalent metal transporter DMT1/SLC11A2

Divalent metal transporter-1 (SLC11A2/DMT1) uses the H+ electrochemical gradient as the driving force to transport divalent metal ions such as Fe2+, Mn2+ and others metals into mammalian cells. DMT1 is ubiquitously expressed, most notably in proximal duodenum, immature erythroid cells, brain and kidney. This transporter mediates H+-coupled transport of ferrous iron across the apical membrane of enterocytes. In addition, in cells such as to erythroid precursors, following transferrin receptor (TfR) mediated endocytosis; it mediates H+-coupled exit of ferrous iron from endocytic vesicles into the cytosol. Dysfunction of human DMT1 is associated with several pathologies such as iron deficiency anemia hemochromatosis, Parkinson's disease and Alzheimer's disease, as well as colorectal cancer and esophageal adenocarcinoma, making DMT1 an attractive target for drug discovery. In the present study, we performed a ligand-based virtual screening of the Princeton database (700,000 commercially available compounds) to search for pharmacophore shape analogs of recently reported DMT1 inhibitors. We discovered a new compound, named pyrimidinone 8, which mediates a reversible linear non-competitive inhibition of human DMT1 (hDMT1) transport activity with a Ki of ∼20 μM. This compound does not affect hDMT1 cell surface expression and shows no dependence on extracellular pH. To our knowledge, this is the first experimental evidence that hDMT1 can be allosterically modulated by pharmacological agents. Pyrimidinone 8 represents a novel versatile tool compound and it may serve as a lead structure for the development of therapeutic compounds for pre-clinical assessment.

Solvation-Driven Charge Transfer and Localization in Metal Complexes

In any physicochemical process in liquids, the dynamical response of the solvent to the solutes out of equilibrium plays a crucial role in the rates and products: the solvent molecules react to the changes in volume and electron density of the solutes to minimize the free energy of the solution, thus modulating the activation barriers and stabilizing (or destabilizing) intermediate states. In charge transfer (CT) processes in polar solvents, the response of the solvent always assists the formation of charge separation states by stabilizing the energy of the localized charges. A deep understanding of the solvation mechanisms and time scales is therefore essential for a correct description of any photochemical process in dense phase and for designing molecular devices based on photosensitizers with CT excited states. In the last two decades, with the advent of ultrafast time-resolved spectroscopies, microscopic models describing the relevant case of polar solvation (where both the solvent and the solute molecules have a permanent electric dipole and the mutual interaction is mainly dipole−dipole) have dramatically progressed. Regardless of the details of each model, they all assume that the effect of the electrostatic fields of the solvent molecules on the internal electronic dynamics of the solute are perturbative and that the solvent−solute coupling is mainly an electrostatic interaction between the constant permanent dipoles of the solute and the solvent molecules. This well-established picture has proven to quantitatively rationalize spectroscopic effects of environmental and electric dynamics (time-resolved Stokes shifts, inhomogeneous broadening, etc.). However, recent computational and experimental studies, including ours, have shown that further improvement is required. Indeed, in the last years we investigated several molecular complexes exhibiting photoexcited CT states, and we found that the current description of the formation and stabilization of CT states in an important group of molecules such as transition metal complexes is inaccurate. In particular, we proved that the solvent molecules are not just spectators of intramolecular electron density redistribution but significantly modulate it. Our results solicit further development of quantum mechanics computational methods to treat the solute and (at least) the closest solvent molecules including the nonperturbative treatment of the effects of local electrostatics and direct solvent−solute interactions to describe the dynamical changes of the solute excited states during the solvent response.

Molecular-Based Magnetism in Bimetallic Two-Dimensional Oxalate-Bridged Networks. An X-ray and Neutron Diffraction Study

Bimetallic, oxalate-bridged compounds with bi- and trivalent transition metals comprise a class of layered materials which express a large variety in their molecular-based magnetic behavior. Because of this, the availability of the corresponding single-crystal structural data is essential to the successful interpretation of the experimental magnetic results. We report in this paper the crystal structure and magnetic properties of the ferromagnetic compound {[N(n-C3H7)4][MnIICrIII(C2O4)3]}n (1), the crystal structure of the antiferromagnetic compound {[N(n-C4H9)4][MnIIFeIII(C2O4)3]}n (2), and the results of a neutron diffraction study of a polycrystalline sample of the ferromagnetic compound {[P(C6D5)4][MnIICrIII(C2O4)3]}n (3). Crystal data:  1, rhombohedral, R3c, a = 9.363(3) Å, c = 49.207(27) Å, Z = 6; 2, hexagonal, P63, a = 9.482(2) Å, c = 17.827(8) Å, Z = 2. The structures consist of anionic, two-dimensional, honeycomb networks formed by the oxalate-bridged metal ions, interleaved by the templating cations. Single-crystal field dependent magnetization measurements as well as elastic neutron scattering experiments on the manganese(II)−chromium(III) samples show the existence of long-range ferromagnetic ordering behavior below Tc = 6 K. The magnetic structure corresponds to an alignment of the spins perpendicular to the network layers. In contrast, the manganese(II)−iron(III) compound expresses a two-dimensional antiferromagnetic ordering.