@article{SchroerToussaintBachmannetal.2021, author = {Schroer, Guido and Toussaint, Val{\´e}rie and Bachmann, Stephanie and P{\"o}ppler, Ann-Christin and Gierlich, Christian Henning and Delidovich, Irina}, title = {Functional Phenylboronate Polymers for the Recovery of Diols, Sugar Alcohols, and Saccharides from Aqueous Solution}, series = {ChemSusChem}, volume = {14}, journal = {ChemSusChem}, number = {23}, doi = {10.1002/cssc.202002887}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-239889}, pages = {5207 -- 5215}, year = {2021}, abstract = {The ongoing transition from fossil to renewable feedstocks demands new efficient processes for an economically viable production of biomass-derived commodities and fine chemicals. Novel energy- and material-efficient product purification and separation will play a crucial role due to altered product and feed composition. The present study comprises the synthesis and tests of cross-linked p-vinylphenylboronate polymers for the separation of 18 diols, sugar alcohols, and saccharides, which can be obtained during biomass processing. The separation was based on molecular recognition, that is, esterification of the phenylboronate with vicinal diols. A correlation of the molecular complexation constant, the polymer swelling, and the maximum adsorption capacity was found. The adsorption curves over time were recorded. Preliminary results on competitive adsorption of binary mixtures showed a high potential for the separation of substrates with significantly different complexation constants. Desorption tests implied easier desorption of substrates that only adsorb on the outer polymer shell.}, language = {en} } @article{MerzMerzKirchneretal.2021, author = {Merz, Viktor and Merz, Julia and Kirchner, Maximilian and Lenhart, Julian and Marder, Todd B. and Krueger, Anke}, title = {Pyrene-Based "Turn-Off" Probe with Broad Detection Range for Cu\(^{2+}\), Pb\(^{2+}\) and Hg\(^{2+}\) Ions}, series = {Chemistry—A European Journal}, volume = {27}, journal = {Chemistry—A European Journal}, number = {31}, doi = {10.1002/chem.202100594}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-256803}, pages = {8118-8126}, year = {2021}, abstract = {Detection of metals in different environments with high selectivity and specificity is one of the prerequisites of the fight against environmental pollution with these elements. Pyrenes are well suited for the fluorescence sensing in different media. The applied sensing principle typically relies on the formation of intra- and intermolecular excimers, which is however limiting the sensitivity range due to masking of e. g. quenching effects by the excimer emission. Herein we report a highly selective, structurally rigid chemical sensor based on the monomer fluorescence of pyrene moieties bearing triazole groups. This sensor can quantitatively detect Cu\(^{2+}\), Pb\(^{2+}\) and Hg\(^{2+}\) in organic solvents over a broad concentrations range, even in the presence of ubiquitous ions such as Na\(^{+}\), K\(^{+}\), Ca\(^{2+}\) and Mg\(^{2+}\). The strongly emissive sensor's fluorescence with a long lifetime of 165 ns is quenched by a 1 : 1 complex formation upon addition of metal ions in acetonitrile. Upon addition of a tenfold excess of the metal ion to the sensor, agglomerates with a diameter of about 3 nm are formed. Due to complex interactions in the system, conventional linear correlations are not observed for all concentrations. Therefore, a critical comparison between the conventional Job plot interpretation, the method of Benesi-Hildebrand, and a non-linear fit is presented. The reported system enables the specific and robust sensing of medically and environmentally relevant ions in the health-relevant nM range and could be used e. g. for the monitoring of the respective ions in waste streams.}, language = {en} } @article{LiaqatSednevStilleretal.2021, author = {Liaqat, Anam and Sednev, Maksim V. and Stiller, Carina and H{\"o}bartner, Claudia}, title = {RNA-cleaving deoxyribozymes differentiate methylated cytidine isomers in RNA}, series = {Angewandte Chemie International Edition}, volume = {60}, journal = {Angewandte Chemie International Edition}, doi = {10.1002/anie.202106517}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-256519}, pages = {19058-19062}, year = {2021}, abstract = {Deoxyribozymes are emerging as modification-specific endonucleases for the analysis of epigenetic RNA modifications. Here, we report RNA-cleaving deoxyribozymes that differentially respond to the presence of natural methylated cytidines, 3-methylcytidine (m\(^3\)C), N\(^4\)-methylcytidine (m\(^4\)C), and 5-methylcytidine (m\(^5\)C), respectively. Using in vitro selection, we found several DNA catalysts, which are selectively activated by only one of the three cytidine isomers, and display 10- to 30-fold accelerated cleavage of their target m\(^3\)C-, m\(^4\)C- or m\(^5\)C-modified RNA. An additional deoxyribozyme is strongly inhibited by any of the three methylcytidines, but effectively cleaves unmodified RNA. The mXC-detecting deoxyribozymes are programmable for the interrogation of natural RNAs of interest, as demonstrated for human mitochondrial tRNAs containing known m\(^3\)C and m\(^5\)C sites. The results underline the potential of synthetic functional DNA to shape highly selective active sites.}, language = {en} } @article{LiaqatSednevStilleretal.2021, author = {Liaqat, Anam and Sednev, Maksim V. and Stiller, Carina and H{\"o}bartner, Claudia}, title = {RNA-Cleaving Deoxyribozymes Differentiate Methylated Cytidine Isomers in RNA}, series = {Angewandte Chemie International Edition}, volume = {60}, journal = {Angewandte Chemie International Edition}, number = {35}, doi = {10.1002/anie.202106517}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-254544}, pages = {19058-19062}, year = {2021}, abstract = {Deoxyribozymes are emerging as modification-specific endonucleases for the analysis of epigenetic RNA modifications. Here, we report RNA-cleaving deoxyribozymes that differentially respond to the presence of natural methylated cytidines, 3-methylcytidine (m\(^3\)C), N\(^4\)-methylcytidine (m\(^4\)C), and 5-methylcytidine (m\(^5\)C), respectively. Using in vitro selection, we found several DNA catalysts, which are selectively activated by only one of the three cytidine isomers, and display 10- to 30-fold accelerated cleavage of their target m\(^3\)C-, m\(^4\)C- or m\(^5\)C-modified RNA. An additional deoxyribozyme is strongly inhibited by any of the three methylcytidines, but effectively cleaves unmodified RNA. The m\(^X\)C-detecting deoxyribozymes are programmable for the interrogation of natural RNAs of interest, as demonstrated for human mitochondrial tRNAs containing known m\(^3\)C and m\(^5\)C sites. The results underline the potential of synthetic functional DNA to shape highly selective active sites.}, 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{EltamanyAbdelmohsenHaletal.2021, author = {Eltamany, Enas E. and Abdelmohsen, Usama Ramadan and Hal, Dina M. and Ibrahim, Amany K. and Hassanean, Hashim A. and Abdelhameed, Reda F. A. and Temraz, Tarek A. and Hajjar, Dina and Makki, Arwa A. and Hendawy, Omnia Magdy and AboulMagd, Asmaa M. and Youssif, Khayrya A. and Bringmann, Gerhard and Ahmed, Safwat A.