Sulfurane [S(IV)]-Mediated Fusion of Benzynes Leads to Helical Dibenzofurans.

Here we disclose a sulfurane-mediated method for the formation of dimeric dibenzofuran helicenes via the reaction between diaryl sulfoxides and hexadehydro-Diels-Alder (HDDA) derived benzynes. A variety of S-shaped and U-shaped helicenes were formed under thermal conditions. Both experimental and DFT studies support a sulfur(IV)-based coupling (aka ligand coupling) mechanism involving tetracarbo-ligated S(IV) intermediates undergoing reductive elimination to afford the helicene products. This process involves the de novo generation of five new rings in a single operation and constitutes a new method for the construction of topologically interesting, polycyclic aromatic compounds.

Dibenzofurans from Lichens - A Pharmacological Overview.

Lichens are a symbiotic association between a fungus (mycobiont) and a green algae/- cyanobacterium (photobiont). Lichens are a source of secondary metabolites, most of them being exclusively for these species, among which dibenzofurans are found. Dibenzofurans are a small group (over 35 different identified compounds), being usnic acid the most studied. In the last 10 years, there has been a growing interest in the pharmacological activity of dibenzofurans. In this work, dibenzofurans isolated from lichens (alectosarmentin, condidymic acid, didymic acid, isousnic acid, isostrepsilic acid, usimines A-C and usnic acid) were reviewed, most of which showed antibacterial, antifungal, and cytotoxic activities. These findings provide future guidance for research on pharmacological activity of dibenzofurans.

Quantum Chemical Investigation of Polychlorinated Dibenzodioxins, Dibenzofurans and Biphenyls: Relative Stability and Planarity Analysis.

All the possible polychlorinated aromatic compounds in the classes of dibenzodioxins (PCDDs), dibenzofurans (PCDFs), and biphenyls (PCBs) were studied by the quantum chemical methods of HF/6-311++G(d,p), B3LYP/6-311++G(d,p), and MP2/cc-pVTZ. The calculated stabilities and structures of these compounds were compared with the available data on their abundance and toxicity. Prediction models for trends in energy and planarity among these congeners were proposed. The results discussed here can help contribute to the understanding of the role of dioxin-like compounds (DLCs) in the environment.

Emission characteristics of dl-PCNs, PCDD/Fs, and dl-PCBs from secondary copper metallurgical plants: Control technology and policy.

This study investigated the characteristics of dl-PCNs, PCDD/Fs and dl-PCBs emitted from two typical secondary copper metallurgical plants processing copper sludge equipped with different sets of air pollution control devices (APCDs). Results indicated that the emission factors of dl-PCNs and PCDD/Fs of plant A are 0.00775 and 1.09 µg TEQ/ton, respectively, which are remarkably lower than those of plant B (3.12, 181 and 25.5 µg TEQ/ton for dl-PCNs, PCDD/Fs and dl-PCBs, respectively). Dl-PCNs contributed 0.7-2.7% of total TEQ for flue gases and up to 2.6% of TEQ for ash samples. The TEQ concentration of dl-PCNs in fly ash individually exceeds the regulated level of 1 ng TEQ/g regulated by Taiwan EPA, indicating that emission and discharge of dl-PCNs should be regulated. The combination of semidry scrubber and activated carbon injection (ACI) + baghouse (BH) is effective for simultaneous removals of dl-PCNs and PCDD/Fs in plant A; while the combination of cyclone, secondary combustion chamber, ACI + BH and wet scrubber (WS) is not optimal for removing dl-PCNs, PCDD/Fs and dl-PCBs. Memory effect occurring within BH and WS is responsible for low removal efficiencies of these POPs in plant B. This study suggests appropriate APCDs for simultaneous removal of three POP groups and recommends the inclusion of dl-PCNs in emission standard.

A new antibacterial dibenzofuran-type phloroglucinol from myrtus communis linn.

