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MgO surface makes it easy to introduce a certain amount of oxygen vacancy and can enhance catalytic reaction activity. Besides, as a silicoaluminate mineral material, halloysite nanotube (HNT) has a unique tubular structure. In this paper, the HNTs@MgO composite was successfully synthesized based on natural clay material HNTs as a carrier, and the CTL sensor based on HNTs@MgO was successfully developed for the rapid determination of ether in air. The HNTs@MgO material was characterized by a series of means such as SEM, XPS, and XRD, which clearly confirmed that MgO successfully combined with HNTs. And the sensor showed good sensitivity and selectivity, with a good linear relationship between CTL intensity and ether concentration in the range of 0.5-190.0 mg/L (R 2  = 0.9942), and the limit of detection (LOD) was 0.18 mg/L (S/N = 3). The RSD values of the results of 11 consecutive measurements by the same sensor and 7 days of consecutive measurements were 1.96% (n = 11) and 3.42% (n = 7), showing good repeatability and reproducibility. At last, the CTL sensor was used to detect air samples, the recoveries ranged from 91.6% to 109.6%. Thus, it was concluded that HNTs@MgO composite is a cost-effective and promising material with potential application in atmospheric detection., (© 2024 John Wiley & Sons Ltd.)

Background: Ether-linked phosphatidylcholines (PCs) include both plasmanyl and plasmenyl PCs, which contain an ether or a vinyl ether bond at the sn-1 linkage position, respectively. Profiling and quantifying ether PCs with accurate structural information is challenging because of the common presence of isomeric and isobaric species in a lipidome., Results: In the present study, radical directed dissociation (RDD) from collision-induced dissociation (CID) of the bicarbonate anion adduct of ether PCs has been investigated to differentiate and relatively quantify ether PCs. Alkyl- and alkenyl- PCs give diagnostic characteristic fragment patterns that enable their confident identification and isomer differentiation. Additionally, the sn-position specific product ions have proven effective for relative quantitation among isomers in ether PCs and their isobaric PC species. Using this methodology, we successfully identified a total of 30 PC-O species, 21 PC-P species at the chain composition level, and 22 species of isobaric PC at the sn-position level in the human plasma lipid extract. The quantitative analysis revealed that ether PCs with a 20:4 fatty acyl chain are relatively more abundant in human plasma. Finally, the profile of ether PCs in type 2 diabetic (T2D) groups compared to normal control groups revealed a significant decrease in PC-O 18:1/20:5. We also found it is the PC species containing a 17-carbon fatty acyl chain, rather than their isobaric ether PCs, that shows a decreasing trend in the T2D groups., Significance: ether-linked PCs are firstly investigated by RDD mass spectrometry., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Hyperpolarized 129 Xe gas was FDA-approved as an inhalable contrast agent for magnetic resonance imaging of a wide range of pulmonary diseases in December 2022. Despite the remarkable success in clinical research settings, the widespread clinical translation of HP 129 Xe gas faces two critical challenges: the high cost of the relatively low-throughput hyperpolarization equipment and the lack of 129 Xe imaging capability on clinical MRI scanners, which have narrow-bandwidth electronics designed only for proton ( 1 H) imaging. To solve this translational grand challenge of gaseous hyperpolarized MRI contrast agents, here we demonstrate the utility of batch-mode production of proton-hyperpolarized diethyl ether gas via heterogeneous pairwise addition of parahydrogen to ethyl vinyl ether. An approximately 0.1-liter bolus of hyperpolarized diethyl ether gas was produced in 1 second and injected in excised rabbit lungs. Lung ventilation imaging was performed using sub-second 2D MRI with up to 2×2 mm 2 in-plane resolution using a clinical 0.35 T MRI scanner without any modifications. This feasibility demonstration paves the way for the use of inhalable diethyl ether as a gaseous contrast agent for pulmonary MRI applications using any clinical MRI scanner., (© 2024 Wiley-VCH GmbH.)

The dehydration of ethanol into diethyl ether over a SO 4 /SiO 2 catalyst was investigated. The SO 4 /SiO 2 catalysts were prepared by the sulfation method using 1, 2, and 3 M of sulfuric acid (SS1, SS2, and SS3) via hydrothermal treatment. This study is focused on the synthesis of a SO 4 /SiO 2 catalyst with high total acidity that can be subsequently utilized to convert ethanol into diethyl ether. The total acidity test revealed that the sulfation process increased the total acidity of SiO 2 . The SS2 catalyst (with 2 M sulfuric acid) displayed the highest total acidity of 7.77 mmol/g, whereas the SiO 2 total acidity was only 0.11 mmol/g. Meanwhile, the SS3 catalyst (with 3 M sulfuric acid) has a lower total acidity of 7.09 mmol/g due to the distribution of sulfate groups on the surface having reached its optimum condition. The crystallinity and structure of the SS2 catalyst were not affected by the hydrothermal treatment or the sulfate process on silica. Furthermore, The SS2 catalyst characteristics in the presence of sulfate lead to a flaky surface in the morphology and non-uniform particle size. In addition, the surface area and pore volume of the SS2 catalyst decreased (482.56-172.26 m 2 /g) and (0.297-0.253 cc/g), respectively, because of the presence of sulfate on the silica surface. The SS2 catalyst's pore shape information explains the formation of non-uniform pore sizes and shapes. Finally, the activity and selectivity of SO 4 /SiO 2 catalysts in the conversion of ethanol to diethyl ether yielded the highest ethanol conversion of 70.01% and diethyl ether product of 9.05% from the SS2 catalyst (the catalyst with the highest total acidity). Variations in temperature reaction conditions (175-225 °C) show an optimum reaction temperature to produce diethyl ether at 200 °C (11.36%)., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Supramolecular gels, as a fascinating and useful class of soft materials, constructed from low-molecular-weight gelators via noncovalent interactions have attracted increasing attention in the past few decades. Dendrimers and dendrons are highly branched and monodisperse macromolecules with a well-defined three-dimensional architecture and multiple surface functionalities. In recent years, poly(benzyl ether) dendrimers and dendrons are found to be powerful candidates for constructing gel phase materials in organic or aqueous media due to the advantages of capability of forming multiple noncovalent interactions and significant steric impact. In this Feature Article, we provide a comprehensive overview of recent progress in supramolecular gels involving poly(benzyl ether) dendritic molecules. Firstly, we outline the molecular design strategies of dendritic gelators with an emphasis on the discussion of their gelating units and position in molecular structures. Subsequently, we discuss the potential applications of dendritic gels in light harvesting, stimuli responsive materials, sensors and environmental remediation. In addition, the potential challenges and future perspectives of poly(benzyl ether) dendritic gels have also been discussed. It is hoped that this feature article will attract increasing attention and provide some valuable insights for the future design and evolution of supramolecular gels.

This study concerns bio-based urethane prepolymers. The relationship between the chemical structure and the thermal and processing parameters of bio-based isocyanate-terminated ether and ester-urethane prepolymers was investigated. Bio-based prepolymers were obtained with the use of bio-monomers such as bio-based diisocyanate, bio-based polyether polyol or polyester polyols. In addition to their composition, the bio-based prepolymers were different in the content of iso-cyanate groups content (ca. 6 and 8%). The process of pre-polymerization and the obtained bio-based prepolymers were analyzed by determining the content of unreacted NCO groups, Fourier transform infrared spectroscopy, proton nuclear magnetic resonance, thermogravimetry, and rheological measurements. The research conducted facilitated the evaluation of the properties and processability of urethane prepolymers based on natural components. The results indicate that a significant impact on the processability has the origin the polyol ingredient as well as the NCO content. The thermal stability of all of the prepolymers is similar. A prepolymer based on a poly-ether polyol is characterized by a lower viscosity at a lower temperature than the prepolymer based on a polyester polyol. The viscosity value depends on the NCO content.