}, title = {Holospiniferoside: A New Antitumor Cerebroside from The Red Sea Cucumber Holothuria spinifera: In Vitro and In Silico Studies}, series = {Molecules}, volume = {26}, journal = {Molecules}, number = {6}, issn = {1420-3049}, doi = {10.3390/molecules26061555}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-234058}, year = {2021}, abstract = {Chemical investigation of the methanolic extract of the Red Sea cucumber Holothuria spinifera led to the isolation of a new cerebroside, holospiniferoside (1), together with thymidine (2), methyl-α-d-glucopyranoside (3), a new triacylglycerol (4), and cholesterol (5). Their chemical structures were established by NMR and mass spectrometric analysis, including gas chromatography-mass spectrometry (GC-MS) and high-resolution mass spectrometry (HRMS). All the isolated compounds are reported in this species for the first time. Moreover, compound 1 exhibited promising in vitro antiproliferative effect on the human breast cancer cell line (MCF-7) with IC\(_{50}\) of 20.6 µM compared to the IC50 of 15.3 µM for the drug cisplatin. To predict the possible mechanism underlying the cytotoxicity of compound 1, a docking study was performed to elucidate its binding interactions with the active site of the protein Mdm2-p53. Compound 1 displayed an apoptotic activity via strong interaction with the active site of the target protein. This study highlights the importance of marine natural products in the design of new anticancer agents.}, language = {en} } @article{AltmannMutWolfetal.2021, author = {Altmann, Stephan and Mut, J{\"u}rgen and Wolf, Natalia and Meißner-Weigl, Jutta and Rudert, Maximilian and Jakob, Franz and Gutmann, Marcus and L{\"u}hmann, Tessa and Seibel, J{\"u}rgen and Ebert, Regina}, title = {Metabolic glycoengineering in hMSC-TERT as a model for skeletal precursors by using modified azide/alkyne monosaccharides}, series = {International Journal of Molecular Sciences}, volume = {22}, journal = {International Journal of Molecular Sciences}, number = {6}, issn = {1422-0067}, doi = {10.3390/ijms22062820}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-259247}, year = {2021}, abstract = {Metabolic glycoengineering enables a directed modification of cell surfaces by introducing target molecules to surface proteins displaying new features. Biochemical pathways involving glycans differ in dependence on the cell type; therefore, this technique should be tailored for the best results. We characterized metabolic glycoengineering in telomerase-immortalized human mesenchymal stromal cells (hMSC-TERT) as a model for primary hMSC, to investigate its applicability in TERT-modified cell lines. The metabolic incorporation of N-azidoacetylmannosamine (Ac\(_4\)ManNAz) and N-alkyneacetylmannosamine (Ac\(_4\)ManNAl) into the glycocalyx as a first step in the glycoengineering process revealed no adverse effects on cell viability or gene expression, and the in vitro multipotency (osteogenic and adipogenic differentiation potential) was maintained under these adapted culture conditions. In the second step, glycoengineered cells were modified with fluorescent dyes using Cu-mediated click chemistry. In these analyses, the two mannose derivatives showed superior incorporation efficiencies compared to glucose and galactose isomers. In time-dependent experiments, the incorporation of Ac\(_4\)ManNAz was detectable for up to six days while Ac\(_4\)ManNAl-derived metabolites were absent after two days. Taken together, these findings demonstrate the successful metabolic glycoengineering of immortalized hMSC resulting in transient cell surface modifications, and thus present a useful model to address different scientific questions regarding glycosylation processes in skeletal precursors.}, language = {en} } @article{WieseDennstaedtHollmannetal.2021, author = {Wiese, Teresa and Dennst{\"a}dt, Fabio and Hollmann, Claudia and Stonawski, Saskia and Wurst, Catherina and Fink, Julian and Gorte, Erika and Mandasari, Putri and Domschke, Katharina and Hommers, Leif and Vanhove, Bernard and Schumacher, Fabian and Kleuser, Burkard and Seibel, J{\"u}rgen and Rohr, Jan and Buttmann, Mathias and Menke, Andreas and Schneider-Schaulies, J{\"u}rgen and Beyersdorf, Niklas}, title = {Inhibition of acid sphingomyelinase increases regulatory T cells in humans}, series = {Brain Communications}, volume = {3}, journal = {Brain Communications}, number = {2}, doi = {10.1093/braincomms/fcab020}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-259868}, year = {2021}, abstract = {Genetic deficiency for acid sphingomyelinase or its pharmacological inhibition has been shown to increase Foxp3\(^+\) regulatory T-cell frequencies among CD4\(^+\) T cells in mice. We now investigated whether pharmacological targeting of the acid sphingomyelinase, which catalyzes the cleavage of sphingomyelin to ceramide and phosphorylcholine, also allows to manipulate relative CD4\(^+\) Foxp3\(^+\) regulatory T-cell frequencies in humans. Pharmacological acid sphingomyelinase inhibition with antidepressants like sertraline, but not those without an inhibitory effect on acid sphingomyelinase activity like citalopram, increased the frequency of Foxp3\(^+\) regulatory T cell among human CD4\(^+\) T cells in vitro. In an observational prospective clinical study with patients suffering from major depression, we observed that acid sphingomyelinase-inhibiting antidepressants induced a stronger relative increase in the frequency of CD4\(^+\) Foxp3\(^+\) regulatory T cells in peripheral blood than acid sphingomyelinase-non- or weakly inhibiting antidepressants. This was particularly true for CD45RA\(^-\) CD25\(^{high}\) effector CD4\(^+\) Foxp3\(^+\) regulatory T cells. Mechanistically, our data indicate that the positive effect of acid sphingomyelinase inhibition on CD4\(^+\) Foxp3\(^+\) regulatory T cells required CD28 co-stimulation, suggesting that enhanced CD28 co-stimulation was the driver of the observed increase in the frequency of Foxp3+ regulatory T cells among human CD4\(^+\) T cells. In summary, the widely induced pharmacological inhibition of acid sphingomyelinase activity in patients leads to an increase in Foxp3+ regulatory T-cell frequencies among CD4\(^+\) T cells in humans both in vivo and in vitro.