An interfacial synthesis route was recently established to prepare epoxide-based membranes for water purification. Herein, the epoxide is dissolved in toluene and reacts with a tertiary amine dissolved in water. However, to date the exact mechanism of the polyether film formation at the water/organic interface is poorly understood. The aim of this work was to bridge the gap between membrane engineering and polymer chemistry by investigating the influence of water on the ring-opening polymerization of a model epoxide monomer, phenyl glycidyl ether (PhGE), by four tertiary amine initiators (i.e., N,N-dimethyl hexylamine, imidazole, 1-methyl imidazole, and N,N,N',N'-tetramethyl hexane diamine). This was done in a homogenous system in toluene, i.e. via solution polymerization, as well as in a heterogenous toluene/water system, i.e., via interfacial polymerization. The pseudo-first order plots of the homogenous system showed long induction periods and slow reaction rates. Surprisingly, a strong catalytic effect of trace amounts of water was observed, as demonstrated by the significant increase in reaction rate (up to 28 times) and a decrease in the induction period (by 10 days), which occurred upon the addition of water. Characterization of the synthesized polymers with ESI-MS indicated successful initiation by all tested tertiary amines, but side reactions also occurred. In addition, polyether formation was successful in the studied interfacial system. The achievable molar mass and the species that initiated the reaction (i.e., amine, PhGE, water/hydroxide) depended both on the amine:epoxide ratio and the pH. Observed discrepancies between the homogeneous and heterogeneous system appear to be largely influenced by the properties of the amine initiator.

In search for new RNA modifications in E. coli tRNA we elucidated a disulfide-bridged dimer of 4-thiouridine which was identified as an ex vivo artifact and is formed during sample handling in the presence of ambient oxygen.

The selective electrocatalytic conversion of CO2 into multicarbon products, such as ethanol, is a major technological challenge. Currently, this reactivity is limited by the sluggish formation of C-C bonds inherent to many single-site catalysts. Here, we report a new tandem electrocatalyst based on earth-abundant elements, which facilitates the selective CO2-to-ethanol conversion. The composite catalyst consists of neighboring cobalt and copper atoms anchored to electrically conductive nitrogen-doped carbon. At low overpotentials (E = -0.8 V vs reversible hydrogen electrode), the system shows high selectivity for ethanol production (faradaic efficiencies >70%), while retaining its reactivity and stability for 18 h. A CO spillover mechanism is proposed as the basis for the observed selectivity, where efficient CO generation at Co sites leads to high local CO concentrations at neighboring Cu sites, thereby favoring C-C coupling and ethanol formation. Operando X-ray absorption spectroscopy reveals a dynamic transformation of the single-site Cu into Cu clusters as actual active sites. In situ infrared spectroscopy reveals the formation of intermediate CO at Co sites, which undergo subsequent spillover and C-C coupling on the Cu clusters. This design concept offers new avenues for noble metal-free tandem electrocatalysts for the conversion of CO2-to-multicarbon products.

'On-water' catalysis entails the significant enhancement of a chemical reaction by water, even when those reactions are known to be water-sensitive. Here, the findings about the anionic ring opening polymerization of epoxides at the static interface between oil and alkaline water are shared. Unexpectedly, high molar mass fractions are observed with the interfacial system presented herein, albeit at very low conversions (< 5%). Styrene oxide, a notably unreactive epoxide, is chosen as the model compound to investigate the influence of several reaction parameters (i.e., pH, type of the initiator salt, polymerization time, interfacial area, solvent, shaking) on the polymerization. Poly(styrene oxide) (PSO) with an Mn of 5300 g mol(-1) is observed via MALDI-ToF MS, with species of at least 8000 g mol(-1). The feasibility of expanding the system to (cyclic) aliphatic and aromatic epoxides, and glycidyl ethers is also explored. The system appears to promote polymerization of epoxides that position at the interface, in such a way that initiation and propagation can occur. A mechanistic interpretation of the interfacial polymerization is suggested. The surprising results obtained in this work urge to revisit the role of water in ionic polymerizations.

