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Sample records for benzoapyrene diol epoxide

  1. Preferential Glutathione Conjugation of a Reverse Diol Epoxide Compared with a Bay Region Diol Epoxide of Benzo[a]pyrene in Human Hepatocytes

    PubMed Central

    Upadhyaya, Pramod; Hochalter, J. Bradley; Balbo, Silvia; McIntee, Edward J.

    2010-01-01

    Many studies have examined the relationship between polymorphisms in glutathione S-transferase genes and cancer in people exposed to polycyclic aromatic hydrocarbons (PAH) such as benzo[a]pyrene (BaP), but the results to date have been modest. Missing from these studies has been an exploration of the formation of the appropriate glutathione conjugates in humans. We incubated human hepatocytes from 10 donors with racemic anti-BaP-7,8-diol-9,10-epoxide (BPDE), believed to be a major ultimate carcinogen of BaP, or with the noncarcinogenic reverse diol epoxide, racemic anti-BaP-9,10-diol-7,8-epoxide (rev-BPDE). Incubations were carried out for 12 or 24 h. We used high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry-selected reaction monitoring at m/z 464 → m/z 317 to analyze the incubation mixtures for the mercapturic acid products that would result from glutathione conjugation. The standard mercapturic acids were synthesized by reaction of BPDE or rev-BPDE with N-acetylcysteine. We obtained convincing evidence in human hepatocytes for mercapturic acid formation from rev-BPDE in all 10 samples, in amounts up to 17 pmol/ml. However, we could detect mercapturic acids from BPDE in only 1 of 10 samples (0.05 pmol/ml). Taken together with our similar previous results of analyses of phenanthrene metabolites in human hepatocytes and human urine, the results of this study indicate that conjugation of BPDE with glutathione is a minor pathway in humans, indicating that glutathione S-transferase genotyping is not an effective method for assessing risk of PAH-induced cancer in humans, at least with respect to the diol epoxide pathway of PAH carcinogenesis. PMID:20547966

  2. Genetic damage induced by benzo[a]pyrene diol epoxide and risk of lung cancer

    SciTech Connect

    Wei, Q.; Cheng, L.; Li, D.

    1997-10-01

    Lung cancer is the paradigm of carcinogen-induced disease. A chemical carcinogen, benzo[a]pyrene, commonly found in tobacco, is both mutagenic and carcinogenic. It is hypothesized that individuals have varying responses to exposure to environmental carcinogens. In this study, we used benzo[a]pyrene diol epoxide (BPDE) as the test mutagen to investigate three in-vitro susceptibility markers in lymphocytes from 51 patients with lung cancer and 172 cancer-free controls. These markers were: BPDE-induced chromosomal aberrations, BPDE-induced DNA adducts, and DNA repair capacity using host cell reactivation assay with BPDE-damaged plasmid. Using the medians of the controls as the cutoff values, increased risk of lung cancer was associated with increased frequency of chromosomal aberrations (OR=6.53; 95% confidence interval (C.I.), 3.74-11.4), increased BPDE-DNA adduct level (odds ratio (OR)=4.7; 95% C.I., 1.2-18.5), and reduced DNA repair capacity (OR=5.7; 95% C.I., 2.1-15.7). In correlation analyses, cellular ability to repair BPDE-induced DNA damage was found to be inversely correlated with the levels of BPDE-induced DNA adducts (n=34; r=0.34; p=0.048) and the levels of BPDE-DNA adducts correlated significantly with the frequency of chromosomal aberrations (n=62; r=0.42; p=0.001). However, cellular ability to repair BPDE-induced DNA damage was not correlated significantly with the frequency of chromosomal aberrations (n=47; r=0.06; p=0.677). These biomarkers have differing sensitivities in measuring repair of damage induced by chemical carcinogens; therefore, the complementary use of these assays should increase the probability of identifying individuals with susceptibility to smoking-related cancers.

  3. BENZO(A)PYRENE DIOL EPOXIDE I BINDS TO DNA AT REPLICATION FORKS (JOURNAL VERSION)

    EPA Science Inventory

    The distribution in replication forks of DNA lesions caused by the treatment of S phase calls with benzo(a)pyrene-diol-epoxide-1 (BPDE-1) was studied in synchronized C3H10T1/2 cells. Sites of carcinogen modification of DNA were identified by polyclonal rabbit antibodies that were...

  4. INTERACTION OF BENZO(A)PYRENE DIOL EPOXIDE WITH SVAO MINICHROMOSOMES

    SciTech Connect

    Gamper, Howard B.; Yokota, Hisao A.; Bartholomew, James C.

    1980-03-01

    SV40 minichromosomes were reacted with (+)7{beta},8{alpha}-dihydroxy-9{alpha},10{alpha}-epoxy- 7,8,9,10-tetrahydrobenzo[a]pyrene (BaP diol epoxide). Low levels of modification (< 5 DNA adducts/minichromosome) did not detectably alter the structure of the minichromosomes but high levels (> 200 DNA adducts/minichromosome) led to extensive fragmentation. Relative to naked SV40 DNA BaP diol epoxide induced alkylation and strand scission of minichromosomal DNA was reduced or enhanced by factors of 1.5 and 2.0, respectively. The reduction in covalent binding was attributed to the presence of histones, which competed with DNA for the hydrocarbon and reduced the probability of BaP diol epoxide intercalation by tightening the helix. The enhancement of strand scission was probably due to the catalytic effect of histones on the rate of S-elimination at apurinic sites, although an altered adduct profile or the presence of a repair endonuclease were not excluded. Staphylococcal nuclease digestion indicated that BaP dial epoxide randomly alkylated the minichromosomal DNA. This is in contrast to studies with cellular chromatin where internucleosomal DNA was preferentially modified. Differences in the minichromosomal protein complement were responsible for this altered susceptibility.

  5. Crystal structure of a benzo[a]pyrene diol epoxide adduct in a ternary complex with a DNA polymerase.

    PubMed

    Ling, Hong; Sayer, Jane M; Plosky, Brian S; Yagi, Haruhiko; Boudsocq, François; Woodgate, Roger; Jerina, Donald M; Yang, Wei

    2004-02-24

    The first occupation-associated cancers to be recognized were the sooty warts (cancers of the scrotum) suffered by chimney sweeps in 18th century England. In the 19th century, high incidences of skin cancers were noted among fuel industry workers. By the early 20th century, malignant skin tumors were produced in laboratory animals by repeatedly painting them with coal tar. The culprit in coal tar that induces cancer was finally isolated in 1933 and determined to be benzo[a]pyrene (BP), a polycyclic aromatic hydrocarbon. A residue of fuel and tobacco combustion and frequently ingested by humans, BP is metabolized in mammals to benzo[a]pyrene diol epoxide (BPDE), which forms covalent DNA adducts and induces tumor growth. In the 70 yr since its isolation, BP has been the most studied carcinogen. Yet, there has been no crystal structure of a BPDE DNA adduct. We report here the crystal structure of a BPDE-adenine adduct base-paired with thymine at a template-primer junction and complexed with the lesion-bypass DNA polymerase Dpo4 and an incoming nucleotide. Two conformations of the BPDE, one intercalated between base pairs and another solvent-exposed in the major groove, are observed. The latter conformation, which can be stabilized by organic solvents that reduce the dielectric constant, seems more favorable for DNA replication by Dpo4. These structures also suggest a mechanism by which mutations are generated during replication of DNA containing BPDE adducts. PMID:14982998

  6. BENZO[a]PYRENE DIOL EPOXIDE PERTURBATION OF CELL CYCLE KINETICS OF SYNCHRONIZED MOUSE LIVER EPITHELIAL CELLS

    SciTech Connect

    Pearlman, A.L.; Navsky, B.N.; Bartholomew, J.C

    1980-07-01

    A cell cycle synchronization system is described for the analysis of the perturbation of cell cycle kinetics and the cycle-phase specificity of chemicals and other agents. We used the system to study the effects of ({+-})r-7, t-8-dihydroxy-t-9, 10-oxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BaP diol epoxide) upon the cell cycle of mouse liver epithelial cells(NMuLi). BaP diol epoxide(0.6 uM) was added to replated cultures of NMuLi cells that had been synchronized in various stages of the cell cycle by centrifugal elutriation. DNA histograms were obtained by flow cytometry as a function of time after replating. The data were analyzed by a computer modeling routine and reduced to a few graphs illustrating the 'net effects' of the BaP diol epoxide relative to controls. BaP diol epoxide slowed S-phase traversal in all samples relative to their respective control. Traversal through G{sub 2}M was also slowed by at least 50%. BaP diol epoxide had no apparent effect upon G{sub 1} traversal by cycling cells, but delayed the recruitment of quiescent G{sub 0} cells by about 2 hrs. The methods described constitute a powerful new approach for probing the cell cycle effects of a wide variety of agents. The present system appears to be extremely sensitive and capable of characterizing the action of agents on each phase of the cell cycle. The methods are automatable and would allow for the assay and possible differential characterization of mutagens and carcinogens.

  7. Analysis of Phenanthrene and Benzo[a]pyrene Tetraol Enantiomers in Human Urine: Relevance to the Bay Region Diol Epoxide Hypothesis of Benzo[a]pyrene Carcinogenesis and to Biomarker Studies

    PubMed Central

    Hecht, Stephen S.; Carmella, Steven G.; Villalta, Peter W.; Hochalter, J. Bradley

    2010-01-01

    One widely accepted metabolic activation pathway of the prototypic carcinogenic polycyclic aromatic hydrocarbon (PAH) benzo[a]pyrene (BaP) proceeds through the “bay region diol epoxide” BaP-(7R,8S)-diol-(9S,10R)-epoxide (2). However, few studies have addressed the analysis of human urinary metabolites of BaP which result from this pathway. Phenanthrene (Phe) is structurally related to BaP, but human exposure to Phe is far greater and its metabolites can be readily detected in urine. Thus, Phe metabolites have been proposed as biomarkers of PAH exposure and metabolic activation. Phe-tetraols in particular could be biomarkers of the diol epoxide pathway. While BaP-tetraols and Phe-tetraols have been previously quantified in human urine, no published studies have determined their enantiomeric composition. This is important because different enantiomers would result from the bay region diol epoxide and “reverse” diol epoxide pathways, the latter being associated with weak mutagenicity and carcinogenicity. We addressed this problem using chiral HPLC to separate the enantiomers of BaP-7,8,9,10-tetraol and Phe-1,2,3,4-tetraol. Urine samples from smokers were subjected to solid-phase extraction, chiral HPLC, and GC-NICI-MS/MS analysis for silylated Phe-1,2,2,4-tetraols. The results demonstrated that >96% of Phe-1,2,3,4-tetraol in smokers’ urine was Phe-(1S,2R,3S,4R)-tetraol (12), resulting from the “reverse” diol epoxide pathway, whereas less than 4% resulted from the “bay region diol epoxide” pathway of Phe metabolism. Urine from creosote workers was similarly analyzed for BaP-7,8,9,10-tetraol enantiomers. In contrast to the results of the Phe-tetraol analyses, 78% of BaP-7,8,9,10-tetraol in these human urine samples was BaP-(7R,8S,9R,10S)-tetraol (3) resulting from the “bay region diol epoxide” pathway of BaP metabolism. These results provide further support for the bay region diol epoxide pathway of BaP metabolism in humans and demonstrate

  8. Fluorescence and mass spectral evidence for the formation of benzo[a]pyrene anti-diol-epoxide-DNA and -hemoglobin adducts in humans.

    PubMed

    Weston, A; Rowe, M L; Manchester, D K; Farmer, P B; Mann, D L; Harris, C C

    1989-02-01

    Highly specific methods are required to detect and quantitate carcinogen-macromolecular adducts in humans who are exposed to complex mixtures of chemical carcinogens. High performance liquid chromatography and fluorescence spectroscopy have been used successfully to detect and identify residues of benzo[a]pyrene-7,10/8,9-tetrahydrotetrol (BP-7,10/8,9-tetrol) that were released upon mild acid hydrolysis of human DNA or hemoglobin. Synchronous fluorescence spectroscopy data indicate that levels of benzo[a]pyrene-diol-epoxide-DNA (BPDE-DNA) adducts as high as 1.54 fmol BPDE/micrograms DNA are formed (1 adduct in 5 million nucleotides) in peripheral blood lymphocytes of coke-oven workers; these data were subsequently corroborated by gas chromatography/mass spectroscopy single ion monitoring analysis (m/z 404+). Additionally, among lung cancer patients, 5 samples of tumor DNA were found to be negative and 1 of 4 samples of corresponding lung tissue was found to be positive. Extraction and purification of BP-7,10/8,9-tetrol from the hemoglobin of smokers suggested levels of bound carcinogen in excess of 1 ng BPDE/gm of hemoglobin. High performance liquid chromatography combined with synchronous fluorescence spectroscopy provides a highly specific method for the detection of covalently bound BP residues in both human hemoglobin and DNA. PMID:2912575

  9. Ataxia-telangiectasia mutated expression is associated with tobacco smoke exposure in esophageal cancer tissues and benzo[a]pyrene diol epoxide in cell lines.

    PubMed

    Jiang, Yan; Liang, Zheng D; Wu, Tsung T; Cao, Liyu; Zhang, Hongfu; Xu, Xiao-Chun

    2007-01-01

    Esophageal cancer is a substantial health problem because of its usually late stage at diagnosis and poor prognosis. Tobacco smoking and alcohol use are the most important risk factors in the development of esophageal squamous cell carcinoma (SCC). Our previous study demonstrated the binding of benzo[a]pyrene diol epoxide (BPDE), a carcinogen present in tobacco smoke and environmental pollution, to the ataxia-telangiectasia mutated (ATM) gene. To understand how this binding affects the alteration of ATM expression and to identify biomarkers for the detection of esophageal cancer, we analyzed ATM mRNA expression in tissue specimens from patients with esophageal SCC and premalignant lesions using in situ hybridization. We then performed in vitro experiments to verify and extend our ex vivo observations. We found that ATM expression was increased in esophageal SCC and its premalignant lesions when compared with normal tissues and that increased ATM expression was associated with tobacco smoke exposure and tumor de-differentiation. Moreover, BPDE induced ATM expression in esophageal SCC cell lines in a time-dependent manner. In summary, the BPDE in tobacco smoke may be responsible for increased ATM expression in premalignant and malignant esophageal tissues. Our findings suggest that the ATM gene should be further evaluated as a biomarker for the early detection of esophageal cancer and tobacco use in patients. PMID:17019709

  10. BENZO[A]PYRENE AND BENZO[C]PHENANTHRENE: THE EFFECT OF STRUCTURE ON THE BINDING OF WATER MOLECULES TO THE DIOL EPOXIDES

    EPA Science Inventory

    ABSTRACT
    The interaction with water of the diol epoxides (DEs) of both a planar and a non-planar PAH have been examined using molecular dynamics. To determine probable water locations around the DE for later use in the study of DE protonation, molecular dynamics simulations u...

  11. Genetic polymorphisms in biotransformation enzymes for benzo[a]pyrene and related levels of benzo[a]pyrene-7,8-diol-9,10-epoxide-DNA adducts in Goeckerman therapy.

    PubMed

    Beranek, Martin; Fiala, Zdenek; Kremlacek, Jan; Andrys, Ctirad; Hamakova, Kvetoslava; Chmelarova, Marcela; Palicka, Vladimir; Borska, Lenka

    2016-07-25

    Goeckerman therapy (GT) for psoriasis combines the therapeutic effect of crude coal tar (CCT) and ultraviolet radiation (UVR). CCT contains polycyclic aromatic hydrocarbons, some of which can form DNA adducts that may induce mutations and contribute to carcinogenesis. The aim of our work was to evaluate the relationship between concentrations of benzo[a]pyrene-7,8-diol-9,10-epoxide-DNA adducts (BPDE-DNA adducts) and rs4646903 (CYP1A1 gene), rs1048943 (CYP1A1), rs1056836 (CYP1B1), rs1051740 (EPHX1), rs2234922 (EPHX1) and rs8175347 (UGT1A1) polymorphic sites, and GSTM1 null polymorphism in 46 patients with chronic stable plaque psoriasis who underwent GT. The level of BPDE-DNA adducts was determined using the OxiSelect BPDE-DNA Adduct ELISA Kit. Polymerase chain reaction (PCR) and restriction fragment length polymorphism analysis (rs4646903, rs1048943, rs1051740, and rs2234922), fragment analysis (rs8175347), real-time PCR (rs1056836), and digital droplet PCR polymorphism (GSTM1) were used. CYP1B1*1/*1 wild-type subjects and CYP1B1*3/*1 heterozygotes for rs1056836 formed significantly higher amounts of BPDE-DNA adducts than CYP1B1*3/*3 homozygotes (p=0.031 and p=0.005, respectively). Regarding rs1051740, individuals with EPHX1*3/*1 heterozygosity revealed fewer adducts than EPHX1*1/*1 wild-type subjects (p=0.026). Our data suggest that CYP1B1/EPHX1 genotyping could help to predict the risk of DNA damage and to optimize doses of coal tar and UVR exposure in psoriatic patients in whom GT was applied. PMID:27188524

  12. Epigallocatechin-3-gallate reduces DNA damage induced by benzo[a]pyrene diol epoxide and cigarette smoke condensate in human mucosa tissue cultures.

    PubMed

    Baumeister, Philipp; Reiter, Maximilian; Kleinsasser, Norbert; Matthias, Christoph; Harréus, Ulrich

    2009-06-01

    Although epidemiological studies indicate cancer preventive effects of diets rich in fruit and vegetables, large clinical intervention studies conducted to evaluate dietary supplementation with micronutrients, mostly vitamins, showed disappointing results in large parts. In contrast, there is encouraging epidemiologic data indicating great chemopreventive potential of a large group of phytochemicals, namely polyphenols. This study shows the DNA protective effect epigallocatechin-3-gallate, a tea catechin, and one of the best-studied substances within this group, on carcinogen-induced DNA fragmentation in upper aerodigestive tract cells. Cell cultures from fresh oropharyngeal mucosa biopsies were preincubated with epigallocatechin-3-gallate in different concentrations before DNA damage was introduced with the metabolically activated carcinogen benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide or cigarette smoke condensate. Effects on resulting DNA fragmentation were measured using the alkaline single-cell microgel electrophoresis (comet assay). Epigallocatechin-3-gallate significantly reduced benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide-induced DNA damage by up to 51% (P<0.001). Fragmentation induced by cigarette smoke condensate could be lowered by 47% (P<0.001). Data suggest a cancer preventive potential of epigallocatechin-3-gallate as demonstrated on a subcellular level. An additional mechanism of tea catechin action is revealed by using a primary mucosa culture model. PMID:19491610

  13. Simulated sunlight and benzo[a]pyrene diol epoxide induced mutagenesis in the human p53 gene evaluated by the yeast functional assay: lack of correspondence to tumor mutation spectra.

    PubMed

    Yoon, Jung-Hoon; Lee, Chong-Soon; Pfeifer, Gerd P

    2003-01-01

    Many mutations in the p53 gene destroy the transcriptional transactivation function of the p53 protein. This function of p53 can be determined in a yeast assay using a p53 responsive reporter gene. The yeast assay could hold promise for the identification of mutagens implicated in human cancer if the p53 mutational spectra obtained with this assay would match human tumor mutation data. Ultraviolet (UV) light from the sun and polycyclic aromatic hydrocarbons, such as benzo[a]pyrene, are strongly implicated in the spectrum of p53 mutations found in human non-melanoma skin cancers and smoking-associated lung cancers, respectively. We have used these two model mutagens to assess the feasibility of using the p53 yeast assay in cancer epidemiology. After treatment of CpG methylated p53 DNA with a solar UV simulator or with benzo[a]pyrene diol epoxide (BPDE), the modified p53 sequences were assayed in yeast for mutational outcome. As expected, BPDE produced predominantly G to T transversions and simulated sunlight produced mostly C to T transitions at dipyrimidine sites in the p53 coding sequence. However, the preferentially mutated p53 sequences (hotspots) in the yeast assay were completely different from those in the mutational spectra found in human lung and skin cancers. The data indicate that this assay is not a reliable measurement of p53 mutagenesis in human tissues and that, perhaps, transcriptional activation is not the primary function of p53 in tumor suppression. PMID:12538356

  14. Oxidative Damage to Nucleic Acids and Benzo(a)pyrene-7,8-diol-9,10-epoxide-DNA Adducts and Chromosomal Aberration in Children with Psoriasis Repeatedly Exposed to Crude Coal Tar Ointment and UV Radiation

    PubMed Central

    Andrys, Ctirad; Palicka, Vladimir; Chmelarova, Marcela; Hamakova, Kvetoslava

    2014-01-01

    The paper presents a prospective cohort study. Observed group was formed of children with plaque psoriasis (n=19) treated by Goeckerman therapy (GT). The study describes adverse (side) effects associated with application of GT (combined exposure of 3% crude coal tar ointment and UV radiation). After GT we found significantly increased markers of oxidative stress (8-hydroxy-2′-deoxyguanosine, 8-hydroxyguanosine, and 8-hydroxyguanine), significantly increased levels of benzo[a]pyrene-7,8-diol-9,10-epoxide (BPDE) DNA adducts (BPDE-DNA), and significantly increased levels of total number of chromosomal aberrations in peripheral lymphocytes. We found significant relationship between (1) time of UV exposure and total number of aberrated cells and (2) daily topical application of 3% crude coal tar ointment (% of body surface) and level of BPDE-DNA adducts. The findings indicated increased hazard of oxidative stress and genotoxic effects related to the treatment. However, it must be noted that the oxidized guanine species and BPDE-DNA adducts also reflect individual variations in metabolic enzyme activity (different extent of bioactivation of benzo[a]pyrene to BPDE) and overall efficiency of DNA/RNA repair system. The study confirmed good effectiveness of the GT (significantly decreased PASI score). PMID:25197429

  15. Quantification of benzo[a]pyrene diol epoxide DNA-adducts by stable isotope dilution liquid chromatography/tandem mass spectrometry.

    PubMed

    Ruan, Qian; Kim, Hye-Young H; Jiang, Hao; Penning, Trevor M; Harvey, Ronald G; Blair, Ian A

    2006-01-01

    Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental pollutants found in car exhausts, charbroiled food, and tobacco smoke. Three pathways for the metabolic activation of B[a]P to ultimate carcinogens have been proposed. The most widely accepted pathway involves cytochrome-P450 (CYP) 1A1- and/or 1B1-mediated formation of B[a]P-7,8-oxide, which undergoes epoxide hydrolase-mediated metabolism to the proximate carcinogen B[a]P-7,8-dihydro-7,8-diol. Further CYP1A1- and/or CYP1B1-mediated activation of the dihydrodiol results in the formation of 7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (B[a]PDE), the ultimate carcinogen. In previous studies, it was demonstrated that (+)-anti-B[a]PDE was the most potent tumorigen of the CYP-derived B[a]PDE diastereomers. We have developed a stable isotope dilution, liquid chromatography multiple reaction monitoring/mass spectrometry (LC-MRM/MS) assay for all eight (+/-)-anti-B[a]PDE-derived dGuo and dAdo DNA-adducts. The LC-MRM/MS assay was rigorously validated and used to show that (+)-anti-trans-B[a]PDE-dGuo was the major adduct formed when naked DNA and human bronchoalveolar adenocarcinoma H358 cells were treated with (+/-)-anti-B[a]PDE. The preference for DNA-adducts derived from (+)-anti-B[a]PDE was even more apparent in cellular DNA. Thus, the increased potency of (+)-anti-B[a]PDE as a tumorigen is most likely due its ability to preferentially form DNA-adducts when compared with (-)-anti-B[a]PDE. Also, the adduct profile suggests that this occurs by binding of (+)-anti-B[a]PDE to DNA in a manner that facilitates covalent binding to dGuo rather than dAdo residues. PMID:16557497

  16. Identification of benzo[a]pyrene 7,8-diol 9,10-epoxide N2-deoxyguanosine in human lung adenocarcinoma cells exposed to cooking oil fumes from frying fish under domestic conditions.