}, language = {en} } @article{SchlauersbachHanioLenzetal.2021, author = {Schlauersbach, Jonas and Hanio, Simon and Lenz, Bettina and Vemulapalli, Sahithya P. B. and Griesinger, Christian and P{\"o}ppler, Ann-Christin and Harlacher, Cornelius and Galli, Bruno and Meinel, Lorenz}, title = {Leveraging bile solubilization of poorly water-soluble drugs by rational polymer selection}, series = {Journal of Controlled Release}, volume = {330}, journal = {Journal of Controlled Release}, edition = {Accepted Version}, doi = {10.1016/j.jconrel.2020.12.016}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-296957}, pages = {36-48}, year = {2021}, abstract = {Poorly water-soluble drugs frequently solubilize into bile colloids and this natural mechanism is key for efficient bioavailability. We tested the impact of pharmaceutical polymers on this solubilization interplay using proton nuclear magnetic resonance spectroscopy, dynamic light scattering, and by assessing the flux across model membranes. Eudragit E, Soluplus, and a therapeutically used model polymer, Colesevelam, impacted the bile-colloidal geometry and molecular interaction. These polymer-induced changes reduced the flux of poorly water-soluble and bile interacting drugs (Perphenazine, Imatinib) but did not impact the flux of bile non-interacting Metoprolol. Non-bile interacting polymers (Kollidon VA 64, HPMC-AS) neither impacted the flux of colloid-interacting nor colloid-non-interacting drugs. These insights into the drug substance/polymer/bile colloid interplay potentially point towards a practical optimization parameter steering formulations to efficient bile-solubilization by rational polymer selection.}, language = {en} } @article{KokicHillenTegunovetal.2021, author = {Kokic, Goran and Hillen, Hauke S. and Tegunov, Dimitry and Dienermann, Christian and Seitz, Florian and Schmitzova, Jana and Farnung, Lucas and Siewert, Aaron and H{\"o}bartner, Claudia and Cramer, Patrick}, title = {Mechanism of SARS-CoV-2 polymerase stalling by remdesivir}, series = {Nature Communications}, volume = {12}, journal = {Nature Communications}, doi = {10.1038/s41467-020-20542-0}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-220979}, year = {2021}, abstract = {Remdesivir is the only FDA-approved drug for the treatment of COVID-19 patients. The active form of remdesivir acts as a nucleoside analog and inhibits the RNA-dependent RNA polymerase (RdRp) of coronaviruses including SARS-CoV-2. Remdesivir is incorporated by the RdRp into the growing RNA product and allows for addition of three more nucleotides before RNA synthesis stalls. Here we use synthetic RNA chemistry, biochemistry and cryoelectron microscopy to establish the molecular mechanism of remdesivir-induced RdRp stalling. We show that addition of the fourth nucleotide following remdesivir incorporation into the RNA product is impaired by a barrier to further RNA translocation. This translocation barrier causes retention of the RNA 3ʹ-nucleotide in the substrate-binding site of the RdRp and interferes with entry of the next nucleoside triphosphate, thereby stalling RdRp. In the structure of the remdesivir-stalled state, the 3ʹ-nucleotide of the RNA product is matched and located with the template base in the active center, and this may impair proofreading by the viral 3ʹ-exonuclease. These mechanistic insights should facilitate the quest for improved antivirals that target coronavirus replication.}, language = {en} } @article{SchindlerMezaChinchaRothetal.2021, author = {Schindler, Dorothee and Meza-Chincha, Anna-Lucia and Roth, Maximilian and W{\"u}rthner, Frank}, title = {Structure-Activity Relationship for Di- up to Tetranuclear Macrocyclic Ruthenium Catalysts in Homogeneous Water Oxidation}, series = {Chemistry—A European Journal}, volume = {27}, journal = {Chemistry—A European Journal}, number = {68}, doi = {10.1002/chem.202100549}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-256792}, pages = {16938-16946}, year = {2021}, abstract = {Two di- and tetranuclear Ru(bda) (bda: 2,2′-bipyridine-6,6′-dicarboxylate) macrocyclic complexes were synthesized and their catalytic activities in chemical and photochemical water oxidation investigated in a comparative manner to our previously reported trinuclear congener. Our studies have shown that the catalytic activities of this homologous series of multinuclear Ru(bda) macrocycles in homogeneous water oxidation are dependent on their size, exhibiting highest efficiencies for the largest tetranuclear catalyst. The turnover frequencies (TOFs) have increased from di- to tetranuclear macrocycles not only per catalyst molecule but more importantly also per Ru unit with TOF of 6 \(^{-1}\) to 8.7 \(^{-1}\) and 10.5 s\(^{-1}\) in chemical and 0.6 s\(^{-1}\) to 3.3 \(^{-1}\) and 5.8 \(^{-1}\) in photochemical water oxidation per Ru unit, respectively. Thus, for the first time, a clear structure-activity relationship could be established for this novel class of macrocyclic water oxidation catalysts.}, language = {en} } @article{LehmannBaumannLambovetal.2021, author = {Lehmann, Matthias and Baumann, Maximilian and Lambov, Martin and Eremin, Alexey}, title = {Parallel polar dimers in the columnar self-assembly of umbrella-shaped subphthalocyanine mesogens}, series = {Advanced Functional Materials}, volume = {31}, journal = {Advanced Functional Materials}, number = {38}, doi = {10.1002/adfm.202104217}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-256343}, year = {2021}, abstract = {The self-assembly of umbrella-shaped mesogens is explored with subphthalocyanine cores and oligo(thienyl) arms with different lengths in the light of their application as light-harvesting and photoconducting materials. While the shortest arm derivatives self-assemble in a conventional columnar phase with a single mesogen as a repeating unit, the more extended derivatives generate dimers that pile up into liquid crystalline columns. In contrast to the antiparallel arrangement known from single crystals, the present mesogens align as parallel dimers in polar columnar phases as confirmed by X-ray scattering, experimental densities, dielectric spectroscopy, second harmonic generation, alignment, and conductivity studies. UV-vis and fluorescence spectroscopies reveal a broad absorption in the visible range and only weak emission of the Q-band. Thus, these light-collecting molecules forming strongly polar columnar mesophases are attractive for application in the area of photoconductive materials.}, language = {en} } @article{PetersKaiserFinketal.2021, author = {Peters, Simon and Kaiser, Lena and Fink, Julian and Schumacher, Fabian and Perschin, Veronika and Schlegel, Jan and Sauer, Markus and Stigloher, Christian and Kleuser, Burkhard and Seibel, Juergen and Schubert-Unkmeir, Alexandra}, title = {Click-correlative light and electron microscopy (click-AT-CLEM) for imaging and tracking azido-functionalized sphingolipids in bacteria}, series = {Scientific Reports}, volume = {11}, journal = {Scientific Reports}, number = {1}, doi = {10.1038/s41598-021-83813-w}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-259147}, pages = {4300}, year = {2021}, abstract = {Sphingolipids, including ceramides, are a diverse group of structurally related lipids composed of a sphingoid base backbone coupled to a fatty acid side chain and modified terminal hydroxyl group. Recently, it has been shown that sphingolipids show antimicrobial activity against a broad range of pathogenic microorganisms. The antimicrobial mechanism, however, remains so far elusive. Here, we introduce 'click-AT-CLEM', a labeling technique for correlated light and electron microscopy (CLEM) based on the super-resolution array tomography (srAT) approach and bio-orthogonal click chemistry for imaging of azido-tagged sphingolipids to directly visualize their interaction with the model Gram-negative bacterium Neisseria meningitidis at subcellular level. We observed ultrastructural damage of bacteria and disruption of the bacterial outer membrane induced by two azido-modified sphingolipids by scanning electron microscopy and transmission electron microscopy. Click-AT-CLEM imaging and mass spectrometry clearly revealed efficient incorporation of azido-tagged sphingolipids into the outer membrane of Gram-negative bacteria as underlying cause of their antimicrobial activity.