Search Results (18)

Gynura divaricata (L.) DC is a long-used medicinal and edible plant in China folk. Its hyperglycemic effects have garnered increasing public attention in recent years. This study revealed that the ethyl acetate (EtOAc) and butanol (BuOH) partition fractions of G. divaricata crude extract exhibited significantly higher α-glucosidase inhibition activity and enhanced glucose uptake ability compared to other fractions. Guided by the hypoglycemic bioassay, these two fractions were subjected to isolation of active compounds using high-speed countercurrent chromatography (HSCCC). A two-phase solvent system composed of hexane-methyl tert-butyl ether (MtBE)-methanol-0.1% TFA water was employed for the separation of the EtOAc fraction by conventional HSCCC through a gradient elution strategy. Five major compounds were obtained and identified as chlorogenic acid (1), 3,4-dicaffeoylquinic acid (2), 3,5-dicaffeoylquinic acid (3), 4,5-dicaffeoylquinic acid (4), and kaempferol-3-O-β-D-glucopyranoside (5) by ESI-MS, ¹HNMR, and ¹³CNMR. The chlorogenic acid and the three dicaffeoylquinic acids were found to display higher inhibitory activities against α-glucosidase compared to the flavonoid. Considering their acidic nature, pH-zone-refining CCC (PHZCCC) was then applied for further scale-up separation using a solvent system MtBE: n-butanol: acetonitrile: water with trifluoroacetic acid (TFA) as a retainer and ammonium hydroxide (NH₄OH) as an eluter. A significantly higher yield of chlorogenic acid was obtained from the BuOH fraction by PZRCCC. Molecular docking between the caffeoylquinic acids and α-glucosidase confirmed their hypoglycemic activities. This study demonstrates that CCC is a powerful tool for preparative separation of active constituents in natural products. This research presents a novel and effective method for the preparative isolation of hypoglycemic compounds from Gynura divaricata. Full article

An overview of solvent replacement strategies shows that there is great progress in green chemistry for replacing hazardous di-polar aprotic solvents, such as N,N-dimethylformamide (DMF), 1-methyl-2-pyrrolidinone (NMP), and 1,4-dioxane (DI), used in processing active industrial ingredients (APIs). In synthetic chemistry, alcohols, carbonates, ethers, eucalyptol, glycols, furans, ketones, cycloalkanones, lactones, pyrrolidinone or solvent mixtures, 2-methyl tetrahydrofuran in methanol, HCl in cyclopentyl methyl ether, or trifluoroacetic acid in propylene carbonate or surfactant water (no organic solvents) are suggested replacement solvents. For the replacement of dichloromethane (DCM) used in chromatography, ethyl acetate ethanol or 2-propanol in heptanes, with or without acetic acid or ammonium hydroxide additives, are suggested, along with methanol acetic acid in ethyl acetate or methyl tert-butyl ether, ethyl acetate in ethanol in cyclohexane, CO₂-ethyl acetate, CO₂-methanol, CO₂-acetone, and CO₂-isopropanol. Supercritical CO₂ (scCO₂) can be used to replace many organic solvents used in processing materials from natural sources. Vegetable, drupe, legume, and seed oils used as co-extractants (mixed with substrate before extraction) can be used to replace the typical organic co-solvents (ethanol, acetone) used in scCO₂ extraction. Mixed solvents consisting of a hydrogen bond donor (HBD) solvent and a hydrogen bond acceptor (HBA) are not addressed in GSK or CHEM21 solvent replacement guides. Published data for 100 water-soluble and water-insoluble APIs in mono-solvents show polarity ranges appropriate for the processing of APIs with mixed solvents. When water is used, possible HBA candidate solvents are acetone, acetic acid, acetonitrile, ethanol, methanol, 2-methyl tetrahydrofuran, 2,2,5,5-tetramethyloxolane, dimethylisosorbide, Cyrene, Cygnet 0.0, or diformylxylose. When alcohol is used, possible HBA candidates are cyclopentanone, esters, lactone, eucalytol, MeSesamol, or diformylxylose. HBA—HBA mixed solvents, such as Cyrene—Cygnet 0.0, could provide interesting new combinations. Solubility parameters, Reichardt polarity, Kamlet—Taft parameters, and linear solvation energy relationships provide practical ways for identifying mixed solvents applicable to API systems. Full article