    PubMed

    Yang, S C; Jenq, S N; Kang, Z C; Lee, H

    2000-10-01

    Lung cancer is the most common cause of cancer death among women in Taiwan. Epidemiological studies of lung cancer in Chinese women indicate that factors other than cigarette smoking are related to lung cancer risk. One such factor may be exposure to carcinogens formed during the cooking of food. The carcinogenic compounds in oil smoke particulates from Chinese cooking practice have not yet been characterized. To reveal the relationship between the high mortality rate of lung cancer in Chinese women and exposure to cooking oil fumes (COF), DNA adduct formation, induced by COF collected from frying fish under domestic conditions, was assessed in human lung adenocarcinoma CL-3 cell lines using the (32)P-postlabeling assay. DNA adduct levels were induced by COF in CL-3 cells in a dose-dependent manner. DNA adducts with a diagonal radioactive zone (DRZ) were observed when CL-3 cells were treated with COF. Surprisingly, only one spot of the DNA adduct profile was in the DRZ. The DNA adduct was analyzed by HPLC coupled with an on-line radioactive detector. The retention time of the major DNA adduct corresponded to that of authentic benzo[a]pyrene 7,8-diol 9, 10-epoxide N2-deoxyguanonsine (BPDE-N2-dG). Moreover, the mass spectrum of the major DNA adduct in CL-3 cells was confirmed to be BPDE-N2-dG by liquid chromatography/mass spectrometry. In conclusion, BPDE-N2-dG adduct formation in human lung cells supports epidemiological findings of an association between cooking fume exposure and lung cancer in Chinese women. PMID:11080053

  17. Detection of benzo[a]pyrene diol epoxide-DNA adducts in peripheral blood lymphocytes and antibodies to the adducts in serum from coke oven workers.

    PubMed Central

    Harris, C C; Vahakangas, K; Newman, M J; Trivers, G E; Shamsuddin, A; Sinopoli, N; Mann, D L; Wright, W E

    1985-01-01

    Coke oven workers are exposed to high levels of carcinogenic polycyclic aromatic hydrocarbons, including benzo[a]pyrene (B[a]P), and are at increased risk of lung cancer. Since B[a]P is enzymatically activated to 7 beta,8 alpha-dihydroxy(9 alpha, 10 alpha)epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (B[a]PDE) that forms adducts with DNA, the presence of these adducts was measured in DNA from peripheral blood lymphocytes by synchronous fluorescence spectrophotometry and enzyme radioimmunoassay. Approximately two-thirds of the workers had detectable levels of B[a]PDE-DNA adducts. Antibodies to the DNA adducts were also found in the serum of 27% of the workers. B[a]PDE-DNA adducts were not detectable in lymphocytes and antibodies to the adducts were not detected in sera from a control group of nonsmoking laboratory workers. DNA adducts and/or antibodies to the adducts indicate exposure to B[a]P and its metabolic activation to the carcinogenic metabolite that covalently binds to and damages DNA. Detection of adducts and antibodies to them may also be useful as internal dosimeters of the pathobiological effective doses of chemical carcinogens. PMID:2413443

  18. Effects of sulfite on the uptake and binding of benzo[a]pyrene diol epoxide in cultured murine respiratory epithelial cells

    SciTech Connect

    Green, J.L.; Jones, B.C.; Reed, G.A. )

    1994-02-01

    Sulfur dioxide (SO[sub 2]) may act as a cocarcinogen with benzo[a]pyrene (BaP) in the respiratory tract. We have modeled this effect by examining the interactions of 7r,8t-dihydroxy-9t,10t-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (anti-BPDE) with sulfite, the physiological form of SO[sub 2], in a murine respiratory epithelial cell line (C10). We exposed C10 cells to [[sup 3]H]-anti-BPDE and determined the effects of 1 and 10 mM sulfite on the uptake and subcellular localization of labeled products. Autoradiographic analysis showed that sulfite doubled the nuclear localization of anti-BPDE-derived materials was not affected by sulfite during the first 60 min, but nuclear localization continued to increase in the sulfite-containing incubations throughout the 4-hr incubation period. Little increase in nuclear localization of anti-BPDE-derived material was noted in the incubations without sulfite after 60 min. Subcellular fractionation was performed to determine the amount of label associated with cytosolic and nuclear fractions and to determine covalent binding to protein and DNA. Sulfite produced a modest increase in the amount of [[sup 3]H]-anti-BPDE-derived products bount to protein; however, binding to nuclear DNA increase by more than 200% with 10 mM sulfite. Analysis of the supernatents from the cytosolic and nuclear fractions of cells exposed to anti-BPDE and sulfite demonstrated the presence of 7r,8t9t-trihydroxy-7,8,9,10-tetrahydrobenzo[a]pyrene-10c- sulfonate (BPT-10-sulfonate). [[sup 3]H]-BPT-10-sulfonate was unable to enter C10 cells, suggesting that it is formed intracellularly. Once formed, this compound may be unable to leave the cell. The observed intracellular formation of BPT-10-sulfonate, a more stable DNA-modifying BaP derivative than BPDE and one which probably cannot leave the cell, could be responsible for this extended time course of nuclear localization and DNA modification.

  19. COMPARATIVE STUDIES OF THE EFFECT OF POLYCYCLIC AROMATIC HYDROCARBON GEOMETRY ON THE HYDROLYSIS OF DIOL EPOXIDES

    EPA Science Inventory

    Comparative studies of the effect of polycyclic aromatic hydrocarbon geometry on the hydrolysis of diol epoxides

    The interaction of the diol epoxides (DEs) of both planar and non-planar PAHs with water have been examined using quantum mechanical and molecular dynamics. Th...

  20. Inhibition of the mutagenicity of bay-region diol epoxides of polycyclic aromatic hydrocarbons by naturally occurring plant phenols: Exceptional activity of ellagic acid

    PubMed Central

    Wood, Alexander W.; Huang, Mou-Tuan; Chang, Richard L.; Newmark, Harold L.; Lehr, Roland E.; Yagi, Haruhiko; Sayer, Jane M.; Jerina, Donald M.; Conney, Allan H.

    1982-01-01

    Ferulic, caffeic, chlorogenic, and ellagic acids, four naturally occurring plant phenols, inhibit the mutagenicity and cytotoxicity of (±)-7β,8α-dihydroxy-9α, 10α-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (B[a]P 7,8-diol-9,10-epoxide-2), the only known ultimate carcinogenic metabolite of benzo[a]pyrene. The mutagenicity of 0.05 nmol of B[a]P 7,8-diol-9,10-epoxide-2 in strain TA100 of Salmonella typhimurium is inhibited 50% by incubation of the bacteria and the diol epoxide with 150 nmol of ferulic acid, 75 nmol of caffeic acid, 50 nmol of chlorogenic acid or, most strikingly, 1 nmol of ellagic acid in the 0.5-ml incubation mixture. A 3-nmol dose of ellagic acid inhibits mutation induction by 90%. Ellagic acid is also a potent antagonist of B[a]P 7,8-diol-9,10-epoxide-2 in Chinese hamster V79 cells. Mutations to 8-azaguanine resistance induced by 0.2 μM diol epoxide are reduced by 50% when tissue culture media also contains 2 μM ellagic acid. Similar to results obtained with the bacteria, ferulic, caffeic, and chlorogenic acids are approximately two orders of magnitude less active than ellagic acid in the mammalian cell assay. The antimutagenic effects of the plant phenols result from their direct interaction with B[a]P 7,8-diol-9,10-epoxide-2, because a concentration-dependent increase in the rate of diol epoxide disappearance in cell-free solutions of 1:9 dioxane/water, pH 7.0, is observed with all four phenols. In parallel with the mutagenicity studies, ellagic acid is 80-300 times more effective than the other phenols in accelerating the disappearance of B[a]P 7,8-diol-9,10-epoxide-2. Ellagic acid at 10 μM increases the disappearance of B[a]P 7,8-diol-9,10-epoxide-2 by approximately 20-fold relative to the spontaneous and hydronium ion-catalyzed hydrolysis of the diol epoxide at pH 7.0. Ellagic acid is a highly potent inhibitor of the mutagenic activity of bay-region diol epoxides of benzo[a]pyrene, dibenzo[a,h]pyrene, and dibenzo[a,i]pyrene, but higher

  1. Preferential Glutathione Conjugation of a Reverse Diol Epoxide Compared to a Bay Region Diol Epoxide of Phenanthrene in Human Hepatocytes: Relevance to Molecular Epidemiology Studies of Glutathione-S-Transferase Polymorphisms and Cancer

    PubMed Central

    Hecht, Stephen S.; Berg, Jeannette Zinggeler; Hochalter, J. Bradley

    2009-01-01

    Bay region diol epoxides are recognized ultimate carcinogens of polycyclic aromatic hydrocarbons (PAH), and in vitro studies have demonstrated that they can be detoxified by conjugation with glutathione, leading to the widely investigated hypothesis that individuals with low activity forms of glutathione-S-transferases are at higher risk of PAH induced cancer, a hypothesis that has found at most weak support in molecular epidemiology studies. A weakness in this hypothesis was that the mercapturic acids resulting from conjugation of PAH bay region diol epoxides had never been identified in human urine. We recently analyzed smokers’ urine for mercapturic acids derived from phenanthrene, the simplest PAH with a bay region. The only phenanthrene diol epoxide-derived mercapturic acid in smokers’ urine was produced from the reverse diol epoxide, anti-phenanthrene-3,4-diol-1,2-epoxide (11), not the bay region diol epoxide, anti-phenanthrene-1,2-diol-3,4-epoxide (10), which does not support the hypothesis noted above. In this study, we extended these results by examining the conjugation of phenanthrene metabolites with glutathione in human hepatocytes. We identified the mercapturic acid N-acetyl-S-(r-4,t-2,3-trihydroxy-1,2,3,4-tetrahydro-c-1-phenanthryl)-L-cysteine (14a), (0.33–35.9 pmol/mL at 10 µM 8, 24h incubation, N = 10) in all incubations with phenanthrene-3,4-diol (8) and the corresponding diol epoxide 11, but no mercapturic acids were detected in incubations with phenanthrene-1,2-diol (7) and only trace amounts were observed in incubations with the corresponding bay region diol epoxide 10. Taken together with our previous results, these studies clearly demonstrate that glutathione conjugation of a reverse diol epoxide of phenanthrene is favored over conjugation of a bay region diol epoxide. Since reverse diol epoxides of PAH are generally weakly or non-mutagenic/carcinogenic, these results, if generalizable to other PAH, do not support the widely held

  2. Determination of polycyclic aromatic hydrocarbons in the urine, benzo(a)pyrene diol epoxide-DNA adducts in lymphocyte DNA, and antibodies to the adducts in sera from coke oven workers exposed to measured amounts of polycyclic aromatic hydrocarbons in the work atmosphere.

    PubMed

    Haugen, A; Becher, G; Benestad, C; Vahakangas, K; Trivers, G E; Newman, M J; Harris, C C

    1986-08-01

    Workers in coke oven plants have a higher incidence of lung cancer than the general population. They are exposed to a variety of chemicals, in particular the polycyclic aromatic hydrocarbons (PAH), including benzo(a)pyrene. To evaluate the genotoxic effects of PAH exposure, air samples and urine samples were analyzed for PAH by capillary gas chromatography and high-performance liquid chromatography, respectively. Since benzo(a)pyrene is activated to 7 beta,8 alpha-dihydroxy-(9 alpha,10 alpha)-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene (BPDE) and binds to DNA, we have used ultrasensitive enzymatic radioimmunoassay and synchronous fluorescence spectrophotometry to measure BPDE-DNA adducts in lymphocyte DNA. The results show that workers were exposed to high concentrations of atmospheric PAH. However, the mean PAH exposure levels are reduced 60% when the workers wore masks during work. When compared to exposure levels, the urinary excretion of PAH was relatively low. Approximately one-third of the workers had detectable putative BPDE-DNA adducts in lymphocytes by ultrasensitive enzymatic radioimmunoassay, and 10% of the samples had emission peaks at 379 nm by synchronous fluorescence spectrophotometry. The four most positive samples were the same in both of the assays. Antibodies to an epitope(s) on BPDE-DNA were found in the sera of approximately one-third of the workers. Detection of DNA adducts and antibodies to these adducts are internal indicators of exposure to benzo(a)pyrene. PMID:3731085

  3. Analysis of phenanthrene diol epoxide mercapturic acid detoxification products in human urine: relevance to molecular epidemiology studies of glutathione S-transferase polymorphisms

    PubMed Central

    Hecht, Stephen S.; Villalta, Peter W.; Hochalter, J.Bradley

    2008-01-01

    Many studies have investigated the effects of glutathione S-transferase (GST) polymorphisms on cancer incidence in people exposed to carcinogenic polycyclic aromatic hydrocarbons (PAHs). The basis for this is that the carcinogenic bay region diol epoxide metabolites of several PAH are detoxified by GSTs in in vitro studies. However, there are no reports in the literature on the identification in urine of the mercapturic acid metabolites that would result from this process in humans. We addressed this by developing a method for quantitation in human urine of mercapturic acids which would be formed from angular ring diol epoxides of phenanthrene (Phe), the simplest PAH with a bay region, and a common environmental pollutant. We prepared standard mercapturic acids by reactions of syn- or anti-Phe-1,2-diol-3,4-epoxide and syn- or anti-Phe-3,4-diol-1,2-epoxide with N-acetylcysteine. Analysis of human urine conclusively demonstrated that the only detectable mercapturic acid of this type—N-acetyl-S-(r-4,t-2,3-trihydroxy-1,2,3,4-tetrahydro-c/t-1-phenanthryl)-L-cysteine (anti-PheDE-1-NAC)—was derived from the ‘reverse diol epoxide’, anti-Phe-3,4-diol-1,2-epoxide, and not from the bay region diol epoxides, syn- or anti-Phe-1,2-diol-3,4-epoxide. Levels of anti-PheDE-1-NAC in the urine of 36 smokers were (mean ± SD) 728 ± 859 fmol/ml urine. The results of this study provide the first evidence for a mercapturic acid of a PAH diol epoxide in human urine, but it was not derived from a bay region diol epoxide as molecular epidemiologic studies have presumed, but rather from a reverse diol epoxide, representative of metabolites with little if any carcinogenic activity. These results demonstrate the need for integration of genotyping and phenotyping information in molecular epidemiology studies. PMID:18477646

  4. SEPARATION OF 32P-LABELED 3'5'-BISPHOSPHATE NUCLEOTIDES OF POLYCYCLIC AROMATIC HYDROCARBON ANTI-DIOL-EPOXIDES AND DERIVATIVES

    EPA Science Inventory

    23P-Postlabeling/HPLC is a highly sensitive analytical method for identification of chemical-modified DNA adducts isolated from experimental animals and human samples. o determine the optimal 32P-postlabeling/HPLC conditions for efficient separation, we employed ten diol-epoxide-...

  5. SEPARATION OF 32P-LABELED 3',5'-BISPHOSPHATE NUCLEOTIDES OF POLYCYCLIC AROMATIC HYDROCARBON ANTI-DIOL-EPOXIDES AND DERIVATIVES

    EPA Science Inventory

    23P-Postlabeling/HPLC is a highly sensitive analytical method for identification of chemical-modified DNA adducts isolated from experimental animals and human samples. o determine the optimal 32P-postlabeling/HPLC conditions for efficient separation, we employed ten diol-epoxide-...

  6. IDENTIFICATION AND QUANTITATION OF BENZO[A]PYRENE DERIVED DNA ADDUCTS FORMED AT LOW ADDUCTION LEVEL IN MICE LUNG TISSUE

    EPA Science Inventory

    The two major metabolic pathways of benzo[a]pyrene (BP), as well as other polycyclic aromatic hydrocarbons, that allow for the induction of DNA lesions are monooxygenation that results in diol epoxides (BPDE), and one-electron oxidation that yields a BP radical cation. The DNA ad...

  7. ON BENZO[A]PYRENE DERIVED DNA ADDUCTS FORMED IN LUNG TISSUE OF MICE

    EPA Science Inventory

    On Benzo [a] pyrene Derived DNA Adducts Formed in Lung Tissue of Mice
    The previously identified major DNA adducts of benzo[a]pyrene (BP) in vitro and in vivo are the stable and unstable adducts formed by reaction of the bay-region diol epoxide of BP (BPDE) and BP radical catio...

  8. BENZO[A]PYRENE AND ITS K-REGION DIOL INDUCE DNA DAMAGE IN C3H10T1/2C18 CELLS AS MEASURED BY THE ALKALINE SINGLE CELL GEL (COMET) ASSAY

    EPA Science Inventory


    160. Benzo[a]pyrene and its K-region diol induce DNA damage in C3HlOTl/2Cl8 cells as measured by the alkaline single cell gel (Comet) assay

    In a continuing series of studies on the genotoxicity ofK-region dihydrodiols of polycyclic aromatic hydrocarbons, we have repo...

  9. Characterization of the SgcF epoxide hydrolase supporting an (R)-vicinal diol intermediate for enediyne antitumor antibiotic C-1027 biosynthesis.

    PubMed

    Lin, Shuangjun; Horsman, Geoffrey P; Chen, Yihua; Li, Wenli; Shen, Ben

    2009-11-18

    C-1027 is a chromoprotein antitumor antibiotic consisting of an apoprotein and the C-1027 chromophore. The C-1027 chromophore possesses four distinct structural moieties-an enediyne core, a deoxy aminosugar, a benzoxazolinate, and an (S)-3-chloro-5-hydroxy-beta-tyrosine-the latter two of which are proposed to be appended to the enediyne core via a convergent biosynthetic strategy. Here we report the in vitro characterization of SgcF, an epoxide hydrolase from the C-1027 biosynthetic gene cluster that catalyzes regio- and stereospecific hydrolysis of styrene oxide, serving as an enediyne core epoxide intermediate mimic, to form a vicinal diol. Abolishment of C-1027 production in the DeltasgcF mutant strain Streptomyces globisporus SB1010 unambiguously establishes that sgcF plays an indispensable role in C-1027 biosynthesis. SgcF efficiently hydrolyzes (S)-styrene oxide, displaying an apparent K(m) of 0.6 +/- 0.1 mM and k(cat) of 48 +/- 1 min(-1), via attack at the alpha-position to exclusively generate the (R)-phenyl vicinal diol, consistent with the stereochemistry of the C-1027 chromophore. These findings support the role of SgcF in the proposed convergent pathway for C-1027 biosynthesis, unveiling an (R)-vicinal diol as a key intermediate. Interestingly, SgcF can also hydrolyze (R)-styrene oxide to afford preferentially the (R)-phenyl vicinal diol via attack at the beta-position, albeit with significantly reduced efficiency (apparent K(m) of 2.0 +/- 0.4 mM and k(cat) = 4.3 +/- 0.3 min(-1)). Although the latter activity unlikely contributes to C-1027 biosynthesis in vivo, such enantioconvergence arising from complementary regioselective hydrolysis of a racemic substrate could be exploited to engineer epoxide hydrolases with improved regio- and/or enantiospecificity. PMID:19856960

  10. Preferential Formation of Benzo[a]pyrene Adducts at Lung Cancer Mutational Hotspots in P53

    NASA Astrophysics Data System (ADS)

    Denissenko, Mikhail F.; Pao, Annie; Tang, Moon-Shong; Pfeifer, Gerd P.

    1996-10-01

    Cigarette smoke carcinogens such as benzo[a]pyrene are implicated in the development of lung cancer. The distribution of benzo[a]pyrene diol epoxide (BPDE) adducts along exons of the P53 gene in BPDE-treated HeLa cells and bronchial epithelial cells was mapped at nucleotide resolution. Strong and selective adduct formation occurred at guanine positions in codons 157, 248, and 273. These same positions are the major mutational hotspots in human lung cancers. Thus, targeted adduct formation rather than phenotypic selection appears to shape the P53 mutational spectrum in lung cancer. These results provide a direct etiological link between a defined chemical carcinogen and human cancer.

  11. The roles of diol epoxide and o-quinone pathways in mouse lung tumorigenesis induced by benzo(a)pyrene: relevance to human lung carcinogenesis

    EPA Science Inventory

    There is sufficient epidemiological evidence supported by experimental data that some PAH-containing complex environmental mixtures pose risks to human health by increasing lung cancer incidence. The International Agency for Research on Cancer has determined that human respirator...

  12. A novel AlEt3-promoted tandem reductive rearrangement of 1-benzyloxy-2,3-epoxides: new route to 2-quaternary 1,3-diol units.

    PubMed

    Li, De Run; Xia, Wu Jiong; Tu, Yong Qiang; Zhang, Fu Min; Shi, Lei

    2003-03-21

    A novel and highly stereoselective tandem rearrangement-reduction reaction of 1-benzyloxy-2,3-epoxide, under the promotion of triethylaluminum (AlEt3), has been developed to construct a quaternary stereocenter and the hydroxymethyl attached to the carbon center in one-step. PMID:12703829

  13. Nuclear respiratory factor 1 overexpression attenuates anti-benzopyrene‑7,8-diol-9,10-epoxide-induced S-phase arrest of bronchial epithelial cells.

    PubMed

    Wu, Jing; Wang, Yaning; Wo, Da; Zhang, Lijuan; Li, Jue

    2016-05-01

    Nuclear respiratory factor 1 (NRF-1) has important roles in the regulation of several key metabolic genes required for cellular growth and respiration. A previous study by our group indicated that NRF‑1 is involved in mitochondrial dysfunction induced by the environmental pollutant benzo[a]pyrene in the 16HBE human bronchial epithelial cell line. In the present study, it was observed that its genotoxic metabolite, anti‑benzopyrene‑7,8‑diol‑9,10‑epoxide (BPDE), triggered cell cycle arrest in S‑phase in 16HBE cells by activating ataxia-telangiectasia (ATM)/checkpoint kinase (Chk)2 and ATM and Rad3 related (ATR)/Chk1 signaling pathways. NRF‑1 expression was suppressed by BPDE after treatment for 6 h. Flow cytometric analysis revealed that NRF‑1 overexpression attenuated cell cycle arrest in S‑phase induced by BPDE. In line with this result, DNA‑damage checkpoints were activated following NRF‑1 overexpression, as demonstrated by increased phosphorylation of ATM, Chk2 and γH2AX, but not ATR and Chk1, according to western blot analysis. It was therefore indicated that NRF‑1 overexpression attenuated BPDE‑induced S‑phase arrest via the ATM/Chk2 signaling pathway. PMID:27035420

  14. Sulfite-dependent mutagenicity of benzo[a]pyrene derivatives.

    PubMed

    Reed, G A

    1987-08-01

    Benzo[a]pyrene (BP) and sulfur dioxide (SO2) are ubiquitous air pollutants and are also components of tobacco smoke. Although SO2 itself is not carcinogenic, concurrent administration with BP results in enhancement of respiratory tract tumorigenesis. In biological systems, SO2 exists as its hydrated form, sulfite (SO3(2-) ). Sulfite readily undergoes autoxidation, generating potent oxidant species. When 7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene (BP-7,8-diol) is included in sulfite autoxidation mixtures it is converted to more polar products, most notably 7,8,9,10-tetrahydroxy-7,8,9,10-tetrahydrobenzo[a]pyrenes (BP tetraols). This implies the intermediacy of 7,8-dihydroxy-9,10-epoxy- 7,8,9,10-tetrahydro-benzo[a]pyrenes (BPDE). We report here the sulfite-dependent conversion of BP-7,8-diol to forms highly mutagenic to Salmonella typhimurium strain TA 98. This activation is observed at BP-7,8-diol concentrations of from 2 to 40 microM and at sulfite concentrations of from 0.5 to 10 mM. In the presence of 10 microM BP-7,8-diol, half-maximal activation is observed at 1.6 mM sulfite. Sulfite itself is neither toxic nor mutagenic to the bacteria under these conditions. The time course of the activation of BP-7,8-diol and its sensitivity to inhibition by antioxidants indicate a requirement for sulfite autoxidation. These data further support the sulfite-dependent epoxidation of BP-7,8-diol. Not only does sulfite convert this promutagen to its active mutagenic form, sulfite also enhances the mutagenic activity of BP diolepoxides toward the tester strain. The reversion frequency in response to 0.1-0.5 microM anti-BPDE is increased by up to 33% in the presence of 1 mM sulfite, and by up to 270% with 10 mM sulfite. The mechanism of this enhancement of anti-BPDE activity is not known, but could be related to inhibition of the glutathione-S-transferase system which has been previously reported for sulfite. These results are discussed in regard to the noted cocarcinogenicity of

  15. Direct Copolymerization of CO2 and Diols

    PubMed Central

    Tamura, Masazumi; Ito, Kazuki; Honda, Masayoshi; Nakagawa, Yoshinao; Sugimoto, Hiroshi; Tomishige, Keiichi

    2016-01-01

    Direct polymerization of CO2 and diols is promising as a simple and environmental-benign method in place of conventional processes using high-cost and/or hazardous reagents such as phosgene, carbon monoxide and epoxides, however, there are no reports on the direct method due to the inertness of CO2 and severe equilibrium limitation of the reaction. Herein, we firstly substantiate the direct copolymerization of CO2 and diols using CeO2 catalyst and 2-cyanopyridine promotor, providing the alternating cooligomers in high diol-based yield (up to 99%) and selectivity (up to >99%). This catalyst system is applicable to various diols including linear C4-C10 α,ω-diols to provide high yields of the corresponding cooligomers, which cannot be obtained by well-known methods such as copolymerization of CO2 and cyclic ethers and ring-opening polymerization of cyclic carbonates. This process provides us a facile synthesis method for versatile polycarbonates from various diols and CO2 owing to simplicity of diols modification. PMID:27075987

  16. Direct Copolymerization of CO2 and Diols

    NASA Astrophysics Data System (ADS)

    Tamura, Masazumi; Ito, Kazuki; Honda, Masayoshi; Nakagawa, Yoshinao; Sugimoto, Hiroshi; Tomishige, Keiichi

    2016-04-01

    Direct polymerization of CO2 and diols is promising as a simple and environmental-benign method in place of conventional processes using high-cost and/or hazardous reagents such as phosgene, carbon monoxide and epoxides, however, there are no reports on the direct method due to the inertness of CO2 and severe equilibrium limitation of the reaction. Herein, we firstly substantiate the direct copolymerization of CO2 and diols using CeO2 catalyst and 2-cyanopyridine promotor, providing the alternating cooligomers in high diol-based yield (up to 99%) and selectivity (up to >99%). This catalyst system is applicable to various diols including linear C4-C10 α,ω-diols to provide high yields of the corresponding cooligomers, which cannot be obtained by well-known methods such as copolymerization of CO2 and cyclic ethers and ring-opening polymerization of cyclic carbonates. This process provides us a facile synthesis method for versatile polycarbonates from various diols and CO2 owing to simplicity of diols modification.