}, language = {en} } @article{FullPanchalGoetzetal.2021, author = {Full, Julian and Panchal, Santosh P. and G{\"o}tz, Julian and Krause, Ana-Maria and Nowak-Kr{\´o}l, Agnieszka}, title = {Modulare Synthese helikal-chiraler Organobor-Verbindungen: Ausschnitte verl{\"a}ngerter Helices}, series = {Angewandte Chemie}, volume = {133}, journal = {Angewandte Chemie}, number = {8}, doi = {10.1002/ange.202014138}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-224385}, pages = {4396 -- 4403}, year = {2021}, abstract = {Zwei Arten helikal-chiraler Verbindungen mit einem oder zwei Boratomen wurden nach einem modularen Ansatz synthetisiert. Die Bildung der helikalen Strukturen erfolgte durch Einf{\"u}hrung von Bor in flexible Biaryl- bzw. Triaryl-Vorstufen, hergestellt aus kleinen achiralen Bausteinen. Die durchgehend ortho-fusionierten Azabora[7]helicene zeichnen sich dabei durch außergew{\"o}hnliche Konfigurationsstabilit{\"a}t, blaue oder gr{\"u}ne Fluoreszenz in L{\"o}sung mit Quantenausbeuten (Φ\(_{fl}\)) von 18-24 \%, gr{\"u}ne oder gelbe Emission im Festk{\"o}rper (Φ\(_{fl}\) bis zu 23 \%) und starke chiroptische Resonanz mit großen Anisotropiefaktoren von bis zu 1.12×10\(^{-2}\) aus. Azabora[9]helicene, aufgebaut aus winkelf{\"o}rmig sowie linear angeordneten Ringen, sind blaue Emitter mit Φ\(_{fl}\) von bis zu 47 \% in CH\(_{2}\)Cl\(_{2}\) und 25 \% im Festk{\"o}rper. DFT-Rechnungen zeigen, dass ihre P-M-Interkonversion {\"u}ber einen komplexeren Weg verl{\"a}uft als im Fall von H1. R{\"o}ntgenstrukturanalyse von Einkristallen zeigt deutliche Unterschiede in der Packungsanordnung von Methyl- und Phenylderivaten auf. Die Molek{\"u}le werden als Prim{\"a}rstrukturen verl{\"a}ngerter Helices vorgeschlagen.}, language = {de} } @article{SchneiderSchauliesSchumacherWiggeretal.2021, author = {Schneider-Schaulies, Sibylle and Schumacher, Fabian and Wigger, Dominik and Sch{\"o}l, Marie and Waghmare, Trushnal and Schlegel, Jan and Seibel, J{\"u}rgen and Kleuser, Burkhard}, title = {Sphingolipids: effectors and Achilles heals in viral infections?}, series = {Cells}, volume = {10}, journal = {Cells}, number = {9}, issn = {2073-4409}, doi = {10.3390/cells10092175}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-245151}, year = {2021}, abstract = {As viruses are obligatory intracellular parasites, any step during their life cycle strictly depends on successful interaction with their particular host cells. In particular, their interaction with cellular membranes is of crucial importance for most steps in the viral replication cycle. Such interactions are initiated by uptake of viral particles and subsequent trafficking to intracellular compartments to access their replication compartments which provide a spatially confined environment concentrating viral and cellular components, and subsequently, employ cellular membranes for assembly and exit of viral progeny. The ability of viruses to actively modulate lipid composition such as sphingolipids (SLs) is essential for successful completion of the viral life cycle. In addition to their structural and biophysical properties of cellular membranes, some sphingolipid (SL) species are bioactive and as such, take part in cellular signaling processes involved in regulating viral replication. It is especially due to the progress made in tools to study accumulation and dynamics of SLs, which visualize their compartmentalization and identify interaction partners at a cellular level, as well as the availability of genetic knockout systems, that the role of particular SL species in the viral replication process can be analyzed and, most importantly, be explored as targets for therapeutic intervention.}, language = {en} } @article{KimLiessStolteetal.2021, author = {Kim, Jin Hong and Liess, Andreas and Stolte, Matthias and Krause, Ana-Maria and Stepanenko, Vladimir and Zhong, Chuwei and Bialas, David and Spano, Frank and W{\"u}rthner, Frank}, title = {An Efficient Narrowband Near-Infrared at 1040 nm Organic Photodetector Realized by Intermolecular Charge Transfer Mediated Coupling Based on a Squaraine Dye}, series = {Advanced Materials}, volume = {33}, journal = {Advanced Materials}, number = {26}, doi = {10.1002/adma.202100582}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-256374}, year = {2021}, abstract = {A highly sensitive short-wave infrared (SWIR, λ > 1000 nm) organic photodiode (OPD) is described based on a well-organized nanocrystalline bulk-heterojunction (BHJ) active layer composed of a dicyanovinyl-functionalized squaraine dye (SQ-H) donor material in combination with PC\(_{61}\)BM. Through thermal annealing, dipolar SQ-H chromophores self-assemble in a nanoscale structure with intermolecular charge transfer mediated coupling, resulting in a redshifted and narrow absorption band at 1040 nm as well as enhanced charge carrier mobility. The optimized OPD exhibits an external quantum efficiency (EQE) of 12.3\% and a full-width at half-maximum of only 85 nm (815 cm\(^{-1}\)) at 1050 nm under 0 V, which is the first efficient SWIR OPD based on J-type aggregates. Photoplethysmography application for heart-rate monitoring is successfully demonstrated on flexible substrates without applying reverse bias, indicating the potential of OPDs based on short-range coupled dye aggregates for low-power operating wearable applications.}, language = {en} } @article{ShenBialasHechtetal.2021, author = {Shen, Chia-An and Bialas, David and Hecht, Markus and Stepanenko, Vladimir and Sugiyasu, Kazunori and W{\"u}rthner, Frank}, title = {Polymorphism in squaraine dye aggregates by self-assembly pathway differentiation: panchromatic tubular dye nanorods versus J-aggregate nanosheets}, series = {Angewandte Chemie International Edition}, journal = {Angewandte Chemie International Edition}, number = {21}, edition = {60}, doi = {10.1002/anie.202102183}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-256443}, pages = {11949-11958}, year = {2021}, abstract = {A bis(squaraine) dye equipped with alkyl and oligoethyleneglycol chains was synthesized by connecting two dicyanomethylene substituted squaraine dyes with a phenylene spacer unit. The aggregation behavior of this bis(squaraine) was investigated in non-polar toluene/tetrachloroethane (98:2) solvent mixture, which revealed competing cooperative self-assembly pathways into two supramolecular polymorphs with entirely different packing structures and UV/Vis/NIR absorption properties. The self-assembly pathway can be controlled by the cooling rate from a heated solution of the monomers. For both polymorphs, quasi-equilibrium conditions between