Several naturally occurring cyclopentenones, such as palmenones and nigrosporiones, exhibit antimicrobial activity. Herein we describe the antimicrobial activity of cyclopentenones and derivatives that can be easily accessed from biomass derivatives furfural and 5-hydroxymethylfurfural. Upon screening a range of functionalized trans-diamino-cyclopentenones (DCPs) and δ-lactone-fused cyclopentenones (LCPs), an oxime ether derivative of DCP was identified that exhibited remarkable antimicrobial activity against Gram-positive bacteria, including resistant strains such as methicillin-resistant S. aureus (MRSA) and vancomycin-resistant E. faecalis (VRE) strains., (© 2021 The Authors. ChemMedChem published by Wiley-VCH GmbH.)

Numerous species of Allium genus have been used in the traditional medicine based on their vast biological effects, e.g., antimicrobial, digestion stimulant, anti-sclerotic, soothing, antiradical or wound healing properties. In this work, unpolar and polar extracts from two lesser-investigated species of Allium growing in Kazakhstan, Allium galanthum Kar. & Kir. (AG) and A. turkestanicum Regel. (AT), were studied for their composition and biological effects. In the HPLC-ESI-QTOF-MS/MS analyses of water and alcoholic extracts simple organic acids, flavonoids and their glycosides were found to be the best represented group of secondary metabolites. On the other hand, in the GC-MS analysis diethyl ether, extracts were found to be rich sources of straight-chain hydrocarbons and their alcohols, fatty acids and sterols. The antimicrobial activity assessment showed a lower activity of polar extracts, however, the diethyl ether extract from AT bulbs and AG chives showed the strongest activity against Bacillus subtilis ATCC 6633, B. cereus ATCC 10876, some species of Staphylococcus ( S. aureus ATCC 25923 and S. epidermidis ATCC 12228) and all tested Candida species ( Candida albicans ATCC 2091, Candida albicans ATCC 10231, Candida glabrata ATCC 90030, Candida krusei ATCC 14243 and Candida parapsilosis ATCC 22019) with a minimum inhibitory concentration of 0.125-0.5 mg/mL. The highest antiradical capacity exhibited diethyl ether extracts from AG bulbs (IC50 = 19274.78 ± 92.11 mg Trolox eq/g of dried extract) in DPPH assay. In ABTS scavenging assay, the highest value of mg Trolox equivalents, 50.85 ± 2.90 was calculated for diethyl ether extract from AT bulbs. The same extract showed the highest inhibition of mushroom tyrosinase (82.65 ± 1.28% of enzyme activity), whereas AG bulb ether extract was the most efficient murine tyrosinase inhibitor (54% of the enzyme activity). The performed tests confirm possible cosmeceutical applications of these plants.

Antibiotic-resistant infections present significant challenges to patients. As a result, there is considerable need for new antibacterial therapies that eradicate pathogenic bacteria through non-conventional mechanisms. Our group has identified a series of halogenated phenazine (HP) agents that induce rapid iron starvation that leads to potent killing of methicillin-resistant Staphylococcus aureus biofilms. Here, we report the design, chemical synthesis and microbiological assessment of a HP-quinone ether prodrug model aimed to (1) eliminate general (off-target) iron chelation, and (2) release an active HP agent through the bioreduction of a quinone trigger. Here, we demonstrate prodrug analogue HP-29-Q to have a stable ether linkage that enables HP release and moderate to good antibacterial activities against lab strains and multi-drug resistant clinical isolates.

Addition of the silylated tag (STag) enables peptides to be highly soluble in CPME, allowing them to be used at high concentrations in a coupling reaction to enhance reactivity and achieve effective synthesis of sterically hindered peptides. We described the development of a continuous one-pot STag-assisted peptide synthesis platform as a method that provides near-stoichiometric, speedy, environmentally friendly, and scalable peptide synthesis.

The sesquiterpene cyclases pentalenene synthase (PenA) and two Δ 6 -protoilludene synthases Omp6 and Omp7 convert a FPP ether into several new tetrahydrofurano terpenoids, one of which is also formed as the main product by the sesquiterpene cyclase BcBOT2. Thus, PenA, Omp6/7, and BcBOT2 follow closely related catalytic pathways and induce similar folding of their diphosphate substrates despite low levels of amino acid sequence similarity. Some of the new terpenoids show pronounced olfactoric properties.

Traditional Chinese medicines (TCMs) have been a rich source of novel drug discovery, and Cassia seed is one of the common TCMs with numerous biological effects. Based on the existing reports on neuroprotection by Cassia seed extract, the present study aims to search possible pharmacological targets behind the neuroprotective effects of the Cassia seeds by evaluating the functional effect of specific Cassia compounds on various G-protein-coupled receptors. Among the four test compounds (cassiaside, rubrofusarin gentiobioside, aurantio-obtusin, and 2-hydroxyemodin 1-methylether), only aurantio-obtusin demonstrated a specific V 1A R antagonist effect (71.80 ± 6.0% inhibition at 100 µM) and yielded an IC 50 value of 67.70 ± 2.41 μM. A molecular docking study predicted an additional interaction of the hydroxyl group at C6 and a methoxy group at C7 of aurantio-obtusin with the Ser341 residue as functional for the observed antagonist effect. In the transient brain ischemia/reperfusion injury C57BL/6 mice model, aurantio-obtusin attenuated the latency time that was reduced in the bilateral common carotid artery occlusion (BCCAO) groups. Likewise, compared to neuronal damage in the BCCAO groups, treatment with aurantio-obtusin (10 mg/kg, p.o.) significantly reduced the severity of damage in medial cornu ammonis 1 (mCA1), dorsal CA1, and cortex regions. Overall, the findings of this study highlight V 1A R as a possible target of aurantio-obtusin for neuroprotection.

Eurysoloids A ( 1 ) and B ( 2 ), two novel diastereomeric sesterterpenoids possessing a pentacyclic 5/6/5/10/5 framework with an unusual macrocyclic ether system, were isolated from Eurysolen gracilis Prain. Their structures were unambiguously determined by spectroscopic, single-crystal X-ray diffraction and DP4+ analyses. A plausible biosynthetic pathway for compounds 1 and 2 was proposed. Both compounds exhibited immunosuppressive activity via inhibiting the production of cytokine IFN-γ of T cells, and compound 2 inhibited adipogenesis in 3T3-L1 adipocytes.