Our continuation on the bio-assay guided isolation from Myrtus communis Linn. led to the discovery of a new dibezofuran type phloroglucinol 1,1'-(1,3,7,9-tetrahydroxydibenzo[b,d]furan-2,8-diyl)bis(ethan-1-one) 1. The structure was established through detailed spectroscopic studies including one and two dimensional NMR spectroscopy and electrospray ionization high resolution mass spectrometer (ESI-HRMS). The crude acetone extract from M. communis (AMA), dichloromethane fraction (DCM), and the isolated pure compound 1 were tested against pathogenic bacteria. Compound 1 displayed higher antibacterial activity against the Gram-positive and Gram-negative Staphlocococus aureus and Escherichia coli respectively as compared to the crude extract and fractions.

Three new dibenzofurans from Cydonia oblonga Mill.

Phytochemical investigation of Cydonia oblonga Mill. collected in Xinjiang province, China, led to the isolation and identification of three new dibenzofurans (1-3) along with one known compound (4). Their structures were elucidated based on HRESIMS, spectroscopic data (IR, UV, 1D, 2D NMR) and X-ray diffraction analysis.

Efficient photocaging of a tight-binding bisubstrate inhibitor of cAMP-dependent protein kinase.

Photocaging of a tight-binding bisubstrate inhibitor of cAMP-dependent protein kinase (PKA) with a nitrodibenzofuran-based group fully abolished its inhibitory potency. The affinity difference between the photocaged and the active inhibitor was over 5 orders of magnitude. The photocaged inhibitor disrupted the PKA holoenzyme in cell lysates upon photolysis under a 398 nm LED.

meta C-H Arylation of Electron-Rich Arenes: Reversing the Conventional Site Selectivity.

Controlling site selectivity of C-H activation without using a directing group remains a significant challenge. While Pd(II) catalysts modulated by a mutually repulsive pyridine-type ligand have been shown to favor the relatively electron-rich carbon centers of arenes, reversing the selectivity to favor palladation at the relatively electron-deficient positions has not been possible. Herein we report the first catalytic system that effectively performs meta C-H arylation of a variety of alkoxy aromatics including 2,3-dihydrobenzofuran and chromane with exclusive meta site selectivity, thus reversing the conventional site selectivity governed by native electronic effects. The identification of an effective ligand and modified norbornene (NBE-CO2Me), as well as taking advantage of the statistics, are essential for achieving the exclusive meta selectivity.

Bioaccumulation of PCDD/Fs in foodstuffs near Bien Hoa and Da Nang airbases: assessment on sources and distribution.

In this survey, food items were collected from vicinities of Bien Hoa and Da Nang airbase and determined for polychloro-dibenzo-dioxins and polychloro-dibenzo-furans (PCDD/Fs) to assess their accumulation, distribution in the local food items, and risk of PCDD/F exposure through consumption of the local foods. Dioxin compounds were determined using isotope dilution method which is slightly modified from US-EPA method 1613B. The dioxin concentration was the highest in fish followed by eggs, chicken, meat (pork and beef), and vegetables. Particularly, in Bien Hoa airbase, the mean concentrations of dioxin on TEQ and lipid basis (except for vegetables) were 26 pg/g for fish, 13 pg/g for eggs, 20 pg/g for chicken, 4.5 pg/g for meat, and 0.34 pg/g fresh wt for vegetables. In Da Nang airbase, the mean levels of dioxin on TEQ and lipid basis were slightly lower, 12.9 pg/g for fish, 8.7 pg/g for eggs, 5.9 pg/g for chicken, 6.7 pg/g for meat, and 0.17 pg/g for vegetables. It has been interesting to observe that free-range chicken expose to higher level of dioxin than caged chicken. In some free-range chicken, the portion of 2,3,7,8-TCDD was relatively high and implying recent exposure to dioxin.

Antimicrobial Activities of Dictyostelium Differentiation-Inducing Factors and Their Derivatives.