monomers and the respective aggregates can be established to derive thermodynamic parameters and insights into the self-assembly mechanisms. AFM measurements revealed a nanosheet structure with a height of 2 nm for the thermodynamically more stable polymorph and a tubular nanorod structure with a helical pitch of 13 nm and a diameter of 5 nm for the kinetically favored polymorph. Together with wide angle X-ray scattering measurements, packing models were derived: the thermodynamic polymorph consists of brick-work type nanosheets that exhibit red-shifted absorption bands as typical for J-aggregates, while the nanorod polymorph consists of eight supramolecular polymer strands of the bis(squaraine) intertwined to form a chimney-type tubular structure. The absorption of this aggregate covers a large spectral range from 550 to 875 nm, which cannot be rationalized by the conventional exciton theory. By applying the Essential States Model and considering intermolecular charge transfer, the aggregate spectrum was adequately reproduced, revealing that the broad absorption spectrum is due to pronounced donor-acceptor overlap within the bis(squaraine) nanorods. The latter is also responsible for the pronounced bathochromic shift observed for the nanosheet structure as a result of the slip-stacked arranged squaraine chromophores.}, language = {en} } @article{PinznerKellerMutetal.2021, author = {Pinzner, Florian and Keller, Thorsten and Mut, J{\"u}rgen and Bechold, Julian and Seibel, J{\"u}rgen and Groll, J{\"u}rgen}, title = {Polyoxazolines with a vicinally double-bioactivated terminus for biomacromolecular affinity assessment}, series = {Sensors}, volume = {21}, journal = {Sensors}, number = {9}, issn = {1424-8220}, doi = {10.3390/s21093153}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-239530}, year = {2021}, abstract = {Interactions between proteins and carbohydrates with larger biomacromolecules, e.g., lectins, are usually examined using self-assembled monolayers on target gold surfaces as a simplified model measuring setup. However, most of those measuring setups are either limited to a single substrate or do not allow for control over ligand distance and spacing. Here, we develop a synthetic strategy, consisting of a cascade of a thioesterification, native chemical ligation (NCL) and thiol-ene reaction, in order to create three-component polymer conjugates with a defined double bioactivation at the chain end. The target architecture is the vicinal attachment of two biomolecule residues to the α telechelic end point of a polymer and a thioether group at the ω chain end for fixating the conjugate to a gold sensor chip surface. As proof-of-principle studies for affinity measurements, we demonstrate the interaction between covalently bound mannose and ConA in surface acoustic wave (SAW) and surface plasmon resonance (SPR) experiments.}, language = {en} } @article{Ravat2021, author = {Ravat, Prince}, title = {Carbo[n]helicenes Restricted to Enantiomerize: An Insight into the Design Process of Configurationally Stable Functional Chiral PAHs}, series = {Chemistry - A European Journal}, volume = {27}, journal = {Chemistry - A European Journal}, number = {12}, doi = {10.1002/chem.202004488}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-225871}, pages = {3957 -- 3967}, year = {2021}, abstract = {The most important stereodynamic feature of carbo[n]helicenes is the interconversion of their enantiomers. The Gibbs activation energy (ΔG≠(T)) of this process, which determines the rate of enantiomerization, dictates the configurational stability of [n]helicenes. High values of ΔG≠(T) are required for applications of functional chiral molecules incorporating [n]helicenes or helicene substructures. This minireview provides an overview of the mechanism, recent developments, and factors affecting the enantiomerization of [n]helicenes, which will accelerate the design process of configurationally stable functional chiral molecules based on helicene substructures. Additionally, this minireview addresses the misconception and irregularities in the recent literature on how the terms "racemization" and "enantiomerization" are used as well as how the activation parameters are calculated for [n]helicenes and related compounds.}, language = {en} } @article{MuellerBessiRichteretal.2021, author = {M{\"u}ller, Diana and Bessi, Irene and Richter, Christian and Schwalbe, Harald}, title = {The Folding Landscapes of Human Telomeric RNA and DNA G-Quadruplexes are Markedly Different}, series = {Angewandte Chemie International Edition}, volume = {60}, journal = {Angewandte Chemie International Edition}, number = {19}, doi = {10.1002/anie.202100280}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-238917}, pages = {10895 -- 10901}, year = {2021}, abstract = {We investigated the folding kinetics of G-quadruplex (G4) structures by comparing the K\(^{+}\)-induced folding of an RNA G4 derived from the human telomeric repeat-containing RNA (TERRA25) with a sequence homologous DNA G4 (wtTel25) using CD spectroscopy and real-time NMR spectroscopy. While DNA G4 folding is biphasic, reveals kinetic partitioning and involves kinetically favoured off-pathway intermediates, RNA G4 folding is faster and monophasic. The differences in kinetics are correlated to the differences in the folded conformations of RNA vs. DNA G4s, in particular with regard to the conformation around the glycosidic torsion angle χ that uniformly adopts anti conformations for RNA G4s and both, syn and anti conformation for DNA G4s. Modified DNA G4s with \(^{19}\)F bound to C2′ in arabino configuration adopt exclusively anti conformations for χ. These fluoro-modified DNA (antiTel25) reveal faster folding kinetics and monomorphic conformations similar to RNA G4s, suggesting the correlation between folding kinetics and pathways with differences in χ angle preferences in DNA and RNA, respectively.}, language = {en} } @article{RennerMahlmeisterAnhaltetal.2021, author = {Renner, Rebecca and Mahlmeister, Bernhard and Anhalt, Olga and Stolte, Matthias and W{\"u}rthner, Frank}, title = {Chiral Perylene Bisimide Dyes by Interlocked Arene Substituents in the Bay Area}, series = {Chemistry - A European Journal}, volume = {27}, journal = {Chemistry - A European Journal}, number = {46}, doi = {10.1002/chem.202101877}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-249070}, pages = {11997 -- 12006}, year = {2021}, abstract = {A series of perylene bisimide (PBI) dyes bearing various aryl substituents in 1,6,7,12 bay positions has been synthesized by Suzuki cross-coupling reaction. These molecules exhibit an exceptionally large and conformationally fixed twist angle of the PBI π-core due to the high steric congestion imparted by the aryl substituents in bay positions. Single crystal X-ray analyses of phenyl-, naphthyl- and pyrenyl-functionalized PBIs reveal interlocked π-π-stacking motifs, leading to conformational chirality and the possibility for the isolation of enantiopure atropoisomers by semipreparative HPLC. The interlocked arrangement endows these molecules with substantial racemization barriers of about 120 kJ mol\(^{-1}\) for the tetraphenyl- and tetra-2-naphthyl-substituted derivatives, which is among the highest racemization barriers for axially chiral PBIs. Variable temperature NMR studies reveal the presence of a multitude of up to fourteen conformational isomers in solution that are interconverted via smaller activation barriers of about 65 kJ mol\(^{-1}\). The redox and optical properties of these core-twisted PBIs have been characterized by cyclic voltammetry, UV/Vis/NIR and fluorescence spectroscopy and their respective atropo-enantiomers were further characterized by circular dichroism (CD) and circular polarized luminescence (CPL) spectroscopy.