  17. Direct Copolymerization of CO2 and Diols.

    PubMed

    Tamura, Masazumi; Ito, Kazuki; Honda, Masayoshi; Nakagawa, Yoshinao; Sugimoto, Hiroshi; Tomishige, Keiichi

    2016-01-01

    Direct polymerization of CO2 and diols is promising as a simple and environmental-benign method in place of conventional processes using high-cost and/or hazardous reagents such as phosgene, carbon monoxide and epoxides, however, there are no reports on the direct method due to the inertness of CO2 and severe equilibrium limitation of the reaction. Herein, we firstly substantiate the direct copolymerization of CO2 and diols using CeO2 catalyst and 2-cyanopyridine promotor, providing the alternating cooligomers in high diol-based yield (up to 99%) and selectivity (up to >99%). This catalyst system is applicable to various diols including linear C4-C10 α,ω-diols to provide high yields of the corresponding cooligomers, which cannot be obtained by well-known methods such as copolymerization of CO2 and cyclic ethers and ring-opening polymerization of cyclic carbonates. This process provides us a facile synthesis method for versatile polycarbonates from various diols and CO2 owing to simplicity of diols modification. PMID:27075987

  18. UVA photoirradiation of benzo[a]pyrene metabolites: induction of cytotoxicity, reactive oxygen species, and lipid peroxidation.

    PubMed

    Xia, Qingsu; Chiang, Hsiu-Mei; Yin, Jun-Jie; Chen, Shoujun; Cai, Lining; Yu, Hongtao; Fu, Peter P

    2015-10-01

    Benzo[a]pyrene (BaP) is a prototype for studying carcinogenesis of polycyclic aromatic hydrocarbons (PAHs). We have long been interested in studying the phototoxicity of PAHs. In this study, we determined that metabolism of BaP by human skin HaCaT keratinocytes resulted in six identified phase I metabolites, for example, BaP trans-7,8-dihydrodiol (BaP t-7,8-diol), BaP t-4,5-diol, BaP t-9,10-diol, 3-hydroxybenzo[a]pyrene (3-OH-BaP), BaP (7,10/8,9)tetrol, and BaP (7/8,9,10)tetrol. The photocytotoxicity of BaP, 3-OH-BaP, BaP t-7,8-diol, BaP trans-7,8-diol-anti-9,10-epoxide (BPDE), and BaP (7,10/8,9)tetrol in the HaCaT keratinocytes was examined. When irradiated with 1.0 J/cm(2) UVA light, these compounds when tested at doses of 0.1, 0.2, and 0.5 μM, all induced photocytotoxicity in a dose-dependent manner. When photoirradiation was conducted in the presence of a lipid (methyl linoleate), BaP metabolites, BPDE, and three related PAHs, pyrene, 7,8,9,10-tetrahydro-BaP trans-7,8-diol, and 7,8,9,10-tetrahydro-BaP trans-9,10-diol, all induced lipid peroxidation. The formation of lipid peroxides by BaP t-7,8-diol was inhibited by NaN3 and enhanced by deuterated methanol, which suggests that singlet oxygen may be involved in the generation of lipid peroxides. The formation of lipid hydroperoxides was partially inhibited by superoxide dismutase (SOD). Electron spin resonance spin trapping experiments indicated that both singlet oxygen and superoxide radical anion were generated from UVA photoirradiation of BPDE in a light dose responding manner. PMID:23552265

  19. Fungal oxidation of benzo(a)pyrene and (+-)-trans-7,8-dihydroxy-7,8-dihydrobenzo(a)pyrene

    SciTech Connect

    Cerniglia, C.E.; Gibson, D.T.

    1980-06-10

    The oxidation of benzo(a)pyrene by intact cells of the filamentous fungus Cunninghamella elegans resulted in the formation of a complex mixture of polar products which were detected by high pressure liquid chromatography. One of the products had a retention time on high pressure liquid chromatography identical with that given by (+-)-7..beta..,8a,9a,10..beta..-tetrahydroxy-7,8,9,10-tetrahydrobenzo(a)pyrene. In addition the absorption and mass spectra given by the fungal metabolite were consistent with this structural assignment. Incubation of (+-)-trans-7,8-dihydrobenzo(a)pyrene with cells of C. elegans led to the formation of the same tetrahydroxymetabolite. Two other products were formed that were identified as new phenolic derivatives of (+-)-trans-7,8-dihydroxy-7,8-dihydrobenzo(a)pyrene. Experiments with (+-)-trans (G-/sup 3/H) 7,8-dihydrobenzo(a)pyrene showed that over a 12-h period 4.0% of the dihydrodiol was converted to ethyl acetate-soluble products and 7..beta..,8..cap alpha..,9..cap alpha..,10..beta..-tetrahydroxy-7,8,9,10-tetrahdrobenzo(a)pyrene accounted for 25% of these metabolites. The results suggest that C. elegans can oxidize benzo(a)pyrene to either (+-)-7..beta..,8..cap alpha..-dihydroxy-9..cap alpha..,10..cap alpha..-epoxy-7,8,9,10-tetrahydroxy(a)pyrene or one of the two possible enantiomers of this compound. Under the experimental conditions, no evidence was found to suggest the formation of (+-)-7..beta..,8..cap alpha..-dihydroxy-9..beta..,10..beta..-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene. Thus, C. elegans has the ability to form at least one of the two diastereomeric benzo(a)pyrene 7,8-diol-9,10-epoxides that have been implicated as the ultimate carcinogenic forms of benzo(a)pyrene in higher organisms.

  20. Photocatalytic degradation of polycyclic aromatic hydrocarbon benzo[a]pyrene by iron oxides and identification of degradation products.

    PubMed

    Gupta, Himanshu; Gupta, Bina

    2015-11-01

    Photocatalytic decay profiles of polycyclic aromatic hydrocarbon (PAH) benzo[a]pyrene (B[a]P) have been investigated on various synthesized iron oxides and on soil surfaces under a set of diverse conditions. Samples were analysed using the developed HPLC procedure. Results of the present study demonstrate fastest photodisintegration of B[a]P on goethite followed by haematite, magnetite, akaganeite and maghemite, respectively. The effect of soil pH, irradiation wavelength and iron oxide and oxalic acid dose on the degradation of B[a]P was evaluated. The studies revealed enhancement in photodegradation in the presence of oxalic acid due to the occurrence of fenton like reaction. The results showed faster B[a]P degradation under short wavelength UV radiation. Rate constants in acidic, neutral and alkaline soils under optimum dissipation conditions were 1.11×10(-2), 7.69×10(-3) and 9.97×10(-3) h(-1), respectively. The study indicates that iron oxides along with oxalic acid are effective photocatalyst for the remediation of benzo[a]pyrene contaminated soil surfaces. The degradation products of B[a]P in the soils of different pH in presence of goethite were identified and degradation pathways proposed. Peaks due to toxic metabolites such as diones, diols and epoxides disappear after 120 h in all the three soils. PMID:25576129

  1. Effect of heavy metals on the metabolism of benzo(a)pyrene in rats

    SciTech Connect

    Honey, S.A.; Yuan, Zhi-Xin; Kumar, S.; Sikka, H.C.

    1996-12-31

    In order to investigate the interaction of heavy metals and PAHs, we have examined the effect of methylmercuric chloride and cadmium chloride on the oxidative metabolism by rats of benzo(a)pyrene [BaP], a model carcinogenic PAR Treatment of male rats with 2.5 or 5.0 mg/kg methylmercury (ip) reduced the rate of metabolism of BaP by liver microsomes by 38.7 and 62.2%, respectively. Cadmium was more potent than methylmercury, decreasing the rate of metabolism of BaP by 28.4, 52.2, and 69.7% by liver microsomes of rats treated with 0.5, 1.0, and 1.5 mg/kg of cadmium, respectively. The liver microsomes from animals treated with methylmercury or cadmium produced a greater proportion of BP-phenols and a lower portion of BP-diols than did the microsomes from untreated animals, suggesting that both metals also inhibit the activity of epoxide hydrase. Neither methylmercury nor cadmium had an effect on the proportion of BP-quinones formed by liver microsomes. Treatment of rats with methylmercury or cadmium did not inhibit the metabolism of BaP by liver microsomes from animals treated with 3-methylcholanthrene (3-MC) prior to metal administration, suggesting that 3-MC treatment protects against the effect of methylmercury or cadmium on the oxidative metabolism of BaP.

  2. Potent Urea and Carbamate Inhibitors of Soluble Epoxide Hydrolases

    NASA Astrophysics Data System (ADS)

    Morisseau, Christophe; Goodrow, Marvin H.; Dowdy, Deanna; Zheng, Jiang; Greene, Jessica F.; Sanborn, James R.; Hammock, Bruce D.

    1999-08-01

    The soluble epoxide hydrolase (sEH) plays a significant role in the biosynthesis of inflammation mediators as well as xenobiotic transformations. Herein, we report the discovery of substituted ureas and carbamates as potent inhibitors of sEH. Some of these selective, competitive tightbinding inhibitors with nanomolar Ki values interacted stoichiometrically with the homogenous recombinant murine and human sEHs. These inhibitors enhance cytotoxicity of trans-stilbene oxide, which is active as the epoxide, but reduce cytotoxicity of leukotoxin, which is activated by epoxide hydrolase to its toxic diol. They also reduce toxicity of leukotoxin in vivo in mice and prevent symptoms suggestive of acute respiratory distress syndrome. These potent inhibitors may be valuable tools for testing hypotheses of involvement of diol and epoxide lipids in chemical mediation in vitro or in vivo systems.

  3. LC/MSMS STUDY OF BENZO[A]PYRENE-7,8-QUINONE ADDUCTION TO GLOBIN TRYPTIC PEPTIDES AND N-ACETYLAMINO ACIDS

    EPA Science Inventory

    Benzo[a]pyrene-7,8-quinone (BPQ) is regarded as a reactive genotoxic compound enzymatically formed from a xenobiotic precursor benzo[a]pyrene-7,8-diol by aldo-keto-reductase family of enzymes. Because BPQ, a Michael electrophile, was previously shown to react with oligonucleotide...

  4. p53 Mutagenesis by benzo[a]pyrene derived radical cations.

    PubMed

    Sen, Sushmita; Bhojnagarwala, Pratik; Francey, Lauren; Lu, Ding; Penning, Trevor M; Field, Jeffrey

    2012-10-15

    Benzo[a]pyrene (B[a]P), a major human carcinogen in combustion products such as cigarette smoke and diesel exhaust, is metabolically activated into DNA-reactive metabolites via three different enzymatic pathways. The pathways are the anti-(+)-benzo[a]pyrene 7,8-diol 9,10-epoxide pathway (P450/epoxide hydrolase catalyzed) (B[a]PDE), the benzo[a]pyrene o-quinone pathway (aldo ketose reductase (AKR) catalyzed) and the B[a]P radical cation pathway (P450 peroxidase catalyzed). We used a yeast p53 mutagenesis system to assess mutagenesis by B[a]P radical cations. Because radical cations are short-lived, they were generated in situ by reacting B[a]P with cumene hydroperoxide (CuOOH) and horse radish peroxidase (HRP) and then monitoring the generation of the more stable downstream products, B[a]P-1,6-dione and B[a]P-3,6-dione. On the basis of B[a]P-1,6 and 3,6-dione formation, approximately 4 μM of radical cation was generated. In the mutagenesis assays, the radical cations produced in situ showed a dose-dependent increase in mutagenicity from 0.25 μM to 10 μM B[a]P with no significant increase seen with further escalation to 50 μM B[a]P. However, mutagenesis was 200-fold less than with the AKR pathway derived B[a]P, 7-8-dione. Mutant p53 plasmids, which yield red colonies, were recovered from the yeast to study the pattern and spectrum of mutations. The mutation pattern observed was G to T (31%) > G to C (29%) > G to A (14%). The frequency of codons mutated by the B[a]P radical cations was essentially random and not enriched at known cancer hotspots. The quinone products of radical cations, B[a]P-1,6-dione and B[a]P-3,6-dione were more mutagenic than the radical cation reactions, but still less mutagenic than AKR derived B[a]P-7,8-dione. We conclude that B[a]P radical cations and their quinone products are weakly mutagenic in this yeast-based system compared to redox cycling PAH o-quinones. PMID:22768918

  5. Heptachlor epoxide

    Integrated Risk Information System (IRIS)

    Heptachlor epoxide ; CASRN 1024 - 57 - 3 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcinogen

  6. Studies on the mutagenic mechanisms of the potent environmental carcinogen, benzo[a]pyrene

    SciTech Connect

    Rodriguez, H.

    1993-01-01

    Environmental chemicals that cause cancer have previously been shown to become chemically linked to the genetic substance, DNA, to give DNA adducts. These adducts appear foreign to the cell and mutations occur when the DNA is being duplicated during cell replication. Mutations in proto-oncogenes can change a normal cell into a cancerous cell. Benzo[a]pyrene is one example of a potent mutagen/carcinogen found ubiquitously in the environment: For example, in the soot from internal combustion engines and power plants, in cigarette smoke, and on charred meat. Benzo[a]pyrene is an indirect-acting mutagen/carcinogen, which must be metabolized inside the body to its ultimate mutagen/carcinogen, the corresponding (+)-anti-diol epoxide ((+)-anti-B[a]PDE) which forms many adducts in DNA. By using a newly developed forward mutation assay (ES87/pUB3) mutations induced by (+)-anti-B[a]PDE were isolated and characterized. SOS induction was shown to enhance frameshift and base pairing mutagenesis; G:C->T:A mutations were preferentially enhanced (approximately twelve-fold). Nearest neighbor analysis was performed assuming a guanine (underlined) was being mutated; SOS enhanced (+)-anti-B[a]PDE base pairing mutagenesis in 5[prime]-(A/T)G-3[prime] sequences more than in 5[prime]-G(A/T)-3[prime] sequences, and in 5[prime]-G(C/G)-3[prime] sequences more than in 5[prime]-G(A/T)-3[prime] sequences. Sequence content affected mutagenesis quantitatively where hot-spots for (+)-anti-B[a]PDE was heated prior to transformation into ES87 cells, an approximately two-fold decrease in mutation frequency was observed. In general, heating did not affect mutagenic specificity. Models are proposed to explain these results. Freeze/thawing pUB3 adducted with (+)-anti-B[a]PDE, also caused both an approximately two-fold decrease in mutation frequency and changes similar to those caused by heating.

  7. Stereochemical aspects in the 4-vinylcyclohexene biotransformation with rat liver microsomes and purified p450s. monoepoxides and diols.

    PubMed

    Chiappe, C; De Rubertis, A; De Carlo, M; Amato, G; Gervasi, P G

    2001-05-01

    The stereochemical course of the biotransformation of 4-vinylcyclohexene (VCH, 1) by liver microsomes from male and female control and induced rats and purified rat P450 2B1 and 2E1 has been determined. The epoxidation of 1, catalyzed by male microsomes, occurs on both the endo- and exocyclic double bond to give four isomeric epoxides, cis-4-vinylcyclohexene 1,2-epoxide (2), trans-4-vinylcyclohexene 1,2-epoxide (3), (4R*,7S*)-4-vinylcyclohexene 7,8-epoxide (4), and (4R*,7R*)-4-vinylcyclohexene 7,8-epoxide (5). On the other hand, microsomes from female rats catalyzed primarily the endocyclic epoxidation. The stereoselectivity of this process was strongly dependent on gender and P450 induction. Only the phenobarbital and pyrazole, at lower levels, were able to enhance the epoxidation of 1 and mostly on the endocyclic double bond. Also, P450 2E1 and 2B1 in a reconstituted system were able to perform the epoxidation of 1 primarily on its endocyclic double bond. The metabolites, cis- and trans-4-vinylcyclohexene 1,2-epoxide (2 and 3, respectively) and the isomeric 4-vinylcyclohexene 7,8-epoxides (4 and 5), were rapidly biotransformed into the corresponding vicinal diols by mEH-catalyzed hydrolysis. The reaction of the endocyclic epoxides occurred with good substrate diastereo- and enantioselectivity favoring the hydrolysis of epoxides (1S,2R,4S)-3 and (1R,2S,4S)-2 to give, before 50% conversion, selectively (1R,2R,4S)-diol (6). At variance, the hydrolysis of the exocyclic epoxides was characterized by a high level of substrate enantioselection associated with a very low, if any, level of substrate diastereoselection, the two epoxides, (4R,7S)-4 and (4R,7R)-5, being hydrolyzed practically with the same rate. On the basis of the major resistance to mEH hydrolysis, the endocyclic epoxides, (1R,2S,4R)-3 and (1S,2R,4R)-2, are expected to be further oxidized, in a stereochemical manner, to the specific mutagenic diepoxides which are thought to play a crucial role in VCH

  8. Data set of optimal parameters for colorimetric red assay of epoxide hydrolase activity.

    PubMed

    de Oliveira, Gabriel Stephani; Adriani, Patricia Pereira; Borges, Flavia Garcia; Lopes, Adriana Rios; Campana, Patricia T; Chambergo, Felipe S

    2016-09-01

    The data presented in this article are related to the research article entitled "Epoxide hydrolase of Trichoderma reesei: Biochemical properties and conformational characterization" [1]. Epoxide hydrolases (EHs) are enzymes that catalyze the hydrolysis of epoxides to the corresponding vicinal diols. This article describes the optimal parameters for the colorimetric red assay to determine the enzymatic activity, with an emphasis on the characterization of the kinetic parameters, pH optimum and thermal stability of this enzyme. The effects of reagents that are not resistant to oxidation by sodium periodate on the reactions can generate false positives and interfere with the final results of the red assay. PMID:27366781

  9. Curcumin and Vitamin E Protect against Adverse Effects of Benzo[a]pyrene in Lung Epithelial Cells

    PubMed Central

    Cai, Qingsong; Lv, Tangfeng; Singh, Kamaleshwar; Gao, Weimin

    2014-01-01

    Benzo[a]pyrene (BaP), a well-known environmental carcinogen, promotes oxidative stress and DNA damage. Curcumin and vitamin E (VE) have potent antioxidative activity that protects cells from oxidative stress and cellular damage. The objectives of the present study were to investigate the adverse effects of BaP on normal human lung epithelial cells (BEAS-2B), the potential protective effects of curcumin and VE against BaP-induced cellular damage, and the molecular mechanisms of action. MTT assay, flow cytometry, fluorescence microplate assay, HPLC, qRT-PCR, and western blot were performed to analyze cytotoxicity, cell cycle, reactive oxygen species (ROS), BaP diol-epoxidation (BPDE)-DNA adducts, gene expression, and protein expression, respectively. Curcumin or VE prevented cells from BaP-induced cell cycle arrest and growth inhibition, significantly suppressed BaP-induced ROS levels, and decreased BPDE-DNA adducts. While CYP1A1 and 1B1 were induced by BaP, these inductions were not significantly reduced by curcumin or VE. Moreover, the level of activated p53 and PARP-1 were significantly induced by BaP, whereas this induction was markedly reduced after curcumin and VE co-treatment. Survivin was significantly down-regulated by BaP, and curcumin significantly restored survivin expression in BaP-exposed cells. The ratio of Bax/Bcl-2 was also significantly increased in cells exposed to BaP and this increase was reversed by VE co-treatment. Taken together, BaP-induced cytotoxicity occurs through DNA damage, cell cycle arrest, ROS production, modulation of metabolizing enzymes, and the expression/activation of p53, PARP-1, survivin, and Bax/Bcl-2. Curcumin and VE could reverse some of these BaP-mediated alterations and therefore be effective natural compounds against the adverse effects of BaP in lung cells. PMID:24664296

  10. Curcumin and vitamin E protect against adverse effects of benzo[a]pyrene in lung epithelial cells.

    PubMed

    Zhu, Wenbin; Cromie, Meghan M; Cai, Qingsong; Lv, Tangfeng; Singh, Kamaleshwar; Gao, Weimin

    2014-01-01

    Benzo[a]pyrene (BaP), a well-known environmental carcinogen, promotes oxidative stress and DNA damage. Curcumin and vitamin E (VE) have potent antioxidative activity that protects cells from oxidative stress and cellular damage. The objectives of the present study were to investigate the adverse effects of BaP on normal human lung epithelial cells (BEAS-2B), the potential protective effects of curcumin and VE against BaP-induced cellular damage, and the molecular mechanisms of action. MTT assay, flow cytometry, fluorescence microplate assay, HPLC, qRT-PCR, and western blot were performed to analyze cytotoxicity, cell cycle, reactive oxygen species (ROS), BaP diol-epoxidation (BPDE)-DNA adducts, gene expression, and protein expression, respectively. Curcumin or VE prevented cells from BaP-induced cell cycle arrest and growth inhibition, significantly suppressed BaP-induced ROS levels, and decreased BPDE-DNA adducts. While CYP1A1 and 1B1 were induced by BaP, these inductions were not significantly reduced by curcumin or VE. Moreover, the level of activated p53 and PARP-1 were significantly induced by BaP, whereas this induction was markedly reduced after curcumin and VE co-treatment. Survivin was significantly down-regulated by BaP, and curcumin significantly restored survivin expression in BaP-exposed cells. The ratio of Bax/Bcl-2 was also significantly increased in cells exposed to BaP and this increase was reversed by VE co-treatment. Taken together, BaP-induced cytotoxicity occurs through DNA damage, cell cycle arrest, ROS production, modulation of metabolizing enzymes, and the expression/activation of p53, PARP-1, survivin, and Bax/Bcl-2. Curcumin and VE could reverse some of these BaP-mediated alterations and therefore be effective natural compounds against the adverse effects of BaP in lung cells. PMID:24664296

  11. Novel, reversible, benzo[a]pyrene metabolite binding sites in closed-circular, single-stranded DNA

    SciTech Connect

    Price, H.L.

    1991-01-01

    The formation of reversible hydrocarbon epoxide-DNA complexes and the simultaneous increase in the reactivity of these bound epoxides is a general phenomenon. The relationship between physical binding, catalysis of epoxide reactions, and the formation of covalent adducts is not clearly understood at present. In these investigations it was found that linear, double-stranded DNA and supercoiled plasmid DNA both bind and enhance the reactivity of epoxide metabolites of benzo[a]pyrene to similar extents. The results of experiments carried out with closed-circular, single-stranded DNA however, indicate that this DNA possesses a unique binding site not present in either linear, double-stranded DNA or supercoiled DNA. Results of kinetic studies revealed that closed-circular, single-stranded DNA was less efficient at catalyzing epoxide reactions that double-stranded DNA. The results of these kinetic studies are explained in terms of a model which takes into account the polyelectrolyte nature of DNA.

  12. Soluble epoxide hydrolase: Gene structure, expression and deletion

    PubMed Central

    Harris, Todd R.; Hammock, Bruce D.

