@article{MerzDietrichNitschetal.2020, author = {Merz, Julia and Dietrich, Lena and Nitsch, J{\"o}rn and Krummenacher, Ivo and Braunschweig, Holger and Moos, Michael and Mims, David and Lambert, Christoph and Marder, Todd B.}, title = {Synthesis, Photophysical and Electronic Properties of Mono-, Di-, and Tri-Amino-Substituted Ortho-Perylenes, and Comparison to the Tetra-Substituted Derivative}, series = {Chemistry - A European Journal}, volume = {26}, journal = {Chemistry - A European Journal}, number = {52}, doi = {10.1002/chem.202001475}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-217835}, pages = {12050 -- 12059}, year = {2020}, abstract = {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.}, language = {en} } @article{HofmannFayezScheineretal.2020, author = {Hofmann, Julian and Fayez, Shaimaa and Scheiner, Matthias and Hoffmann, Matthias and Oerter, Sabrina and Appelt-Menzel, Antje and Maher, Pamela and Maurice, Tangui and Bringmann, Gerhard and Decker, Michael}, title = {Sterubin: Enantioresolution and Configurational Stability, Enantiomeric Purity in Nature, and Neuroprotective Activity in Vitro and in Vivo}, series = {Chemistry - A European Journal}, volume = {26}, journal = {Chemistry - A European Journal}, number = {32}, doi = {10.1002/chem.202001264}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-215993}, pages = {7299 -- 7308}, year = {2020}, abstract = {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.}, language = {en} } @phdthesis{Wolf2021, author = {Wolf, Natalia}, title = {Synthese multifunktionaler Farbstoffe und Linker zur Visualisierung biologischer Strukturen}, doi = {10.25972/OPUS-20531}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-205312}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2021}, abstract = {Durch stetige Entwicklung der Mikroskopiemethoden in den letzten Jahrzehnten ist es nun m{\"o}glich Strukturen und Abl{\"a}ufe in biologischen Systemen detaillierter darzustellen als mit der von Abbe entdeckten maximalen Aufl{\"o}sungsgrenze. 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 gr{\"u}n 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 interdisziplin{\"a}ren Zusammenarbeit zwischen Chemikern, Physikern und Biologen profitiert, immer mehr an Bedeutung - die bioorthogonale Click-Chemie. Sie erm{\"o}glicht eine effiziente Fluoreszenzmarkierung der biologischen Strukturen unter minimalem Eingriff in die Abl{\"a}ufe der Zelle. Dazu m{\"u}ssen allerdings sowohl Farbstoffe als auch die biologisch aktiven Substanzen chemisch modifiziert werden, da nur dadurch die Bioorthogonalit{\"a}t gew{\"a}hrleistet werden kann. Mittlerweile existiert eine breite Palette an fluoreszierenden Farbstoffen, die das komplette sichtbare Spektrum abdecken und sich f{\"u}r diverse Mikroskopiemethoden eignen. Allerdings gibt es zwei Farbstoffklassen, die sich aus der gesamten F{\"u}lle abheben und sich f{\"u}r hochaufl{\"o}sende bildgebende Experimente auf Einzelmolek{\"u}lebene eignen. Zum einen ist es die Farbstofffamilie der Cyanine und insbesondere der wasserl{\"o}slichen Pentamethincyanine, die reversibel und kontrolliert zum Photoschalten animiert werden k{\"o}nnen und in der stochastisch optischen Rekonstruktionsmikroskopie Anwendung finden. Zum anderen ist es die Gruppe, der Rhodamine und Fluoresceine, die zu Xanthenfarbstoffen geh{\"o}ren 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 M{\"o}glichkeiten zur Syntheseoptimierung beider Farbstoffklassen zu finden, damit diese im Folgenden weiterentwickelt und an die biologische Fragestellung angepasst werden k{\"o}nnen. Die Arbeit unterteilt sich deshalb in Relation an die oben genannten Farbstoffklassen in zwei Bereiche. Im ersten Teil wurden Projekte basierend auf den wasserl{\"o}slichen Pentamethincyaninen behandelt. Im zweiten Teil besch{\"a}ftigte sich die Arbeit mit Projekten, die auf Xanthen-Farbstoffen aufbauen.