}, language = {en} } @article{WuerthnerMezaChinchaSchindleretal.2021, author = {W{\"u}rthner, Frank and Meza-Chincha, Ana-Lucia and Schindler, Dorothee and Natali, Mirco}, title = {Effects of Photosensitizers and Reaction Media on Light-Driven Water Oxidation with Trinuclear Ruthenium Macrocycles}, series = {ChemPhotoChem}, volume = {5}, journal = {ChemPhotoChem}, number = {2}, doi = {10.1002/cptc.202000133}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-230116}, pages = {173-183}, year = {2021}, abstract = {Photocatalytic water oxidation is a promising process for the production of solar fuels and the elucidation of factors that influence this process is of high significance. Thus, we have studied in detail light-driven water oxidation with a trinuclear Ru(bda) (bda: 2,2'-bipyridine-6,6'-dicarboxylate) macrocycle MC3 and its highly water soluble derivative m-CH\(_2\)NMe\(_2\)-MC3 using a series of ruthenium tris(bipyridine) complexes as photosensitizers under varied reaction conditions. Our investigations showed that the catalytic activities of these Ru macrocycles are significantly affected by the choice of photosensitizer (PS) and reaction media, in addition to buffer concentration, light intensity and concentration of the sensitizer. Our steady-state and transient spectroscopic studies revealed that the photocatalytic performance of trinuclear Ru(bda) macrocycles is not limited by their intrinsic catalytic activities but rather by the efficiency of photogeneration of oxidant PS\(^+\) and its ability to act as an oxidizing agent to the catalysts as both are strongly dependent on the choice of photosensitizer and the amount of employed organic co-solvent.}, language = {en} } @article{WuerthnerNoll2021, author = {W{\"u}rthner, Frank and Noll, Niklas}, title = {A Calix[4]arene-Based Cyclic Dinuclear Ruthenium Complex for Light-Driven Catalytic Water Oxidation}, series = {Chemistry - A European Journal}, volume = {27}, journal = {Chemistry - A European Journal}, number = {1}, doi = {10.1002/chem.202004486}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-230030}, pages = {444-450}, year = {2021}, abstract = {A cyclic dinuclear ruthenium(bda) (bda: 2,2'-bipyridine-6,6'-dicarboxylate) complex equipped with oligo(ethylene glycol)-functionalized axial calix[4]arene ligands has been synthesized for homogenous catalytic water oxidation. This novel Ru(bda) macrocycle showed significantly increased catalytic activity in chemical and photocatalytic water oxidation compared to the archetype mononuclear reference [Ru(bda)(pic)\(_2\)]. Kinetic investigations, including kinetic isotope effect studies, disclosed a unimolecular water nucleophilic attack mechanism of this novel dinuclear water oxidation catalyst (WOC) under the involvement of the second coordination sphere. Photocatalytic water oxidation with this cyclic dinuclear Ru complex using [Ru(bpy)\(_3\)]Cl\(_2\) as a standard photosensitizer revealed a turnover frequency of 15.5 s\(^{-1}\) and a turnover number of 460. This so far highest photocatalytic performance reported for a Ru(bda) complex underlines the potential of this water-soluble WOC for artificial photosynthesis.}, language = {en} } @article{SchaeferBuehlerHeyeretal.2021, author = {Sch{\"a}fer, Natalie and B{\"u}hler, Michael and Heyer, Lisa and R{\"o}hr, Merle I. S. and Beuerle, Florian}, title = {Endohedral Hydrogen Bonding Templates the Formation of a Highly Strained Covalent Organic Cage Compound}, series = {Chemistry—A European Journal}, volume = {27}, journal = {Chemistry—A European Journal}, number = {19}, doi = {10.1002/chem.202005276}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-256762}, pages = {6077-6085}, year = {2021}, abstract = {A highly strained covalent organic cage compound was synthesized from hexahydroxy tribenzotriquinacene (TBTQ) and a meta-terphenyl-based diboronic acid with an additional benzoic acid substituent in 2'-position. Usually, a 120° bite angle in the unsubstituted ditopic linker favors the formation of a [4+6] cage assembly. Here, the introduction of the benzoic acid group is shown to lead to a perfectly preorganized circular hydrogen-bonding array in the cavity of a trigonal-bipyramidal [2+3] cage, which energetically overcompensates the additional strain energy caused by the larger mismatch in bite angles for the smaller assembly. The strained cage compound was analyzed by mass spectrometry and \(^{1}\)H, \(^{13}\)C and DOSY NMR spectroscopy. DFT calculations revealed the energetic contribution of the hydrogen-bonding template to the cage stability. Furthermore, molecular dynamics simulations on early intermediates indicate an additional kinetic effect, as hydrogen bonding also preorganizes and rigidifies small oligomers to facilitate the exclusive formation of smaller and more strained macrocycles and cages.}, language = {en} } @article{MieczkowskiSteinmetzgerBessietal.2021, author = {Mieczkowski, Mateusz and Steinmetzger, Christian and Bessi, Irene and Lenz, Ann-Kathrin and Schmiedel, Alexander and Holzapfel, Marco and Lambert, Christoph and Pena, Vladimir and H{\"o}bartner, Claudia}, title = {Large Stokes shift fluorescence activation in an RNA aptamer by intermolecular proton transfer to guanine}, series = {Nature Communications}, volume = {12}, journal = {Nature Communications}, doi = {10.1038/s41467-021-23932-0}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-254527}, pages = {3549}, year = {2021}, abstract = {Fluorogenic RNA aptamers are synthetic functional RNAs that specifically bind and activate conditional fluorophores. The Chili RNA aptamer mimics large Stokes shift fluorescent proteins and exhibits high affinity for 3,5-dimethoxy-4-hydroxybenzylidene imidazolone (DMHBI) derivatives to elicit green or red fluorescence emission. Here, we elucidate the structural and mechanistic basis of fluorescence activation by crystallography and time-resolved optical spectroscopy. Two co-crystal structures of the Chili RNA with positively charged DMHBO+ and DMHBI+ ligands revealed a G-quadruplex and a trans-sugar-sugar edge G:G base pair that immobilize the ligand by π-π stacking. A Watson-Crick G:C base pair in the fluorophore binding site establishes a short hydrogen bond between the N7 of guanine and the phenolic OH of the ligand. Ultrafast excited state proton transfer (ESPT) from the neutral chromophore to the RNA was found with a time constant of 130 fs and revealed the mode of action of the large Stokes shift fluorogenic RNA aptamer.