High-performance counter-current chromatography (HPCCC) was used as a tool for the isolation and fractionation of phenolic compounds (PCs) in extracts from wine lees (WL) and grape pomace (GP). The biphasic solvent systems applied for HPCCC separation were n-butanol:methyl tert-butyl ether:acetonitrile:water (3:1:1:5) with 0.1% trifluoroacetic acid (TFA) and n-hexane:ethyl acetate:methanol:water (1:5:1:5). After refining the ethanol:water extracts of GP and WL by-products by ethyl acetate extraction, the latter system yielded an enriched fraction of the minor family of flavonols. Recoveries of 112.9 and 105.9 mg of purified flavonols (myricetin, quercetin, isorhamnetin, and kaempferol) in GP and WL, respectively, from 500 mg of ethyl acetate extract (equivalent to 10 g of by-product) were obtained. The HPCCC fractionation and concentration capabilities were also exploited for the characterization and tentative identification of constitutive PCs by ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS). In addition to the isolation of the enriched flavonol fraction, a total of 57 PCs in both matrixes were identified, 12 of which were reported for the first time in WL and/or GP. The application of HPCCC to GP and WL extracts may be a powerful approach to isolate large amounts of minor PCs. The composition of the isolated fraction demonstrated quantitative differences in the individual compound composition of GP and WL, supporting the potential exploitation of these matrixes as sources of specific flavonols for technological applications. Full article

A novel synthesis of ultrahigh molecular weight poly(methyl methacrylate) (PMMA) using organosulfur compounds combined with a catalytical amount of transition metal carboxylates as an initiator has been developed. The combination of 1-octanethiol with palladium trifluoroacetate (Pd(CF₃COO)₂) was found to be a very efficient initiator for the polymerization of methyl methacrylate (MMA). An ultrahigh molecular weight PMMA with a number-average molecular weight of 1.68 × 10⁶ Da and a weight-average molecular weight of 5.38 × 10⁶ Da has been synthesized at the optimal formulation of [MMA]:[Pd(CF₃COO)₂]:[1-octanethiol] = 94,300:8:23 at 70 °C. A kinetic study showed that the reaction orders with respect to Pd(CF₃COO)₂, 1-octanethiol, and MMA are 0.64, 1.26, and 1.46, respectively. A variety of techniques such as proton nuclear magnetic resonance spectroscopy (¹H NMR), electrospray ionization mass spectroscopy (ESI-MS), size exclusion chromatography (SEC), X-ray photoelectron spectroscopy (XPS), transmission electron microscopy (TEM), and electron paramagnetic resonance spectroscopy (EPR) were employed to characterize the produced PMMA and palladium nanoparticles (Pd NPs). The results revealed that Pd(CF₃COO)₂ was firstly reduced by the excess of 1-octanethiol to form Pd NPs at the early stage of the polymerization, followed by the adsorption of 1-octanethiol on the surface of nanoparticles and subsequent generation of corresponding thiyl radicals to initiate the polymerization of MMA. Full article

Ten novel bifunctional quaternary ammonium salt phase-transfer organocatalysts were synthesized in four steps from (+)-camphor-derived 1,3-diamines. These quaternary ammonium salts contained either (thio)urea or squaramide hydrogen bond donor groups in combination with either trifluoroacetate or iodide as the counteranion. Their organocatalytic activity was evaluated in electrophilic heterofunctionalizations of β-keto esters and in the Michael addition of a glycine Schiff base with methyl acrylate. α-Fluorination and chlorination of β-keto esters proceeded with full conversion and low enantioselectivities (up to 29% ee). Similarly, the Michael addition of a glycine Schiff base with methyl acrylate proceeded with full conversion and up to 11% ee. The new catalysts have been fully characterized; the stereochemistry at the C-2 chiral center was unambiguously determined. Full article