Biological structure-function relationships offer incomparable paradigms for charge-transfer (CT) science and its implementation in solar-energy engineering, organic electronics, and photonics. Electrets are systems with co-directionally oriented electric dopes with immense importance for CT science, and bioinspired molecular electrets are polyamides of anthranilic-acid derivatives with designs originating from natural biomolecular motifs. This publication focuses on the synthesis of molecular electrets with ether substituents. As important as ether electret residues are for transferring holes under relatively high potentials, the synthesis of their precursors presents formidable challenges. Each residue in the molecular electrets is introduced as its 2-nitrobenzoic acid (NBA) derivative. Hence, robust and scalable synthesis of ether derivatives of NBA is essential for making such hole-transfer molecular electrets. Purdie-Irvine alkylation, using silver oxide, produces with 90% yield the esters of the NBA building block for iso-butyl ether electrets. It warrants additional ester hydrolysis for obtaining the desired NBA precursor. Conversely, Williamson etherification selectively produces the same free-acid ether derivative in one-pot reaction, but a 40% yield. The high yields of Purdie-Irvine alkylation and the selectivity of the Williamson etherification provide important guidelines for synthesizing building blocks for bioinspired molecular electrets and a wide range of other complex ether conjugates.

A series of fluorinated 7-hydroxycoumarin derivatives containing an oxime ether moiety have been designed, synthesized and evaluated for their antifungal activity. All the target compounds were determined by 1 H-NMR, 13 C-NMR, FTIR and HR-MS spectra. The single-crystal structures of compounds 4e , 4h , 5h and 6c were further confirmed using X-ray diffraction. The antifungal activities against Botrytis cinerea ( B. cinerea ), Alternaria solani ( A. solani ), Gibberella zeae ( G. zeae ), Rhizoctorzia solani ( R. solani ), Colletotrichum orbiculare ( C. orbiculare ) and Alternaria alternata ( A. alternata ) were evaluated in vitro. The preliminary bioassays showed that some of the designed compounds displayed the promising antifungal activities against the above tested fungi. Strikingly, the target compounds 5f and 6h exhibited outstanding antifungal activity against B. cinerea at 100 μg/mL, with the corresponding inhibition rates reached 90.1 and 85.0%, which were better than the positive control Osthole (83.6%) and Azoxystrobin (46.5%). The compound 5f was identified as the promising fungicide candidate against B. cinerea with the EC 50 values of 5.75 μg/mL, which was obviously better than Osthole (33.20 μg/mL) and Azoxystrobin (64.95 μg/mL). Meanwhile, the compound 5f showed remarkable antifungal activities against R. solani with the EC 50 values of 28.96 μg/mL, which was better than Osthole (67.18 μg/mL) and equivalent to Azoxystrobin (21.34 μg/mL). The results provide a significant foundation for the search of novel fluorinated 7-hydroxycoumarin derivatives with good antifungal activity.

Nanoporous microparticles prepared from poly(ether imide) (PEI) are discussed as candidate adsorber materials for the removal of uremic toxins during apheresis. Polymers exhibiting such porosity can induce the formation of micro-gas/air pockets when exposed to fluids. Such air presenting material surfaces are reported to induce platelet activation and thrombus formation. Physical or chemical treatments prior to implantation are discussed to reduce the formation of such gas nuclei. Here, we report about the influence of different rewetting procedures - as chemical treatments with solvents - on the thrombogenicity of hydrophobic PEI microparticles and PEI microparticles hydrophilized by covalent attachment of poly(vinyl pyrrolidone) (PVP) of two different chain lengths.Autoclaved dry PEI particles of all types with a diameter range of 200 - 250 μm and a porosity of about 84% ±2% were either rewetted directly with phosphate buffered saline (24 h) or after immersion in an ethanol-series. Thrombogenicity of the particles was studied in vitro upon contact with human sodium citrated whole blood for 60 min at 5 rpm vertical rotation. Numbers of non-adherent platelets were quantified, and adhesion of blood cells was qualitatively analyzed by bright field microscopy. Platelet activation (percentage of CD62P positive platelets and amounts of soluble P-Selectin) and platelet function (PFA100 closure times) were analysed.Retention of blood platelets on the particles was similar for all particle types and both rewetting procedures. Non-adherent platelets were less activated after contact with ethanol-treated particles of all types compared to those rewetted with phosphate buffered saline as assessed by a reduced number of CD62P-positive platelets and reduced amounts of secreted P-Selectin (P < 0.05 each). Interestingly, the hydrophilic surfaces significantly increased the number of activated platelets compared to hydrophobic PEI regardless of the rewetting agent. This suggests that, apart from wettability, other material properties might be more important to regulate platelet activation. PFA100 closure times were reduced and within the reference ranges in the ethanol group, however, significantly increased in the saline group. No substantial difference was detected between the tested surface modifications. In summary, rewetting with ethanol resulted in a reduced thrombogenicity of all studied microparticles regardless of their wettability, most likely resulting from the evacuation of air from the nanoporous particles.

Isodehydrodigallic acid, which is an important component of several ellagitannin compounds, was easily synthesized using a classical Ullmann condensation reaction.

Off-line two-dimensional countercurrent chromatography has been widely applied to the isolation of complex samples, but little research on the investigation of orthogonality in the selection of biphasic solvent systems is available. In the present work, the orthogonality in the selection of a biphasic solvent system for liquid-liquid chromatographic separation of aqueous extract and ether extract from the traditional Chinese medicinal plant Polygonum cuspidatum Sieb. et Zucc was evaluated by the correlation coefficient and space occupancy rate. In total, 25 different biphasic solvent systems were tested, and 313 system combinations were analysed. A convex hull methodology was used to determine the separation space and to optimize separation conditions. The correlation coefficient matrix was transformed into dendrograms and a colour map to visualize the dissimilarity between, and orthogonality for, all solvent systems. The aqueous extracts from Polygonum cuspidatum were separated using selected biphasic solvent systems with high orthogonality: ethyl acetate-ethanol-water (70:1:70, v/v) and petroleum ether-ethyl acetate-water (1:5:5, v/v). The ether extracts from Polygonum cuspidatum were also separated using selected biphasic solvent systems with high orthogonality: petroleum-ethyl acetate-methanol-aqueous 0.25 M NH 3 •H 2 O (5:5:5:5, v/v) and petroleum-ethyl acetate-methanol-water (5:5:5:5, v/v). Thirteen compounds were successfully obtained. The experimental results demonstrated that the evaluation of orthogonality provided an alternative strategy to select an applicable solvent system for the separation of complex samples using off-line two-dimensional countercurrent chromatography., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. The authors declare the following financial interests/personal relationships which may be considered as potential competing interests., (Copyright © 2020. Published by Elsevier B.V.)

Although trehalose has recently gained interest because of its pharmaceutical potential, its clinical use is hampered due to its low bioavailability. Hence, hydrolysis-resistant trehalose analogues retaining biological activity could be of interest. In this study, 34 4- and 6- O -substituted trehalose derivatives were synthesised using an ether- or carbamate-type linkage. Their hydrolysis susceptibility and inhibitory properties were determined against two trehalases, i.e. porcine kidney and Mycobacterium smegmatis . With the exception of three weakly hydrolysable 6- O -alkyl derivatives, the compounds generally showed to be completely resistant. Moreover, a number of derivatives was shown to be an inhibitor of one or both of these trehalases. For the strongest inhibitors of porcine kidney trehalase IC 50 values of around 10 mM could be determined, whereas several compounds displayed sub-mM IC 50 against M. smegmatis trehalase. Dockings studies were performed to explain the observed influence of the substitution pattern on the inhibitory activity towards porcine kidney trehalase.