}, language = {en} } @article{IvanovaKoesterHolsteinetal.2021, author = {Ivanova, Svetlana and K{\"o}ster, Eva and Holstein, Julian J. and Keller, Niklas and Clever, Guido H. and Bein, Thomas and Beuerle, Florian}, title = {Isoreticular crystallization of highly porous cubic covalent organic cage compounds}, series = {Angewandte Chemie International Edition}, volume = {60}, journal = {Angewandte Chemie International Edition}, number = {32}, doi = {10.1002/anie.202102982}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-256462}, pages = {17455-17463}, year = {2021}, abstract = {Modular frameworks featuring well-defined pore structures in microscale domains establish tailor-made porous materials. For open molecular solids however, maintaining long-range order after desolvation is inherently challenging, since packing is usually governed by only a few supramolecular interactions. Here we report on two series of nanocubes obtained by co-condensation of two different hexahydroxy tribenzotriquinacenes (TBTQs) and benzene-1,4-diboronic acids (BDBAs) with varying linear alkyl chains in 2,5-position. n-Butyl groups at the apical position of the TBTQ vertices yielded soluble model compounds, which were analyzed by mass spectrometry and NMR spectroscopy. In contrast, methyl-substituted cages spontaneously crystallized as isostructural and highly porous solids with BET surface areas and pore volumes of up to 3426 m\(^2\) g\(^{-1}\) and 1.84 cm\(^3\) g\(^{-1}\). Single crystal X-ray diffraction and sorption measurements revealed an intricate cubic arrangement of alternating micro- and mesopores in the range of 0.97-2.2 nm that are fine-tuned by the alkyl substituents at the BDBA linker.}, language = {en} } @article{TurkinHolzapfelAgarwaletal.2021, author = {Turkin, Arthur and Holzapfel, Marco and Agarwal, Mohit and Fischermeier, David and Mitric, Roland and Schweins, Ralf and Gr{\"o}hns, Franziska and Lambert, Christoph}, title = {Solvent Induced Helix Folding of Defined Indolenine Squaraine Oligomers}, series = {Chemistry—A European Journal}, volume = {27}, journal = {Chemistry—A European Journal}, number = {32}, doi = {10.1002/chem.202101063}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-256869}, pages = {8380-8389}, year = {2021}, abstract = {A protecting group strategy was employed to synthesise a series of indolenine squaraine dye oligomers up to the nonamer. The longer oligomers show a distinct solvent dependence of the absorption spectra, that is, either a strong blue shift or a strong red shift of the lowest energy bands in the near infrared spectral region. This behaviour is explained by exciton coupling theory as being due to H- or J-type coupling of transition moments. The H-type coupling is a consequence of a helix folding in solvents with a small Hansen dispersity index. DOSY NMR, small angle neutron scattering (SANS), quantum chemical and force field calculations agree upon a helix structure with an unusually large pitch and open voids that are filled with solvent molecules, thereby forming a kind of clathrate. The thermodynamic parameters of the folding process were determined by temperature dependent optical absorption spectra.}, language = {en} } @article{ZhangRadackiBraunschweigetal.2021, author = {Zhang, Fangyuan and Radacki, Krzysztof and Braunschweig, Holger and Lambert, Christoph and Ravat, Prince}, title = {Zinc-[7]helicenocyanine and its discrete π-stacked homochiral Dimer}, series = {Angewandte Chemie International Edition}, volume = {60}, journal = {Angewandte Chemie International Edition}, doi = {10.1002/anie.202109380}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-256534}, pages = {23656-23660}, year = {2021}, abstract = {In this communication, we demonstrate a novel approach to prepare a discrete dimer of chiral phthalocyanine (Pc) by exploiting the flexible molecular geometry of helicenes, which enables structural interlocking and strong aggregation tendency of Pcs. Synthesized [7]helicene-Pc hybrid molecular structure, zinc-[7]helicenocyanine (Zn-7HPc), exclusively forms a stable dimeric pair consisting of two homochiral molecules. The dimerization constants were estimated to be as high as 8.96×10\(^6\) M\(^{-1}\) and 3.42×107 M\(^{-1}\) in THF and DMSO, respectively, indicating remarkable stability of dimer. In addition, Zn\(^{-7}\)HPc exhibited chiral self-sorting behavior, which resulted in preferential formation of a homochiral dimer also in the racemic sample. Two phthalocyanine subunits in the dimeric form strongly communicate with each other as revealed by a large comproportionation constant and observation of an IV-CT band for the thermodynamically stable mixed-valence state.}, language = {en} } @article{KabingerStillerSchmitzovaetal.2021, author = {Kabinger, Florian and Stiller, Carina and Schmitzov{\´a}, Jana and Dienemann, Christian and Kokic, Goran and Hillen, Hauke S. and H{\"o}bartner, Claudia and Cramer, Patrick}, title = {Mechanism of molnupiravir-induced SARS-CoV-2 mutagenesis}, series = {Nature Structural \& Molecular Biology}, volume = {28}, journal = {Nature Structural \& Molecular Biology}, doi = {10.1038/s41594-021-00651-0}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-254603}, pages = {740-746}, year = {2021}, abstract = {Molnupiravir is an orally available antiviral drug candidate currently in phase III trials for the treatment of patients with COVID-19. Molnupiravir increases the frequency of viral RNA mutations and impairs SARS-CoV-2 replication in animal models and in humans. Here, we establish the molecular mechanisms underlying molnupiravir-induced RNA mutagenesis by the viral RNA-dependent RNA polymerase (RdRp). Biochemical assays show that the RdRp uses the active form of molnupiravir, β-d-\(N^4\)-hydroxycytidine (NHC) triphosphate, as a substrate instead of cytidine triphosphate or uridine triphosphate. When the RdRp uses the resulting RNA as a template, NHC directs incorporation of either G or A, leading to mutated RNA products. Structural analysis of RdRp-RNA complexes that contain mutagenesis products shows that NHC can form stable base pairs with either G or A in the RdRp active center, explaining how the polymerase escapes proofreading and synthesizes mutated RNA. This two-step mutagenesis mechanism probably applies to various viral polymerases and can explain the broad-spectrum antiviral activity of molnupiravir.}, language = {en} } @article{WehRueheHerbertetal.2021, author = {Weh, Manuel and R{\"u}he, Jessica and Herbert, Benedikt and Krause, Ana-Maria and W{\"u}rthner, Frank}, title = {Deracemization of Carbohelicenes by a Chiral Perylene Bisimide Cyclophane Template Catalyst}, series = {Angewandte Chemie International Edition}, volume = {60}, journal = {Angewandte Chemie International Edition}, number = {28}, doi = {10.1002/anie.202104591}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-244787}, pages = {15323 -- 15327}, year = {2021}, abstract = {Deracemization describes the conversion of a racemic mixture of a chiral molecule into an enantioenriched mixture or an enantiopure compound without structural modifications. Herein, we report an inherently chiral perylene bisimide (PBI) cyclophane whose chiral pocket is capable of transforming a racemic mixture of [5]-helicene into an enantioenriched mixture with an enantiomeric excess of 66 \%. UV/Vis and fluorescence titration studies reveal this cyclophane host composed of two helically twisted PBI dyes has high binding affinities for the respective homochiral carbohelicene guests, with outstanding binding constants of up to 3.9×10\(^{10}\) m\(^{-1}\) for [4]-helicene. 