TY - JOUR A1 - Merz, Julia A1 - Dietrich, Lena A1 - Nitsch, Jörn A1 - Krummenacher, Ivo A1 - Braunschweig, Holger A1 - Moos, Michael A1 - Mims, David A1 - Lambert, Christoph A1 - Marder, Todd B. T1 - Synthesis, Photophysical and Electronic Properties of Mono‐, Di‐, and Tri‐Amino‐Substituted Ortho‐Perylenes, and Comparison to the Tetra‐Substituted Derivative JF - Chemistry – A European Journal N2 - We synthesized a series of new mono‐, di‐, tri‐ and tetra‐substituted perylene derivatives with strong bis(para‐methoxyphenyl)amine (DPA) donors at the uncommon 2,5,8,11‐positions. The properties of our new donor‐substituted perylenes were studied in detail to establish a structure‐property relationship. Interesting trends and unusual properties are observed for this series of new perylene derivatives, such as a decreasing charge transfer (CT) character with increasing number of DPA moieties and individual reversible oxidations for each DPA moiety. Thus, (DPA)‐Per possesses one reversible oxidation while (DPA)\(_{4}\)‐Per has four. The mono‐ and di‐substituted derivatives display unusually large Stokes shifts not previously reported for perylenes. Furthermore, transient absorption measurements of the new derivatives reveal an excited state with lifetimes of several hundred microseconds, which sensitizes singlet oxygen with quantum yields of up to 0.83. KW - borylation KW - intersystem crossing KW - luminescence KW - polycyclic aromatic hydrocarbon KW - triarylamine Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-217835 VL - 26 IS - 52 SP - 12050 EP - 12059 ER - TY - JOUR A1 - Hofmann, Julian A1 - Fayez, Shaimaa A1 - Scheiner, Matthias A1 - Hoffmann, Matthias A1 - Oerter, Sabrina A1 - Appelt‐Menzel, Antje A1 - Maher, Pamela A1 - Maurice, Tangui A1 - Bringmann, Gerhard A1 - Decker, Michael T1 - Sterubin: Enantioresolution and Configurational Stability, Enantiomeric Purity in Nature, and Neuroprotective Activity in Vitro and in Vivo JF - Chemistry – A European Journal N2 - Alzheimer′s disease (AD) is a neurological disorder with still no preventive or curative treatment. Flavonoids are phytochemicals with potential therapeutic value. Previous studies described the flavanone sterubin isolated from the Californian plant Eriodictyon californicum as a potent neuroprotectant in several in vitro assays. Herein, the resolution of synthetic racemic sterubin (1) into its two enantiomers, (R)‐1 and (S)‐1, is described, which has been performed on a chiral chromatographic phase, and their stereochemical assignment online by HPLC‐ECD coupling. (R)‐1 and (S)‐1 showed comparable neuroprotection in vitro with no significant differences. While the pure stereoisomers were configurationally stable in methanol, fast racemization was observed in the presence of culture medium. We also established the occurrence of extracted sterubin as its pure (S)‐enantiomer. Moreover, the activity of sterubin (1) was investigated for the first time in vivo, in an AD mouse model. Sterubin (1) showed a significant positive impact on short‐ and long‐term memory at low dosages. KW - Alzheimer′s disease KW - chiral resolution KW - circular dichroism KW - Eriodictyon californicum KW - flavonoids KW - sterubin Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-215993 VL - 26 IS - 32 SP - 7299 EP - 7308 ER - TY - THES A1 - Wolf, Natalia T1 - Synthese multifunktionaler Farbstoffe und Linker zur Visualisierung biologischer Strukturen T1 - Synthesis of multifunctional dyes and linkers for visualization of biological structures N2 - Durch stetige Entwicklung der Mikroskopiemethoden in den letzten Jahrzehnten ist es nun möglich Strukturen und Abläufe in biologischen Systemen detaillierter darzustellen als mit der von Abbe entdeckten maximalen Auflösungsgrenze. Oft werden dabei Fluoreszenzmarker benutzt, welche die unsichtbare Welt der Mikrobiologie und