The continuous deciphering of crucial biological roles of RNA modifications and their involvement in various pathological conditions, together with their key roles in the use of RNA-based therapeutics, has reignited interest in studying the occurrence and identity of non-canonical ribonucleoside structures during the past years. Discovery and structural elucidation of new modified structures is usually achieved by combination of liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) at the nucleoside level and stable isotope labeling experiments. This approach, however, has its pitfalls as demonstrated in the course of the present study: we structurally elucidated a new nucleoside structure that showed significant similarities to the family of (c)t6A modifications and was initially considered a genuine modification, but subsequently turned out to be an in vitro formed glycerol ester of t6A. This artifact is generated from ct6A during RNA hydrolysis upon addition of enzymes stored in glycerol containing buffers in a mildly alkaline milieu, and was moreover shown to undergo an intramolecular transesterification reaction. Our results demand for extra caution, not only in the discovery of new RNA modifications, but also with regard to the quantification of known modified structures, in particular chemically labile modifications, such as ct6A, that might suffer from exposure to putatively harmless reagents during the diverse steps of sample preparation.

Centaurea is a genus compromising over 250 herbaceous flowering species and is used traditionally to treat several ailments. Among the Egyptian Centaurea species, C. lipii was reported to be cytotoxic against multidrug-resistant cancer cells. In this context, we aimed to explore the metabolome of C. lipii and compare it to other members of the genus in pursuance of identifying its bioactive principles. An LC-MS/MS analysis approach synchronized with feature-based molecular networks was adopted to offer a holistic overview of the metabolome diversity of the Egyptian Centaurea species. The studied plants included C. alexandrina, C. calcitrapa, C. eryngioides, C. glomerata, C. lipii, C. pallescens, C. pumilio, and C. scoparia. Their constitutive metabolome showed diverse chemical classes such as cinnamic acids, sesquiterpene lactones, flavonoids, and lignans. Linking the recorded metabolome to the previously reported cytotoxicity identified sesquiterpene lactones as the major contributors to this activity. To confirm our findings, bioassay-guided fractionation of C. lipii was adopted and led to the isolation of the sesquiterpene lactone cynaropicrin with an IC50 of 1.817 µM against the CCRF-CEM leukemia cell line. The adopted methodology highlighted the uniqueness of the constitutive metabolome of C. lipii and determined the sesquiterpene lactones to be the responsible cytotoxic metabolites.

The fields of RNA modification and RNA damage both exhibit a plethora of non-canonical nucleoside structures. While RNA modifications have evolved to improve RNA function, the term RNA damage implies detrimental effects. Based on stable isotope labelling and mass spectrometry, we report the identification and characterisation of 2-methylthio-1,N6-ethenoadenosine (ms2 ϵA), which is related to 1,N6-ethenoadenine, a lesion resulting from exposure of nucleic acids to alkylating chemicals in vivo. In contrast, a sophisticated isoprene labelling scheme revealed that ms2 ϵA biogenesis involves cleavage of a prenyl moiety in the known transfer RNA (tRNA) modification 2-methylthio-N6-isopentenyladenosine (ms2 i6 A). The relative abundance of ms2 ϵA in tRNAs from translating ribosomes suggests reduced function in comparison to its parent RNA modification, establishing the nature of the new structure in a newly perceived overlap of the two previously separate fields, namely an RNA modification damage.

AbstractDie Bereiche RNA‐Modifikation und RNA‐Schaden weisen beide eine Vielzahl nicht‐kanonischer Nukleosidstrukturen auf. Während sich RNA‐Modifikationen zur Verbesserung der RNA‐Funktion entwickelt haben, impliziert die Bezeichnung RNA‐Schaden negative Auswirkungen. Auf Grundlage der Markierung mit stabilen Isotopen und Massenspektrometrie berichten wir von der Identifizierung und Charakterisierung von 2‐Methylthio‐1,N6‐ethenoadenosin (ms2ϵA), welches mit 1,N6‐Ethenoadenin, einer Läsion, die durch Exposition von Nukleinsäuren gegenüber alkylierenden Chemikalien in vivo entsteht, verwandt ist. Im Gegensatz dazu zeigte ein ausgefeiltes Konzept zur Isopren‐Markierung, dass die Biogenese von ms2ϵA die Spaltung eines Prenylrests in der bekannten transfer‐RNA (tRNA)‐Modifikation 2‐Methylthio‐N6‐isopentenyladenosin (ms2i6A) beinhaltet. Die relative Häufigkeit von ms2ϵA in tRNAs von translatierenden Ribosomen lässt eine verminderte Funktionalität im Vergleich zur ursprünglichen RNA‐Modifikation vermuten, wodurch die Natur der neuen Struktur in einer neu wahrgenommenen Überschneidung der beiden zuvor getrennten Bereiche, nämlich ein RNA‐Modifikationsschaden, begründet wird.