In this study, a fast, concise and reliable ultra-high performance liquid chromatography-fluorescence (UHPLC/FLD) detection method for simultaneous quantification of avermectins (AVMs), including avermectin (AVM), ivermectin (IVM), emamectin (EMM), moxidectin (MOX) and doramectin (DOR) in six aquatic foods was established. Based on the QuEChERS pretreatment method, the samples were extracted with 0.2% (v/v) ammonia acetonitrile. N-methyl imidazole mixed with acetonitrile (1:1, v/v) and trifluoroacetic anhydride with acetonitrile (1:2, v/v) were used as derivatization reagents. The mobile phase consists of acetonitrile and water with a flow rate of 1.0 mL/min. An Infinity Lab Poroshell 120 EC-C18 column was used for optimum chromatographic separation of target analytes at 40 °C; the excitation and emission wavelengths were set at 365 nm and 465 nm, respectively. In six kinds of aquatic foods, the limits of detection (LODs) of AVM, IVM, EMM, MOX, and DOR were 2.7 μg/kg, 1.8 μg/kg, 2.1 μg/kg, 1.2 μg/kg, and 2.7 μg/kg, respectively, and the limits of quantification (LOQs) of AVM, IVM, EMM, MOX, and DOR were 5 μg/kg, 4.5 μg/kg, 4.5 μg/kg, 3.5 μg/kg and 5.0 μg/kg, respectively. The recoveries were all above 85.38% when the samples were spiked with the target compounds at the concentration level of 5, 10, 50, and 100 μg/kg. The intra-day and inter-day relative standard deviations (RSDs) were all less than 15%. This method considers the requirements of sensitivity, accuracy, and economics of the instrument. Full article

Annual ryegrass toxicity (ARGT) is an often-fatal poisoning of livestock that consume annual ryegrass infected by the bacterium Rathayibacter toxicus. This bacterium is carried into the ryegrass by a nematode, Anguina funesta, and produces toxins within seed galls that develop during the flowering to seed maturity stages of the plant. The actual mechanism of biochemical transformation of healthy seeds to nematode and bacterial gall-infected seeds remains unclear and no clear-cut information is available on what type of volatile organic compounds accumulate in the respective galls. Therefore, to fill this research gap, the present study was designed to analyze the chemical differences among nematode galls (A. funesta), bacterial galls (R. toxicus) and healthy seeds of annual ryegrass (Lolium rigidum) by using direct immersion solid-phase microextraction (DI-SPME) coupled with gas chromatography–mass spectrometry (GC-MS). The method was optimized and validated by testing its linearity, sensitivity, and reproducibility. Fifty-seven compounds were identified from all three sources (nematode galls, bacterial galls and healthy seed), and 48 compounds were found to be present at significantly different (p < 0.05) levels in the three groups. Five volatile organic compounds (hexanedioic acid, bis(2-ethylhexyl) ester), (carbonic acid, but-2-yn-1-yl eicosyl ester), (fumaric acid, 2-ethylhexyl tridec-2-yn-1-yl ester), (oct-3-enoylamide, N-methyl-N-undecyl) and hexacosanoic acid are the most frequent indicators of R. toxicus bacterial infection in ryegrass, whereas the presence of 15-methylnonacosane, 13-methylheptacosane, ethyl hexacosyl ether, heptacosyl acetate and heptacosyl trifluoroacetate indicates A. funesta nematode infestation. Metabolites occurring in both bacterial and nematode galls included batilol (stearyl monoglyceride) and 9-octadecenoic acid (Z)-, tetradecyl ester. Among the chemical functional group, esters, fatty acids, and alcohols together contributed more than 70% in healthy seed, whereas this contribution was 61% and 58% in nematode and bacterial galls, respectively. This study demonstrated that DI-SPME is a valid technique to study differentially expressed metabolites in infected and healthy ryegrass seed and may help provide better understanding of the biochemical interactions between plant and pathogen to aid in management of ARGT. Full article