Bis(2-chloroethyl) ether (BCEE) has become one of the most frequently detected chlorinated ether contaminants in the US and Europe, and is classified as a B2 carcinogen. In this study, the degradation rate of BCEE by mercury lamps, xenon lamp and electromagnetic induction electrodeless lamp (EIEL) activated persulfate were compared, and EIEL activated persulfate was confirmed to have higher degradation capability and lower energy consumption. In this sense, the degradation kinetics and mechanism in EIEL system were further investigated. The degradation reaction followed pseudo first-order, and the removal rate of BCEE exceeded 95% in 60 min when the initial pH, the concentration of BCEE and Na 2 S 2 O 8 were 3, 4 mg L -1 and 15 mM, respectively. Presence of inorganic anions and humic acids would reduce the degradation rate constant. In accordance with the results of electron paramagnetic resonance and quenching experiments, SO 4 - · was dominant in the acidic regime and OH· was dominant in the alkaline regime. Meanwhile, OH· had higher degradation rate with BCEE when initial pH was 7. Seven degradation products were identified and the reaction pathways included OH· substitution and free radical coupling. Although the total organic carbon was eliminated slowly during the degradation of BCEE, the predicted toxicity of most degradation products to Fathead minnow, Daphnia magna and oral rat were lower than BCEE., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objectives: This study is aimed to explore the blending process of Dahuang soda tablets. These are composed of two active pharmaceutical ingredients (APIs, emodin and emodin methyl ether) and four kinds of excipients (sodium bicarbonate, starch, sucrose, and magnesium stearate). Also, the objective is to develop a more robust model to determine the blending end-point., Methods: Qualitative and quantitative methods based on near-infrared (NIR) spectroscopy were established to monitor the homogeneity of the powder during the blending process. A calibration set consisting of samples from 15 batches was used to develop two types of calibration models with the partial least squares regression (PLSR) method to explore the influence of density on the model robustness. The principal component analysis-moving block standard deviation (PCA-MBSD) method was used for the end-point determination of the blending with the process spectra., Results: The model with different densities showed better prediction performance and robustness than the model with fixed powder density. In addition, the blending end-points of APIs and excipients were inconsistent because of the differences in the physical properties and chemical contents among the materials of the design batches. For the complex systems of multi-components, using the PCA-MBSD method to determine the blending end-point of each component is difficult. In these conditions, a quantitative method is a more suitable alternative., Conclusions: Our results demonstrated that the effect of density plays an important role in improving the performance of the model, and a robust modeling method has been developed.

A library of amine, oxime, ether, epoxy and acyl derivatives of the benzobicyclo[3.2.1]octene were synthesized and evaluated as inhibitors of both human acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). The majority of the tested compounds exhibited higher selectivity for BChE. Structural adjustment for AChE seems to have been achieved by acylation, and the furan ring opening of furo-benzobicyclo[3.2.1]octadiene results for compound 51 with the highest AChE affinity (IC 50 = 8.3 µM). Interestingly, its analogue, an oxime ether with a benzobicyclo[3.2.1]-skeleton, compound 32 was one of the most potent BChE inhibitors in this study (IC 50 = 31 µM), but not as potent as endo- 43 , an ether derivative of the benzobicyclo[3.2.1]octene with an additional phenyl substituent (IC 50 = 17 µM). Therefore, we identified several cholinesterase inhibitors with a potential for further development as potential drugs for the treatment of neurodegenerative diseases., Competing Interests: The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Hydroxyethyl cellulose (HeC) maintains high water solubility over a wide temperature range even in a high temperature region where other nonionic chemically modified cellulose ethers, such as methyl cellulose (MC) and hydroxypropylmethyl cellulose (HpMC), demonstrate cloud points. In order to clarify the reason for the high solubility of HeC, the temperature dependence of the hydration number per glucopyranose unit, n H , for the HeC samples was examined by using extremely high frequency dielectric spectrum measuring techniques up to 50 GHz over a temperature range from 10 to 70 °C. HeC samples with a molar substitution number ( MS ) per glucopyranose unit by hydroxyethyl groups ranging from 1.3 to 3.6 were examined in this study. All HeC samples dissolve into water over the examined temperature range and did not show their cloud points. The value of n H for the HeC sample possessing the MS of 1.3 was 14 at 20 °C and decreased gently with increasing temperature and declined to 10 at 70 °C. The n H values of the HeC samples are substantially larger than the minimum critical n H value of ca. 5 necessary to be dissolved into water for cellulose ethers such as MC and HpMC, even in a high temperature range. Then, the HeC molecules possess water solubility over the wide temperature range. The temperature dependence of n H for the HeC samples and triethyleneglycol, which is a model compound for substitution groups of HeC, is gentle and they are similar to each other. This observation strongly suggests that the hydration/dehydration behavior of the HeC samples was essentially controlled by that of their substitution groups.

The constitutions of five metabolites formed during co-metabolic, anaerobic degradation of diethyl ether by the denitrifying betaproteobacterium Aromatoleum sp. strain HxN1 were elucidated by comparison of mass spectrometric and gas chromatographic data with those of synthetic reference standards. Furthermore, the absolute configurations of two stereogenic centers in the metabolites were established. Based on these results a degradation pathway for diethyl ether by Aromatoleum sp. HxN1 analogous to that of n-hexane is proposed. Synthesis of both enantiomers of methyl (E)-4-ethoxy-2-pentenoate was accomplished by etherification of ethyl (R)- or (S)-lactate, followed by hydrolysis of the ester group and reduction to furnish 2-ethoxy-1-propanol. The primary alcohol was converted by a Swern oxidation followed by a Horner-Wadsworth-Emmons reaction to methyl (E)-4-ethoxy-2-pentenoate that was finally hydrogenated to methyl 4-ethoxypentanoate. Methyl (S)-4-ethoxy-3-oxopentanoate was prepared by conversion of (S)-2-ethoxypropanoyl chloride with Meldrum's acid. Reduction of the resulting β-oxoester with NaBH4 or baker's yeast gave both diastereoisomers of methyl 4-ethoxy-3-hydroxypentanoate. The stereocenter at C-3 of the main diastereoisomer produced with baker's yeast was determined by Mosher ester analysis to be (R)-configurated. Dimethyl 2-(1-ethoxyethyl)succinate was prepared by Michael addition of nitroethane to diethyl maleate, followed by conjugate addition of sodium ethanolate, hydrolysis and esterification with diazomethane.

The long identified toxic gas, hydrogen sulfide (H 2 S), which has also been confirmed as the third gaseous signaling molecule following NO and CO, plays important roles in various physiological and pathological process. The current most established quantification method for H 2 S is HPLC method coupled with fluorescence detection after derivatization with a costly fluorescent reagent, Monobromobimane (MBB). However, The MBB method is characterized by strict reaction condition, long reaction time, tedious operation, and inconsistent reported results. In this study, based on the thiolysis reaction of 7-nitro-2, 1, 3-benzoxadiazole (NBD) ether, the commonly used chromatographic modifier 4-chloro-7-nitro-2,1,3- benzoxadiazole (NBDCl) and four probes (NBDOMe, NBDOEt, NBDOTFE and NBDOCMR) synthesized from NBDCl were tested as alternatives for fast quantification of H 2 S by LC-MS/MS. The reaction product between NBD ethers/NBDCl and H 2 S showed special pink color visible to the naked eye and was easy to synthesize and separate in lab; it also showed good retention on common chromatographic columns and high instrument response; therefore it is a good determinand. After establishment of LC-MS/MS methods for all the related compounds, the reaction conditions were optimized for all the probes with H 2 S. Then the stability, selectivity, reaction rate, sensitivity and quantitative linear relationship between the reaction product and H 2 S concentration were studied for each probe. Finally, NBDOEt was selected for LC-MS/MS detection of H 2 S. In comparision with the MBB method, the established NBDOEt method showed matched sensitivity and linearity, better selectivity, and higher repeatability; and had the advantages of easy operation, simple reaction condition, and cheap raw materials. The method was successfully validated and applied to determination of Na 2 S content in Na 2 S∙9H 2 O bulk drug and injection. In conclusion, NBDOEt is a promising option for quantification of H 2 S in abiotic matrix., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020. Published by Elsevier B.V.)