At the end of its life cycle, the cellular slime mold Dictyostelium discoideum forms a fruiting body consisting of spores and a multicellular stalk. Originally, the chlorinated alkylphenone differentiation-inducing factors (DIFs) -1 and -3 were isolated as stalk cell inducers in D. discoideum. Later, DIFs and their derivatives were shown to possess several biologic activities including antitumor and anti-Trypanosoma properties. In this study, we examined the antibacterial activities of approximately 30 DIF derivatives by using several bacterial species. Several of the DIF derivatives strongly suppressed the growth of the Gram-positive bacteria Staphylococcus aureus, Bacillus subtilis, and Enterococcus faecalis and Enterococcus faecium, at minimum inhibitory concentrations (MICs) in the sub-micromolar to low-micromolar range. In contrast, none of the DIF derivatives evaluated had any noteworthy effect on the growth of the Gram-negative bacterium Escherichia coli (MIC, >100 µM). Most importantly, several of the DIF derivatives strongly inhibited the growth of methicillin-resistant S. aureus and vancomycin-resistant E. faecalis and E. faecium. Transmission electron microscopy revealed that treatment with DIF derivatives led to the formation of distinct multilayered structures consisting of cell wall or plasma membrane in S. aureus. The present results suggest that DIF derivatives are good lead compounds for developing novel antimicrobials.

Quantum Chemical and Kinetic Study on Radical/Molecule Formation Mechanism of Pre-Intermediates for PCTA/PT/DT/DFs from 2-Chlorothiophenol and 2-Chlorophenol Precursors.

Polychlorinated phenoxathiins (PCPTs), polychlorinated dibenzothiophenes (PCDTs), and polychlorinated thianthrenes (PCTAs) are sulfur analogues of polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDD/DFs). Chlorothiophenols (CTPs) and chlorophenols (CPs) are key precursors for the formation of PCTA/PT/DTs, which can react with H or OH to form chloro(thio)phenoxy radical, sulfydryl/hydroxyl-substituted phenyl radicals, and (thio)phenoxyl diradicals. However, previous radical/radical PCTA/DT formation mechanisms in the literature failed to explain the higher concentration of PCDTs than that of PCTAs under the pyrolysis or combustion conditions. In this work, a detailed thermodynamics and kinetic calculations were carried out to investigate the pre-intermediate formation for PCTA/PT/DTs from radical/molecule coupling of the 2-C(T)P with their key radical species. Our study showed that the radical/molecule coupling mechanism explains the gas-phase formation of PCTA/PT/DTs in both thermodynamic and kinetic perspectives. The S/C coupling modes to form thioether-(thio)enol intermediates are preferable over the O/C coupling modes to form ether-(thio)enol intermediates. Thus, although the radical/molecule coupling of chlorophenoxy radical with 2-C(T)P has no effect on the PCDD/PT formation, the radical/molecule coupling of chlorothiophenoxy radical with 2-C(T)P plays an important role in the PCTA/PT formation. Most importantly, the pre-PCDT intermediates formation pathways from the couplings of sulfydryl/hydroxyl-substituted phenyl radical with 2-C(T)P and (thio)phenoxyl diradicals with 2-C(T)P are more favorable than pre-PCTA/PT intermediates formation pathways from the coupling of chlorothiophenoxy radical with 2-C(T)P, which provides reasonable explanation for the high PCDT-to-PCTA ratio in the environment.

Pentachlorophenol, polychlorinated dibenzo-p-dioxins and polychlorinated dibenzo furans in surface soil surrounding pentachlorophenol-treated utility poles on the Kenai National Wildlife Refuge, Alaska USA.