}, subject = {Farbstoff}, language = {de} } @article{AbdelhameedHabibGodaetal.2020, author = {Abdelhameed, Reda F. A. and Habib, Eman S. and Goda, Marwa S. and Fahim, John Refaat and Hassanean, Hashem A. and Eltamany, Enas E. and Ibrahim, Amany K. and AboulMagd, Asmaa M. and Fayez, Shaimaa and Abd El-kader, Adel M. and Al-Warhi, Tarfah and Bringmann, Gerhard and Ahmed, Safwat A. and Abdelmohsen, Usama Ramadan}, title = {Thalassosterol, a New Cytotoxic Aromatase Inhibitor Ergosterol Derivative from the Red Sea Seagrass Thalassodendron ciliatum}, series = {Marine Drugs}, volume = {18}, journal = {Marine Drugs}, number = {7}, doi = {10.3390/md18070354}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-236085}, year = {2020}, abstract = {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.}, language = {en} } @article{AbdelhameedEltamanyHaletal.2020, author = {Abdelhameed, Reda F. A. and Eltamany, Enas E. and Hal, Dina M. and Ibrahim, Amany K. and AboulMagd, Asmaa M. and Al-Warhi, Tarfah and Youssif, Khayrya A. and Abd El-kader, Adel M. and Hassanean, Hashim A. and Fayez, Shaimaa and Bringmann, Gerhard and Ahmed, Safwat A. and Abdelmohsen, Usama Ramadan}, title = {New cytotoxic cerebrosides from the Red Sea cucumber Holothuria spinifera supported by in-silico studies}, series = {Marine Drugs}, volume = {18}, journal = {Marine Drugs}, number = {8}, issn = {1660-3397}, doi = {10.3390/md18080405}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-211089}, year = {2020}, abstract = {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.}, language = {en} } @article{SanchezNayaStepanenkoMandeletal.2021, author = {Sanchez-Naya, Roberto and Stepanenko, Vladimir and Mandel, Karl and Beuerle, Florian}, title = {Modulation of Crystallinity and Optical Properties in Composite Materials Combining Iron Oxide Nanoparticles and Dye-Containing Covalent Organic Frameworks}, series = {Organic Materials}, volume = {3}, journal = {Organic Materials}, doi = {10.1055/s-0040-1722655}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-231480}, pages = {17-24}, year = {2021}, abstract = {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.}, language = {en} } @article{GoetzKunzFinketal.2020, author = {G{\"o}tz, Ralph and Kunz, Tobias C. and Fink, Julian and Solger, Franziska and Schlegel, Jan and Seibel, J{\"u}rgen and Kozjak-Pavlovic, Vera and Rudel, Thomas and Sauer, Markus}, title = {Nanoscale imaging of bacterial infections by sphingolipid expansion microscopy}, series = {Nature Communications}, volume = {11}, journal = {Nature Communications}, doi = {10.1038/s41467-020-19897-1}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-231248}, year = {2020}, abstract = {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.}, language = {en} } @article{WehnerRoehrStepanenkoetal.2020, author = {Wehner, Marius and R{\"o}hr, Merle Insa Silja and Stepanenko, Vladimir and W{\"u}rthner, Frank}, title = {Control of self-assembly pathways toward conglomerate and racemic supramolecular polymers}, series = {Nature Communications}, volume = {11}, journal = {Nature Communications}, doi = {10.1038/s41467-020-19189-8}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-230580}, year = {2020}, abstract = {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.}, language = {en} } @phdthesis{Roos2021, author = {Roos, Markus}, title = {Synthesis, Photophysics and Photocatalysis of [FeFe] Complex Containing Dyads and Bimolecular Systems}, doi = {10.25972/OPUS-23453}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-234537}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2021}, abstract = {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.}, subject = {Fotokatalyse}, language = {en} } @article{BinasBessiSchwalbe2020, author = {Binas, Oliver and Bessi, Irene and Schwalbe, Harald}, title = {Structure Validation of G-Rich RNAs in Noncoding Regions of the Human Genome}, series = {ChemBioChem}, volume = {21}, journal = {ChemBioChem}, number = {11}, doi = {10.1002/cbic.201900696}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-214892}, pages = {1656 -- 1663}, year = {2020}, abstract = {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.}, language = {en} }