Ether lipids (ELs) are lipids characterized by the presence of either an ether linkage (alkyl lipids) or a vinyl ether linkage [i.e., plasmalogens (Pls)] at the sn 1 position of the glycerol backbone, and they are enriched in PUFAs at the sn 2 position. In this review, we highlight that ELs have various biological functions, act as a reservoir for second messengers (such as PUFAs) and have roles in many diseases. Some of the biological effects of ELs may be associated with their ability to regulate ion channels that control excitation-contraction/secretion/mobility coupling and therefore cell physiology. These channels are embedded in lipid membranes, and lipids can regulate their activities directly or indirectly as second messengers or by incorporating into membranes. Interestingly, ELs and EL-derived PUFAs have been reported to play a key role in several pathologies, including neurological disorders, cardiovascular diseases, and cancers. Investigations leading to a better understanding of their mechanisms of action in pathologies have opened a new field in cancer research. In summary, newly identified lipid regulators of ion channels, such as ELs and PUFAs, may represent valuable targets to improve disease diagnosis and advance the development of new therapeutic strategies for managing a range of diseases and conditions., (Copyright © 2020 Fontaine et al.)

Short-chain fatty acids (SCFAs) are gut microbiota metabolites recognized for their beneficial effects on the host organism. In this study, a simple and rapid sample preparation method combined to SCFAs analysis by direct injection and gas chromatography coupled with flame ionization detection (GC-FID), for the determination and quantification of eight SCFAs (acetic, propionic, i-butyric, butyric, i-valeric, valeric, i-caproic and caproic acids) in rat, mice and human faeces and in fermentation fluids samples, has been developed and validated. The method consists of extraction of the SCFAs by ethyl ether after acidification of the samples. The effect of the number of extractions has been assessed in order to optimize the procedure and to obtain a satisfactory yield for all the analyzed SCFAs. The increase of the extracted analytes quantity was significant passing from 1 to 2 and from 2 to 3 extractions (P < 0.05), while no significant differences were found performing 3, 4 or 5 extractions (P > 0.05). The SCFAs extracted are directly analyzed by GC-FID without derivatization and separated on a polyethylene glycol nitroterephthalic acid modified coated capillary column, with a chromatographic run time of 13 min. The proposed method showed good sensitivity, with limits of quantifications in the range 0.14-0.48 µM for SCFAs from propionic to caproic acids and 2.12 µM for acetic acid; recovery was between 80.8 and 108.8% and intraday and interday repeatability in the range 0.6-5.0% of precision (RSD, %) The optimized method is suitable for the quantitative analysis of SCFAs in real samples of rat, mouse and human faeces and in fermentation fluids, and it can be applied also to very small amount of faecal sample (20 mg)., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Carbohydrates contain numerous hydroxyl groups and sometimes amine functionalities which lead to a variety of complex structures. In order to discriminate each hydroxyl group for the synthesis of complex oligosaccharides, protecting group manipulations are essential. Although the primary role of a protecting group is to temporarily mask a particular hydroxyl/amino group, it plays a greater role in tuning the reactivity of coupling partners as well as regioselectivity and stereoselectivity of glycosylations. Several protecting groups offer anchimeric assistance in glycosylation. They also alter the solubility of substrates and thereby influence the reaction outcome. Since oligosaccharides comprise branched structures, the glycosyl donors and acceptors need to be protected with orthogonal protected groups that can be selectively removed one at a time without affecting other groups. This minireview is therefore intended to provide a discussion on new protecting groups for amino and hydroxyl groups, which have been introduced over last ten years in the field of carbohydrate synthesis. These protecting groups are also useful for synthesizing non-carbohydrate target molecules as well., (© 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Hyaluronan (HA)-based hydrogels obtained by crosslinking the biopolymer via ether bonds are widely used in clinical practice. There is interest in improving the design of these gels to match specific properties. Here, the possibility to tune HA-hydrogel behavior by adjusting the molecular weight distribution of the biopolymer undergoing crosslinking was investigated. Three HA samples (500, 1100 and 1600 kDa) underwent reaction with 1,4-butandioldiglycidyl-ether(BDDE) under reported conditions and the crosslinked products were characterized for chemical modification extent, swelling, rheological behavior, cohesivity, sensitivity to enzymatic degradation and effect on Human Dermal Fibroblasts (HDF). HA hydrolysis, under the highly alkaline crosslinking conditions, was also studied for the first time. The main achievements are that 1) varying HA chain length affects hydrogel behavior less than expected, due to the de-polymerization occurring alongside crosslinking, that reduces the differences in sample size 2) when differences in chain length persist notwithstanding hydrolysis, lowering HA size is a means to prepare more concentrated formulations, expected to exhibit longer duration and better cohesivity in vivo, while retaining a certain rigidity, preserving biocompatibility and slightly influencing HDF behavior in relation to CollagenI production. The study shed light on aspects concerning BDDE-HA gel manufacturing and contributed to the improvement of their design., Competing Interests: Declaration of competing interest None., (Copyright © 2018. Published by Elsevier B.V.)

In the present work, the palladium (Pd) modification and supporting effect of W/TiO 2 catalysts on catalytic ethanol dehydration to ethylene and diethyl ether were investigated. The Pd modification with different sequence of Pd and W impregnation on the catalysts was prepared by the incipient wetness impregnation technique. The catalyst characterization and activity testing revealed that the different sequence during impregnation influenced the physicochemical properties and ethanol conversion of catalyst. The differences in structure and surface properties were investigated by XRD, BET, SEM, EDX, XPS and NH 3 -TPD. Upon the reaction temperature between 200 to 400°C, it was found that the conversion increased with increasing of temperature for all catalysts. The Pd incorporated into catalysts enhanced the ethanol conversion depending on the sequence of impregnation. At low temperature (ca. 200 to 300°C), diethyl ether is a major product and the Pd modification over W/TiO 2 catalyst resulted in increased diethyl ether yield. This is because an increase of ethanol conversion was obtained with Pd modification, while diethyl ether selectivity did not change. This can be attributed to the higher amount of weak acids sites present after Pd modification into catalyst. Among all catalysts, the PdW/TiO 2 catalyst (coimpregnation) achieved the highest diethyl ether yield of 41.4% at 300℃. At high temperature (ca. 350 to 400°C), ethylene is the major product. The W/Pd/TiO 2 catalyst (with sequential impregnation of Pd on TiO 2 followed by W) exhibited the highest ethylene yield of 68.1% at 400°C. It can be concluded that the modification of Pd onto W/TiO 2 upon different sequence of Pd and W impregnation can improve the diethyl ether and ethylene yield in catalytic ethanol dehydration.