2D NMR studies and single-crystal X-ray analysis demonstrate that the observed strong and enantioselective binding of homochiral carbohelicenes and the successful template-catalyzed deracemization of [5]-helicene can be explained by the enzyme-like perfect shape complementarity of the macrocyclic supramolecular host.}, language = {en} } @article{MieczkowskiSteinmetzgerBessietal.2021, author = {Mieczkowski, Mateusz and Steinmetzger, Christian and Bessi, Irene and Lenz, Ann-Kathrin and Schmiedel, Alexander and Holzapfel, Marco and Lambert, Christoph and Pena, Vladimir and H{\"o}bartner, Claudia}, title = {Large Stokes shift fluorescence activation in an RNA aptamer by intermolecular proton transfer to guanine}, series = {Nature Communications}, volume = {12}, journal = {Nature Communications}, doi = {10.1038/s41467-021-23932-0}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-270274}, year = {2021}, abstract = {Fluorogenic RNA aptamers are synthetic functional RNAs that specifically bind and activate conditional fluorophores. The Chili RNA aptamer mimics large Stokes shift fluorescent proteins and exhibits high affinity for 3,5-dimethoxy-4-hydroxybenzylidene imidazolone (DMHBI) derivatives to elicit green or red fluorescence emission. Here, we elucidate the structural and mechanistic basis of fluorescence activation by crystallography and time-resolved optical spectroscopy. Two co-crystal structures of the Chili RNA with positively charged DMHBO+ and DMHBI+ ligands revealed a G-quadruplex and a trans-sugar-sugar edge G:G base pair that immobilize the ligand by π-π stacking. A Watson-Crick G:C base pair in the fluorophore binding site establishes a short hydrogen bond between the N7 of guanine and the phenolic OH of the ligand. Ultrafast excited state proton transfer (ESPT) from the neutral chromophore to the RNA was found with a time constant of 130 fs and revealed the mode of action of the large Stokes shift fluorogenic RNA aptamer.}, language = {en} } @article{Roehr2021, author = {R{\"o}hr, Merle I. S.}, title = {New theoretical methods for the exploration of functional landscapes}, series = {International Journal of Quantum Chemistry}, volume = {121}, journal = {International Journal of Quantum Chemistry}, number = {24}, doi = {10.1002/qua.26747}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-257682}, year = {2021}, abstract = {Molecular functionality can be often directly attributed to given properties of the electronic wavefunction. Analogous to the potential energy surface, these properties can be represented as a function of the nuclear coordinates, giving rise to molecular "functional landscapes." However, so far there has been no possibility for their systematic investigation. This perspective aims to discuss the development of new theoretical methods based on the multistate extension of the metadynamics approach, employing electronic collective variables. This emerging methodology allows to explore functional landscapes and to gain a deeper understanding of the structure-function relation in molecules and complex molecular systems in the ground and excited electronic state.}, language = {en} } @article{ZimniakKirschnerHilpertetal.2021, author = {Zimniak, Melissa and Kirschner, Luisa and Hilpert, Helen and Geiger, Nina and Danov, Olga and Oberwinkler, Heike and Steinke, Maria and Sewald, Katherina and Seibel, J{\"u}rgen and Bodem, Jochen}, title = {The serotonin reuptake inhibitor Fluoxetine inhibits SARS-CoV-2 in human lung tissue}, series = {Scientific Reports}, volume = {11}, journal = {Scientific Reports}, doi = {10.1038/s41598-021-85049-0}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-259820}, pages = {5890}, year = {2021}, abstract = {To circumvent time-consuming clinical trials, testing whether existing drugs are effective inhibitors of SARS-CoV-2, has led to the discovery of Remdesivir. We decided to follow this path and screened approved medications "off-label" against SARS-CoV-2. Fluoxetine inhibited SARS-CoV-2 at a concentration of 0.8 mu g/ml significantly in these screenings, and the EC50 was determined with 387 ng/ml. Furthermore, Fluoxetine reduced viral infectivity in precision-cut human lung slices showing its activity in relevant human tissue targeted in severe infections. Fluoxetine treatment resulted in a decrease in viral protein expression. Fluoxetine is a racemate consisting of both stereoisomers, while the S-form is the dominant serotonin reuptake inhibitor. We found that both isomers show similar activity on the virus, indicating that the R-form might specifically be used for SARS-CoV-2 treatment. Fluoxetine inhibited neither Rabies virus, human respiratory syncytial virus replication nor the Human Herpesvirus 8 or Herpes simplex virus type 1 gene expression, indicating that it acts virus-specific. Moreover, since it is known that Fluoxetine inhibits cytokine release, we see the role of Fluoxetine in the treatment of SARS-CoV-2 infected patients of risk groups.}, language = {en} } @article{SchembriKimLiessetal.2021, author = {Schembri, Tim and Kim, Jin Hong and Liess, Andreas and Stepanenko, Vladimir and Stolte, Matthias and W{\"u}rthner, Frank}, title = {Semitransparent Layers of Social Self-Sorting Merocyanine Dyes for Ultranarrow Bandwidth Organic Photodiodes}, series = {Advanced Optical Materials}, volume = {9}, journal = {Advanced Optical Materials}, number = {15}, doi = {10.1002/adom.202100213}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-244762}, year = {2021}, abstract = {Two dipolar merocyanines consisting of the same π-conjugated chromophore but different alkyl substituents adopt very different packing arrangements in their respective solid state with either H- or J-type exciton coupling, leading to ultranarrow absorption bands at 477 and 750 nm, respectively, due to exchange narrowing. The social self-sorting behavior of these push-pull chromophores in their mixed thin films is evaluated and the impact on morphology as well as opto-electronical properties is determined. The implementation of this well-tuned two-component material with tailored optical features allows to optimize planar heterojunction organic photodiodes with fullerene ​(C\(_{60}\)) with either dual or single wavelength selectivity in the blue and NIR spectral range with ultranarrow bandwidths of only 11 nm (200 cm\(^{-1}\)) and an external quantum efficiency of up to 18\% at 754 nm under 0 V bias. The application of these photodiodes as low-power consuming heart rate monitors is demonstrated by a reflectance-mode photoplethysmography (PPG) sensor.}, language = {en} }