Composite surface soil samples were collected at 0, 25, and 50 cm from the base of 12 utility poles on the Kenai National Wildlife Refuge in Alaska, to assess the extent to which pentachlorophenol, polychlorinated dibenzo-p-dioxins and polychlorinated dibenzo furans may have leached from pentachlorophenol-treated poles. Six pairs of utility poles were included, consisting of an "old" pole manufactured in 1959 or 1963, a "new" pole manufactured within the past 20 years, and a suitable background soil sample from the same vicinity. Old poles had greater concentrations of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) equivalents (TEQs) near the pole base and at 25 cm than "new" poles did. For all 12 poles combined, the mean pentachlorophenol levels in soil were 1810, 157, and 17.8 ppm dry weight (d.w.) near the pole bases, at 25 and 50 cm from the poles, respectively, while the mean total TEQ levels in soil were 15,200, 5170, and 1510 parts per trillion d.w. at those distances. Surface soil levels of pentachlorophenol and TCDD-TEQs exceeded both human health and ecological risk-based screening levels. The design and results of this study were similar to another project in Montreal, Quebec in Canada. Together the results are cause for concern, indicating that millions of similarly treated utility poles in North America may be point sources of pentachlorophenol and dioxins/furans to soil.

Catalytic decomposition of dioxins and other unintentional POPs in flue gas from a municipal waste incinerator (MWI) in China: a pilot testing.

Unintentionally produced persistent organic pollutants (UPOPs) include polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs), dioxin-like polychlorinated biphenyls (dl-PCBs), pentachlorobenzene (PeCBz), and hexachlorobenzene (HxCBz). With the booming of municipal waste incinerators (MWIs) in China, the emission of UPOPs has generated great concern. As an alternative technology of dioxin control, catalytic decomposition has not been used in China, mainly due to the absence of national demonstration projects. Also, the simultaneous removal of various UPOPs has not been well investigated.In this study, a pilot-scale selective catalytic oxidative (SCO) system using a self-developed honeycomb catalyst was built and tested in a typical municipal waste incinerator (MWI) of China. The original concentration of PCDD/Fs in flue gas after the treatment of activated carbon injection (ACI) still exceeded the national emission standard (0.1 ng I-TEQ/Nm3), while the concentrations of PeCBz and HxCBz were one order of magnitude higher than that of PCDD/Fs. For the testing temperature varying from 300 to 200 °C, the removal efficiency of PCDD/Fs range from 39 to 95 %, followed by dl-PCBs with the range of 56-89 %. PeCBz and HxCBz were also removed, though their removal efficiencies were lower than those of PCDD/Fs and dl-PCBs. Both temperature and degree of chlorination influence the removal efficiencies.

The inherent matrix properties of lichen metabolites in matrix-assisted laser desorption ionization time-of-flight mass spectrometry.

RATIONALE: Light-absorbing secondary metabolites from lichens were recently reported to exhibit promising Laser Desorption Ionization (LDI) properties, enabling their direct detection from crude lichen extracts. In addition, many of them display close structural homologies to commercial Matrix-Assisted Laser Desorption Ionization (MALDI) matrices, which is incentive for the evaluation of their matrical properties. The current study systematically evaluated the matrix effects of several structural classes of lichen metabolites: monoaromatic compounds, quinone derivatives, dibenzofuran-related molecules and the shikimate-derived vulpinic acid. Their matrical properties were tested against a wide range of structurally diverse analytes including alkaloids, coumarins, flavonoids and peptides. METHODS: Triplicate automatic positive-ion mode MALDI analyses were carried out and ionization efficiencies were compared with those of structurally related reference matrices (i.e. DHB, HCCA, dithranol and usnic acid) in terms of (i) analyte absolute intensities and (ii) Matrix Suppressing Effect (MSE) scores. RESULTS: Monoaromatic lichen metabolites revealed matrical properties similar to those of DHB when obtained under comparable experimental conditions. Likewise, anthraquinone metabolites triggered ionization of tested analytes in a similar way to the structurally related dithranol. Finally, dibenzofuran derivatives displayed a broad ionization profile, reminiscent of that of (+)-usnic acid. CONCLUSIONS: Lichen metabolites exhibit interesting MALDI matrix properties, especially for medium and low molecular weight analytes. For many of the tested molecules, matrix ion formation was very limited. This proof-of-concept study paves the way for follow-up investigations to assess the matrix properties of lichen metabolites against a wider array of analytes as well as adapting experimental settings to individually optimize the performance of successfully tested candidates.