deren biochemische Prozesse illuminieren. Diese werden entweder durch Expression, wie z.B. das grün fluoreszierende Protein (GFP), in das zu untersuchende Objekt eingebracht oder durch klassische Markierungsmethoden mithilfe von fluoreszierenden Immunkonjugaten installiert. Jedoch gewinnt eine alternative Strategie, die von der interdisziplinären Zusammenarbeit zwischen Chemikern, Physikern und Biologen profitiert, immer mehr an Bedeutung – die bioorthogonale Click-Chemie. Sie ermöglicht eine effiziente Fluoreszenzmarkierung der biologischen Strukturen unter minimalem Eingriff in die Abläufe der Zelle. Dazu müssen allerdings sowohl Farbstoffe als auch die biologisch aktiven Substanzen chemisch modifiziert werden, da nur dadurch die Bioorthogonalität gewährleistet werden kann. Mittlerweile existiert eine breite Palette an fluoreszierenden Farbstoffen, die das komplette sichtbare Spektrum abdecken und sich für diverse Mikroskopiemethoden eignen. Allerdings gibt es zwei Farbstoffklassen, die sich aus der gesamten Fülle abheben und sich für hochauflösende bildgebende Experimente auf Einzelmolekülebene eignen. Zum einen ist es die Farbstofffamilie der Cyanine und insbesondere der wasserlöslichen Pentamethincyanine, die reversibel und kontrolliert zum Photoschalten animiert werden können und in der stochastisch optischen Rekonstruktionsmikroskopie Anwendung finden. Zum anderen ist es die Gruppe, der Rhodamine und Fluoresceine, die zu Xanthenfarbstoffen gehören und sich durch gute photophysikalische Eigenschaften auszeichnen. Trotz der Beliebtheit stellt ihre Darstellung immer noch eine Herausforderung dar und limitiert deren Einsatz. Deshalb war es notwendig im Rahmen der vorliegenden Arbeit Möglichkeiten zur Syntheseoptimierung beider Farbstoffklassen zu finden, damit diese im Folgenden weiterentwickelt und an die biologische Fragestellung angepasst werden können. Die Arbeit unterteilt sich deshalb in Relation an die oben genannten Farbstoffklassen in zwei Bereiche. Im ersten Teil wurden Projekte basierend auf den wasserlöslichen Pentamethincyaninen behandelt. Im zweiten Teil beschäftigte sich die Arbeit mit Projekten, die auf Xanthen-Farbstoffen aufbauen. N2 - Due to steady development in microscopy methods during the last decades its now possible to visualize biological structures in more detail than Abbes low would allow. Frequently fluorescence labeling is used to illuminate the world of microbiology and its processes. There are two classical methods to introduce fluorescent markers to the target of interest. The first way is to use the expression of fluorescent proteins like GFP (green fluorescent protein). The second one is the application of fluorescent immunoconjugates. However, an alternative strategy that benefits from the interdisciplinary cooperation between chemists, physicists and biologists is becoming increasingly important – bioorthogonal click chemistry. It enables efficient fluorescent labelling of biological structures with minimal influence in cell processes. But this requires chemical modification of both dyes and the biologically active substances, as this is the only way to guarantee bioorthogonal click reactions. In the meantime, a wide range of fluorescent dyes is available that cover the entire visible spectrum and are suitable for various microscopy methods. However, there are two classes of dyes that stand out from the rest and are suitable for high-resolution imaging experiments at the single molecule level. On the one hand, there is the dye family of cyanines and in particular the water-soluble pentamethine cyanines, which can be reversibly and in a controlled manner animated to photoswitch. Therefore, they are used in stochastic optical reconstruction microscopy like dStorm. On the other hand, there is the group of rhodamines and fluoresceins, which belong to xanthene dyes