    2013-01-01

    Mammalian soluble epoxide hydrolase (sEH) converts epoxides to their corresponding diols through the addition of a water molecule. sEH readily hydrolyzes lipid signaling molecules, including the epoxyeicosatrienoic acids (EETs), epoxidized lipids produced from arachidonic acid by the action of cytochrome p450s. Through its metabolism of the EETs and other lipid mediators, sEH contributes to the regulation of vascular tone, nociception, angiogenesis and the inflammatory response. Because of its central physiological role in disease states such as cardiac hypertrophy, diabetes, hypertension, and pain sEH is being investigated as a therapeutic target. This review begins with a brief introduction to sEH protein structure and function. sEH evolution and gene structure are then discussed before human small nucleotide polymorphisms and mammalian gene expression are described in the context of several disease models. The review ends with an overview of studies that have employed the sEH knockout mouse model. PMID:23701967

  13. Biodegradation of heptachlor and heptachlor epoxide-contaminated soils by white-rot fungal inocula.

    PubMed

    Purnomo, Adi Setyo; Putra, Surya Rosa; Shimizu, Kuniyoshi; Kondo, Ryuichiro

    2014-10-01

    The ability of certain white-rot fungi (WRF) inocula to transform heptachlor and heptachlor epoxide and its application in artificially contaminated soil were investigated. Fungal inoculum of Pleurotus ostreatus eliminated approximately 89 % of heptachlor after 28 days of incubation, and chlordene was detected as the primary metabolite. The fungal inoculum of Pleurotus ostreatus had the highest ability to degrade heptachlor epoxide; approximately 32 % were degraded after 28 days of incubation, and heptachlor diol was detected as the metabolite product. Because Pleurotus ostreatus transformed heptachlor into a less toxic metabolite and could also effectively degrade heptachlor epoxide, it was then selected to be applied to artificially contaminated soil. The spent mushroom waste (SMW) of Pleurotus ostreatus degraded heptachlor and heptachlor epoxide by approximately 91 and 26 %, respectively, over 28 days. This finding indicated that Pleurotus ostreatus SMW could be used to bioremediate heptachlor- and heptachlor epoxide-contaminated environments. PMID:24840358

  14. Mutual in vivo interactions between benzo[a]pyrene and tributyltin in brook trout (Salvelinus fontinalis)

    SciTech Connect

    Padros, J.; Pelletier, E.; Reader, S.; Denizeau, F.

    2000-04-01

    Tributyltin (TBT), an organometal used as an antifouling biocide, has been reported to inhibit cytochrome P450 (P450) 1A isozyme. Benzo[a]pyrene (BaP), a widespread carcinogenic polycyclic aromatic hydrocarbon, is both metabolized and bioactivated to carcinogenic BaP diol-epoxide (BPDE) metabolites primarily by hepatic P450 1A. Hence, TBT may inhibit the metabolism and bioactivation of BaP. This study was therefore designed to examine the potential in vivo interactions between BaP and TBT in a model fish. Male brook trout (Salelinus fontinalis) were given a single intraperitoneal injection of either BaP, TBT, or both in combination. After 48 h, blood, bile, and liver samples were collected and analyzed for a suite of biomarkers associated with P450 activity, BaP metabolism and bioactivation, and TBT metabolism. The results showed that TBT significantly inhibited (a) the induction of hepatic P450 1A-mediated ethoxyresorufin O-deethylase (EROD) and P450-mediated 3-cyano-7-ethoxycoumarin-O-deethylase (CN-ECOD) activities by BaP, (b) the formation of biliary BaP metabolites, and (c) the formation of (+)-anti-BPDE-plasma albumin adducts as measured by high-performance liquid chromatography-fluorescence. Notably, TBT alone did not inhibit EROD activity but induced CN-ECOD activity. Gas chromatography-mass spectrometry analysis indicated that the combined BaP + TBT dose resulted in higher levels of dibutyltin metabolites in the bite (p < 0.05). The present study supports the hypothesis that a single, high dose of TBT can antagonize the metabolism and bioactivation of BaP at least by inhibiting the induction of P4501A. On the other hand, BaP unexpectedly potentiated the metabolism of TBT, suggesting that hepatic isoforms other than P3501A may be responsible for TBT metabolism. Finally, this study supports the utility of a biomarker approach to screen potential xenobiotic interactions in aquatic organisms and to obtain mechanistic insights.

  15. A Method for the Preparation of Differentiated trans-1,2-Diol Derivatives with Enantio- and Diastereocontrol

    PubMed Central

    Lim, Sang Min; Hill, Nicholas; Myers, Andrew G.

    2009-01-01

    We describe a synthetic sequence that allows for the preparation of optically active trans-1,2-diol monosilyl ether derivatives from ketones, providing a new means for retrosynthetic simplification of differentiated diol and polyol targets. The sequence involves silyl enol ether formation, Shi asymmetric epoxidation, then regio- and stereospecific addition of hydride, methide, or higher alkylide. The tactical combination presented has not been integrated in synthetic problem solving, so far as we are aware, but has promise for broad application, we believe. PMID:19341239

  16. Benzo[a]pyrene and tumor necrosis factor-α coordinately increase genotoxic damage and the production of proinflammatory mediators in alveolar epithelial type II cells.

    PubMed

    Umannová, Lenka; Machala, Miroslav; Topinka, Jan; Schmuczerová, Jana; Krčmář, Pavel; Neča, Jiří; Šujanová, Klára; Kozubík, Alois; Vondráček, Jan

    2011-10-10

    Alveolar type II epithelial (AEII) cells regulate lung inflammatory response and, simultaneously, they are a target of environmental carcinogenic factors. We employed an in vitro model of rat AEII cells, the RLE-6TN cell line, in order to analyze the interactive effects of tumor necrosis factor-α (TNF-α), a cytokine which plays a key role in the initiation of inflammatory responses in the lung, and benzo[a]pyrene (BaP), a highly carcinogenic polycyclic aromatic hydrocarbon. TNF-α strongly augmented the formation of stable BaP diol epoxide-DNA adducts in AEII cells, which was associated with enhanced p53-Ser15 phosphorylation and decreased cell survival. The increased genotoxicity of BaP was associated with altered expression of cytochrome P450 (CYP) enzymes involved in its bioactivation, a simultaneous suppression of CYP1A1 and enhancement of CYP1B1 expression. Importantly, BaP and TNF-α acted synergistically to upregulate key inflammatory regulators in AEII cells, including the expression of inducible NO synthase and cyclooxygenase-2 (COX-2), and enhanced prostaglandin E2 production and expression of proinflammatory cytokines, such as TNF-α, interleukin-1β and interleukin-6. We observed that BaP and TNF-α together strongly activated p38 kinase, a principal regulator of inflammatory response. SB202190, a specific p38 inhibitor, prevented induction of both COX-2 and proinflammatory cytokines, thus confirming that p38 activity was crucial for the observed inflammatory reaction. Taken together, our data demonstrated, for the first time, that a proinflammatory cytokine and an environmental PAH may interact to potentiate both DNA damage and the inflammatory response in AEII cells, which may occur through coordinated upregulation of p38 activity. PMID:21745554

  17. Epoxidation catalyst and process

    DOEpatents

    Linic, Suljo; Christopher, Phillip

    2010-10-26

    Disclosed herein is a catalytic method of converting alkenes to epoxides. This method generally includes reacting alkenes with oxygen in the presence of a specific silver catalyst under conditions suitable to produce a yield of the epoxides. The specific silver catalyst is a silver nanocrystal having a plurality of surface planes, a substantial portion of which is defined by Miller indices of (100). The reaction is performed by charging a suitable reactor with this silver catalyst and then feeding the reactants to the reactor under conditions to carry out the reaction. The reaction may be performed in batch, or as a continuous process that employs a recycle of any unreacted alkenes. The specific silver catalyst has unexpectedly high selectivity for epoxide products. Consequently, this general method (and its various embodiments) will result in extraordinarily high epoxide yields heretofore unattainable.

  18. Succinic anhydrides from epoxides

    SciTech Connect

    Coates, Geoffrey W.; Rowley, John M.

    2013-07-09

    Catalysts and methods for the double carbonylation of epoxides are disclosed. Each epoxide molecule reacts with two molecules of carbon monoxide to produce a succinic anhydride. The reaction is facilitated by catalysts combining a Lewis acidic species with a transition metal carbonyl complex. The double carbonylation is achieved in single process by using reaction conditions under which both carbonylation reactions occur without the necessity of isolating or purifying the product of the first carbonylation.

  19. Succinic anhydrides from epoxides

    SciTech Connect

    Coates, Geoffrey W; Rowley, John M

    2014-12-30

    Catalysts and methods for the double carbonylation of epoxides are disclosed. Each epoxide molecule reacts with two molecules of carbon monoxide to produce a succinic anhydride. The reaction is facilitated by catalysts combining a Lewis acidic species with a transition metal carbonyl complex. The double carbonylation is achieved in single process by using reaction conditions under which both carbonylation reactions occur without the necessity of isolating or purifying the product of the first carbonylation.

  20. CHARACTERIZATION OF STABLE BENZO(A)PYRENE-7,8-QUINONE-DNA ADDUCTS IN CALF THYMUS DNA

    EPA Science Inventory

    Benzo[alpyrene-7,8-dione (BPQ) is a reactive aldo-keto reductase-mediated product of B[a]P-7,8-diol, a major P450/epoxide hydrolase metabolite of the multi-species carcinogen, B[a]P. The role of BPQ in B[a]P's genotoxicity and carcinogenesis is evolving. Toxicity pathways involvi...

  1. Bioactive lipid profiling reveals drug target engagement of a soluble epoxide hydrolase inhibitor in a murine model of tobacco smoke exposure

    PubMed Central

    Nording, Malin L.; Yang, Jun; Hoang, Laura; Zamora, Vanessa; Uyeminami, Dale; Espiritu, Imelda; Pinkerton, Kent E.; Hammock, Bruce D.; Luria, Ayala

    2015-01-01

    The inflammatory process underlying chronic obstructive pulmonary disease (COPD) may be caused by tobacco smoke (TS) exposure. Previous studies show that epoxyeicosatrienoic acids (EETs) possess promising anti-inflammatory properties, therefore stabilization of EETs and other fatty acid epoxides through inhibition of soluble epoxide hydrolase (sEH) was investigated in mouse models of acute and sub-chronic inflammation caused by TS exposure. During the entire TS exposure, the potent sEH inhibitor 1-(1-methylsulfonyl-piperidin-4-yl)-3-(4-trifluoromethoxy-phenyl)-urea (TUPS) was given via drinking water. To assess drug target engagement of TUPS, a tandem mass spectrometry method was used for bioactive lipid profiling of a broad range of fatty acid metabolites, including EETs, and their corresponding diols (DHETs) derived from arachidonic acid, as well as epoxides and diols derived from other fatty acids. Several, but not all, plasma epoxide/diol ratios increased in mice treated with sEH inhibitor, compared to non-treated mice suggesting a wider role for sEH involving more fatty acid precursors besides arachidonic acid. This study supports qualitative use of epoxide/diol ratios explored by bioactive lipid profiling to indicate drug target engagement in mouse models of TS exposure relevant to COPD, which may have ramifications for future therapeutic interventions of sEH. PMID:27076918

  2. Neutrophils amplify the formation of DNA adducts by benzo[a]pyrene in lung target cells.

    PubMed

    Borm, P J; Knaapen, A M; Schins, R P; Godschalk, R W; Schooten, F J

    1997-09-01

    Inflammatory cells and their reactive oxygen metabolites can cause mutagenic effects in lung cells. The purpose of this study was to investigate the ability of activated neutrophils to modulate DNA binding of benzo[a]pyrene (B[a]P), a known carcinogen, in lung target cells. Equivalent numbers of rat lung epithelial cells (RLE-6TN cell line) and freshly isolated human blood neutrophils (PMN) were coincubated in vitro for 2 hr after addition of benzo[a]pyrene (0.5 microM) or two of its trans-diol metabolites, with or without stimulation with phorbol myristate acetate (PMA). DNA adducts of B[a]P-metabolites were determined in target cells using 32P-postlabeling; oxidative DNA damage (7-hydro-8-oxo-2'-deoxyguanosine [8-oxodG]) was evaluated by high performance liquid chromatography with electrochemical detection. Increased DNA adducts were observed in lung cells coincubated with polymorphonuclear leukocytes (PMN). Activation of PMN with PMA, or addition of more activated PMN in relation to the number of lung cells, further increased the number of adducts, the latter in a dose-response manner. Incubation with B[a]P-4,5-diol did not result in any adduct formation, while B[a]P-7,8-diol led to a significant number of adducts. Moreover, PMA-activated PMN strongly enhanced adduct formation by B[a]P-7,8-diol, but not 8-oxodG, in lung cells. The addition of antioxidants to the coincubations significantly reduced the number of adducts. Results suggest that an inflammatory response in the lung may increase the biologically effective dose of polycyclic aromatic hydrocarbons (PAHs), and may be relevant to data interpretation and risk assessment of PAH-containing particulates. PMID:9400705

  3. Microbial production of short chain diols.

    PubMed

    Jiang, Yudong; Liu, Wei; Zou, Huibin; Cheng, Tao; Tian, Ning; Xian, Mo

    2014-01-01

    Short chain diols (propanediols, butanediols, pentanediols) have been widely used in bulk and fine chemical industries as fuels, solvents, polymer monomers and pharmaceutical precursors. The chemical production of short chain diols from fossil resources has been developed and optimized for decades. Consideration of the exhausting fossil resources and the increasing environment issues, the bio-based process to produce short chain diols is attracting interests. Currently, a variety of biotechnologies have been developed for the microbial production of the short chain diols from renewable feed-stocks. In order to efficiently produce bio-diols, the techniques like metabolically engineering the production strains, optimization of the fermentation processes, and integration of a reasonable downstream recovery processes have been thoroughly investigated. In this review, we summarized the recent development in the whole process of bio-diols production including substrate, microorganism, metabolic pathway, fermentation process and downstream process. PMID:25491899

  4. Dicarbonyl reduction by single enzyme for the preparation of chiral diols.

    PubMed

    Chen, Yijun; Chen, Chen; Wu, Xuri

    2012-03-01

    Chiral diols are a group of key building blocks useful for preparing a variety of important chiral chemicals. While the preparation of optically pure diols is generally not an easy task in synthetic organic chemistry, three classes of enzymes, namely dicarbonyl reductase, dioxygenase and epoxide hydrolase, display remarkable ability to stereoselectively introduce two hydroxyl groups in a single-step enzymatic conversion. In this tutorial review, we pay special attention to dicarbonyl reductases that directly produce chiral diols through the bio-reduction of two carbonyl groups. The dicarbonyl reductases include diketoreductase, α-acetoxy ketone reductase and sepiapterin reductase. We present these exceptional enzymes in the context of source and properties, structure and catalytic mechanism as well as biocatalytic application. In addition to the broad substrate specificity, the excellent stereoselectivity and high catalytic efficiency of these enzymes have positioned them as valuable biocatalysts. With more sophisticated understanding of the structure-function relationship, the practical utilities of these enzymes associated with their interesting chemistry will be considerably appreciated over time. Moreover, rational redesign and molecular evolution of these unusual biocatalysts will truly enable their broader applications in the synthesis of chiral diols in the future. PMID:22222186

  5. One step synthesis of 6-oxo-cholestan-3β,5α-diol

    SciTech Connect

    Voisin, Maud; Silvente-Poirot, Sandrine; Poirot, Marc

    2014-04-11

    Highlights: • Cholesterol-5,6-epoxides are metabolized into cholestane-3β,5α,6β-triol (CT) in cancer cells. • 6-Oxo-cholestan-3β,5α-diol (OCDO) is a putative metabolite of CT. • The one step syntheses of CT and OCDO from cholesterol are reported. • The one step syntheses of labelled CT and OCDO are reported. - Abstract: Cholesterol metabolism has been recently linked to cancer, highlighting the importance of the characterization of new metabolic pathways in the sterol series. One of these pathways is centered on cholesterol-5,6-epoxides (5,6-ECs). 5,6-ECs can either generate dendrogenin A, a tumor suppressor present in healthy mammalian tissues, or the carcinogenic cholestane-3β,5α,6β-triol (CT) and its putative metabolite 6-oxo-cholestan-3β,5α-diol (OCDO) in tumor cells. We are currently investigating the identification of the enzyme involved in OCDO biosynthesis, which would be highly facilitated by the use of commercially unavailable [{sup 14}C]-cholestane-3β,5α,6β-triol and [{sup 14}C]-6-oxo-cholestan-3β,5α-diol. In the present study we report the one-step synthesis of [{sup 14}C]-cholestane-3β,5α,6β-triol and [{sup 14}C]-6-oxo-cholestan-3β,5α-diol by oxidation of [{sup 14}C]-cholesterol with iodide metaperiodate (HIO{sub 4})

  6. Synthesis of cyclic carbonates from diols and CO2 catalyzed by carbenes.

    PubMed

    Bobbink, Felix D; Gruszka, Weronika; Hulla, Martin; Das, Shoubhik; Dyson, Paul J

    2016-09-14

    The synthesis of cyclic carbonates from epoxides and CO2 is a well-established reaction, whereas the synthesis of cyclic carbonates from diols and CO2 is considerably more challenging, and few efficient catalysts are available. Here, we describe heterocyclic carbene catalysts, including one derived from a cheap and efficient thiazolium salt, for this latter reaction. The reaction proceeds at atmospheric pressure in the presence of an alkyl halide and Cs2CO3. Reaction mechanisms for the transformations involved are also proposed. PMID:27514459

  7. BENZO[A]PYRENE-7,8-QUINONE FORMS COVALENT-DNA ADDUCTS IN VITRO BUT NONE WERE DETECTED IN THE LUNGS OR LIVERS OF STRAIN A/J MICE IN VIVO

    EPA Science Inventory

    Benzo[a]pyrene (B[a]P) is a potent human and rodent lung carcinogen. This activity has been ascribed in part to the formation of B[a]P-7,8-dio1-9,10-epoxide (BPDE)-DNA adducts. Other carcinogenic mechanisms have been proposed: 1.] The induction of apurinic sites from radical cati...

  8. Evaluation of ovotoxicity induced by 7, 12-dimethylbenz[a]anthracene and its 3,4-diol metabolite utilizing a rat in vitro ovarian culture system

    SciTech Connect

    Igawa, Yoshiyuki; Keating, Aileen F. Rajapaksa, Kathila S.; Sipes, I. Glenn; Hoyer, Patricia B.

    2009-02-01

    The polycyclic aromatic hydrocarbon 7, 12-dimethylbenz[a]anthracene, (DMBA), targets and destroys all follicle types in rat and mouse ovaries. DMBA requires bioactivation to DMBA-3,4-diol-1,2-epoxide for ovotoxicity via formation of the intermediate, DMBA-3,4-diol (catalyzed by microsomal epoxide hydrolase; mEH). mEH was shown to be involved in DMBA bioactivation for ovotoxicity induction in B6C3F{sub 1} mouse ovaries. The current study compared DMBA and DMBA-3,4-diol mediated ovotoxicity, and investigated mEH involvement in DMBA-3,4-diol bioactivation in Fischer 344 (F344) rat ovary. F344 postnatal day (PND) 4 rat ovaries were cultured in vehicle control or media containing 1) DMBA or DMBA-3,4-diol (12.5 nM - 1 {mu}M; 15 days); 2) DMBA (1 {mu}M; 6 h - 15 days); and 3) DMBA (1 {mu}M) or DMBA-3,4-diol (75 nM) {+-} the mEH activity inhibitor cyclohexene oxide (CHO; 2 mM; 4 days). Ovaries were histologically evaluated and mEH mRNA and protein were measured by reverse transcriptase PCR or Western blotting, respectively. Ovotoxicity following 15 days of culture occurred (P < 0.05) at lower concentrations of DMBA-3,4-diol (12.5 nM - primordial; 75 nM - primary) than DMBA (75 nM - primordial; 375 nM - primary). The temporal pattern of mEH expression following DMBA exposure showed mRNA up-regulation (P < 0.05) on day 2, with increased protein (P < 0.05) on day 4, the earliest time of observed follicle loss (P < 0.05). mEH inhibition prevented DMBA-induced, but not DMBA-3,4-diol-induced ovotoxicity. These results demonstrate a conserved response in mice and rats for ovarian mEH involvement in DMBA bioactivation to its ovotoxic, 3,4-diol-1,2-epoxide form.

  9. Evaluation of ovotoxicity induced by 7, 12-dimethylbenz[a]anthracene and its 3,4-diol metabolite utilizing a rat in vitro ovarian culture system

    PubMed Central

    Igawa, Yoshiyuki; Keating, Aileen F.; Rajapaksa, Kathila S.; Sipes, I. Glenn; Hoyer, Patricia B.

    2009-01-01

    The polycyclic aromatic hydrocarbon 7, 12-dimethylbenz[a]anthracene, (DMBA), targets and destroys all follicle types in rat and mouse ovaries. DMBA requires bioactivation to DMBA-3,4-diol-1,2-epoxide for ovotoxicity via formation of the intermediate, DMBA-3,4-diol (catalyzed by microsomal epoxide hydrolase; mEH). mEH was shown to be involved in DMBA bioactivation for ovotoxicity induction in B6C3F1 mouse ovaries. The current study compared DMBA and DMBA-3,4-diol mediated ovotoxicity, and investigated mEH involvement in DMBA-3,4-diol bioactivation in Fischer 344 (F344) rat ovary. F344 postnatal day (PND) 4 rat ovaries were cultured in vehicle control or media containing 1) DMBA or DMBA-3,4-diol (12.5 nM - 1 μM; 15 days); 2) DMBA (1μM; 6 h -15 days); and 3) DMBA (1μM) or DMBA-3,4-diol (75 nM) ± the mEH activity inhibitor cyclohexene oxide (CHO; 2 mM; 4 days). Ovaries were histologically evaluated and mEH mRNA and protein were measured by reverse transcriptase PCR or Western blotting, respectively. Ovotoxicity following 15 days of culture occurred (P < 0.05) at lower concentrations of DMBA-3,4-diol (12.5 nM - primordial; 75 nM - primary) than DMBA (75 nM - primordial; 375 nM - primary). The temporal pattern of mEH expression following DMBA exposure showed mRNA up-regulation (P < 0.05) on day 2, with increased protein (P < 0.05) on day 4, the earliest time of observed follicle loss (P < 0.05). mEH inhibition prevented DMBA-induced, but not DMBA-3,4-diol-induced ovotoxicity. These results demonstrate a conserved response in mice and rats for ovarian mEH involvement in DMBA bioactivation to its ovotoxic, 3,4-diol-1,2-epoxide form. PMID:19027032

  10. Friction reducing properties and stability of epoxidized oleochemicals

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We have studied the properties of epoxidized oleochemical methyl esters including epoxidized soybean oil, epoxidized methyl oleate, epoxidized methyl linoleate, and epoxidized methyl linolenate. We have compared these materials to a similar series of unmodified olefins. Several interesting trends ...

  11. Microbial production of epoxides

    DOEpatents

    Clark, Thomas R.; Roberto, Francisco F.

    2003-06-10

    A method for microbial production of epoxides and other oxygenated products is disclosed. The method uses a biocatalyst of methanotrophic bacteria cultured in a biphasic medium containing a major amount of a non-aqueous polar solvent. Regeneration of reducing equivalents is carried out by using endogenous hydrogenase activity together with supplied hydrogen gas. This method is especially effective with gaseous substrates and cofactors that result in liquid products.

  12. Microbiological Transformations. 33. Fungal Epoxide Hydrolases Applied to the Synthesis of Enantiopure Para-Substituted Styrene Oxides. A Mechanistic Approach.

    PubMed

    Pedragosa-Moreau, S.; Morisseau, C.; Zylber, J.; Archelas, A.; Baratti, J.; Furstoss, R.