A major challenge in liposomal research is to minimize the leakage of encapsulated cargo from either uncontrolled passive permeability across the liposomal membrane or upon fusion with other membranes. We previously showed that liposomes made from pure Archaea-inspired bipolar tetraether lipids exhibit exceptionally low permeability of encapsulated small molecules due to their capability to form more tightly packed membranes compared to typical monopolar lipids. Here, we demonstrate that liposomes made of synthetic bipolar tetraether lipids can also undergo membrane fusion, which is commonly accompanied by content leakage of liposomes when using typical bilayer-forming lipids. Importantly, we demonstrate calcium-mediated fusion events between liposome made of glycerolmonoalkyl glycerol tetraether lipids with phosphatidic acid headgroups (GMGTPA) occur without liposome content release, which contrasts with liposomes made of bilayer-forming EggPA lipids that displayed ~80% of content release under the same fusogenic conditions. NMR spectroscopy studies of a deuterated analog of GMGTPA lipids reveal the presence of multiple rigid and dynamic conformations, which provide evidence for the possibility of these lipids to form intermediate states typically associated with membrane fusion events. The results support that biomimetic GMGT lipids possess several attractive properties (e.g., low permeability and non-leaky fusion capability) for further development in liposome-based technologies.

The white-rot fungus Pleurotus sapidus (PSA) biosynthesizes the bicyclic monoterpenoids 3,6-dimethyl-2,3,3a,4,5,7a-hexahydrobenzofuran (dill ether) ( 1 ) and 3,6-dimethyl-3a,4,5,7a-tetrahydro-1-benzofuran-2(3 H )-one (wine lactone) ( 2 ). Submerged cultures grown in different media were analyzed by gas chromatography-mass spectrometry. The stereochemistry of the formed isomers was elucidated by comparing their retention indices to those of reference compounds by enantioselective multidimensional gas chromatography. The basidiomycete produced the rare (3 R ,3a R ,7a S ) and (3 S ,3a R ,7a S ) stereoisomers of dill ether and wine lactone. Kinetic analyses of the volatilome and bioprocess parameters revealed that the biosynthesis of the bicyclic monoterpenoids correlated with the availability of the primary carbon source glucose. Spiking the media with 13 C-labeled glucose demonstrated that the compounds were produced de novo . Supplementation studies i.a. with isotopically labeled substrates further identified limonene and p -menth-1-en-9-ol as intermediate compounds in the fungal pathways. PSA was able to biotransform all enantiomeric forms of the latter compounds to the respective isomers of dill ether and wine lactone.

Parthenolide (PTL) strongly inhibits the detyrosination of microtubules and accelerates neuronal growth. In order to access cyclic ether derivatives of PTL, ring-closing metathesis (RCM) was investigated in comparison to intramolecular sulfone alkylation. Incompatibility of RCM with epoxides was found in this setting. Biological evaluation for tubulin carboxypeptidase inhibition indicated that the epoxide is crucial for parthenolide's activity.

Tunable properties prompt the development of different "tailor-made" functional ionic liquids (FILs) for specific tasks. FILs with an ether group are good solvents for many organic compounds and enzymatic reactions. However, ionic composition influences the solubility by affecting the physiochemical properties of these FILs. To address the structure effect, a series of novel FILs with a mono-ether group (ME) based on imidazole were prepared through cationic functionalization and anionic exchange reactions, and characterized by NMR, mass spectroscopy, and Thermogravimetric analysis (TGA). The effect of ionic composition (cationic structure and anions) on density, viscosity, ionic conductivity, electrochemical window, and thermal properties of these ME-FILs were systematically investigated. In general, the viscosity and heat capacity increases with the bigger cationic volume of ME-FILs; in particular, the 2-alkyl substitution of imidazolium enhances the viscosity remarkably, whereas the density and conductivity decrease on the condition of the same [NTf 2 ] - anion; For these ME-FILs with the same cations, the density follows the order of [NTf 2 ] - > [PF 6 ] - > [BF 4 ] - . The viscosity follows the order of [PF 6 ] - > [BF 4 ] - > [NTf 2 ] - . Ion conductivity follows the order of [NTf 2 ] - ≈ [BF 4 ] - > [PF 6 ] - . It is noted that the dynamic density has a good linear relationship with the temperature, and the slopes are the same for all ME-FILs. Furthermore, these ME-FILs have broad electrochemical windows and glass transition temperatures in addition to a cold crystallization and a melt temperature for ME-FIL 7 . Therefore, the cationic structure and counter anion affect the physicochemical properties of these ME-FILs together.

Polyether-ether-ketone (peek) is one of the most common materials used for load-bearing orthopedic devices owing to its radiolucency and favorable mechanical properties. However, current smooth-surfaced peek implants can lead to fibrous capsule formation. To overcome this issue, here, peek specimens with well-defined internal cross-linked structures (macropore diameters of 1.0-2.0 mm) were fabricated using a three-dimensional (3D) printer, and an acid-etched microporous surface was achieved using injection-molding technology. The cell adhesion properties of smooth and microporous peek specimens was compared in vitro through a scanning electron microscope (SEM), and the soft tissue responses to the both microporous and cross-linked structure of different groups were determined in vivo using a New Zealand white rabbit model, and examined through histologic staining and separating test. The results showed that the acid-etched microporous surface promoted human skin fibroblasts (HSF) adherence, while internal cross-linked structure improved the ability of the peek specimen to form a mechanical combination with soft tissue, especially with the 1.5 mm porous specimen. The peek specimens with both the internal cross-linked structure and external acid-etched microporous surface could effectively promote the close integration of soft tissue and prevent formation of fibrous capsules, demonstrating the potential for clinical application in surgical repair.

Plasmalogens, the most prominent ether (phospho)lipids in mammals, are structural components of most cellular membranes. Due to their physicochemical properties and abundance in the central nervous system, a role of plasmalogens in neurotransmission has been proposed, but conclusive data are lacking. Here, we targeted this issue in the glyceronephosphate O-acyltransferase (Gnpat) KO mouse, a model of complete deficiency in ether lipid biosynthesis. Throughout the study, focusing on adult male animals, we found reduced brain levels of various neurotransmitters. In the dopaminergic nigrostriatal tract, synaptic endings but not neuronal cell bodies were affected. Neurotransmitter turnover was altered in ether lipid-deficient murine as well as human post-mortem brain tissue. A generalized loss of synapses did not account for the neurotransmitter deficits, since the levels of several presynaptic proteins appeared unchanged. However, reduced amounts of vesicular monoamine transporter indicate a compromised vesicular uptake of neurotransmitters. As exemplified by norepinephrine, the release of neurotransmitters from Gnpat KO brain slices was diminished in response to strong electrical and chemical stimuli. Finally, addressing potential phenotypic correlates of the disturbed neurotransmitter homeostasis, we show that ether lipid deficiency manifests as hyperactivity and impaired social interaction. We propose that the lack of ether lipids alters the properties of synaptic vesicles leading to reduced amounts and release of neurotransmitters. These features likely contribute to the behavioral phenotype of Gnpat KO mice, potentially modeling some human neurodevelopmental disorders like autism or attention deficit hyperactivity disorder., (© The Author(s) 2019. Published by Oxford University Press.)