and are characterized by good photophysical properties. Despite their popularity, their synthesis still poses a challenge and limits their use. Therefore, it was necessary to find ways to optimize the synthesis of both dye classes within the scope of the present work, so that they can be further developed and adapted to the biological question. This thesis is therefore divided into two parts in relation to the two above mentioned dye classes. In the first part three projects based on the water-soluble pentamethine cyanines were addressed. In the second part the work dealt with projects based on the HMSiR-dyes. KW - Farbstoff KW - Cyanin KW - Rhodaminderivate KW - Click-Chemie KW - Farbstoffsynthese KW - Pentamethincyanine KW - Siliziumrhodaminderivate KW - bioorthogonale Click-Chemie KW - Synthese Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-205312 ER - TY - JOUR A1 - Abdelhameed, Reda F. A. A1 - Habib, Eman S. A1 - Goda, Marwa S. A1 - Fahim, John Refaat A1 - Hassanean, Hashem A. A1 - Eltamany, Enas E. A1 - Ibrahim, Amany K. A1 - AboulMagd, Asmaa M. A1 - Fayez, Shaimaa A1 - Abd El-kader, Adel M. A1 - Al-Warhi, Tarfah A1 - Bringmann, Gerhard A1 - Ahmed, Safwat A. A1 - Abdelmohsen, Usama Ramadan T1 - Thalassosterol, a New Cytotoxic Aromatase Inhibitor Ergosterol Derivative from the Red Sea Seagrass Thalassodendron ciliatum JF - Marine Drugs N2 - Thalassodendron ciliatum (Forssk.) Den Hartog is a seagrass belonging to the plant family Cymodoceaceae with ubiquitous phytoconstituents and important pharmacological potential, including antioxidant, antiviral, and cytotoxic activities. In this work, a new ergosterol derivative named thalassosterol (1) was isolated from the methanolic extract of T. ciliatum growing in the Red Sea, along with two known first-reported sterols, namely ergosterol (2) and stigmasterol (3), using different chromatographic techniques. The structure of the new compound was established based on 1D and 2D NMR spectroscopy and high-resolution mass spectrometry (HR-MS) and by comparison with the literature data. The new ergosterol derivative showed significant in vitro antiproliferative potential against the human cervical cancer cell line (HeLa) and human breast cancer (MCF-7) cell lines, with IC\(_{50}\) values of 8.12 and 14.24 µM, respectively. In addition, docking studies on the new sterol 1 explained the possible binding interactions with an aromatase enzyme; this inhibition is beneficial in both cervical and breast cancer therapy. A metabolic analysis of the crude extract of T. ciliatum using liquid chromatography combined with high-resolution electrospray ionization mass spectrometry (LC-ESI-HR-MS) revealed the presence of an array of phenolic compounds, sterols and ceramides, as well as di- and triglycerides. KW - cytotoxic activity KW - ergosterol derivative KW - metabolic analysis KW - docking studies KW - seagrass KW - Thalassodendron ciliatum Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-236085 VL - 18 IS - 7 ER - TY - JOUR A1 - Abdelhameed, Reda F. A. A1 - Eltamany, Enas E. A1 - Hal, Dina M. A1 - Ibrahim, Amany K. A1 - AboulMagd, Asmaa M. A1 - Al-Warhi, Tarfah A1 - Youssif, Khayrya A. A1 - Abd El-kader, Adel M. A1 - Hassanean, Hashim A. A1 - Fayez, Shaimaa A1 - Bringmann, Gerhard A1 - Ahmed, Safwat A. A1 - Abdelmohsen, Usama Ramadan T1 - New cytotoxic cerebrosides from the Red Sea cucumber Holothuria spinifera supported by in-silico studies JF - Marine Drugs N2 - Bioactivity-guided fractionation of a methanolic extract of the Red Sea cucumber Holothuria spinifera and LC-HRESIMS-assisted dereplication resulted in the isolation of four compounds, three new cerebrosides, spiniferosides A (1), B (2), and C (3), and cholesterol sulfate (4). The chemical structures of the isolated compounds were established on the basis of their 1D NMR and HRMS spectral data. Metabolic