    1996-10-18

    The biohydrolysis of differently para-substituted styrene oxide derivatives was studied, using whole cells of the fungi Aspergillus niger or Beauveria sulfurescens. These microorganisms proved to be equipped with epoxide hydrolases which are able to achieve these hydrolyses with high enantioselectivity. This allowed the preparation of the optically active epoxides and of the corresponding vicinal diols which were obtained with good to excellent enantiomeric purity. These two microorganisms proved to be enantiocomplementary. A mechanistic study, carried out using a crude lyophilized enzymatic extract from A.niger, indicated via Hammet coefficient plotting that this hydrolysis is very probably due to a general base-catalyzed process. PMID:11667667

  13. Structural characterization of telechelic polyisobutylene diol.

    PubMed

    Banerjee, Sanjib; Shah, Priyank N; Jeong, Youncheol; Chang, Taihyun; Seethamraju, Kasyap; Faust, Rudolf

    2015-01-01

    The chemical homogeneity of telechelic polyisobutylene diol (PIB-diol), prepared by hydroboration-oxidation of allyl telechelic PIB obtained by reacting living PIB with allyltrimethylsilane, was investigated by liquid chromatography at critical conditions (LCCC) and HPLC coupled with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). A normal phase gradient HPLC method was developed that was able to separate the as-synthesized PIB-diol into three components; PIB-diol, PIB-monool and PIB without any OH functionality. These were analyzed by MALDI-TOF MS, which suggested that the reaction of living PIB with allyltrimethylsilane was incomplete. LCCC using refractive index (RI) detector as a concentration detector allowed separation and quantification of PIB species according to their chemical heterogeneity (PIB-diol=95.3%, PIB-monool=3.3%, non-functional PIB=1.4%). The calculated number average functionality (Fn) of PIB-diol=1.94 suggests high quality of PIB-diol suitable for high molecular weight polyurethane synthesis. PMID:25533396

  14. Comparison of the kinetics of various biomarkers of benzo[a]pyrene exposure following different routes of entry in rats.

    PubMed

    Moreau, Marjory; Bouchard, Michèle

    2015-07-01

    The effect of route of exposure on the kinetics of key biomarkers of exposure to benzo[a]pyrene (BaP), a known human carcinogen, was studied. Rats were exposed to an intravenous, intratracheal, oral and cutaneous dose of 40 µmol kg(-1) BaP. BaP and several metabolites were measured in blood, urine and feces collected at frequent intervals over 72 h post-treatment, using high-performance liquid chromatography/fluorescence. Only BaP and 3-hydroxyBaP (3-OHBaP) were detectable in blood at all time points. There were route-to-route differences in the excreted amounts (% dose) of metabolites but the observed time courses of the excretion rate were quite similar. In urine, total amounts of BaP metabolites excreted over the 0-72 h period followed the order: trans-4,5-dihydrodiolBaP (4,5-diolBaP) ≥ 3-OHBaP > 7-OHBaP ≥ 7,8-diolBaP after intravenous injection and intratracheal instillation; 3-OHBaP ≈ 7-OHBaP ≥ 4,5-diolBaP > 7,8-diolBaP after cutaneous application; 3-OHBaP ≥ 4,5-diolBaP ≈ 7-OHBaP > 7,8-diolBaP following oral administration. In feces, total amounts of BaP metabolites recovered were: 7-OHBaP ≈ 3-OHBaP > 4,5-diolBaP > 7,8-diolBaP > BaP-7,8,9,10-tetrol following all administration routes. For all exposure routes, excretion of 4,5- and 7,8-diolBaP was almost complete over the 0-24 h period in contrast with that of 3- and 7-OHBaP. This study confirms the interest of measuring multiple metabolites due to route-to-route differences in the relative excretion of the different biomarkers and in the time courses of diolBaPs versus OHBaPs. Concentration ratios of the different metabolites may help indicate time and main route of exposure. PMID:25348660

  15. Microbial Cell Factories for Diol Production.

    PubMed

    Sabra, W; Groeger, C; Zeng, An-Ping

    2016-01-01

    Diols are compounds with two hydroxyl groups and have a wide range of appealing applications as chemicals and fuels. In particular, five low molecular diol compounds, namely 1,3-propanediol (1,3-PDO), 1,2-propanediol (1,2-PDO), 2,3-butanediol (2,3-BDO), 1,3-butanediol (1,3-BDO), and 1,4-butanediol (1,4-BDO), can be biotechnologically produced by direct microbial bioconversion of renewable materials. In this review, we summarize recent developments in the microbial production of diols, especially regarding the engineering of typical microbial strains as cell factory and the development of corresponding bioconversion processes. PMID:26475465

  16. Predictive model for epoxide hydrolase-generated stereochemistry in the biosynthesis of nine-membered enediyne antitumor antibiotics.

    PubMed

    Horsman, Geoffrey P; Lechner, Anna; Ohnishi, Yasuo; Moore, Bradley S; Shen, Ben

    2013-08-01

    Nine-membered enediyne antitumor antibiotics C-1027, neocarzinostatin (NCS), and kedarcidin (KED) possess enediyne cores to which activity-modulating peripheral moieties are attached via (R)- or (S)-vicinal diols. We have previously shown that this stereochemical difference arises from hydrolysis of epoxide precursors by epoxide hydrolases (EHs) with different regioselectivities. The inverting EHs, such as SgcF, hydrolyze an (S)-epoxide substrate to yield an (R)-diol in C-1027 biosynthesis, whereas the retaining EHs, such as NcsF2 and KedF, hydrolyze an (S)-epoxide substrate to yield an (S)-diol in NCS and KED biosynthesis. We now report the characterization of a series of EH mutants and provide a predictive model for EH regioselectivity in the biosynthesis of the nine-membered enediyne antitumor antibiotics. A W236Y mutation in SgcF increased the retaining activity toward (S)-styrene oxide by 3-fold, and a W236Y/Q237M double mutation in SgcF, mimicking NcsF2 and KedF, resulted in a 20-fold increase in the retaining activity. To test the predictive utility of these mutations, two putative enediyne biosynthesis-associated EHs were identified by genome mining and confirmed as inverting enzymes, SpoF from Salinospora tropica CNB-440 and SgrF (SGR_625) from Streptomyces griseus IFO 13350. Finally, phylogenetic analysis of EHs revealed a familial classification according to inverting versus retaining activity. Taken together, these results provide a predictive model for vicinal diol stereochemistry in enediyne biosynthesis and set the stage for further elucidating the origins of EH regioselectivity. PMID:23844627

  17. A predictive model for epoxide hydrolase-generated stereochemistry in the biosynthesis of 9-membered enediyne antitumor antibiotics

    PubMed Central

    Horsman, Geoffrey P.; Lechner, Anna; Ohnishi, Yasuo; Moore, Bradley S.; Shen, Ben

    2013-01-01

    Nine-membered enediyne antitumor antibiotics C-1027, neocarzinostatin (NCS), and kedarcidin (KED) possess enediyne cores to which activity-modulating peripheral moieties are attached via (R)- or (S)-vicinal diols. We have previously shown that this stereochemical difference arises from hydrolysis of epoxide precursors by epoxide hydrolases (EHs) with different regioselectivities – the “inverting” EH, such as SgcF, hydrolyzes an (S)-epoxide substrate to yield an (R)-diol in C-1027 biosynthesis, while the “retaining” EHs, such as NcsF2 and KedF, hydrolyze an (S)-epoxide substrate to yield an (S)-diol in NCS and KED biosynthesis. We now report the characterization of a series of EH mutants and provide a predictive model for EH regioselectivity in the biosynthesis of the 9-membered enediyne antitumor antibiotics. A W236Y mutation in SgcF increased the retaining activity towards (S)-styrene oxide 3-fold, and a W236Y/Q237M double mutation in SgcF, mimicking NcsF2 and KedF, resulted in a 20-fold increase in the retaining activity. To test the predictive utility of these mutations, two putative enediyne biosynthesis-associated EHs were identified by genome mining and confirmed as inverting enzymes – SpoF from Salinospora tropica CNB-440 and SgrF (SGR_625) from Streptomyces griseus IFO 13350. Finally, phylogenetic analysis of EHs revealed a familial classification according to inverting versus retaining activity. Taken together, these results provide a predictive model for the vicinal diol stereochemistry in enediyne biosynthesis and set the stage for further elucidating the origins of EH regioselectivity. PMID:23844627

  18. Dysregulation of Soluble Epoxide Hydrolase and Lipidomic Profiles in Anorexia Nervosa

    PubMed Central

    Shih, Pei-an Betty; Yang, Jun; Morisseau, Christophe; German, J. Bruce; Van Zeeland, Ashley; Armando, Aaron M.; Quehenberger, Oswald; Bergen, Andrew W.; Magistretti, Pierre; Berrettini, Wade; Halmi, Katherine Ann; Schork, Nicholas; Hammock, Bruce D.; Kaye, Walter

    2015-01-01

    Individuals with anorexia nervosa (AN) restrict eating and become emaciated. AN tend to have an aversion to foods rich in fat. Because Epoxide Hydrolase 2 (EPHX2) was identified as a novel AN susceptibility gene, and because its protein product, soluble epoxide hydrolase (sEH), converts bioactive epoxides of polyunsaturated fatty acid (PUFA) to the corresponding diols, lipidomic and metabolomic targets of EPHX2 were assessed to evaluate the biological functions of EPHX2 and their role in AN. Epoxide substrates of sEH and associated oxylipins were measured in ill AN, recovered AN, and gender- and race-matched controls. PUFA and oxylipin markers were tested as potential biomarkers for AN. Oxylipin ratios were calculated as proxy markers of in vivo sEH activity. Several free- and total PUFAs were associated with AN diagnosis and with AN recovery. AN displayed elevated n-3 PUFAs and may differ from controls in PUFA elongation and desaturation processes. Cytochrome P450 pathway oxylipins from arachidonic acid, linoleic acid, alpha-linolenic acid, and docosahexaenoic acid PUFAs are associated with AN diagnosis. The diol:epoxide ratios suggest the sEH activity is higher in AN compared to controls. Multivariate analysis illustrates normalization of lipidomic profiles in recovered ANs. EPHX2 influences AN risk through in vivo interaction with dietary PUFAs. PUFA composition and concentrations as well as sEH activity may contribute to the pathogenesis and prognosis of AN. Our data support the involvement of EPHX2-associated lipidomic and oxylipin dysregulations in AN, and reveal their potential as biomarkers to assess responsiveness to future intervention or treatment. PMID:25824304

  19. Dysregulation of soluble epoxide hydrolase and lipidomic profiles in anorexia nervosa.

    PubMed

    Shih, P B; Yang, J; Morisseau, C; German, J B; Zeeland, A A Scott-Van; Armando, A M; Quehenberger, O; Bergen, A W; Magistretti, P; Berrettini, W; Halmi, K A; Schork, N; Hammock, B D; Kaye, W

    2016-04-01

    Individuals with anorexia nervosa (AN) restrict eating and become emaciated. They tend to have an aversion to foods rich in fat. Because epoxide hydrolase 2 (EPHX2) was identified as a novel AN susceptibility gene, and because its protein product, soluble epoxide hydrolase (sEH), converts bioactive epoxides of polyunsaturated fatty acid (PUFA) to the corresponding diols, lipidomic and metabolomic targets of EPHX2 were assessed to evaluate the biological functions of EPHX2 and their role in AN. Epoxide substrates of sEH and associated oxylipins were measured in ill AN, recovered AN and gender- and race-matched controls. PUFA and oxylipin markers were tested as potential biomarkers for AN. Oxylipin ratios were calculated as proxy markers of in vivo sEH activity. Several free- and total PUFAs were associated with AN diagnosis and with AN recovery. AN displayed elevated n-3 PUFAs and may differ from controls in PUFA elongation and desaturation processes. Cytochrome P450 pathway oxylipins from arachidonic acid, linoleic acid, alpha-linolenic acid and docosahexaenoic acid PUFAs are associated with AN diagnosis. The diol:epoxide ratios suggest the sEH activity is higher in AN compared with controls. Multivariate analysis illustrates normalization of lipidomic profiles in recovered ANs. EPHX2 influences AN risk through in vivo interaction with dietary PUFAs. PUFA composition and concentrations as well as sEH activity may contribute to the pathogenesis and prognosis of AN. Our data support the involvement of EPHX2-associated lipidomic and oxylipin dysregulations in AN, and reveal their potential as biomarkers to assess responsiveness to future intervention or treatment. PMID:25824304

  20. Quantitation of Benzo[a]pyrene Metabolic Profiles in Human Bronchoalveolar H358) Cells by Stable Isotope Dilution Liquid Chromatography-Atmospheric Chemical Ionization Mass Spectrometry

    PubMed Central

    Lu, Ding; Harvey, Ronald G.; Blair, Ian A.; Penning, Trevor M.

    2013-01-01

    Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental pollutants and are carcinogenic in multiple organs and species. Benzo[a]pyrene (B[a]P) is a representative PAH and has been studied extensively for its carcinogenicity and toxicity. B[a]P itself is chemically inert and requires metabolic activation to exhibit its toxicity and carcinogenicity. Three major metabolic pathways have been well documented. The signature metabolites generated from the radical cation (peroxidase or monooxygenase mediated) pathway are B[a]P-1,6-dione and B[a]P-3,6-dione, the signature metabolite generated from the diol-epoxide (P450 mediated) pathway is B[a]P-r-7,t-8,t-9,c-10-tetrahydrotetrol (B[a]P-tetrol-1) and the signature metabolite generated from the o-quinone (aldo-keto reductase mediated) pathway is B[a]P-7,8-dione. The contributions of these different metabolic pathways to cancer initiation and the exploitation of this information for cancer prevention are still under debate. With the availability of a library of [13C4]-labeled B[a]P metabolite internal standards, we developed a sensitive stable isotope dilution atmospheric pressure chemical ionization tandem mass spectrometry method to address this issue by quantitating B[a]P metabolites from each metabolic pathway in human lung cells. This analytical method represents a 500 fold increased sensitivity compared with a method using HPLC-radiometric detection. The limit of quantitation (LOQ) was determined to be 6 fmol on column for 3-hydroxybenzo[a]pyrene (3-OH-B[a]P), the generally accepted biomarker for B[a]P exposure. This high level of sensitivity and robustness of the method was demonstrated in a study of B[a]P metabolic profiles in human bronchoalveolar H358 cells induced or uninduced with the AhR ligand, 2,3,7,8-tetrachlorodibenzodioxin (TCDD). All the signature metabolites were detected and successfully quantitated. Our results suggest that all three metabolic pathways contribute equally in the overall

  1. Epoxide hydrolase of Trichoderma reesei: Biochemical properties and conformational characterization.

    PubMed

    de Oliveira, Gabriel Stephani; Adriani, Patricia Pereira; Borges, Flavia Garcia; Lopes, Adriana Rios; Campana, Patricia T; Chambergo, Felipe S

    2016-08-01

    Epoxide hydrolases (EHs) are enzymes that are present in all living organisms and catalyze the hydrolysis of epoxides to the corresponding vicinal diols. EHs have biotechnological potential in chiral chemistry. We report the cloning, purification, enzymatic activity, and conformational analysis of the TrEH gene from Trichoderma reesei strain QM9414 using circular dichroism spectroscopy. The EH gene has an open reading frame encoding a protein of 343 amino acid residues, resulting in a molecular mass of 38.2kDa. The enzyme presents an optimum pH of 7.2, and it is highly active at temperatures ranging from 23 to 50°C and thermally inactivated at 70°C (t1/2=7.4min). The Michaelis constants (Km) were 4.6mM for racemic substrate, 21.7mM for (R)-(+)-styrene oxide and 3.0mM for (S)-(-)-styrene oxide. The kcat/Km analysis indicated that TrEH is enantioselective and preferentially hydrolyzes (S)-(-)-styrene oxide. The conformational stability studies suggested that, despite the extreme conditions (high temperatures and extremely acid and basic pHs), TrEH is able to maintain a considerable part of its regular structures, including the preservation of the native cores in some cases. The recombinant protein showed enantioselectivity that was distinct from other fungus EHs, making this protein a potential biotechnological tool. PMID:27177457

  2. Evaluation of adjuvants for a candidate conjugate vaccine against benzo[a]pyrene.

    PubMed

    Schellenberger, Mario T; Farinelle, Sophie; Willième, Stéphanie; Muller, Claude P

    2011-01-01

    We have recently developed an experimental vaccine based on benzo[a]pyrene (B[a]P) conjugated to tetanus toxoid as a carrier protein. In combination with Freund adjuvant, this vaccine induces high levels of B[a]P-specific antibodies to protect against detrimental effects of this carcinogen. Here we evaluate this conjugate vaccine by replacing Freund adjuvant by adjuvants that are potentially compatible with their use in humans. We showed that all adjuvants tested induced specific antibodies against B[a]P and 7,8-diol-B[a]P, its carcinogenic metabolite. The best antibody levels were obtained with Quil A, MF-59 and Alum. Biological activity in terms of enhanced retention of B[a]P was confirmed in mice immunised with Quil A, Montanide, Alum and MF-59. Our findings demonstrate that a vaccination against B[a]P is feasible in combination with adjuvants licensed in humans. PMID:21245662

  3. Deep eutectic solvents (DESs) are viable cosolvents for enzyme-catalyzed epoxide hydrolysis.

    PubMed

    Lindberg, Diana; de la Fuente Revenga, Mario; Widersten, Mikael

    2010-06-01

    A special group of ionic liquids, deep eutectic solvents (DESs) have been tested as cosolvents in enzyme-catalyzed hydrolysis of a chiral (1,2)-trans-2-methylstyrene oxide. The choline chloride:ethane diol (ET), choline chloride:glycerol (GLY) and choline:chloride:urea (REL) DESs were included in the reaction mixtures with epoxide and the potato epoxide hydrolase StEH1. The effect of the DESs on enzyme function was primarily elevations of K(M) (up to 20-fold) and with lesser effects on turnover numbers (twofold variation). The regioselectivity in hydrolysis of the (1R,2R)-2-trans-methylstyrene oxide was altered in the presence of GLY or ET to favor epoxide ring opening at the benzylic carbon (R=2.33), enhancing the regioselectivity observed in buffer-only systems (R=1.35). The DES solutions dissolved 1.5-fold higher epoxide concentrations as compared to phosphate buffer. The total conversion of high concentration (40 g/l) of (1S,2S)-MeSO was not negatively affected by addition of 40% GLY. PMID:20438773

  4. Effects of dynamic exercise on plasma arachidonic acid epoxides and diols in human volunteers

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Metabolites of the cytochrome P450 pathway may contribute to vasodilation of the vasculature of skeletal muscle during exercise. We determined effects of exercise intensity and duration on plasma concentrations of specific metabolites in the epoxyeicosatrienoic acid family. This allowed us to dete...

  5. Multiphoton spectral analysis of benzo[a]pyrene uptake and metabolism in a rat liver cell line

    SciTech Connect

    Barhoumi, Rola; Mouneimne, Youssef; Ramos, Ernesto; Morisseau, Christophe; Hammock, Bruce D.; Safe, Stephen; Parrish, Alan R.; Burghardt, Robert C.

    2011-05-15

    Dynamic analysis of the uptake and metabolism of polycyclic aromatic hydrocarbons (PAHs) and their metabolites within live cells in real time has the potential to provide novel insights into genotoxic and non-genotoxic mechanisms of cellular injury caused by PAHs. The present work, combining the use of metabolite spectra generated from metabolite standards using multiphoton spectral analysis and an 'advanced unmixing process', identifies and quantifies the uptake, partitioning, and metabolite formation of one of the most important PAHs (benzo[a]pyrene, BaP) in viable cultured rat liver cells over a period of 24 h. The application of the advanced unmixing process resulted in the simultaneous identification of 8 metabolites in live cells at any single time. The accuracy of this unmixing process was verified using specific microsomal epoxide hydrolase inhibitors, glucuronidation and sulfation inhibitors as well as several mixtures of metabolite standards. Our findings prove that the two-photon microscopy imaging surpasses the conventional fluorescence imaging techniques and the unmixing process is a mathematical technique that seems applicable to the analysis of BaP metabolites in living cells especially for analysis of changes of the ultimate carcinogen benzo[a]pyrene-r-7,t-8-dihydrodiol-t-9,10-epoxide. Therefore, the combination of the two-photon acquisition with the unmixing process should provide important insights into the cellular and molecular mechanisms by which BaP and other PAHs alter cellular homeostasis.

  6. Molecular biology of environmental aromatic hydrocarbons. Progress report, January 1, 1980-December 31,1980

    SciTech Connect

    Weiss, S. B.

    1980-07-01

    Studies on three different aspects of hydrocarbon action have been investigated. These studies concern: I) the biochemical effect of benzo(a)pyrene-diol-epoxide (BPDE) on the replication of Simian virus 40; II) the reaction of benzo(a)pyrene-7,8-diol (BPD) with viral DNA; and III) the effect of PAH derivatives on RNA transcription.

  7. Direct Cross-Couplings of Propargylic Diols.

    PubMed

    Green, Nicholas J; Willis, Anthony C; Sherburn, Michael S

    2016-08-01

    [Pd(PPh3 )4 ] catalyzes a Suzuki-Miyaura-like twofold cross-coupling sequence between underivatized propargylic diols and either aryl or alkenyl boronic acids to furnish highly substituted 1,3-dienes. Thus, 2,3-diaryl-1,3-butadienes and their dialkenic congeners ([4]dendralenes) are delivered in a (pseudo)halogen-free, single-step synthesis which supersedes existing methods. Allenols are also readily formed. Treatment of these single- and twofold cross-coupled products with acid leads to remarkably short syntheses of highly-substituted benzofulvenes and aryl indenes, respectively. PMID:27375221

  8. Diol Dehydratase-Reactivase Is Essential for Recycling of Coenzyme B12 in Diol Dehydratase.

    PubMed

    Toraya, Tetsuo; Tanokuchi, Aya; Yamasaki, Ai; Nakamura, Takehiro; Ogura, Kenichi; Tobimatsu, Takamasa

    2016-01-12

    Holoenzymes of adenosylcobalamin-dependent diol and glycerol dehydratases undergo mechanism-based inactivation by glycerol and O2 inactivation in the absence of substrate, which accompanies irreversible cleavage of the coenzyme Co-C bond. The inactivated holodiol dehydratase and the inactive enzyme·cyanocobalamin complex were (re)activated by incubation with NADH, ATP, and Mg(2+) (or Mn(2+)) in crude extracts of Klebsiella oxytoca, suggesting the presence of a reactivating system in the extract. The reducing system with NADH could be replaced by FMNH2. When inactivated holoenzyme or the enzyme·cyanocobalamin complex, a model of inactivated holoenzyme, was incubated with purified recombinant diol dehydratase-reactivase (DD-R) and an ATP:cob(I)alamin adenosyltransferase in the presence of FMNH2, ATP, and Mg(2+), diol dehydratase activity was restored. Among the three adenosyltransferases (PduO, EutT, and CobA) of this bacterium, PduO and CobA were much more efficient for the reactivation than EutT, although PduO showed the lowest adenosyltransfease activity toward free cob(I)alamin. These results suggest that (1) diol dehydratase activity is maintained through coenzyme recycling by a reactivating system for diol dehydratase composed of DD-R, PduO adenosyltransferase, and a reducing system, (2) the releasing factor DD-R is essential for the recycling of adenosycobalamin, a tightly bound, prosthetic group-type coenzyme, and (3) PduO is a specific adenosylating enzyme for the DD reactivation, whereas CobA and EutT exert their effects through free synthesized coenzyme. Although FMNH2 was mainly used as a reductant in this study, a natural reducing system might consist of PduS cobalamin reductase and NADH. PMID:26704729

  9. Soluble epoxide hydrolase expression in a porcine model of arteriovenous graft stenosis and anti-inflammatory effects of a soluble epoxide hydrolase inhibitor

    PubMed Central

    Sanders, William G.; Morisseau, Christophe; Hammock, Bruce D.; Cheung, Alfred K.