In ongoing attempts to efficiently utilize abundant natural gas, there has been steady scientific and industrial interest in using an environmentally benign and inexpensive oxidant (dioxygen O₂) for the direct catalytic oxidation of methane to oxygenate products under mild conditions. Here, we report the homogeneous bis(tetramethylammonium) tetrachlorocobaltate ([Me₄N]₂CoCl₄)-catalyzed methane oxidation to methyl trifluoroacetate (MeTFA) with dioxygen O₂ in trifluoroacetic acid (HTFA) media. [Me₄N]₂CoCl₄ had the highest catalytic activity among previously reported homogeneous cobalt-based catalyst systems; the turnover of methane to MeTFA reached 8.26 mol_ester mol_metal⁻¹h⁻¹ at 180 °C. Results suggest that the ionic form of the catalyst makes the Co species more soluble in the HTFA media; consequently, an active catalyst form, [CoTFA_xCl_y]²⁻, can form very rapidly. Furthermore, chloride anions dissociated from CoCl₄²⁻ appear to suppress oxidation of the solvent HTFA, thereby driving the reaction toward methane oxidation. The effects of reaction time, catalyst concentration, O₂ and methane pressure, and reaction temperature on MeTFA production were also investigated. Full article

Conversion from superoxide (O₂⁻) to hydroperoxide (OOH⁻) on the metal center of oxygenases and oxidases is recognized to be a key step to generating an active species for substrate oxidation. In this study, reactivity of cobalt(III)-superoxido complexes supported by facially-capping tridentate tris(3,5-dimethyl-4-X-pyrazolyl)hydroborate ([HB(pz^Me2,X)₃]⁻; Tp^Me2,X) and bidentate bis(1-methyl-imidazolyl)methylborate ([B(Im^N-Me)₂Me(Y)]⁻; L^Y) ligands toward H-atom donating reagent (2-hydroxy-2-azaadamantane; AZADOL) has been explored. The oxygenation of the cobalt(II) precursors give the corresponding cobalt(III)-superoxido complexes, and the following reaction with AZADOL yield the hydroperoxido species as has been characterized by spectroscopy (UV-vis, resonance Raman, EPR). The reaction of the cobalt(III)-superoxido species and a reducing reagent ([Co^II(C₅H₅)₂]; cobaltocene) with proton (trifluoroacetic acid; TFA) also yields the corresponding cobalt(III)-hydroperoxido species. Kinetic analyses of the formation rates of the cobalt(III)-hydroperoxido complexes reveal that second-order rate constants depend on the structural and electronic properties of the cobalt-supporting chelating ligands. An electron-withdrawing ligand opposite to the superoxide accelerates the hydrogen atom transfer (HAT) reaction from AZADOL due to an increase in the electrophilicity of the superoxide ligand. Shielding the cobalt center by the alkyl group on the boron center of bis(imidazolyl)borate ligands hinders the approaching of AZADOL to the superoxide, although the steric effect is insignificant. Full article

The mechanisms of three selected identity substitution reactions at phosphorus and sulfur occurring with stereospecific inversion have been investigated using density functional theory (DFT). The first identity reaction between methoxyl anion and methyl ethylphenylphosphinate 1 reported in 1963 has been shown to proceed in a stepwise fashion according to the addition–elimination (A–E) mechanism involving formation of a pentacoordinate phosphorus intermediate (TBI-1). In contrast, the results of DFT studies of the identity chloride exchange reaction in (ethoxy)ethylphosphonochloridothionate 3 in acetone solution provided evidence that it proceeds synchronously according to the classical Ingold’s S_N2-P mechanism. DFT calculations of the methoxyl–methoxy exchange reaction at sulfur in methyl p-toluenesulfinate 4 catalyzed by trifluoroacetic acid in methanol revealed that it proceeds stepwise (A–E mechanism), involving the formation of the high-coordinate sulfurane intermediate. In both identity transesterification reactions, 1 and 4, the transiently formed trigonal bipyramidal intermediates with the two methoxyl groups occupying apical positions (TBI-1 and TBI-4) have higher free energy barriers for the Berry-type pseudorotation than those for direct decomposition to starting phosphinate and sulfinate ensuring stereospecific inversion of configuration at the phosphinyl and sulfinyl centers. Thus, the DFT method proved its usefulness in the distinction between both mechanisms that are often indistinguishable by kinetic measurements. Full article