profiling of the H. spinifera extract indicated the presence of diverse secondary metabolites, mostly hydroxy fatty acids, diterpenes, triterpenes, and cerebrosides. The isolated compounds were tested for their in vitro cytotoxicities against the breast adenocarcinoma MCF-7 cell line. Compounds 1, 2, 3, and 4 displayed promising cytotoxic activities against MCF-7 cells, with IC\(_{50}\) values of 13.83, 8.13, 8.27, and 35.56 µM, respectively, compared to that of the standard drug doxorubicin (IC\(_{50}\) 8.64 µM). Additionally, docking studies were performed for compounds 1, 2, 3, and 4 to elucidate their binding interactions with the active site of the SET protein, an inhibitor of protein phosphatase 2A (PP2A), which could explain their cytotoxic activity. This study highlights the important role of these metabolites in the defense mechanism of the sea cucumber against fouling organisms and the potential uses of these active molecules in the design of new anticancer agents. KW - LC-HRESIMS KW - Holothuria spinifera KW - cerebrosides KW - molecular docking KW - cytotoxicity Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-211089 SN - 1660-3397 VL - 18 IS - 8 ER - TY - JOUR A1 - Sanchez-Naya, Roberto A1 - Stepanenko, Vladimir A1 - Mandel, Karl A1 - Beuerle, Florian T1 - Modulation of Crystallinity and Optical Properties in Composite Materials Combining Iron Oxide Nanoparticles and Dye-Containing Covalent Organic Frameworks JF - Organic Materials N2 - Two series of organic–inorganic composite materials were synthesized through solvothermal imine condensation between diketopyrrolopyrrole dialdehyde DPP-1 and 5,10,15,20-tetrakis(4-aminophenyl)porphyrin (TAPP) in the presence of varying amounts of either amino- or carboxy-functionalized superparamagnetic iron oxide nanoparticles (FeO). Whereas high FeO loading induced cross-linking of the inorganic nanoparticles by amorphous imine polymers, a lower FeO content resulted in the formation of crystalline covalent organic framework domains. All hybrid materials were analyzed by magnetization measurements, powder X-ray diffraction, electron microscopy, IR, and UV/Vis absorption spectroscopy. Crystallinity, chromophore stacking, and visible absorption features are directly correlated to the mass fraction of the components, thus allowing for a fine-tuning of materials properties. KW - covalent organic frameworks KW - diketopyrrolopyrroles KW - porphyrins KW - iron oxide nanoparticles KW - hybrid materials KW - superparamagnetism Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-231480 VL - 3 ER - TY - JOUR A1 - Götz, Ralph A1 - Kunz, Tobias C. A1 - Fink, Julian A1 - Solger, Franziska A1 - Schlegel, Jan A1 - Seibel, Jürgen A1 - Kozjak-Pavlovic, Vera A1 - Rudel, Thomas A1 - Sauer, Markus T1 - Nanoscale imaging of bacterial infections by sphingolipid expansion microscopy JF - Nature Communications N2 - Expansion microscopy (ExM) enables super-resolution imaging of proteins and nucleic acids on conventional microscopes. However, imaging of details of the organization of lipid bilayers by light microscopy remains challenging. We introduce an unnatural short-chain azide- and amino-modified sphingolipid ceramide, which upon incorporation into membranes can be labeled by click chemistry and linked into hydrogels, followed by 4x to 10x expansion. Confocal and structured illumination microscopy (SIM) enable imaging of sphingolipids and their interactions with proteins in the plasma membrane and membrane of intracellular organelles with a spatial resolution of 10-20nm. As our functionalized sphingolipids accumulate efficiently in pathogens, we use sphingolipid ExM to investigate bacterial infections of human HeLa229 cells by Neisseria gonorrhoeae, Chlamydia trachomatis and Simkania negevensis with a resolution so far only provided by electron microscopy. In