    2012-01-01

    Synthetic arteriovenous (AV) grafts, placed between an artery and vein, are used for hemodialysis but often fail due to stenosis, typically at the vein-graft anastomosis. This study recorded T lymphocyte and macrophage accumulation at the vein-graft anastomosis, suggesting a role for inflammation in stenosis development. Epoxyeicosatrienoic acids (EETs), products of cytochrome P-450 epoxidation of arachidonic acid, have vasculoprotective and anti-inflammatory effects including inhibition of platelet activation, cell migration, and adhesion. EETs are hydrolyzed by soluble epoxide hydrolase (sEH) to less active diols. The effects of a specific inhibitor of sEH (sEHI) on cytokine release from human monocytes and mouse bone marrow–derived macrophages (BMMΦ) from wild-type (WT) and sEH knockout (KO) animals were investigated. Expression of sEH protein increased over time at the anastomosis as evaluated by immunohistochemistry. Pre-exposure of adherent human monocytes to sEHI (5 μM) significantly inhibited lipopolysaccharide-induced release of monocyte chemotactic protein-1 (MCP-1) and tumor necrosis factor-α and enhanced the EET-to-diol ratio. Release of MCP-1 from WT BMMΦ was significantly inhibited but release from sEH KO BMMΦ was not attenuated indicating the specificity of the sEHI. In contrast, sEHI did not inhibit the release of macrophage inflammatory protein-1 or interleukin-6. Nuclear translocation of NF-κB, as assessed by immunocytochemical staining, was not decreased with sEHI in monocytes, but the phosphorylation of JNK was completely abrogated, suggesting this pathway is the target of sEHI effects in monocytes. These results suggest that sEHI may be useful for inhibition of inflammation and subsequently stenosis in AV grafts. PMID:22621785

  10. Soluble epoxide hydrolase: A potential target for metabolic diseases.

    PubMed

    He, Jinlong; Wang, Chunjiong; Zhu, Yi; Ai, Ding

    2016-05-01

    Epoxyeicosatrienoic acids (EETs), important lipid mediators derived from arachidonic acid, have many beneficial effects in metabolic diseases, including atherosclerosis, hypertension, cardiac hypertrophy, diabetes, non-alcoholic fatty liver disease, and kidney disease. Epoxyeicosatrienoic acids can be further hydrolyzed to less active diols by the enzyme soluble epoxide hydrolase (sEH). Increasing evidence suggests that inhibition of sEH increases levels of EETs, which have anti-inflammatory effects and can prevent the development of hypertension, atherosclerosis, heart failure, fatty liver, and multiple organ fibrosis. Arachidonic acid is the most abundant omega-6 polyunsaturated fatty acid (PUFA) and shares the same set of enzymes with omega-3 PUFAs, such as docosahexaenoic acid and eicosapentaenoic acid. The omega-3 PUFAs and metabolites, such as regioisomeric epoxyeicosatetraenoic acids and epoxydocosapentaenoic acids, have been reported to have strong vasodilatory and anti-inflammatory effects. Therefore, sEH may be a potential therapeutic target for metabolic disorders. In this review, we focus on our and other recent studies of the functions of sEH, including the effects of its eicosanoid products from both omega-3 and omega-6 PUFAs, in various metabolic diseases. We also discuss the possible cellular and molecular mechanisms underlying the regulation of sEH. PMID:26621325

  11. Cloning and characterization of an epoxide hydrolase from Cupriavidus metallidurans-CH34.

    PubMed

    Kumar, Ranjai; Wani, Shadil Ibrahim; Chauhan, Nar Singh; Sharma, Rakesh; Sareen, Dipti

    2011-09-01

    A putative epoxide hydrolase-encoding gene was identified from the genome sequence of Cupriavidus metallidurans CH34. The gene was cloned and overexpressed in Escherichia coli with His(6)-tag at its N-terminus. The epoxide hydrolase (CMEH) was purified to near homogeneity and was found to be a homodimer, with subunit molecular weight of 36 kDa. The CMEH had broad substrate specificity as it could hydrolyze 13 epoxides, out of 15 substrates tested. CMEH had high specific activity with 1,2-epoxyoctane, 1,2-epoxyhexane, styrene oxide (SO) and was also found to be active with meso-epoxides. The enzyme had optimum pH and temperature of 7.5 and 37°C respectively, with racemic SO. Biotransformation of 80 mM SO with recombinant whole E. coli cells expressing CMEH led to 56% ee(P) of (R)-diol with 77.23% conversion in 30 min. The enzyme could hydrolyze (R)-SO, ∼2-fold faster than (S)-SO, though it accepted both (R)- and (S)-SO with similar affinity as K(m)(R) and K(m)(S) of CMEH were 2.05±0.42 and 2.11±0.16 mM, respectively. However, the k(cat)(R) and k(cat)(S) for the two enantiomers of SO were 4.80 and 3.34 s(-1), respectively. The wide substrate spectrum exhibited by CMEH combined with the fast conversion rate makes it a robust biocatalyst for industrial use. Regioselectivity studies with enantiopure (R)- and (S)-SO revealed that with slightly altered regioselectivity, CMEH has a high potential to synthesize an enantiopure (R)-PED, through an enantioconvergent hydrolytic process. PMID:21515382

  12. Organocatalyzed enantioselective desymmetrization of aziridines and epoxides

    PubMed Central

    2013-01-01

    Summary Enantioselective desymmetrization of meso-aziridines and meso-epoxides with various nucleophiles by organocatalysis has emerged as a cutting-edge approach in recent years. This review summarizes the origin and recent developments of enantioselective desymmetrization of meso-aziridines and meso-epoxides in the presence of organocatalysts. PMID:24062828

  13. Metabolism of benzo(a)pyrene by fish cells in culture

    SciTech Connect

    Thornton, S.C.; Diamond, L.; Baird, W.M.

    1982-07-01

    Benzo(a)pyrene (BaP) metabolism was studied in cell lines derived from rainbow trout (RTG-2), bluegill fry (BF-2), and fathead minnow (FHM). Confluent cultures were exposed to /sup 3/H-BaP (0.5 nmol/ml), and, after various exposure times, metabolites were extracted from the media with an organic solvent and analyzed by high-pressure liquid chromatography. BF-2 and RTG-2 cells converted 63% of the BaP to water-soluble metabolites within 24 h, while FHM cells converted only 12%. BF-2 and RTG-2 cells metabolized more than 90% of the BaP by 48h, while only 67% of the BaP was converted to water-soluble metabolites by FHM cells after 96h. The major organic-solvent-extractable metabolites in all three cell lines were 9,10-dihydroxy-9,10-dihydrobenzo(a)pyrene and unidentified polar metabolites. Of the water-soluble metabolites formed by BF-2, FHM, and RTG-2 cells, 67, 42, and 19%, respectively, were converted to ethyl-acetate-extractable metabolites by treatment with ..beta..-glucuronidase. All three cell lines formed a glucuronide of 7,8-dihydroxy-7,8-dihydrobenzo(a)pyrene (7,8-diol); in BF-2 and FHM cells, the 7,8-diol represented almost half of the metabolites released by ..beta..-glucuronidase treatment. Thus, cell lines derived from three widely distributed species of freshwater fish have the capacity to metabolize BaP to a form that is a proximate carcinogen in rodents and to produce a water-soluble conjugate of this metabolite.

  14. CARBINOLAMINES AND GEMINAL DIOLS IN AQUEOUS ENVIRONMENTAL ORGANIC CHEMISTRY

    EPA Science Inventory

    Organic chemistry textbooks generally treat geminal diols as curiosities-exceptions to the stability of the C=O double bond. However, most aldehydes of environmental significance, to wit, trichloroethanal (chloral), methanala (formaldehyde), ethanal (acetaldehyde), and propanal ...

  15. Characterization of Hovi-mEH1, a microsomal epoxide hydrolase from the glassy-winged sharpshooter Homalodisca vitripennis.

    PubMed

    Kamita, Shizuo G; Oshita, Grant H; Wang, Peng; Morisseau, Christophe; Hammock, Bruce D; Nandety, Raja Sekhar; Falk, Bryce W

    2013-08-01

    Epoxide hydrolase (EH) is an enzyme in the α/β-hydrolase fold superfamily that uses a water molecule to transform an epoxide to its corresponding diol. In insects, EHs metabolize among other things critical developmental hormones called juvenile hormones (JHs). EHs also play roles in the detoxification of toxic compounds that are found in the insect's diet or environment. In this study, a full-length cDNA encoding an epoxide hydrolase, Hovi-mEH1, was obtained from the xylem-feeding insect Homalodisca vitripennis. H. vitripennis, commonly known as the glassy-winged sharpshooter, is an economically important vector of plant pathogenic bacteria such as Xylella fastidiosa. Hovi-mEH1 hydrolyzed the general EH substrates cis-stilbene oxide and trans-diphenylpropene oxide with specific activities of 47.5 ± 6.2 and 1.3 ± 0.5 nmol of diol formed min⁻¹ mg⁻¹, respectively. Hovi-mEH1 metabolized JH III with a Vmax of 29.3 ± 1.6 nmol min⁻¹ mg⁻¹, kcat of 0.03 s⁻¹, and KM of 13.8 ± 2.0 μM. These Vmax and kcat values are similar to those of known JH metabolizing EHs from lepidopteran and coleopteran insects. Hovi-mEH1 showed 99.1% identity to one of three predicted EH-encoding sequences that were identified in the transcriptome of H. vitripennis. Of these three sequences only Hovi-mEH1 clustered with known JH metabolizing EHs. On the basis of biochemical, phylogenetic, and transcriptome analyses, we hypothesize that Hovi-mEH1 is a biologically relevant JH-metabolizing enzyme in H. vitripennis. PMID:23704009

  16. Toluene Monooxygenase-Catalyzed Epoxidation of Alkenes

    PubMed Central

    McClay, Kevin; Fox, Brian G.; Steffan, Robert J.

    2000-01-01

    Several toluene monooxygenase-producing organisms were tested for their ability to oxidize linear alkenes and chloroalkenes three to eight carbons long. Each of the wild-type organisms degraded all of the alkenes that were tested. Epoxides were produced during the oxidation of butene, butadiene, and pentene but not hexene or octadiene. A strain of Escherichia coli expressing the cloned toluene-4-monooxygenase (T4MO) of Pseudomonas mendocina KR1 was able to oxidize butene, butadiene, pentene, and hexene but not octadiene, producing epoxides from all of the substrates that were oxidized. A T4MO-deficient variant of P. mendocina KR1 oxidized alkenes that were five to eight carbons long, but no epoxides were detected, suggesting the presence of multiple alkene-degrading enzymes in this organism. The alkene oxidation rates varied widely (ranging from 0.01 to 0.33 μmol of substrate/min/mg of cell protein) and were specific for each organism-substrate pair. The enantiomeric purity of the epoxide products also varied widely, ranging from 54 to >90% of a single epoxide enantiomer. In the absence of more preferred substrates, such as toluene or alkenes, the epoxides underwent further toluene monooxygenase-catalyzed transformations, forming products that were not identified. PMID:10788354

  17. Analysis of tetrahydroxylated benzo[a]pyrene isomers in hair as biomarkers of exposure to benzo[a]pyrene.

    PubMed

    Grova, Nathalie; Hardy, Emilie M; Meyer, Pauline; Appenzeller, Brice M R

    2016-03-01

    A first gas chromatography-tandem mass spectrometry (GC-MS/MS) method was designed for analysis of four tetrahydroxylated benzo[a]pyrene metabolites (benzo[a]pyrene-r-7,t-8,t-9,c-10-tetrahydrotetrol, benzo[a]pyrene-r-7,t-8,t-9,t-10-tetrahydrotetrol, benzo[a]pyrene-r-7,t-8,c-9,c-10-tetrahydrotetrol, and benzo[a]pyrene-r-7,t-8,c-9,t-10-tetrahydrotetrol) in hair. Hair powder extract was submitted to liquid-solid extraction, followed by C18 solid-phase purification. The analytes were derivatized with use of N-methyl-N-(trimethylsilyl)trifluoroacetamide and then analyzed by GC-MS/MS in negative chemical ionization mode. The calibration curve was linear from the limit of quantification (LOQ) to 20 pg/mg in hair. The coefficient of determination of the calibration curve was more than 0.975 for all the analytes investigated. The LOQs ranged from 0.075 to 0.2 pg/mg in hair. The method was afterward applied to the analysis of hair of 16 rats randomly allocated to experimental groups receiving 16 polycyclic aromatic hydrocarbons solubilized in oil at 0 or 0.8 mg/kg body weight by oral administration three times per week for 90 days. The analysis of monohydroxylated and dihydroxylated benzo[a]pyrenes was conducted in parallel by GC-MS/MS on the same samples. All tetrahydroxylated benzo[a]pyrene isomers were detected in hair samples collected from rats exposed to polycyclic aromatic hydrocarbons. Benzo[a]pyrene-r-7,t-8,t-9,c-10-tetrahydrotetrol, the most abundant isomer in hair of treated rats, was also the principal isomer released in DNA adduct hydrolysis in humans. Moreover, the benzo[a]pyrene-r-7,t-8,t-9,c-10-tetrahydrotetrol concentrations in hair were significantly greater than those of 2-hydroxybenzo[a]pyrene, 1-hydroxybenzo[a]pyrene, 7-hydroxybenzo[a]pyrene, and 4-hydroxybenzo[a]pyrene and similar to those of 9-hydroxybenzo[a]pyrene and 3-hydroxybenzo[a]pyrene. The method was also sufficiently sensitive to monitor environmental levels of exposure because two hair

  18. Benzo[a]pyrene Uptake by Bacteria and Yeast

    PubMed Central

    Moore, B. G.; Harrison, Arthur P.

    1965-01-01

    Moore, B. G. (Oak Ridge National Laboratory, Oak Ridge, Tenn.), and Arthur P. Harrison, Jr. Benzo[a]pyrene uptake by bacteria and yeast. J. Bacteriol. 90:989–1000. 1965.—Various Enterobacteriaceae and yeast incubated in a medium containing 25 μg/ml of H3-benzo[a]pyrene (30% serum in the medium dissolves the hydrocarbon) retain radioactivity after washings with fresh 30% serum-medium. This radioactivity is defined as bound and represents intact benzo[a]pyrene. Factors relating to the binding of benzo[a]pyrene (benzo[a]pyrene uptake) have been studied in detail with Escherichia coli Ma, a triple auxotroph requiring l-leucine, uracil, and thymine. In defined medium, benzo[a]pyrene uptake by normally growing cells is 10−10 to 2 × 10−10 μg per cell. Uptake is the same in suspensions lacking leucine and containing chloramphenicol where there is neither measurable protein synthesis nor cell division. Uptake is diminished, but not eliminated, by autoclaving the cells; thus, some uptake occurs in the absence of enzymatic activity. Uptake is enhanced by heat shock, thymine deprivation, uracil deprivation, and exposure to penicillin. Thus, uptake is affected by the physiological state of the cells. Either the cells play a direct (enzymatic) role in uptake, or they affect uptake indirectly by increasing or altering the benzo[a]pyrene-binding structure. Physical fractionation of cells demonstrates that this structure is associated with the cell wall-membrane complex. All but 1% of the bound radioactivity is extracted with ethyl alcohol-ether. This residual radioactivity is defined as fixed, and may be associated with cell protein. The extracted radioactivity is identified as benzo[a]pyrene. Very little hydrocarbon is metabolized. Adverse photodynamic effects, increase in mutation, and dimunition in bacteriophage replication (in whole cells) have not been observed in the benzo[a]pyrene cultures. PMID:5321405

  19. Determinants of Reactivity and Selectivity in Soluble Epoxide Hydrolase from Quantum Mechanics/Molecular Mechanics Modeling

    PubMed Central

    2012-01-01

    Soluble epoxide hydrolase (sEH) is an enzyme involved in drug metabolism that catalyzes the hydrolysis of epoxides to form their corresponding diols. sEH has a broad substrate range and shows high regio- and enantioselectivity for nucleophilic ring opening by Asp333. Epoxide hydrolases therefore have potential synthetic applications. We have used combined quantum mechanics/molecular mechanics (QM/MM) umbrella sampling molecular dynamics (MD) simulations (at the AM1/CHARMM22 level) and high-level ab initio (SCS-MP2) QM/MM calculations to analyze the reactions, and determinants of selectivity, for two substrates: trans-stilbene oxide (t-SO) and trans-diphenylpropene oxide (t-DPPO). The calculated free energy barriers from the QM/MM (AM1/CHARMM22) umbrella sampling MD simulations show a lower barrier for phenyl attack in t-DPPO, compared with that for benzylic attack, in agreement with experiment. Activation barriers in agreement with experimental rate constants are obtained only with the highest level of QM theory (SCS-MP2) used. Our results show that the selectivity of the ring-opening reaction is influenced by several factors, including proximity to the nucleophile, electronic stabilization of the transition state, and hydrogen bonding to two active site tyrosine residues. The protonation state of His523 during nucleophilic attack has also been investigated, and our results show that the protonated form is most consistent with experimental findings. The work presented here illustrates how determinants of selectivity can be identified from QM/MM simulations. These insights may also provide useful information for the design of novel catalysts for use in the synthesis of enantiopure compounds. PMID:22280021

  20. Pharmacokinetics: time-dependent changes--autoinduction of carbamazepine epoxidation

    SciTech Connect

    Bertilsson, L.; Tomson, T.; Tybring, G.

    1986-07-01

    Drugs labeled with stable isotopes have been useful to study time-dependent changes in kinetics. Early studies suggested that carbamazepine (CBZ) may induce its own metabolism, but this could not be proved until tetradeuterium-labeled CBZ (CBZ-D4) was synthesized and then given to patients. CBZ-D4 was administered to three children during long-term treatment of epilepsy with CBZ. After 17 to 32 days of treatment, the plasma clearance of CBZ-D4 was doubled, but during the next four months, there was no further increase, indicating that autoinduction was complete within one month. Two patients with chronic alcoholism were treated with CBZ for five days. Half of the first dose of 600 mg was comprised of CBZ-D4. The half-life of this CBZ-D4 dose in the two patients (20 and 26 hr, respectively) was similar to the post-steady-state half-life of CBZ (23 hr in both patients) measured later. A single dose of CBZ given one week after the last maintenance dose had a longer half-life (46 and 45 hr, respectively), which probably is close to the disposition of the drug before starting the treatment with CBZ. This shows that autoinduction of CBZ metabolism was completed during the very first doses of CBZ. Autoinduction also disappeared rapidly after stopping the treatment. We have shown that it is mainly the epoxide-diol pathway that is induced, both during autoinduction and after induction with other antiepileptic agents.

  1. Kinetic Resolution in Asymmetric Epoxidation using Iminium Salt Catalysis

    PubMed Central

    2013-01-01

    The first reported examples of kinetic resolution in epoxidation reactions using iminium salt catalysis are described, providing up to 99% ee in the epoxidation of racemic cis-chromenes. PMID:23862687

  2. Microwave-mediated selective monotetrahydropyranylation of symmetrical diols catalyzed by iodine.

    PubMed

    Deka, N; Sarma, J C

    2001-03-23

    Selective protection of one hydroxyl group as its tetrahydropyranyl ether in 1,n-symmetrical diol is achieved by iodine-catalyzed reaction of the diol with dihydropyranyl ether under microwave irradiation. PMID:11300886

  3. Human serum albumin-benzo[a]pyrene anti-diol epoxide adduct structure elucidation by fluorescence line narrowing spectroscopy.

    PubMed

    Day, B W; Doxtader, M M; Rich, R H; Skipper, P L; Singh, K; Dasari, R R; Tannenbaum, S R

    1992-01-01

    Cryogenic (4-10 K) laser-induced vibrationless ground state and vibronic excited state fluorescence emission spectra of the adducts resulting from reaction in vitro of human serum albumin and the carcinogen (+-)-r-7,t-8-dihydroxy-c-9,c-10-epoxy-7,8,9,10- tetrahydrobenzo[a]-pyrene were recorded in order to determine the structures formed. Comparison of these fluorescence line-narrowed (FLN) spectra to those obtained from BaP-7,8,9,10- tetrahydrotetrols, synthetic N-t-BOC-alaninate ester, and N tau- and N pi-histidine amine anti-BaPDE adducts revealed that a mixture of adduct types are formed with the protein. Extensive dialysis of the adducted protein simplified the FLN spectrum, causing it to become nearly identical to the FLN spectrum obtained from the stable peptide adduct. Comparison of the FLN spectra of the synthetic histidine adducts to those obtained from peptide adducts isolated from enzymic digestion of the adducted protein indicated that only one of the imidazole nitrogens is the nucleophile which forms a stable adduct with anti-BaPDE. The FLN studies confirm that N tau-histidine adducts are formed between human serum albumin and the C-10 position of anti-BaPDE. PMID:1581540

  4. Epoxide-metabolizing enzymes in mammary gland and liver from BALB/c mice and effects of inducers on enzyme activity.

    PubMed

    Silva, M H; Wixtrom, R N; Hammock, B D

    1988-03-15

    Epoxide hydrolases (EC 3.3.2.3) (EH) are hydrolytic enzymes which may play an important role in the activation and detoxification of mammary carcinogens. In this study, microsomal, cytosolic, and cholesterol epoxide hydrolases along with glutathione S-transferase were characterized in liver and mammary gland from nulliparous and lactating BALB/c mice and from mice transplanted with preneoplastic hyperplastic outgrowths. Clofibrate, butylated hydroxyanisole, and beta-naphthoflavone were used to induce EH. Significant epoxide hydrolysis was observed in microsomal and cytosolic subcellular fractions assayed with cis- and trans-stilbene oxide, benzo(a)pyrene-4,5-oxide, and cholesterol epoxide. The hydrolysis rates were significantly different for nulliparous and lactating animals, in both mammary gland and liver. Clofibrate increased the activity of all forms of EH in liver, but not mammary gland. Butylated hydroxyanisole and beta-naphthoflavone appeared to induce cytosolic glutathione S-transferase as well as some, but not all, forms of EH in liver and mammary gland regardless of hormonal stimuli. The inducers produced different effects in mammary gland as compared with liver. This may be due to either differing amounts of inducer reaching the target site or different regulation of the enzymes in mammary gland and liver. Hyperplastic outgrowths and liver from hyperplastic outgrowth-transplanted animals demonstrated significantly different EH and cytosolic glutathione S-transferase activities from those of nulliparous and lactating animals. This observation offers preliminary evidence that levels of epoxide-metabolizing enzymes are altered when mammary tissue is transformed. Mammary gland cytosolic EH was purified by affinity chromatography and compared to that from liver by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, Western blotting, enzyme-linked immunosorbent assay, isoelectric focusing, and enzyme inhibition by 4-phenylchalcone oxide. Cytosolic EH

  5. OXIDATION OF MONOTETRAHYDROPYRANYLATED SHORT-CHAIN SYMMETRICAL DIOLS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The free hydroxyl functions of monotetrahydropyranylated three- to five-carbon symmetrical primary diols are oxidized to aldehydes, without cleavage of the protective group. By using a pyridinium dichromate in CH2Cl2, the oxidation procedure improved for these specific compounds. Anhydrous MgSO4 se...

  6. Analyses of procyanidins in foods using Diol phase HPLC

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Separation of procyanidins using silica-based HPLC suffered from poor resolution for higher oligomers and low sensitivity due to the fluorescence quenching effects of methylene chloride in the mobile phase. Optimization of a published Diol-phase HPLC method resulted in near baseline separation for p...

  7. Alkene epoxidation employing metal nitro complexes

    DOEpatents

    Andrews, M.A.; Cheng, C.W.; Kelley, K.P.

    1982-07-15

    Process for converting alkenes to form epoxides utilizes transition metal nitro complexes of the formula: M(RCN)/sub 2/XNO/sub 2/ wherein M is palladium or platinum, R is an alkyl or aryl group containing up to 12 carbon atoms, and X is a monoanionic, monodentate ligand such as chlorine, optionally in the presence of molecular oxygen.

  8. Epoxidation of Methyl Oleate using Heterogeneous Catalyst

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In this work we studied the catalytic activity of commercial alumina, and laboratory synthesized alumina doped with Lewis acid metals, in the epoxidation of methyl oleate with aqueous hydrogen peroxide. It was observed that the reaction yields increased when the amount of catalyst, the quantity of ...

  9. Determination of equivalent weight of epoxides

    SciTech Connect

    Selig, W.S.

    1987-01-15

    Hydrogen bromide is generated in situ by the addition of perchloric acid to quaternary ammonium bromide. The HBr rapidly opens the oxirane (epoxide) ring. The excess hydrogen bromide is sensed and indicated by the electrode couple in the potentiometric titration. 2 refs.

  10. Epoxidation of methyl oleate using heterogeneous catalyst

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A variety of synthetic processes have been reported, utilizing epoxidized soybean oil and corresponding epoxy fatty ester systems, as intermediates to obtain industrially significant materials, e.g. bio-based polymers, emollients, chemical solvents, fuel additives, and lubricants. One of the reason...

  11. Polymerization of epoxidized triglycerides with fluorosulfonic acid

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The use of triglycerides as agri-based renewable raw materials for the development of new products is highly desirable in view of uncertain future petroleum prices. A new method of polymerizing epoxidized soybean oil has been devised with the use of fluorosulfonic acid. Depending on the reaction con...

  12. Functionalization of Oleyl Carbonate by Epoxidation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Increasing interest in commercial applications due to their physical properties and relatively straightforward synthesis. Herein, oleyl carbonate (1), an olechemical-based compound derived from oleyl alcohol, was epoxidized utilizing performic acid generated in situ from formic acid and 50% H2O2. ...

  13. DIFFERENCES IN DETECTION OF DNA ADDUCTS IN THE 32P-POSTLABELING ASSAY AFTER EITHER 1-BUTANOL EXTRACTION OR NUCLEASE P1 TREATMENT

    EPA Science Inventory

    The use of nuclease Pl treatment and 1-butanol extraction to increase the sensitivity of the 32P-postlabe1ling assay for DNA adducts have been compared. lthough similar results were obtained with the two methods for standard adducts formed with benzo(a)pyrene diol epoxide I, nucl...