Periodate, a platform oxidizer, can be electrochemically recycled in a self-cleaning process. Electrosynthesis of periodate is well established at boron-doped diamond (BDD) anodes. However, recovered iodate and other iodo species for recycling can contain traces of organic impurities from previous applications. For the first time, it was shown that the organic impurities do not hamper the electrochemical re-oxidation of used periodate. In a hydroxyl-mediated environment, the organic compounds form CO2 and H2 O during the degradation process. This process is often referred to as "cold combustion" and provides orthogonal conditions to periodate synthesis. To demonstrate the strategy, different dyes, pharmaceutically active ingredients, and iodine compounds were added as model contaminations into the process of electrochemical periodate production. UV/Vis spectroscopy, NMR spectroscopy, and mass spectrometry (MS) were used to monitor the degradation of organic molecules, and liquid chromatography-MS was used to control the purity of periodate. As a representative example, dimethyl 5-iodoisophthalate (2 mm), was degraded in 90, 95, and 99 % while generating 0.042, 0.054, and 0.082 kilo equiv. of periodate, respectively. In addition, various organic iodo compounds could be fed into the periodate generation for upcycling such iodo-containing waste, for example, contrast media.

Depression and anxiety disorders are widespread diseases, and they belong to the leading causes of disability and greatest burdens on healthcare systems worldwide. It is expected that the numbers will dramatically rise during the COVID-19 pandemic. Established medications are not sufficient to adequately treat depression and are not available for everyone. Plants from traditional medicine may be promising alternatives to treat depressive symptoms. The model organism Chaenorhabditis elegans was used to assess the stress reducing effects of methanol/dichlormethane extracts from plants used in traditional medicine. After initial screening for antioxidant activity, nine extracts were selected for in vivo testing in oxidative stress, heat stress, and osmotic stress assays. Additionally, anti-aging properties were evaluated in lifespan assay. The extracts from Acanthopanax senticosus, Campsis grandiflora, Centella asiatica, Corydalis yanhusuo, Dan Zhi, Houttuynia cordata, Psoralea corylifolia, Valeriana officinalis, and Withaniasomnifera showed antioxidant activity of more than 15 Trolox equivalents per mg extract. The extracts significantly lowered ROS in mutants, increased resistance to heat stress and osmotic stress, and the extended lifespan of the nematodes. The plant extracts tested showed promising results in increasing stress resistance in the nematode model. Further analyses are needed, in order to unravel underlying mechanisms and transfer results to humans.

Background: Irritable bowel syndrome (IBS) is a functional bowel disorder, in which recurrent abdominal pain is associated with defecation or a change in bowel habits. STW 5-II is a combination of six medicinal herbs with a clinically proven efficacy in managing IBS. Aim: This study aims to establish an in vitro IBS model using mouse intestinal organoids and to explore the anti-inflammatory and tight junction protective activities of the multi-herbal preparation STW 5-II. Methods: Intestinal organoids were cultured in 1:1 Matrigel (TM) and medium domes. Inflammation and tight junction disruption were induced by a cocktail of cytokines (TNF alpha, IFN gamma, IL-1 beta, IL-6) and bacterial proteins (LPS, flagellin). Organoids were treated with different concentrations of STW 5-II, and its multi-target activity was assessed using microarray analyses, RT-qPCR, immunofluorescence, western blot, immunohistochemistry, and a FITC permeability assay. In addition, we analyzed the expression of pNF-kappa B, pSTAT1, iNOS and ZO-1. In silico analyses were conducted to predict and identify the active components that may be responsible in mediating the multi-target anti-inflammatory activity of STW 5-II. Results: An organoid based IBS model was successfully established. STW 5-II effectively reduced the cytokines-induced overexpression of the pro-inflammatory mediators pNF-kappa B, pSTAT1 and iNOS. Moreover, STW 5-II attenuated cytokine-mediated downregulation of the tight junction protein, ZO-1. This finding was confirmed by a FITC permeability assay. In silico analyses revealed a promising inhibitory activity of some isolated compounds from STW 5-II against NF-kappa B, STAT1 and iNOS. Conclusion: STW 5-II possesses multiple anti-inflammatory as well as tight junction protective activities that could explain its clinically proven efficacy in managing IBS symptoms.