particular, sphingolipid ExM allows us to visualize the inner and outer membrane of intracellular bacteria and determine their distance to 27.6 +/- 7.7nm. Imaging of lipid bilayers using light microscopy is challenging. Here the authors label cells using a short chain click-compatible ceramide to visualize mammalian and bacterial membranes with expansion microscopy. KW - nanoscale imaging KW - bacterial infection KW - sphingolipid expansion microscopy Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-231248 VL - 11 ER - TY - JOUR A1 - Wehner, Marius A1 - Röhr, Merle Insa Silja A1 - Stepanenko, Vladimir A1 - Würthner, Frank T1 - Control of self-assembly pathways toward conglomerate and racemic supramolecular polymers JF - Nature Communications N2 - Homo- and heterochiral aggregation during crystallization of organic molecules has significance both for fundamental questions related to the origin of life as well as for the separation of homochiral compounds from their racemates in industrial processes. Herein, we analyse these phenomena at the lowest level of hierarchy - that is the self-assembly of a racemic mixture of (R,R)- and (S,S)-PBI into 1D supramolecular polymers. By a combination of UV/vis and NMR spectroscopy as well as atomic force microscopy, we demonstrate that homochiral aggregation of the racemic mixture leads to the formation of two types of supramolecular conglomerates under kinetic control, while under thermodynamic control heterochiral aggregation is preferred, affording a racemic supramolecular polymer. FT-IR spectroscopy and quantum-chemical calculations reveal unique packing arrangements and hydrogen-bonding patterns within these supramolecular polymers. Time-, concentration- and temperature-dependent UV/vis experiments provide further insights into the kinetic and thermodynamic control of the conglomerate and racemic supramolecular polymer formation. Homo- and heterochiral aggregation is a process of interest to prebiotic and chiral separation chemistry. Here, the authors analyze the self-assembly of a racemic mixture into 1D supramolecular polymers and find homochiral aggregation into conglomerates under kinetic control, while under thermodynamic control a racemic polymer is formed. KW - perylene bismide dye KW - nucleation-elongation KW - PI stacking KW - polymerization KW - complexity KW - mechanism KW - crystals KW - kinetics KW - growth Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-230580 VL - 11 ER - TY - THES A1 - Roos, Markus T1 - Synthesis, Photophysics and Photocatalysis of [FeFe] Complex Containing Dyads and Bimolecular Systems T1 - Synthese, Photophysik und Photokatalyse von [FeFe]-Komplex enthaltenden Dyaden und bimolekularen Systemen N2 - In the course of this work, a total of three photocatalytically active dyads for proton reduction could be synthesized together with the associated individual components. Two of them, D1 and D2, comprised a [Ru(bpy)3]2+ photosensitizer and D3 an [Ir(ppy)2bpy]+ photosensitizer. A Ppyr3-substituted propyldithiolate [FeFe] complex was used as catalyst in all systems. The absorption spectroscopic and electrochemical investigations showed that an inner-dyadic electronic coupling is effectively prevented in the dyads due to conjugation blockers within the bridging units used. The photocatalytic investigations exhibited that all dyad containing two-component systems (2CS) showed a significantly worse performance than the corresponding bimolecular three-component systems (3CS). Transient absorption spectroscopy showed that the 2CS behave very similarly to the associated multicomponent systems during photocatalysis. The electron that was intended for the intramolecular transfer from the photosensitizer unit to the catalyst unit within the dyads remains at the photosensitizer for a relatively long time, analogous to the 3CS and despite the