  14. Characterization of two juvenile hormone epoxide hydrolases by RNA interference in the Colorado potato beetle.

    PubMed

    Lü, Feng-Gong; Fu, Kai-Yun; Guo, Wen-Chao; Li, Guo-Qing

    2015-10-10

    In insect, juvenile hormone (JH) titers are tightly regulated in different development stages through synthesis and degradation pathways. During JH degradation, JH epoxide hydrolase (JHEH) converts JH to JH diol, and hydrolyses JH acid to JH acid diol. In this study, two full length LdJHEH cDNAs were cloned from Leptinotarsa decemlineata, and were provisionally designated LdJHEH1 and LdJHEH2. Both mRNAs were detectable in the thoracic muscles, brain-corpora cardiaca-corpora allata complex, foregut, midgut, hindgut, ventral ganglia, Malpighian tubules, fat bodies, epidermis, and hemocytes of the day 2 fourth-instar larvae, and in female ovaries as well as male reproductive organs of the adults. Moreover, both LdJHEH1 and LdJHEH2 were expressed throughout all larval life, with the highest peaks occurring 32h after ecdysis of the final (fourth) instar larvae. Four double-stranded RNAs (dsRNAs) (dsJHEH1-1, dsJHEH1-2, dsJHEH2-1, dsJHEH2-2) respectively targeting LdJHEH1 and LdJHEH2 were constructed and bacterially expressed. Ingestion of dsJHEH1-1, dsJHEH1-2, dsJHEH2-1, dsJHEH2-2, and a mixture of dsJHEH1-1+dsJHEH2-1 successfully knocked down corresponding target gene function, and significantly increased JH titer and upregulated Krüppel homolog 1 (LdKr-h1) mRNA level. Knockdown of either LdJHEH1 or LdJHEH2, or both genes slightly reduced larval weight and delayed larval development, and significantly impaired adult emergence. Therefore, it is suggested that knockdown LdJHEH1 and LdJHEH2 affected JH degradation in the Colorado potato beetle. PMID:26079572

  15. Benzo(a)pyrene causes PRKAA1/2-dependent ID2 loss in trophoblast stem cells.

    PubMed

    Xie, Yufen; Abdallah, Mazen E; Awonuga, Awoniyi O; Slater, Jill A; Puscheck, Elizabeth E; Rappolee, Dan A

    2010-06-01

    Benzo(a)pyrene (BaP), a cigarette smoke component, is metabolized to diol esters (BPDE) that bind to DNA and form mutagenic BPDE-DNA adducts. BaP activates stress enzymes including stress-activated protein kinase/jun kinase (MAPK8/9) in embryos, AMP-activated protein kinase alpha1/2 subunits (PRKAA1/2) in somatic cells, and inhibits the proliferation of trophoblast cell lineages. The loss of transcription factor inhibitor of differentiation (ID)2 is required for the initial differentiation of mouse trophoblast stem cells (TSC) in implanting mouse embryo to produce the first placental hormone, chorionic sommatomammotropin (CSH)1. Here we demonstrate that BaP activates PRKAA1/2 and causes ID2 protein loss in TSC in a time- and dose-dependent manner. Although PRKAA1/2 was activated at low BaP doses, PRKAA1/2-dependent ID2 protein loss occurred at a dose that was similar to the threshold that results in a significant decrease in TSC accumulation and decreased fraction of proliferating TSC. This suggests a possible relationship between stress-induced declines in cell accumulation and stem cell differentiation when BaP levels are high. The threshold BaP dose that induces significant ID2 loss is in the range of a 2-3 pack/day habit, suggesting that this mechanism may be involved with implantation failure in smoking women. PMID:20422711

  16. Alterations in the metabolism of benzo(a)pyrene in syrian hamster embryo (SHE) cells pretreated with phenolic antioxidants

    SciTech Connect

    Strniste, G.F.; Okinaka, R.T.; Chen, D.J.

    1983-01-01

    Inhibition of chemical- or raddiation-induced neoplasia has been observed in animals whose diets were supplemented with antioxidants commonly used as food additives. Inhibition of the carcinogenicity of benzo(a)pyrene (BaP) or of 7,12-dimenthylbenz(a)anthracene (DMBA) - in rats has been achieved by the addition of the phenolic antioxidants butylated hydroxyanisole (BHA) or butylated hydroxytoluene (BHT) to the diet. Our data suggest that in SHE cells antioxidants inhibit the overall metabolism of BaP to its various oxidized moieties including 7,8-diol- and 7,8,9,10-tetrol-BaP. A plausible explanation for our results with SHE cells is that the antioxidants interact directly with AHH, thus inhibiting AHH metabolic capacity. From analysis of nuclear material from SHE cells (+- antioxidants) incubated for 36 hours with BaP at 1 ..mu..g/ml, it is calculated that 4.6, 2.4 and 2.9 pmol BaP are bound to the DNA isolated from 10/sup 7/ nuclei of control, BHA-(20 ..mu..g/ml) and p-MP-(10 ..mu..g/ml) treated cultures, respectively.

  17. Genetic analysis of the soluble epoxide hydrolase gene, EPHX2, in subclinical cardiovascular disease in the Diabetes Heart Study

    PubMed Central

    BURDON, KATHRYN P; LEHTINEN, ALLISON B; LANGEFELD, CARL D; CARR, J JEFFREY; RICH, STEPHEN S; FREEDMAN, BARRY I; HERRINGTON, DAVID; BOWDEN, DONALD W

    2016-01-01

    Epoxide hydrolase is involved in metabolism of vasoactive and anti-inflammatory epoxyeicosatrienoic acids to their corresponding diols. Consequently, epoxide hydrolase 2 (EPHX2) is a candidate cardiovascular disease (CVD) gene. We investigated EPHX2 for association with subclinical CVD in European American (EA) and African American (AA) families from the Diabetes Heart Study. The R287Q polymorphism was associated with carotid artery calcified plaque (CarCP) in EAs. Other EPHX2 polymorphisms were associated with coronary artery calcified plaque (CorCP), CarCP or carotid artery intima-media thickness (IMT). Polymorphism rs7837347 was associated with all traits in the AAs (p=0.003, 0.001 and 0.017, respectively). Polymorphism rs7003694 displayed association with IMT (p=0.017) and, along with rs747276, a trend towards association with CorCP in diabetic EAs (p=0.057 and 0.080, respectively). These results provide additional evidence that EPHX2 contributes to the risk of subclinical CVD, although the true trait defining polymorphisms may not be identified and the effect size could be small. PMID:18537101

  18. Asymmetric Allylboration of Acyl Imines Catalyzed by Chiral Diols

    PubMed Central

    Lou, Sha; Moquist, Philip N.; Schaus, Scott E.

    2008-01-01

    Chiral BINOL-derived diols catalyze the enantioselective asymmetric allylboration of acyl imines. The reaction requires 15 mol% of (S)-3,3′-Ph2-BINOL as the catalyst and allyldiisopropoxyborane as the nucleophile. The reaction products are obtained in good yields (75 – 94%) and high enantiomeric ratios (95:5 – 99.5:0.5) for aromatic and aliphatic imines. High diastereoselectivities (dr > 98:2) and enantioselectivities (er > 98:2) are obtained in the reactions of acyl imines with crotyldiisopropoxyboranes. This asymmetric transformation is directly applied to the synthesis of maraviroc, the selective CCR5 antagonist with potent activity against HIV-1 infection. Mechanistic investigations of the allylboration reaction including IR, NMR, and mass spectrometry study indicate that acyclic boronates are activated by chiral diols via exchange of one of the boronate alkoxy groups with activation of the acyl imine via hydrogen bonding. PMID:18020334

  19. A xanthanolide diol and a dimeric xanthanolide from Xanthium species.

    PubMed

    Ahmed, A A; Mahmoud, A A; El-Gamal, A A

    1999-06-01

    Extracts of the aerial parts of Xanthium strumarium and fruit of X. pungens afforded a new Xanthanolide diol derivative, 11alpha,13-dihydroxyxanthatin and a new dimeric xanthanolide sesquiterpene lactone, pungiolide C, in addition to some known compounds. The structures of the new compounds were determined by spectroscopic methods particularly high resolution (1)H-, (13)C-NMR and 2D (1)H- (1)H and (1)H- (13)C COSY NMR analysis. PMID:17260271

  20. Stereochemistry of the epoxidation of internal perfluoroalkenes with sodium hypochlorite

    SciTech Connect

    Filyakova, T.I.; Peschanskii, N.V.; Kodess, M.I.; Zapevalov, A.Ya.; Kolenko, I.P.

    1988-07-20

    The authors studied the epoxidation of the mixture of cis and trans isomers of internal disubstituted perfluoroalkenes with sodium hypochlorite. Epoxidation was realized with an alkaline aqueous solution of sodium hypochlorite in the presence of acetonitrile. The epoxidation of the geometric isomers of internal disubstituted perfluoroalkenes by sodium hypochlorite is stereospecific. The /sup 19/F NMR spectra of the cis and trans isomers of internal perfluoroolefin oxides were obtained, and the relationships are discussed.

  1. Epoxide composites with thermally reduced graphite oxide and their properties

    NASA Astrophysics Data System (ADS)

    Arbuzov, A. A.; Muradyan, V. E.; Tarasov, B. P.; Sokolov, E. A.; Babenko, S. D.

    2016-05-01

    The properties of epoxide composites modified by thermal reduced graphite oxide are studied. The dielectric permittivities of epoxide composites with additives of up to 1.5 wt % of reduced graphite oxide are studied at a frequency of 9.8 GHz. It is shown that despite its low electrical conductivity, the large specific surface area of reduced graphite oxide allows us to create epoxide composites with high complex dielectric permittivities and dielectric loss tangents.

  2. Diol-linked microporous networks of cubic siloxane cages.

    PubMed

    Wada, Yuko; Iyoki, Kenta; Sugawara-Narutaki, Ayae; Okubo, Tatsuya; Shimojima, Atsushi

    2013-01-28

    A new class of inorganic-organic hybrid porous materials has been synthesized by a reaction between octa(hydridosilsesquioxane) (H(8)Si(8)O(12)), which has a double-four-ring (D4R) structure, and various diols, such as 1,3-propanediol (PD), 1,4-cyclohexanediol (CHD), and 1,3-adamantanediol (AD). Solid-state (29) Si magic-angle-spinning NMR spectroscopic analysis confirmed that most of the corner Si-H groups reacted with diols to form Si-O-C bonds with retention of the D4R cage. Nitrogen adsorption-desorption studies showed that the products are microporous solids with high BET surface areas (up to ≈580 m(2) g(-1) for CHD- and AD-linked products). If n-alkanediols are used as linkers, the surface area becomes smaller as the number of carbon atoms is increased. The thermal and hydrolytic stability of the products strongly depend on the type of diol linkers. The highest stabilities are found for the AD-linked products, which are thermally stable up to around 400 °C and remain intact even after being soaked in water for 1 day. In contrast, the PD-linked product is easily hydrolyzed in water to give microporous silica. These results offer a new route toward a series of silica-based porous materials with unique structures and properties. PMID:23203900

  3. The ERβ ligand 5α-androstane, 3β,17β-diol (3β-diol) regulates hypothalamic oxytocin (Oxt) gene expression.

    PubMed

    Sharma, Dharmendra; Handa, Robert J; Uht, Rosalie M

    2012-05-01

    The endocrine component of the stress response is regulated by glucocorticoids and sex steroids. Testosterone down-regulates hypothalamic-pituitary-adrenal (HPA) axis activity; however, the mechanisms by which it does so are poorly understood. A candidate testosterone target is the oxytocin gene (Oxt), given that it too inhibits HPA activity. Within the paraventricular nucleus of the hypothalamus, oxytocinergic neurons involved in regulating the stress response do not express androgen receptors but do express estrogen receptor-β (ERβ), which binds the dihydrotestosterone metabolite 3β,17β-diol (3β-diol). Testosterone regulation of the HPA axis thus appears to involve the conversion to the ERβ-selective ligand 5α-androstane, 3β-diol. To study mechanisms by which 3β-diol could regulate Oxt expression, we used a hypothalamic neuronal cell line derived from embryonic mice that expresses Oxt constitutively and compared 3β-diol with estradiol (E2) effects. E2 and 3β-diol elicited a phasic response in Oxt mRNA levels. In the presence of either ligand, Oxt mRNA levels were increased for at least 60 min and returned to baseline by 2 h. ERβ occupancy preceded an increase in Oxt mRNA levels in the presence of 3β-diol but not E2. In tandem with ERβ occupancy, 3β-diol increased occupancy of the Oxt promoter by cAMP response element-binding protein and steroid receptor coactivator-1 at 30 min. At the same time, 3β-diol led to the increased acetylation of histone H4 but not H3. Taken together, the data suggest that in the presence of 3β-diol, ERβ associates with cAMP response element-binding protein and steroid receptor coactivator-1 to form a functional complex that drives Oxt gene expression. PMID:22434086

  4. The ERβ Ligand 5α-androstane, 3β,17β-diol (3β-diol) Regulates Hypothalamic Oxytocin (Oxt) Gene Expression

    PubMed Central

    Sharma, Dharmendra; Handa, Robert J.

    2012-01-01

    The endocrine component of the stress response is regulated by glucocorticoids and sex steroids. Testosterone down-regulates hypothalamic-pituitary-adrenal (HPA) axis activity; however, the mechanisms by which it does so are poorly understood. A candidate testosterone target is the oxytocin gene (Oxt), given that it too inhibits HPA activity. Within the paraventricular nucleus of the hypothalamus, oxytocinergic neurons involved in regulating the stress response do not express androgen receptors but do express estrogen receptor-β (ERβ), which binds the dihydrotestosterone metabolite 3β,17β-diol (3β-diol). Testosterone regulation of the HPA axis thus appears to involve the conversion to the ERβ-selective ligand 5α-androstane, 3β-diol. To study mechanisms by which 3β-diol could regulate Oxt expression, we used a hypothalamic neuronal cell line derived from embryonic mice that expresses Oxt constitutively and compared 3β-diol with estradiol (E2) effects. E2 and 3β-diol elicited a phasic response in Oxt mRNA levels. In the presence of either ligand, Oxt mRNA levels were increased for at least 60 min and returned to baseline by 2 h. ERβ occupancy preceded an increase in Oxt mRNA levels in the presence of 3β-diol but not E2. In tandem with ERβ occupancy, 3β-diol increased occupancy of the Oxt promoter by cAMP response element-binding protein and steroid receptor coactivator-1 at 30 min. At the same time, 3β-diol led to the increased acetylation of histone H4 but not H3. Taken together, the data suggest that in the presence of 3β-diol, ERβ associates with cAMP response element-binding protein and steroid receptor coactivator-1 to form a functional complex that drives Oxt gene expression. PMID:22434086

  5. Simple Epoxide Formation for the Organic Laboratory Using Oxone

    ERIC Educational Resources Information Center

    Broshears, Williams C.; Esteb, John J.; Richter, Jeremy; Wilson, Anne M.

    2004-01-01

    Epoxide chemistry is widely used in organic synthesis and regularly discussed in organic chemistry textbooks. An experiment to generate dimethyldioxirane in situ from acetone using Oxone is explained.

  6. The electron-impact promoted fragmentation of aurone epoxides.

    NASA Technical Reports Server (NTRS)

    Brady, B. A.; O'Sullivan, W. I.; Duffield, A. M.

    1972-01-01

    The mass spectra of six aurone epoxides have been rationalized with the aid of high resolution mass spectrometry and metastable ion evidence. These compounds fragment in a well defined manner and mechanisms are proposed for the formation of their characteristic ions. Some similarity was observed between the mass spectra of 6-methoxyaurone epoxide (II), 4-hydroxy-7-methoxy-3-phenylcoumarin (VII) and 7-methoxyflavonol (IX). The possibility that VII and IX are intermediates in the fragmentation of epoxide II is discussed. Thermal rearrangement of aurone epoxide II was shown to yield the corresponding flavonol IX and coumarin VII.

  7. Oral treatment of rodents with soluble epoxide hydrolase inhibitor 1-(1-propanoylpiperidin-4-yl)-3-[4-(trifluoromethoxy)phenyl]urea (TPPU): Resulting drug levels and modulation of oxylipin pattern.

    PubMed

    Ostermann, Annika I; Herbers, Jan; Willenberg, Ina; Chen, Rongjun; Hwang, Sung Hee; Greite, Robert; Morisseau, Christophe; Gueler, Faikah; Hammock, Bruce D; Schebb, Nils Helge

    2015-09-01

    Epoxides from polyunsaturated fatty acids (PUFAs) are potent lipid mediators. In vivo stabilization of these epoxides by blockade of the soluble epoxide hydrolase (sEH) leads to anti-inflammatory, analgesic and normotensive effects. Therefore, sEH inhibitors (sEHi) are a promising new class of drugs. Herein, we characterized pharmacokinetic (PK) and pharmacodynamic properties of a commercially available potent sEHi 1-(1-propanoylpiperidin-4-yl)-3-[4-(trifluoromethoxy)phenyl]urea (TPPU). Cell culture studies suggest its high absorption and metabolic stability. Following administration in drinking water to rats (0.2, 1, and 5mg TPPU/L with 0.2% PEG400), TPPU's blood concentration increased dose dependently within the treatment period to reach an almost steady state after 8 days. TPPU was found in all the tissues tested. The linoleic epoxide/diol ratios in most tissues were dose dependently increased, indicating significant sEH inhibition. Overall, administration of TPPU with the drinking water led to systemic distribution as well as high drug levels and thus makes chronic sEH inhibition studies possible. PMID:26117215

  8. Identification of metabolites from benzo[a]pyrene oxidation by ligninolytic enzymes of Polyporus sp. S133.

    PubMed

    Hadibarata, Tony; Kristanti, Risky Ayu

    2012-11-30

    The biodegradation of benzo[a]pyrene (BaP) by using Polyporus sp. S133, a white-rot fungus isolated from oil-contaminated soil was investigated. Approximately 73% of the initial concentration of BaP was degraded within 30 d of incubation. The isolation and characterization of 3 metabolites by thin layer chromatography, column chromatography, and UV-vis spectrophotometry in combination with gas chromatography-mass spectrometry, indicated that Polyporus sp. S133 transformed BaP to BaP-1,6-quinone. This quinone was further degraded in 2 ways. First, BaP-1,6-quinone was decarboxylated and oxidized to form coumarin, which was then hydroxylated to hydroxycoumarin, and finally to hydroxyphenyl acetic acid by addition of an epoxide group. Second, Polyporus sp. S133 converted BaP-1,6-quinone into a major product, 1-hydroxy-2-naphthoic acid. During degradation, free extracellular laccase was detected with reduced activity of lignin peroxidase, manganese-dependent peroxidase and 2,3-dioxygenase, suggesting that laccase and 1,2-dioxygenase might play an important role in the transformation of PAHs compounds. PMID:22835655

  9. Modulatory effects of catechin hydrate against genotoxicity, oxidative stress, inflammation and apoptosis induced by benzo(a)pyrene in mice.

    PubMed

    Shahid, Ayaz; Ali, Rashid; Ali, Nemat; Hasan, Syed Kazim; Bernwal, Preeti; Afzal, Shekh Mohammad; Vafa, Abul; Sultana, Sarwat

    2016-06-01

    Benzo(a)pyrene [B(a)P], a polycyclic aromatic hydrocarbon (PAH) is a strong mutagen and potent carcinogen. The aim of the present study was to investigate the efficacy of catechin hydrate against B(a)P induced genotoxicity, oxidative stress, inflammation, apoptosis and to explore its underlying molecular mechanisms in the lungs of Swiss albino mice. Administration of B(a)P (125 mg/kg b. wt., p. o.) increased the activities of toxicity markers such as LPO, LDH and B(a)P metabolizing enzymes [NADPH-cytochrome P450 reductase (CYPOR) and microsomal epoxide hydrolase (mEH)] with subsequent decrease in the activities of tissue anti-oxidant armory (SOD, CAT, GPx, GR, GST, QR and GSH). It also caused DNA damage and activation of apoptotic and inflammatory pathway by upregulation of TNF-α, IL-6, NF-kB, COX-2, p53, bax, caspase-3 and down regulating Bcl-2. However, pre-treatment with catechin at a dose of 20 and 40 mg/kg significantly decreased LDH, LPO, B(a)P metabolizing enzymes and increased anti-oxidant armory as well as regulated apoptosis and inflammation in lungs. Histological results also supported the protective effects of catechin. The findings of the present studies suggested that catechin as an effective natural product attenuates B(a)P induced lung toxicity. PMID:27020533

  10. The epoxidation of limonene over the TS-1 and Ti-SBA-15 catalysts.

    PubMed

    Wróblewska, Agnieszka

    2014-01-01

    Limonene belongs to a group of very important intermediates used in the production of fine chemicals. This monoterpene compound can be obtained from peels of oranges or lemon which are a (biomass) waste from the orange juice industry. Thus, limonene is a renewable, easy available and a relatively cheap compound. This work presents preliminary studies on the process of limonene epoxidation over zeolite type catalysts such as: TS-1 and Ti-SBA-15. In these studies methanol was used as a solvent and as an oxidizing agent a 60 wt % hydrogen peroxide solution was applied. The activity of each catalyst was investigated for four chosen temperatures (0 °C, 40 °C, 80 °C and 120 °C). The reaction time was changed from 0.5 to 24 h. For each catalyst the most beneficial conditions (the appropriate temperature and the reaction time) have been established. The obtained results were compared and the most active catalyst was chosen. These studies have also shown different possible ways of limonene transformation, not only in the direction of 1,2-epoxylimonene and its corresponding diol, but also in direction of carveol, carvone and perillyl alcohol-compounds with a lot of applications. The possible mechanisms of formation of the allylic oxidation products were proposed. PMID:25460313

  11. The Androgen Metabolite, 5α-Androstane-3β,17β-Diol (3β-Diol), Activates the Oxytocin Promoter Through an Estrogen Receptor-β Pathway

    PubMed Central

    Hiroi, Ryoko; Lacagnina, Anthony F.; Hinds, Laura R.; Carbone, David G.; Uht, Rosalie M.

    2013-01-01

    Testosterone has been shown to suppress the acute stress-induced activation of the hypothalamic-pituitary-adrenal axis; however, the mechanisms underlying this response remain unclear. The hypothalamic-pituitary-adrenal axis is regulated by a neuroendocrine subpopulation of medial parvocellular neurons in the paraventricular nucleus of the hypothalamus (PVN). These neurons are devoid of androgen receptors (ARs). Therefore, a possibility is that the PVN target neurons respond to a metabolite in the testosterone catabolic pathway via an AR-independent mechanism. The dihydrotestosterone metabolite, 5α-androstane-3β,17β-diol (3β-diol), binds and activates estrogen receptor-β (ER-β), the predominant ER in the PVN. In the PVN, ER-β is coexpressed with oxytocin (OT). Therefore, we tested the hypothesis that 3β-diol regulates OT expression through ER-β activation. Treatment of ovariectomized rats with estradiol benzoate or 3β-diol for 4 days increased OT mRNA selectively in the midcaudal, but not rostral PVN compared with vehicle-treated controls. 3β-Diol treatment also increased OT mRNA in the hypothalamic N38 cell line in vitro. The functional interactions between 3β-diol and ER-β with the human OT promoter were examined using an OT promoter-luciferase reporter construct (OT-luc). In a dose-dependent manner, 3β-diol treatment increased OT-luc activity when cells were cotransfected with ER-β, but not ER-α. The 3β-diol–induced OT-luc activity was reduced by deletion of the promoter region containing the composite hormone response element (cHRE). Point mutations of the cHRE also prevented OT-luc activation by 3β-diol. These results indicate that 3β-diol induces OT promoter activity via ER-β–cHRE interactions. PMID:23515287

  12. 40 CFR 721.2675 - Perfluoroalkyl epoxide (generic name).

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Perfluoroalkyl epoxide (generic name). 721.2675 Section 721.2675 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC... Substances § 721.2675 Perfluoroalkyl epoxide (generic name). (a) Chemical substances and significant new...

  13. 40 CFR 721.2675 - Perfluoroalkyl epoxide (generic name).

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Perfluoroalkyl epoxide (generic name). 721.2675 Section 721.2675 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC... Substances § 721.2675 Perfluoroalkyl epoxide (generic name). (a) Chemical substances and significant new...