Steam-explosion lignin (SEL) was extracted with ethanol from steam-exploded hardwood (okoumé, Aucoumea klaineana Pierre) pretreated at various severities after neutral or acidic impregnation. The SELs were subjected to structural characterization by 2D HSQC NMR, 31 P NMR, and SEC and compared with milled-wood lignin (MWL). A strong decrease in the β- O-4 content is observed with increasing steam-explosion severity accompanied by a gradual increase in molecular mass. Cα-oxidized S units (S', Hibbert's ketones) were quantified by NMR and used as a marker of the hydrolytic mechanism; naphthol was used as a carbonium-ion scavenger. It has been observed that mixed reactions of hydrolysis and homolysis are involved, but the SEL is mainly cleaved homolytically, favoring recondensation through radical coupling even at low reaction severity. However, acidic preimpregnation of wood prior to steam explosion enhanced the carbonium-ion pathway.

Naturstoff reagent A (diphenylboric acid 2-aminoethyl ester [DPBA]) has been used historically in plant science to observe polyphenolic pigments, such as flavonoids, whose fluorescence requires enhancement to be visible by microscopy. Flavonoids are common dietary constituents and are the focus of considerable attention because of their potential as novel therapies for numerous diseases. The molecular basis of therapeutic activity is only gradually being established, and one strand of such research is making use of the social amoeba Dictyostelium discoideum. We extended the application of DPBA to flavonoid imaging in these preclinical studies, and report the first method for use of DPBA in this eukaryotic model microbe and its applicability alongside subcellular markers. This in vivo fluorescence imaging provided a useful adjunct to parallel chemical and genetic studies.

To improve the thermal stability and adsorption performance, xanthan gum was modified with acrylamide and trimethylolpropane triglycidyl ether (TTE). The modified xanthan gum (XGTTE) was characterized by Fourier transform infrared (FT-IR) spectroscopy, X-ray diffractogram (XRD), differential scanning calorimetry (DSC) and scanning electron microscopy (SEM). The characteristic peaks at 3449, 1655, 1611 and 1420 cm -1 in the FT-IR confirm the modification. The XGTTE crystal grew well upon addition of TTE. The XRD and DSC data revealed that the XGTTE enhanced its thermal stability. Analysis of SEM revealed that the grafting introduced major changes on the microstructure making it porous and resulting in the adsorption of crystal violet (CV) with flocculation. The CV adsorption capacity of the hydrogel with different dosages of TTE (XGTTE2, XGTTE3, XGTTE4, XGTTE5 and XGTTE6) were between 28.13 with 35.12 mg/g. In addition, the adsorption capacity, thermal stability, and swelling property of XGTTE4 were the best., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Raya liver deodorized oil contains high concentrations of eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA) and docosahexaenoic acid (DHA). The present study investigated the processes of urea complexation (UC) and molecular distillation (MD) to determine the most adequate operation conditions for each process, separately and together, aiming to obtain highly concentrated EPA, DPA and DHA ethyl esters with chemical indicator values permitted by the current legislation for edible oils., Results: In the second stage of MD, a concentration of 820.27 g kg -1 in the distillate and 951.06 g kg -1 of omega-3 fatty acid ethyl esters in the residue was obtained. The distillate showed values of free fatty acids, peroxide and p-anisidine lower than the maximum allowed for edible oils in accordance with the current legislation., Conclusion: The use of UC and MD together has revealed a significant improvement in the total concentration of omega-3 fatty acid ethyl esters in the final product and good application prospects. © 2018 Society of Chemical Industry., (© 2018 Society of Chemical Industry.)

Guided by TNF-α secretion inhibitory activity assay, four taraxastane-type triterpenoids, including two new ones, 22-oxo-20-taraxasten-3β, 30-diol (1) and 22α-hydroxy-20-taraxasten-30β, 30-triol (2), have been obtained from an active fraction of the petroleum ether-soluble extract of the the medicinal and edible plant Cirsium setosum. Their structures were elucidated by spectroscopic data and CD data analysis. In the TNF-α secretion inhibitory activity assay, compounds 1 and 2 were active with the IC 50 of 2.6 and 3.8 μmol·L -1 , respectively. In addition, compounds 1 and 2 showed moderately selective cytotoxicity against the human ovarian cancer (A2780) and colon cancer (HCT-8) cell lines., (Copyright © 2019 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.)

Exosomes are a type of extracellular vesicle released from cells after fusion of multivesicular bodies with the plasma membrane. These vesicles are often enriched in cholesterol, SM, glycosphingolipids, and phosphatidylserine. Lipids not only have a structural role in exosomal membranes but also are essential players in exosome formation and release to the extracellular environment. Our knowledge about the importance of lipids in exosome biology is increasing due to recent technological developments in lipidomics and a stronger focus on the biological functions of these molecules. Here, we review the available information about the lipid composition of exosomes. Special attention is given to ether lipids, a relatively unexplored type of lipids involved in membrane trafficking and abundant in some exosomes. Moreover, we discuss how the lipid composition of exosome preparations may provide useful information about their purity. Finally, we discuss the role of phosphoinositides, membrane phospholipids that help to regulate membrane dynamics, in exosome release and how this process may be linked to secretory autophagy. Knowledge about exosome lipid composition is important to understand the biology of these vesicles and to investigate possible medical applications., (Copyright © 2019 Skotland et al. Published by The American Society for Biochemistry and Molecular Biology, Inc.)

BF 3 ·Et 2 O-catalyzed double aldol condensation between acetylated steroid sapogenins and terephtalaldehyde led to acetylated dimeric spirostanols linked through a 1,4-dimethylidenebenzene moiety in moderate to good yields. The E configurations of the introduced double bonds were corroborated by NOE experiments. Saponification of the dimeric steroids led to the corresponding dimeric spirostanols., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Despite the advances in the discovery of various types of anticancer drugs for curing acute lymphoblastic leukemia (ALL), their toxicity and unfavorable side effects remained as big limitations for therapeutical applications. In this regard, natural products such as Streptomyces -derived agents have shown potential applications as anticancer drugs. The present study deals with evaluating the anti-carcinogenic activity of the ether extracted metabolites derived from Streptomyces on nalm-6 and molt-4 ALL cell lines. MTT assay was performed to evaluate the cytotoxicity effect of Streptomyces sp on nalm-6 and molt-4 cell lines. Apoptosis and proliferation were evaluated by Flow cytometry. Quantitative real-time RT-PCR (qRT-PCR) and western blot were performed to investigate the effect of these metabolites on the mRNA and protein expression levels of P53, Bax, and Bcl2. In both cell lines, extracted metabolites significantly inhibited cell growth and increased apoptosis. Although P53, Bax mRNA and protein expressions were increased, Bcl-2 expression decreased in treated cells compared with control. In addition, the G0/G1 arrest of Nalm-6 cells was induced. These findings of this work show that the ether-extracted metabolites from Streptomyces levis ABRIINW111 can be used as an anti-carcinogenic for acute lymphoblastic leukemia cells., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

A new family of cellulosic ether polymeric excipients has been recently engineered for fabrication of amorphous solid dispersions of active pharmaceutical ingredients via hot-melt extrusion (HME). These hydroxypropyl methyl cellulose excipients enable plasticizer-free melt processing at much lower temperatures (135-160 °C) due to their substantially reduced glass transition temperatures ( T g = 98-110 °C). The novel amorphous cellulose ethers were found to be rheologically solidlike well above their glass transition ( T g + 70 °C). We demonstrate that in the pharmaceutically relevant HME processing temperature range these polymers behave similarly to yield-stress fluids and flow only when the applied stress exceeds a critical stress value. This critical stress value (0.50 ± 0.05 MPa, 150 °C) is surprisingly high but is easily achieved under typical HME conditions. The origin of their yield-stress fluidlike behavior is hypothesized to arise from hydrogen bonds of the HPMC materials that act as physical cross-links and do not relax within the measured temperature and time window unless the applied stress exceeds the critical stress value. Support for this hypothesis arises from infrared spectroscopic estimates of the free and bound hydrogen bond levels at end-use temperatures.