In the present work, the polyphenolic profile of a complex matrix such as Amontillado sherry has been processed by means of high-speed counter-current chromatography (HSCCC) and characterized by HPLC-DAD-MS. An Amberlite XAD-7 column was used to obtain the wine extract, and three different biphasic solvent systems were applied for HSCCC separation: MTBE (methyl tert-butyl ether)/n-butanol/acetonitrile/water (1.1/3/1.1/5+0.1% trifluoroacetic acid), MTBE/n-butanol/acetonitrile/water (2/2/1/5), and hexane/ethyl acetate/ethanol/water (1/5/1/5). As a result, 42 phenolic compounds and furanic derivatives have been identified by means of HPLC-DAD-MS, with 11 of them being identified for the first time in Sherry wines: 3-feruloylquinic acid, isovanillin, ethyl vanillate, furoic acid, dihydro-p-coumaric acid, 6-O-feruloylglucose, ethyl gallate, hydroxytyrosol, methyl protocatechuate, homoveratric acid and veratraldehyde. In addition, the antioxidant capacity (ABTS) of the obtained fractions was determined, revealing higher values in those fractions in which compounds such as gallic acid, protocatechuic acid, protocatechualdehyde, trans-caftaric acid, syringic acid, isovanillin or tyrosol, among others, were present. This is the first time that HSCCC has been used to characterize the phenolic composition of Sherry wines. Full article

Primary production in Mono Lake, a hypersaline soda lake rich in dissolved inorganic arsenic, is dominated by Picocystis strain ML. We set out to determine if this photoautotrophic picoplankter could metabolize inorganic arsenic and in doing so form unusual arsenolipids (e.g., arsenic bound to 2-O-methyl ribosides) as reported in other saline ecosystems and by halophilic algae. We cultivated Picocystis strain ML on a seawater-based medium with either low (37 µM) or high (1000 µM) phosphate in the presence of arsenite (400 µM), arsenate (800 µM), or without arsenic additions (ca 0.025 µM). Cultivars formed a variety of organoarsenic compounds, including a phytyl 2-O-methyl arsenosugar, depending upon the cultivation conditions and arsenic exposure. When the cells were grown at low P, the organoarsenicals they produced when exposed to both arsenite and arsenate were primarily arsenolipids (~88%) with only a modest content of water-soluble organoarsenic compounds (e.g., arsenosugars). When grown at high P, sequestration shifted to primarily water-soluble, simple methylated arsenicals such as dimethylarsinate; arsenolipids still constituted ~32% of organoarsenic incorporated into cells exposed to arsenate but < 1% when exposed to arsenite. Curiously, Picocystis strain ML grown at low P and exposed to arsenate sequestered huge amounts of arsenic into the cells accounting for 13.3% of the dry biomass; cells grown at low P and arsenite exposure sequestered much lower amounts, equivalent to 0.35% of dry biomass. Extraction of a resistant phase with trifluoroacetate recovered most of the sequestered arsenic in the form of arsenate. Uptake of arsenate into low P-cultivated cells was confirmed by X-ray fluorescence, while XANES/EXAFS spectra indicated the sequestered arsenic was retained as an inorganic iron precipitate, similar to scorodite, rather than as an As-containing macromolecule. Samples from Mono Lake demonstrated the presence of a wide variety of organoarsenic compounds, including arsenosugar phospholipids, most prevalent in zooplankton (Artemia) and phytoplankton samples, with much lower amounts detected in the bottom sediments. These observations suggest a trophic transfer of organoarsenicals from the phytoplankton (Picocystis) to the zooplankton (Artemia) community, with efficient bacterial mineralization of any lysis-released organoarsenicals back to inorganic oxyanions before they sink to the sediments. Full article