covalently bound catalyst. It is therefore assumed that this intramolecular electron transfer is likely to be hindered as a result of the weak electronic coupling caused by the bridge units used. Instead, the system bypasses this through an intermolecular transfer to other dyad molecules in the immediate vicinity. In addition, with the help of emission quenching experiments and electrochemical investigations, it could be clearly concluded that all investigated systems proceed via the reductive quenching mechanism during photocatalysis. N2 - Im Rahmen dieser Arbeit konnten insgesamt drei photokatalytisch aktive Dyaden zur Protonenreduktion zusammen mit den zugehörigen Einzelkomponenten synthetisiert werden. Zwei von ihnen, D1 und D2, umfassten einen [Ru(bpy)3]2+-Photosensibilisator und D3 einen [Ir(ppy)2bpy]+-Photosensibilisator. Als Katalysator wurde in allen Systemen ein Ppyr3-substituierter Propyldithiolat-[FeFe]-Komplex verwendet. Die absorptionsspektroskopischen und elektrochemischen Untersuchungen zeigten, dass eine innerdyadische elektronische Kopplung aufgrund von Konjugationsblockern innerhalb der verwendeten Brückeneinheiten wirksam verhindert wird. Die photokatalytischen Untersuchungen zeigten, dass alle dyadenhaltigen Zweikomponentensysteme (2CS) eine signifikant schlechtere Leistung zeigten als die entsprechenden bimolekularen Dreikomponentensysteme (3CS). Mithilfe der transienten Absorptionsspektroskopie konnte gezeigt werden, dass sich die 2CS während der Photokatalyse sehr ähnlich wie die zugehörigen Mehrkomponentensysteme verhalten. Das Elektron, das für den intramolekularen Transfer von der Photosensibilisatoreinheit zur Katalysatoreinheit innerhalb der Dyaden vorgesehen war, verbleibt analog zu den 3CS und trotz des kovalent gebundenen Katalysators relativ lange am Photosensibilisator. Es wird daher angenommen, dass dieser intramolekulare Elektronentransfer wahrscheinlich aufgrund der schwachen elektronischen Kopplung, die durch die verwendeten Brückeneinheiten verursacht wird, behindert wird. Stattdessen umgeht das System dies durch einen intermolekularen Transfer zu anderen Dyadenmolekülen in unmittelbarer Nähe. Darüber hinaus konnte mithilfe von Emissionslöschungsexperimenten und elektrochemischen Untersuchungen eindeutig darauf geschlossen werden, dass alle untersuchten Systeme während der Photokatalyse über den reduktiven Löschmechanismus ablaufen. KW - Fotokatalyse KW - Elektronentransfer KW - proton reduction KW - [FeFe] hydrogenase mimic KW - dyad KW - ruthenium photosensitizer KW - iridium photosensitizer KW - Protonenreduktion KW - [FeFe]-Hydrogenase Imitator KW - Dyade KW - Ruthenium-Photosensibilisator KW - Iridium-Photosensibilisator Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-234537 ER - TY - JOUR A1 - Binas, Oliver A1 - Bessi, Irene A1 - Schwalbe, Harald T1 - Structure Validation of G‐Rich RNAs in Noncoding Regions of the Human Genome JF - ChemBioChem N2 - We present the rapid biophysical characterization of six previously reported putative G‐quadruplex‐forming RNAs from the 5′‐untranslated region (5′‐UTR) of silvestrol‐sensitive transcripts for investigation of their secondary structures. By NMR and CD spectroscopic analysis, we found that only a single sequence—[AGG]\(_{2}\)[CGG]\(_{2}\)C—folds into a single well‐defined G‐quadruplex structure. Sequences with longer poly‐G strands form unspecific aggregates, whereas CGG‐repeat‐containing sequences exhibit a temperature‐dependent equilibrium between a hairpin and a G‐quadruplex structure. The applied experimental strategy is fast and provides robust readout for G‐quadruplex‐forming capacities of RNA oligomers. KW - biophysical investigation KW - circular dichroism KW - G-quadruplexes KW - NMR spectroscopy KW - RNA Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-214892 VL - 21 IS - 11 SP - 1656 EP - 1663 ER -