Callistemenonone A, a novel dearomatic dibenzofuran-type acylphloroglucinol with antimicrobial activity from Callistemon viminalis.

A new acylphloroglucinol with a novel architecture including an unprecedented dearomatic dibenzofuran core, named callistemenonone A (1), was isolated from the leaves of Callistemon viminalis (Myrtaceae). The structure was fully characterized on the basis of extensive spectroscopic analysis, including UV, HRESIMS, as well as 1D and 2D NMR spectral data (HSQC, HMBC, and ROESY). The deduced structure represents the first example of a natural dibenzofuran with two phenyl moieties coupling through tertiary hydroxy and ketal carbons. A plausible biogenetic pathway involving oxidative coupling and dearomatization as key steps is proposed to account for the biosynthesis of this novel class of dibenzofuran. Moreover, antimicrobial assays, in conjunction with the time-killing and biophysical studies, revealed that 1 exerted potent bactericidal activity against a panel of methicillin resistant pathogenic microbes with a unique mechanism.

Synthesis, bioactivity, 3D-QSAR studies of novel dibenzofuran derivatives as PTP-MEG2 inhibitors.

PTP-MEG2 plays a critical role in the diverse cell signalling processes, so targeting PTP-MEG2 is a promising strategy for various human diseases treatments. In this study, a series of novel dibenzofuran derivatives was synthesized and assayed for their PTP-MEG2 inhibitory activities. 10a with highest inhibitory activity (320 nM) exhibited significant selectivity for PTP-MEG2 over its close homolog SHP2, CDC25 (IC50 > 50 µM). By means of the powerful ''HipHop'' technique, a 3D-QSAR study was carried out to explore structure activity relationship of these molecules. The generated pharmacophore model revealed that the one RA, three Hyd, and two HBA features play an important role in binding to the active site of the target protein-PTP-MEG2. Docking simulation study indicated that 10a achieved its potency and specificity for PTP-MEG2 by targeting unique nearby peripheral binding pockets and the active site. The absorption, distribution, metabolism and excretion (ADME) predictions showed that the 11 compounds hold high potential to be novel lead compounds for targeting PTP-MEG2. Our findings here can provide a new strategy or useful insights for designing the effective PTP-MEG2 inhibitors.

Theoretical study on the formation mechanism of pre-intermediates for PXDD/Fs from 2-Bromophenol and 2-Chlorophenol precursors via radical/molecule reactions.

This study investigates reaction pathways for the formation of pre-PXDD/F intermediates via a radical/molecule mechanism. Thermodynamic and kinetic parameters for the combination reactions of 2-bromophenol (2-BP) and 2-chlorophenol (2-CP) precursors with key radical species including the phenoxy radicals, the phenyl radicals and the phenoxyl diradicals were calculated in detail. The couplings of phenoxy radicals with 2-B(C)P tend to produce pre-PXDD intermediates of halogenated o-phenoxyphenol. The combinations of phenyl and phenoxyl diradicals with 2-B(C)P produce two types of structures, i.e., dihydroxybiphenyl and o-phenoxyphenyl, which exclusively act as prestructures of PXDFs. These condensation reactions, especially those involving the phenyl C atom sites in phenyl and phenoxyl diradicals, are proven to be both thermodynamically and kinetically favorable and are nearly comparable with the corresponding steps involved in the radical/radical reactions. Most importantly, reactions of phenyl and phenoxyl diradicals with halogenated phenols solely lead to the formation of PXDFs, which to some extent provides a plausible explanation for the high PXDF-to-PXDD ratios in the real environment. Therefore, our study reveals the pivotal role of the radical/molecule mechanism in homogeneous gas-phase PXDD/F formation, especially in PXDF formation. The present results fill in a knowledge gap that has hitherto existed regarding dioxin formation and improve our understanding of PXDD/F formation characteristics in the environment.