Polymeric nanomaterials made from amphiphilic block copolymers are increasingly used in the treatment of tumor tissues. In this work, we firstly synthesized the amphiphilic block copolymer PBnMA-b-P(BAPMA-co-PEGMA) via reversible addition-fragmentation chain transfer (RAFT) polymerization using benzyl methacrylate (BnMA), poly (ethylene glycol) methyl ether methacrylate (PEGMA), and 3-((tert-butoxycarbonyl)amino)propyl methacrylate (BAPMA) as the monomers. Subsequently, PBnMA-b-P(APMA-co-PEGMA)@NIR 800 with photothermal conversion property was obtained by deprotection of the tert-butoxycarbonyl (BOC) groups of PBAPMA chains with trifluoroacetic acid (TFA) and post-modification with carboxyl functionalized ketocyanine dye (NIR 800), and it could self-assemble into micelles in CH₃OH/water mixed solvent. The NIR photothermal conversion property of the post-modified micelles were investigated. Under irradiation with NIR light (λ_max = 810 nm, 0.028 W/cm²) for 1 h, the temperature of the modified micelles aqueous solution increased to 53 °C from 20 °C, which showed the excellent NIR photothermal conversion property. Full article

Polyporus umbellatus is a well-known and important medicinal fungus in Asia. Its polysaccharides possess interesting bioactivities such as antitumor, antioxidant, hepatoprotective and immunomodulatory effects. A qualitative and quantitative method has been established for the analysis of 12 monosaccharides comprising polysaccharides of Polyporus umbellatus based on high-performance liquid chromatography coupled with electrospray ionization–ion trap–time of flight–mass spectrometry. The hydrolysis conditions of the polysaccharides were optimized by orthogonal design. The results of optimized hydrolysis were as follows: neutral sugars and uronic acids 4 mol/L trifluoroacetic acid (TFA), 6 h, 120 °C; and amino sugars 3 mol/L TFA, 3 h, 100 °C. The resulting monosaccharides derivatized with 1-phenyl-3-methyl-5-pyrazolone have been well separated and analyzed by the established method. Identification of the monosaccharides was carried out by analyzing the mass spectral behaviors and chromatography characteristics of 1-phenyl-3-methyl-5-pyrazolone labeled monosaccharides. The results showed that polysaccharides in Polyporus umbellatus were composed of mannose, glucosamine, rhamnose, ribose, lyxose, erythrose, glucuronic acid, galacturonic acid, glucose, galactose, xylose, and fucose. Quantitative recoveries of these monosaccharides in the samples were in the range of 96.10–103.70%. This method is simple, accurate, and sensitive for the identification and quantification of monosaccharides, and can be applied to the quality control of Polyporusumbellatus as a natural medicine. Full article

Fluorination of 13-epimeric estrones and their 17-deoxy counterparts was performed with Selectfluor as the reagent. In acetonitrile or trifluoroacetic acid (TFA), 10β-fluoroestra-1,4-dien-3-ones were formed exclusively. Mechanistic investigations suggest that fluorinations occurred via SET in acetonitrile, but another mechanism was operative in TFA. Simultaneous application of N-chlorosuccinimide (NCS) and Selectfluor in TFA led to a 1.3:1 mixture of 10β-fluoroestra-1,4-dien-3-one and 10β-chloroestra-1,4-dien-3-one as the main products. The potential inhibitory action of the 10-fluoro- or 10-chloroestra-1,4-dien-3-one products on human aromatase was investigated via in vitro radiosubstrate incubation. The classical estrane conformation with trans ring anellations and a 13β-methyl group seems to be crucial for the inhibition of the enzyme, while test compounds bearing the 13β-methyl group exclusively displayed potent inhibitory action with submicromolar or micromolar IC₅₀ values. Concerning molecular level explanation of biological activity or inactivity, computational simulations were performed. Docking studies reinforced that besides the well-known Met374 H-bond connection, the stereocenter in the 13 position has an important role in the binding affinity. The configuration inversion at C-13 results in weaker binding of 13α-estrone derivatives to the aromatase enzyme. Full article