An efficient, inexpensive, and reliable synthesis of diaminomaleonitrile (DAMN, 1) is described starting from readily available acetone cyanohydrin as the source of hydrogen cyanide (HCN). Diaminomaleonitrile (DAMN) is known to be an important intermediate in heterocyclic and medicinal chemistry as well as being a possible precursor for the origin of life's hypothesis within prebiotic chemistry. The mechanism of its formation through organosulfur catalysis has been investigated by electrospray ionization mass spectrometry (ESI-MS) using two newly synthesized cationic "marker" molecules as a tool that allows for sensitive detection. As a result, the proposed mechanism of a thiocyanate-mediated synthesis of the HCN tetramer DAMN starting from organic disulfides was confirmed.

The popular beverage green tea possesses chemopreventive activity against various types of tumors. However, the effects of its chemopreventive effect on hematological malignancies have not been defined. In the present study, we evaluated antitumor efficacies of a specific green tea, sencha tea, on sensitive and multidrug-resistant leukemia and a panel of nine multiple myelomas (MM) cell lines. We found that sencha extracts induced cytotoxicity in leukemic cells and MM cells to different extents, yet its effect on normal cells was limited. Furthermore, sencha extracts caused G2/M and G0/G1 phase arrest during cell cycle progression in CCRF/CEM and KMS-12-BM cells, respectively. Specifically, sencha-MeOH/H2O extracts induced apoptosis, ROS, and MMP collapse on both CCRF/CEM and KMS-12-BM cells. The analysis with microarray and COMPARE in 53 cell lines of the NCI panel revealed diverse functional groups, including cell morphology, cellular growth and proliferation, cell cycle, cell death, and survival, which were closely associated with anti-tumor effects of sencha tea. It is important to note that PI3K/Akt and NF-κB pathways were the top two dominant networks by ingenuity pathway analysis. We demonstrate here the multifactorial modes of action of sencha tea leading to chemopreventive effects of sencha tea against cancer.

The concentrations of submicron aerosol particles in maritime regions around Antarctica are influenced by the extent of sea ice. This effect is two ways: on one side, sea ice regulates the production of particles by sea spray (primary aerosols); on the other side, it hosts complex communities of organisms emitting precursors for secondary particles. Past studies documenting the chemical composition of fine aerosols in Antarctica indicate various potential primary and secondary sources active in coastal areas, in offshore marine regions, and in the sea ice itself. In particular, beside the well-known sources of organic and sulfur material originating from the oxidation of dimethylsulfide (DMS) produced by microalgae, recent findings obtained during the 2015 PEGASO cruise suggest that nitrogen-containing organic compounds are also produced by the microbiota colonizing the marginal ice zone. To complement the aerosol source apportionment performed using online mass spectrometric techniques, here we discuss the outcomes of offline spectroscopic analysis performed by nuclear magnetic resonance (NMR) spectroscopy. In this study we (i) present the composition of ambient aerosols over open-ocean waters across bioregions, and compare it to the composition of (ii) seawater samples and (iii) bubble-bursting aerosols produced in a sea-spray chamber onboard the ship. Our results show that the process of aerosolization in the tank enriches primary marine particles with lipids and sugars while depleting them of free amino acids, providing an explanation for why amino acids occurred only at trace concentrations in the marine aerosol samples analyzed. The analysis of water-soluble organic carbon (WSOC) in ambient submicron aerosol samples shows distinct NMR fingerprints for three bioregions: (1) the open Southern Ocean pelagic environments, in which aerosols are enriched with primary marine particles containing lipids and sugars; (2) sympagic areas in the Weddell Sea, where secondary organic compounds, including methanesulfonic acid and semivolatile amines abound in the aerosol composition; and (3) terrestrial coastal areas, traced by sugars such as sucrose, emitted by land vegetation. Finally, a new biogenic chemical marker, creatinine, was identified in the samples from the Weddell Sea, providing another confirmation of the importance of nitrogen-containing metabolites in Antarctic polar aerosols.