Dibenzofurans and Pseudodepsidones from the Lichen Stereocaulon paschale Collected in Northern Quebec.

Chemical investigation of the methanol extract of the lichen Stereocaulon paschale collected in Nunavik, Canada, led to the isolation and identification of two new dibenzofurans (1 and 3) and 11 known lichen metabolites. The structures of the new compounds were established by analysis of 1D and 2D NMR spectroscopic and high-resolution mass spectrometric data. Herein, the first isolation of ascomatic acid dibenzofuran derivatives (1-3) from a whole lichen organism is reported. In addition, some of the isolated metabolites showed antibacterial activity against the oral pathogens Porphyromonas gingivalis and Streptococcus mutans.

The OH-initiated atmospheric chemical reactions of polyfluorinated dibenzofurans and polychlorinated dibenzofurans: A comparative theoretical study.

The atmospheric chemical reactions of some polyfluorinated dibenzofurans (PFDFs) and polychlorinated dibenzofurans (PCDFs), initiated by OH radical, were investigated by performing theoretical calculations using density functional theory (DFT) and B3LYP/6-311++G(2df,p) method. The obtained results indicate that OH addition reactions of PFDFs and PCDFs occurring at C1∼4 and CA sites are thermodynamic spontaneous changes and the branching ratio of the PF(C)DF-OH adducts is decided primarily by kinetic factor. The OH addition reactions of PFDFs taking place at fluorinated C1∼4 positions are kinetically comparable with those occurring at nonfluorinated C1∼4 positions, while OH addition reactions of PCDFs occurring at chlorinated C1∼4 sites are negligible. The total rate constants of the addition reactions of PFDFs or PCDFs become smaller with consecutive fluorination or chlorination, and substituting at C1 position has more adverse effects than substitution at other sites. The succedent O2 addition reactions of PF(C)DF-OH adducts are thermodynamic nonspontaneous processes under the atmospheric conditions, and have high Gibbs free energies of activation (ΔrG≠). The substituted dibenzofuranols are the primary oxidation products for PCDFs under the atmospheric conditions. However, other oxidative products may also be available for PFDFs besides substituted dibenzofuranols.

Expression of Biphenyl Synthase Genes and Formation of Phytoalexin Compounds in Three Fire Blight-Infected Pyrus communis Cultivars.

Pear (Pyrus communis) is an economically important fruit crop. Drops in yield and even losses of whole plantations are caused by diseases, most importantly fire blight which is triggered by the bacterial pathogen Erwinia amylovora. In response to the infection, biphenyls and dibenzofurans are formed as phytoalexins, biosynthesis of which is initiated by biphenyl synthase (BIS). Two PcBIS transcripts were cloned from fire blight-infected leaves and the encoded enzymes were characterized regarding substrate specificities and kinetic parameters. Expression of PcBIS1 and PcBIS2 was studied in three pear cultivars after inoculation with E. amylovora. Both PcBIS1 and PcBIS2 were expressed in 'Harrow Sweet', while only PcBIS2 transcripts were detected in 'Alexander Lucas' and 'Conference'. Expression of the PcBIS genes was observed in both leaves and the transition zone of the stem; however, biphenyls and dibenzofurans were only detected in stems. The maximum phytoalexin level (~110 µg/g dry weight) was observed in the transition zone of 'Harrow Sweet', whereas the concentrations were ten times lower in 'Conference' and not even detectable in 'Alexander Lucas'. In 'Harrow Sweet', the accumulation of the maximum phytoalexin level correlated with the halt of migration of the transition zone, whereby the residual part of the shoot survived. In contrast, the transition zones of 'Alexander Lucas' and 'Conference' advanced down to the rootstock, resulting in necrosis of the entire shoots.