Toward Lung Ventilation Imaging Using Hyperpolarized Diethyl Ether Gas Contrast Agent.

Hyperpolarized 129Xe 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 129Xe gas faces two critical challenges: the high cost of the relatively low-throughput hyperpolarization equipment and the lack of 129Xe imaging capability on clinical MRI scanners, which have narrow-bandwidth electronics designed only for proton (1H) 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 mm2 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.

The potency of hydrothermally prepared sulfated silica (SO4/SiO2) as a heterogeneous acid catalyst for ethanol dehydration into diethyl ether.

The dehydration of ethanol into diethyl ether over a SO4/SiO2 catalyst was investigated. The SO4/SiO2 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 SO4/SiO2 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 SiO2. The SS2 catalyst (with 2 M sulfuric acid) displayed the highest total acidity of 7.77 mmol/g, whereas the SiO2 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 m2/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 SO4/SiO2 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%).

Functional supramolecular gels based on poly(benzyl ether) dendrons and dendrimers.

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.

Eco-Friendly Ether and Ester-Urethane Prepolymer: Structure, Processing and Properties.

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.

The Phenolic Compounds Profile and Cosmeceutical Significance of Two Kazakh Species of Onions: Alliumgalanthum and A. turkestanicum.

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, Alliumgalanthum 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.

Silylated Tag-Assisted Peptide Synthesis: Continuous One-Pot Elongation for the Production of Difficult Peptides under Environmentally Friendly Conditions.

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.

Functionalized Cyclopentenones and an Oxime Ether as Antimicrobial Agents.

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.

On the Search of a Silver Bullet for the Preparation of Bioinspired Molecular Electrets with Propensity to Transfer Holes at High Potentials.

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.

Neuroprotective Effect of Aurantio-Obtusin, a Putative Vasopressin V1A Receptor Antagonist, on Transient Forebrain Ischemia Mice Model.

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 V1AR antagonist effect (71.80 ± 6.0% inhibition at 100 µM) and yielded an IC50 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 V1AR as a possible target of aurantio-obtusin for neuroprotection.

Mechanistic Similarities of Sesquiterpene Cyclases PenA, Omp6/7, and BcBOT2 Are Unraveled by an Unnatural "FPP-Ether" Derivative.

The sesquiterpene cyclases pentalenene synthase (PenA) and two Δ6-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.

Immunosuppressive and Adipogenesis Inhibitory Sesterterpenoids with a Macrocyclic Ether System from Eurysolen gracilis.

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.

Preparation of Isodehydrodigallic Acid Using Ullmann Condensation.

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

Novel Fluorinated 7-Hydroxycoumarin Derivatives Containing an Oxime Ether Moiety: Design, Synthesis, Crystal Structure and Biological Evaluation.

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 1H-NMR, 13C-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), Alternariasolani (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 EC50 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 EC50 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.

The influence of different rewetting procedures on the thrombogenicity of nanoporous poly(ether imide) microparticles.

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.

Synthesis, trehalase hydrolytic resistance and inhibition properties of 4- and 6-substituted trehalose derivatives.

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 IC50 values of around 10 mM could be determined, whereas several compounds displayed sub-mM IC50 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.

A near-infrared spectroscopy-based end-point determination method for the blending process of Dahuang soda tablets.

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.

Orthogonality in the selection of biphasic solvent systems for off-line two-dimensional countercurrent chromatography from Polygonum cuspidatum Sieb. et Zucc.

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 NH3•H2O (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.

Benzobicyclo[3.2.1]octene Derivatives as a New Class of Cholinesterase Inhibitors.

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 (IC50 = 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 (IC50 = 31 µM), but not as potent as endo-43, an ether derivative of the benzobicyclo[3.2.1]octene with an additional phenyl substituent (IC50 = 17 µM). Therefore, we identified several cholinesterase inhibitors with a potential for further development as potential drugs for the treatment of neurodegenerative diseases.

Hydration/Dehydration Behavior of Hydroxyethyl Cellulose Ether in Aqueous Solution.

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, nH, 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 nH 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 nH values of the HeC samples are substantially larger than the minimum critical nH 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 nH 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.

Degradation kinetics and mechanism of bis(2-chloroethyl) ether by electromagnetic induction electrodeless lamp activated persulfate.

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 Na2S2O8 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, SO4-· 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.