Organosulfates (OSs) have been observed as substantial constituents of atmospheric organic aerosol (OA) in a wide range of environments; however, the chemical composition, sources, and formation mechanism of OSs are still not well understood. In this study, we first created an "OS precursor map" based on the elemental composition of previous OS chamber experiments. Then, according to this "OS precursor map", we estimated the possible sources and molecular structures of OSs in atmospheric PM2.5 (particles with aerodynamic diameter ≤ 2.5 μm) samples, which were collected in urban areas of Beijing (China) and Mainz (Germany) and analyzed by ultrahigh-performance liquid chromatography (UHPLC) coupled with an Orbitrap mass spectrometer. On the basis of the "OS precursor map", together with the polarity information provided by UHPLC, OSs in Mainz samples are suggested to be mainly derived from isoprene/glyoxal or other unknown small polar organic compounds, while OSs in Beijing samples were generated from both isoprene/glyoxal and anthropogenic sources (e.g., long-chain alkanes and aromatics). The nitrooxy-OSs in the clean aerosol samples were mainly derived from monoterpenes, while much fewer monoterpene-derived nitrooxy-OSs were obtained in the polluted aerosol samples, showing that nitrooxy-OS formation is affected by different precursors in clean and polluted air conditions.

Arylated products are found in various fields of chemistry and represent essential entities for many applications. Therefore, the formation of this structural feature represents a central issue of contemporary organic synthesis. By the action of electricity the necessity of leaving groups, metal catalysts, stoichiometric oxidizers, or reducing agents can be omitted in part or even completely. The replacement of conventional reagents by sustainable electricity not only will be environmentally benign but also allows significant short cuts in electrochemical synthesis. In addition, this methodology can be considered as inherently safe. The current survey is organized in cathodic and anodic conversions as well as by the number of leaving groups being involved. In some electroconversions the reagents used are regenerated at the electrode, whereas in other electrotransformations free radical sequences are exploited to afford a highly sustainable process. The electrochemical formation of the aryl-substrate bond is discussed for aromatic substrates, heterocycles, other multiple bond systems, and even at saturated carbon substrates. This survey covers most of the seminal work and the advances of the past two decades in this area.

PURPOSE:Inflammatory processes are involved in many diseases. The bark of Cinnamomum verum and its extracts are well known for anti-inflammatory effects, but the underlying active compounds and chemical mechanisms are not yet fully identified. The objective of this study was to elucidate how cinnamon extract, specifically active compounds, and their combinations influence the signaling pathways of inflammation, especially through toll-like receptors TLR2 and TLR4.METHODS:Bioassay-guided fractionation was performed for standard ethanolic cinnamon extract using high performance liquid chromatography followed by compound identification in the determined active fractions by high-resolution mass spectrometry and gas chromatography-mass spectrometry. THP-1 monocytes were pre-incubated with cinnamon extract, cinnamon fractions or its compounds and stimulated with lipopolysaccharides (LPS), followed by determination of interleukin 8 (IL-8) secretion, and phosphorylation of protein kinase B (Akt), nuclear factor (NF)-κB inhibitor alpha (IκBα) and p38. Furthermore, testing was performed in stimulated HEK-TLR2 and HEK-TLR4 reporter cells for direct receptor agonistic effects.RESULTS:Among the identified compounds, trans-cinnamaldehyde and p-cymene significantly reduced the LPS-dependent IL-8 secretion in THP-1 monocytes. Synergistic anti-inflammatory effects were observed for combinations of trans-cinnamaldehyde with p-cymene, cinnamyl alcohol or cinnamic acid. Moreover, cinnamon extract as well as trans-cinnamaldehyde and p-cymene mitigated the phosphorylation of Akt and IκBα.CONCLUSIONS:Trans-cinnamaldehyde and p-cymene contribute to the strong anti-inflammatory effects of cinnamon extract. Furthermore, our experiments indicate that also synergistic effects among compounds that do not exhibit anti-inflammatory effects themselves might be present to positively influence the beneficial effects of cinnamon bark extract.