We have previously reported that a cell-free extract prepared from Geobacillus thermodenitrificans UZO 3 reductively cleaves diaryl ether bonds of 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD), a dioxin with the highest toxicity, in a sequential fashion producing 3',4',4,5-tetrachloro-2-hydroxydiphenyl ether (TCDE) as the intermediate, and 3,4-dichlorophenol (DCP) as the final reaction product. The detection of TCDE implicated the discovery of an unprecedented dioxin-degrading enzyme that reductively cleaves the diaryl ether bonds. In this study, we report the cloning and sequencing of the dioxin reductive etherase gene dreE which codes for the 2,3,7,8-TCDD-degrading enzyme. We showed that dreE was expressed in Escherichia coli and that the product of the expression could reductively cleave diaryl ether bonds of 2,3,7,8-TCDD to produce TCDE. Furthermore, we established that the amino acid sequence encoded by dreE was homologous to an enzyme with yet unknown function that is encoded by a gene located in the riboflavin (vitamin B2) biosynthesis operon in Bacillus subtilis. We also showed that the amino acid sequence possesses a coenzyme A (CoA) binding site that is conserved in the N-acyltransferase superfamily. For the first time, the degradation of 2,3,7,8-TCDD at the molecular level using a enzyme of bacterial origin has been demonstrated. A novel mechanism model for the reductive cleavage of diaryl ether bond of 2,3,7,8-TCDD was also proposed., (Copyright © 2018 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.)

Polyether polyols are often used in formulated systems, but their complete characterization is challenging, because of simultaneous heterogeneities in chemical composition, molecular weight and functionality. One-dimensional liquid chromatography-mass spectrometry is commonly used to characterize polyether polyols. However, the separation power of this technique is not sufficient to resolve the complexity of such samples entirely. In this study, comprehensive two-dimensional liquid chromatography hyphenated with high-resolution mass spectrometry (LC × LC-HRMS) was used for the characterization of (i) castor oil ethoxylates (COEs) reacted with different mole equivalents of ethylene oxide and (ii) a blended formulation consisting of glycerol ethoxylate, glycerol propoxylate and glycerol ethoxylate-random-propoxylate copolymers. Retention in the first (hydrophilic-interaction-chromatography) dimension was mainly governed by degree of ethoxylation, while the second reversed-phase dimension resolved the samples based on degree of propoxylation (blended formulation) or alkyl chain length (COEs). For different COE samples, we observed the separation of isomer distributions of various di-, tri- and tetra-esters, and such positional isomers were studied by tandem mass spectrometry (LC-MS/MS). This revealed characteristic fragmentation patterns, which allowed discrimination of the isomers based on terminal or internal positioning of the fatty-acid moieties and provided insight in the LC × LC retention behavior of such species., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)

Twenty-three compounds in two series of ferrocene-based anilides, with the general formula C5H5-Fe-C5H4-C6H4-NH-CO-C6H4-R (where R = H, F, Cl, CH3 and OCH3), have been successfully synthesized. The compounds were characterized by elemental analysis and FTIR, 1H NMR and 13C NMR spectroscopy. Two compounds (M07 and P09) were characterized by X-ray crystallography. Solid state studies indicate that ferrocene derivatives with the conformation of meta amide substituents engage in intermolecular H-bonding, which stabilizes the meta derivatives over their para analogues. The H-bonding takes place when the conformation of the ferrocene changes by rotation around the C-N bond, favoring interactions between two molecules in adjacent layers in the solid state. The potential importance of this H-bonding to the biological effects of these molecules was investigated using both experimental and computational studies. All the compounds were found to inhibit butyrylcholinesterase. The most active compound shows 50% inhibition at a concentration of 9 ± 0.2 μM, similar to the known drug galantamine (with an IC50 of 8 μM). Compounds with the ferrocene moiety meta to the amide linkage were consistently found to be slightly more active than the other structural isomers, suggesting that the H-bonding may only slightly increase the overall affinity for the protein. Computational studies confirmed the limited effects of the H-bonding in the presence and absence of water in the active site of butyrylcholinesterase, supporting the importance of hydrophobicity for inhibitors of this enzyme.

Electrospun beta-cyclodextrin (βCD)-based polymers can combine a high surface-to-volume ratio and a high loading/controlled-release-system potential. In this work, pyromellitic dianhydride (PMDA)/βCD-based nanosponge microfibers were used to study the capability to host a common insect repellent ( N , N -diethyl-3-toluamide (DEET)) and to monitor its release over time. Fibrous samples characterized by an average fibrous diameter of 2.8 ± 0.8 µm were obtained and subsequently loaded with DEET, starting from a 10 g/L diethyl ether (DEET) solution. The loading capacity of the system was assessed via HPLC/UV⁻Vis analysis and resulted in 130 mg/g. The releasing behavior was followed by leaving fibrous DEET-loaded nanosponge samples in air at room temperature for a period of between 24 h and 2 weeks. The releasing rate and the amount were calculated by thermogravimetric analysis (TGA), and the release of the repellent was found to last for over 2 weeks. Eventually, both the chemical composition and sample morphology were proven to play a key role for the high sample loading capacity, determining the microfibers' capability to be applied as an effective controlled-release system.

Objective: The goal of the present work was to make novel co-polymeric micellar carriers for the delivery of docetaxel (DTX)., Significance: Co-polymeric micelles can not only solubilize DTX and eliminate the need for toxic surfactants to dissolve it, but also cause passive targeting of the drug to the tumor and reduce its toxic side effects., Methods: Poly(styrene-maleic acid) (SMA) was conjugated to poly (amide-ether-ester-imide)-poly ethylene glycol (PAEEI-PEG). Copolymer synthesis was proven by Fourier transform infrared (FTIR) and 1 H-nuclear magnetic resonance ( 1 H-NMR). The SMA-PAEEI-PEG micelles loaded with DTX were prepared and their critical micelle concentration (CMC), zeta potential, particle size, entrapment efficiency, and their release efficiency were studied. MCF-7 and MDA-MB231 breast cancer cells were used to evaluate the cellular uptake and cytotoxicity of the micelles. The antitumor activity of the DTX-loaded nanomicelles was measured in Balb/c mice., Results: The FTIR and HNMR spectroscopy confirmed successful conjugation of SMA and PAEEI-PEG. The drug loading efficiency was in the range of 34.01-72.75% and drug release lasted for 120 h. The CMC value of the micelles was affected by the SMA/PAEEI-PEG ratio and was in the range of 29.85-14.28 µg/ml. The DTX-loaded micelles showed five times more cytotoxicity than the free drug. The DTX loaded micelles were more effective in tumor growth suppression in vivo and the animals showed an enhanced rate of survival., Conclusion: The results show that the SMA-PAEEI-PEG micelles of DTX could potentially provide a suitable parenteral formulation with more stability, higher cytotoxicity, and improved antitumor activity.