  14. 40 CFR 721.2675 - Perfluoroalkyl epoxide (generic name).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Perfluoroalkyl epoxide (generic name). 721.2675 Section 721.2675 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC... Substances § 721.2675 Perfluoroalkyl epoxide (generic name). (a) Chemical substances and significant new...

  15. 40 CFR 721.2675 - Perfluoroalkyl epoxide (generic name).

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Perfluoroalkyl epoxide (generic name). 721.2675 Section 721.2675 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC... Substances § 721.2675 Perfluoroalkyl epoxide (generic name). (a) Chemical substances and significant new...

  16. 40 CFR 721.2675 - Perfluoroalkyl epoxide (generic name).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Perfluoroalkyl epoxide (generic name). 721.2675 Section 721.2675 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC... Substances § 721.2675 Perfluoroalkyl epoxide (generic name). (a) Chemical substances and significant new...

  17. Identification of Epoxide-Derived Metabolite(s) of Benzbromarone.

    PubMed

    Wang, Kai; Wang, Hui; Peng, Ying; Zheng, Jiang

    2016-04-01

    Benzbromarone (BBR) is a benzofuran derivative that has been quite useful for the treatment of gout; however, it was withdrawn from European markets in 2003 because of reported serious incidents of drug-induced liver injury. BBR-induced hepatotoxicity has been suggested to be associated with the formation of a quinone intermediate. The present study reported epoxide-derived intermediate(s) of BBR. An N-acetylcysteine (NAC) conjugate derived from epoxide metabolite(s) was detected in both microsomal incubations of BBR and urine samples of mice treated with BBR. The NAC conjugate was identified as 6-NAC BBR. Ketoconazole suppressed the bioactivation of BBR to the epoxide intermediate(s), and the CYP3A subfamily was the primary enzyme responsible for the formation of the epoxide(s). The present study provided new information on metabolic activation of BBR. PMID:26792818

  18. Epoxides--is there a human health problem?

    PubMed Central

    Manson, M M

    1980-01-01

    The purpose of this review is to consider whether epoxides represent a hazard to human health. Possible means of occupational and non-occupational exposure are discussed with reference to the production and uses of industrially important compounds and other epoxides, such as naturally occurring plant and fungal products. In addition to epoxides themselves, unsaturated compounds that may be metabolised in vivo to epoxides are included, since this appears to be a further important means of exposure. The toxicology, in particular carcinogenicity and mutagenicity, is discussed, along with a brief outline of the biochemistry such as metabolism, binding to cell constituents, and DNA repair mechanisms. The question of interactions between different epoxides in vivo is also raised. PMID:7004476

  19. Regiospecific Epoxidation of Carvone: A Discovery-Oriented Experiment for Understanding the Selectivity and Mechanism of Epoxidation Reactions

    ERIC Educational Resources Information Center

    Mak, Kendrew K. W.; Lai, Y. M.; Siu, Yuk-Hong

    2006-01-01

    This article describes a discovery-oriented experiment for demonstrating the selectivity of two epoxidation reactions. Peroxy acids and alkaline H[subscript 2]O[subscript 2] are two commonly used reagents for alkene epoxidation. The former react preferentially with electron-rich alkenes while the latter works better with alpha,beta-unsaturated…

  20. Determination of 3-Monochloropropane-1,2-diol and 2-Monochloropropane-1,3-diol (MCPD) Esters and Glycidyl Esters by Microwave Extraction in Different Foodstuffs.

    PubMed

    Marc, Corinne; Drouard-Pascarel, Valérie; Rétho, Cécile; Janvion, Patrice; Saltron, Frédéric

    2016-06-01

    This paper describes a method for the determination of 3-monochloropropane-1,2-diol and 2-monochloropropane-1,3-diol (MCPD) esters and glycidyl esters in various foodstuffs, which are isolated using microwave extraction. The next step is based on alkaline-catalyzed ester cleavage. The released glycidol is transformed into monobromopropanediol (MBPD). All compounds are derivatized in free diols (MCPD and MBPD) with phenylboronic acid and analyzed by gas chromatography-mass spectrometry (GC-MS). The method was validated for oils with a limit of quantitation (LOQ) of 0.1 mg/kg, for chips and crisps with a LOQ of 0.02 mg/kg, and for infant formula with a LOQ of 0.0025 mg/L. Recoveries of each sample were controlled by standard addition on extracts before derivatization. Quantitation was performed by the addition of isotopically labeled glycidyl and 3-monochloropropane-1,2-diol (3-MCPD) esters. PMID:27133957

  1. 40 CFR 721.2625 - Reaction product of alkane-diol and epichlorohydrin.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...) TOXIC SUBSTANCES CONTROL ACT SIGNIFICANT NEW USES OF CHEMICAL SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.2625 Reaction product of alkane-diol and epichlorohydrin. (a) Chemical... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Reaction product of alkane-diol...

  2. 40 CFR 721.2625 - Reaction product of alkane-diol and epichlorohydrin.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...) TOXIC SUBSTANCES CONTROL ACT SIGNIFICANT NEW USES OF CHEMICAL SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.2625 Reaction product of alkane-diol and epichlorohydrin. (a) Chemical... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Reaction product of alkane-diol...

  3. 40 CFR 721.2625 - Reaction product of alkane-diol and epichlorohydrin.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...) TOXIC SUBSTANCES CONTROL ACT SIGNIFICANT NEW USES OF CHEMICAL SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.2625 Reaction product of alkane-diol and epichlorohydrin. (a) Chemical... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Reaction product of alkane-diol...

  4. 40 CFR 721.2625 - Reaction product of alkane-diol and epichlorohydrin.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...) TOXIC SUBSTANCES CONTROL ACT SIGNIFICANT NEW USES OF CHEMICAL SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.2625 Reaction product of alkane-diol and epichlorohydrin. (a) Chemical... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Reaction product of alkane-diol...

  5. 40 CFR 721.2625 - Reaction product of alkane-diol and epichlorohydrin.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...) TOXIC SUBSTANCES CONTROL ACT SIGNIFICANT NEW USES OF CHEMICAL SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.2625 Reaction product of alkane-diol and epichlorohydrin. (a) Chemical... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Reaction product of alkane-diol...

  6. Preliminary physiologically based pharmacokinetic models for benzo[a]pyrene and dibenzo[def,p]chrysene in rodents

    SciTech Connect

    Crowell, Susan Ritger; Amin, Shantu G.; Anderson, Kim A.; Krishnegowda, Gowdahalli; Sharma, Arun K.; Soelberg, Jolen J.; Williams, David E.; Corley, Richard A.

    2011-12-15

    Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental contaminants generated as byproducts of natural and anthropogenic combustion processes. Despite significant public health concern, physiologically based pharmacokinetic (PBPK) modeling efforts for PAHs have so far been limited to naphthalene, plus simpler PK models for pyrene, nitropyrene, and benzo[a]pyrene (B[a]P). The dearth of published models is due in part to the high lipophilicity, low volatility, and myriad metabolic pathways for PAHs, all of which present analytical and experimental challenges. Our research efforts have focused upon experimental approaches and initial development of PBPK models for the prototypic PAH, B[a]P, and the more potent, albeit less studied transplacental carcinogen, dibenzo[def,p]chrysene (DBC). For both compounds, model compartments included arterial and venous blood, flow limited lung, liver, richly perfused and poorly perfused tissues, diffusion limited fat, and a two compartment theoretical gut (for oral exposures). Hepatic and pulmonary metabolism was described for both compounds, as were fractional binding in blood and fecal clearance. Partition coefficients for parent PAH along with their diol and tetraol metabolites were estimated using published algorithms and verified experimentally for the hydroxylated metabolites. The preliminary PBPK models were able to describe many, but not all, of the available data sets, comprising multiple routes of exposure (oral, intravenous) and nominal doses spanning several orders of magnitude. Supported by Award Number P42 ES016465 from the National Institute of Environmental Health Sciences. -- Highlights: Black-Right-Pointing-Pointer We present PBPK models for benzo[a]pyrene (B[a]P) and dibenzo[def,p]chrysene (DBC). Black-Right-Pointing-Pointer B[a]P model accurately predicts data from multiple sources over a wide dose range. Black-Right-Pointing-Pointer DBC model was based on the B[a]P model as less chemical specific

  7. A Protocol for NMR Analysis of the Enantiomeric Excess of Chiral Diols Using an Achiral Diboronic Acid Template.

    PubMed

    Tickell, David A; Lampard, Emma V; Lowe, John P; James, Tony D; Bull, Steven D

    2016-08-01

    A practically simple derivatization protocol for determining the enantiopurity of chiral diols by (1)H NMR spectroscopic analysis is described. Diols were treated with 0.5 equiv of 1,3-phenyldiboronic acid to afford mixtures of diastereomeric boronate esters whose homochiral/heterochiral ratios are an accurate reflection of the diol's enantiopurity. PMID:27385049

  8. IRIS Toxicological Review of Benzo[a]pyrene (External Review Draft)

    EPA Science Inventory

    The IRIS Toxicological Review of Benzo[a]pyrene was released for external peer review in September 2014. The EPA’s Science Advisory Board’s (SAB) Chemical Assessment Advisory Committee (CAAC) conducted a peer review of the scientific basis supporting the benzo[a]pyrene assessmen...

  9. Bacterial Expression and HTS Assessment of Soluble Epoxide Hydrolase Phosphatase.

    PubMed

    Klingler, Franca-Maria; Wolf, Markus; Wittmann, Sandra; Gribbon, Philip; Proschak, Ewgenij

    2016-08-01

    Soluble epoxide hydrolase (sEH) is a bifunctional enzyme that possesses an epoxide hydrolase and lipid phosphatase activity (sEH-P) at two distinct catalytic domains. While the physiological role of the epoxide hydrolase domain is well understood, the consequences of the phosphatase activity remain unclear. Herein we describe the bacterial expression of the recombinant N-terminal domain of sEH-P and the development of a high-throughput screening protocol using a sensitive and commercially available substrate fluorescein diphosphate. The usability of the assay system was demonstrated and novel inhibitors of sEH-P were identified. PMID:27009944

  10. Purification and specificity of a human microsomal epoxide hydratase

    PubMed Central

    Oesch, Franz

    1974-01-01

    Epoxide hydratase was solubilized from human liver microsomal fractions and purified to an extent where the specific activity was 40-fold greater than that of the liver homogenate. Combination of homogenate and purified preparation showed that the increase in activity was not due to the removal of an inhibitor. Monosubstituted oxiranes with a lipophilic substituent larger than an ethyl group (isopropyl, t-butyl, n-hexyl, phenyl) readily interacted as substrates or inhibitors with this purified human epoxide hydratase, whereas those with a small substituent (methyl, ethyl, vinyl) were inactive, probably reflecting greater affinity of the former epoxides owing to lipophilic binding sites near the active site of the enzyme. In a series of oxiranes having a lipophilic substituent of sufficient size (styrene oxides), monosubstituted as well as 1,1- and cis-1,2-disubstituted oxiranes readily served as substrates or inhibitors of the enzyme, but not the trans-1,2-disubstituted, tri- or tetra-substituted oxiranes. trans-Substitution at the oxirane ring apparently prevents access of the oxirane ring to the active site by steric hindrance. Epoxide hydratase was also solubilized from microsomal fractions of rat and guinea-pig liver and purified by the same procedure. Structural requirements for effective interaction of substrates, inhibitors and activators were qualitatively identical for epoxide hydratase from the three sources. However, several quantitative differences were observed. Thus human hepatic epoxide hydratase seems to be very similar to, although not identical with, the enzyme from guinea pig or rat. Studies with epoxide hydratase from the latter two species therefore appear to be significant with respect to man. In addition, knowledge of structural requirements for epoxides to serve as substrates for human epoxide hydratase may prove useful for drug design. Compounds which need aromatic or olefinic moieties for their desired effect would not be expected to lead

  11. Carcinogenicity and mechanistic insights on the behavior of epoxides and epoxide-forming chemicals.

    PubMed

    Melnick, Ronald L

    2002-12-01

    Many epoxides and their precursors are high production volume chemicals that have major uses in the polymer industry and as intermediates in the manufacture of other chemicals. Several of these chemicals were demonstrated to be carcinogenic in laboratory animal studies conducted by the Ramazzini Foundation (e.g., vinyl chloride, acrylonitrile, styrene, styrene oxide, and benzene) and by the National Toxicology Program (e.g., ethylene oxide, 1,3-butadiene, isoprene, chloroprene, acrylonitrile, glycidol, and benzene). The most common sites of tumor induction were lung, liver, harderian gland, and circulatory system in mice; Zymbal's gland and brain in rats; and mammary gland and forestomach in both species. Differences in cancer outcome among studies of epoxide chemicals may be related to differences in study design (e.g., dose, duration, and route of exposure; observation period; animal strains), as well as biological factors affecting target organ dosimetry of the DNA-reactive epoxide (toxicokinetics) and tissue response (toxicodynamics). N7-Alkylguanine, N1-alkyladenine, and cyclic etheno adducts, as well as K-ras and p53 mutations, have been detected in animals and/or workers exposed to several of these chemicals. The classifications of these chemical carcinogens by IARC and NTP are based on animal and human data and results of mechanistic studies. Reducing occupational and environmental exposures to these chemicals will certainly reduce human cancer risks. PMID:12562636

  12. Correlation between production of benzo(A)pyrene metabolites and BPDE I-DG adduct levels in human epithelial cells in vitro pretreated with cytochrome P450 inhibitors or inducer

    SciTech Connect

    Lehman, T.A.; Milo, G.E.

    1987-05-01

    Human epidermal keratinocytes were established from neonatal foreskins. Cultures were pretreated for 24 hr with either butylated hydroxyanisole (BHA), methyl butylated hydroxyanisole (MeBHA) or 7,8 benzoflavone (7,8BF). For metabolite detection studies, cultures were treated with radiolabeled benzo(a)pyrene (BP) for 24 hr. Ethyl acetate soluble metabolites were extracted for HPLC analysis. BHA and 7,8BF pretreatment both significantly decreased intracellular production of 7,8 diol BP compared to cultures treated only with radiolabeled BP. MeBHA pretreatment greatly increased intracellular 7,8 diol BP formation compared to BP treated controls. For DNA adduct analysis, cultures were pretreated as described above, and then treated for 24 hr with non-radiolabeled BP. Cellular DNA was isolated and /sup 32/P-postlabeled for adduct analysis. Cultures pretreated with either BHA or 7,8BF formed significantly fewer BPDE I-dG adducts than nonpretreated cultures, while cultures pretreated with MeBHa formed more BPDE I-dG adducts. Thus, BHA and 7,8BF act similarly in reducing BP activation and adduct formation while MeBHa, a structural analog of BHA, increases BP activation and adduct formation in human keratinocyte cultures in vitro.

  13. Two-step biocatalytic route to biobased functional polyesters from omega-carboxy fatty acids and diols.

    PubMed

    Yang, Yixin; Lu, Wenhua; Zhang, Xiaoyan; Xie, Wenchun; Cai, Minmin; Gross, Richard A

    2010-01-11

    Biobased omega-carboxy fatty acid monomers 1,18-cis-9-octadecenedioic, 1,22-cis-9-docosenedioic, and 1,18-cis-9,10-epoxy-octadecanedioic acids were synthesized in high conversion yields from oleic, erucic and epoxy stearic acids by whole-cell biotransformations catalyzed by C. tropicalis ATCC20962. Maximum volumetric yields in shake-flasks were 17.3, 14.2, and 19.1 g/L after 48 h conversion for oleic acid and 72 h conversions for erucic and epoxy stearic acids, respectively. Studies in fermentor with better control of pH and glucose feeding revealed that conversion of oleic acid to 1,18-cis-9-octadecenedioic acid by C. tropicalis ATCC20962 occurred with productivities up to 0.5 g/L/h. The conversion of omega-carboxy fatty acid monomers to polyesters was then studied using immobilized Candida antarctica Lipase B (N435) as catalyst. Polycondensations with diols were performed in bulk as well as in diphenyl ether. The retension of functionality from fatty acid, to omega-carboxy fatty acid monomer and to corresponding polyesters resulted in polymers with with unsaturated and epoxidized repeat units and M(w) values ranging from 25000 to 57000 g/mol. These functional groups along chains disrupted crystallization giving materials that are low melting (23-40 degrees C). In contrast, saturated polyesters prepared from 1,18-octadecanedioic acid and 1,8-octanediol have correspondingly higher melting transitions (88 degrees C). TGA results indicated that all synthesized polyesters showed high thermal stabilities. Thus, the preparation of functional monomers from C. tropicalis omega-oxidation of fatty acids provides a wide range of new monomer building blocks to construct functional polymers. PMID:20000460

  14. Orally Bioavailable Potent Soluble Epoxide Hydrolase Inhibitors

    PubMed Central

    Hwang, Sung Hee; Tsai, Hsing-Ju; Liu, Jun-Yan; Morisseau, Christophe; Hammock, Bruce D.

    2008-01-01

    A series of N,N′-disubstituted ureas having a conformationally restricted cis- or trans-1,4-cyclohexane α to the urea were prepared and tested as soluble epoxide hydrolase (sEH) inhibitors. This series of compounds showed low nanomolar to picomolar activities against recombinant human sEH. Both isomers showed similar potencies, but the trans isomers were more metabolically stable in human hepatic microsomes. Furthermore, these new potent inhibitors show a greater metabolic stability in vivo than previously described sEH inhibitors. We demonstrated that trans-4-[4-(3-adamantan-1-ylureido)cyclohexyloxy]benzoic acid 13g (t-AUCB, IC50 = 1.3 ± 0.05 nM) had excellent oral bioavailability (98%, n = 2) and blood area under the curve in dogs and was effective in vivo to treat hypotension in lipopolysaccharide challenged murine models. PMID:17616115

  15. Redesign of coenzyme B(12) dependent diol dehydratase to be resistant to the mechanism-based inactivation by glycerol and act on longer chain 1,2-diols.

    PubMed

    Yamanishi, Mamoru; Kinoshita, Koichiro; Fukuoka, Masaki; Saito, Takuya; Tanokuchi, Aya; Ikeda, Yuuki; Obayashi, Hirokazu; Mori, Koichi; Shibata, Naoki; Tobimatsu, Takamasa; Toraya, Tetsuo

    2012-03-01

    Coenzyme B(12) dependent diol dehydratase undergoes mechanism-based inactivation by glycerol, accompanying the irreversible cleavage of the coenzyme Co-C bond. Bachovchin et al. [Biochemistry16, 1082-1092 (1977)] reported that glycerol bound in the G(S) conformation, in which the pro-S-CH(2) OH group is oriented to the hydrogen-abstracting site, primarily contributes to the inactivation reaction. To understand the mechanism of inactivation by glycerol, we analyzed the X-ray structure of diol dehydratase complexed with cyanocobalamin and glycerol. Glycerol is bound to the active site preferentially in the same conformation as that of (S)-1,2-propanediol, i.e. in the G(S) conformation, with its 3-OH group hydrogen bonded to Serα301, but not to nearby Glnα336. k(inact) of the Sα301A, Qα336A and Sα301A/Qα336A mutants with glycerol was much smaller than that of the wild-type enzyme. k(cat) /k(inact) showed that the Sα301A and Qα336A mutants are substantially more resistant to glycerol inactivation than the wild-type enzyme, suggesting that Serα301 and Glnα336 are directly or indirectly involved in the inactivation. The degree of preference for (S)-1,2-propanediol decreased on these mutations. The substrate activities towards longer chain 1,2-diols significantly increased on the Sα301A/Qα336A double mutation, probably because these amino acid substitutions yield more space for accommodating a longer alkyl group on C3 of 1,2-diols. Database Structural data are available in the Protein Data Bank under the accession number 3AUJ. Structured digital abstract • Diol dehydrase gamma subunit, Diol dehydrase beta subunit and Diol dehydrase alpha subunit physically interact by X-ray crystallography (View interaction). PMID:22221669

  16. Hydrogen transfer in catalysis by adenosylcobalamin-dependent diol dehydratase.

    PubMed

    Moore, K W; Bachovchin, W W; Gunter, J B; Richards, J H

    1979-06-26

    Studies [bachovchin, W. W., et al. (1978) Biochemistry 17, 2218] of the mechanism of inactivation of adenosylcobalamin-dependent diol dehydratase have led to the development of a general method to describe the kinetics of a reaction pathway containing a reservoir of mobile hydrogen. Analysis by this method of catalytic rate measurements for mixtures of 1,2-propanediol and 1,1-dideuterio-1,2-propanediol supports a mechanism involving an intermediate with three equivalent hydrogens, in which hydrogen transfer from this intermediate to product is the major rate-contributing step. Other results using tritium as a trace label [essenberg, M. K., et al. (1971) J. Am. Chem. Soc. 93, 1242] are considered in light of these deuterium isotope studies. PMID:383139

  17. Molecular Epoxidation Reactions Catalyzed by Rhenium, Molybdenum, and Iron Complexes.

    PubMed

    Kück, Jens W; Reich, Robert M; Kühn, Fritz E

    2016-02-01

    Epoxidations are of high relevance in many organic syntheses, both in industry and academia. In this personal account, the development of rhenium, molybdenum, and iron complexes in molecular epoxidation catalysis is presented. Methyltrioxorhenium (MTO) is the benchmark catalyst for these reactions, with a thoroughly investigated mechanism and reactivity profile. More recently, highly active molecular molybdenum and iron catalysts have emerged, challenging the extraordinary role of MTO in epoxidation catalysis with high turnover frequencies (TOFs). This development is highlighted in its use of cheaper, more readily available metals, and the challenges of using base metals in catalysis are discussed. These results show the promise that relatively cheap and abundant metals, such as molybdenum and iron, hold for the future of epoxidation catalysis. PMID:26776087

  18. Investigation of copper(II) tetrafluoroborate catalysed epoxide opening

    PubMed Central

    Capes, Amy S.; Crossman, Arthur T.; Webster, Lauren A.; Ferguson, Michael A.J.; Gilbert, Ian H.

    2011-01-01

    We report the extension of the copper(II) tetrafluoroborate catalysed opening of epoxides with alcohols to include a wider variety of alcohols, a range of solvents and a method to purify the products from the reaction. PMID:22505782

  19. Regioselective Acylation of Diols and Triols: The Cyanide Effect.

    PubMed

    Peng, Peng; Linseis, Michael; Winter, Rainer F; Schmidt, Richard R

    2016-05-11

    Central topics of carbohydrate chemistry embrace structural modifications of carbohydrates and oligosaccharide synthesis. Both require regioselectively protected building blocks that are mainly available via indirect multistep procedures. Hence, direct protection methods targeting a specific hydroxy group are demanded. Dual hydrogen bonding will eventually differentiate between differently positioned hydroxy groups. As cyanide is capable of various kinds of hydrogen bonding and as it is a quite strong sterically nondemanding base, regioselective O-acylations should be possible at low temperatures even at sterically congested positions, thus permitting formation and also isolation of the kinetic product. Indeed, 1,2-cis-diols, having an equatorial and an axial hydroxy group, benzoyl cyanide or acetyl cyanide as an acylating agent, and DMAP as a catalyst yield at -78 °C the thermodynamically unfavorable axial O-acylation product; acyl migration is not observed under these conditions. This phenomenon was substantiated with 3,4-O-unproteced galacto- and fucopyranosides and 2,3-O-unprotected mannopyranosides. Even for 3,4,6-O-unprotected galactopyranosides as triols, axial 4-O-acylation is appreciably faster than O-acylation of the primary 6-hydroxy group. The importance of hydrogen bonding for this unusual regioselectivity could be confirmed by NMR studies and DFT calculations, which indicate favorable hydrogen bonding of cyanide to the most acidic axial hydroxy group supported by hydrogen bonding of the equatorial hydroxy group to the axial oxygen. Thus, the "cyanide effect" is due to dual hydrogen bonding of the axial hydroxy group which enhances the nucleophilicity of the respective oxygen atom, permitting an even faster reaction for diols than for mono-ols. In contrast, fluoride as a counterion favors dual hydrogen bonding to both hydroxy groups leading to equatorial O-acylation. PMID:27104625

  20. Long-chain Diols as a Lacustrine Paleothermometer: Calibration, Caveats, and Future Possibilities

    NASA Astrophysics Data System (ADS)

    Phelps, S. R.; Russell, J. M.; Loomis, S. E.

    2013-12-01

    The fractional abundances of long-chain alkyl 1,13-, 1,14-, and 1,15-diols and the long-chain diol index (LDI) are a novel and promising tool for marine paleotemperature reconstructions. However, little is known about the precise organismal source of these compounds or the efficacy of this paleotemperature proxy in lacustrine environments. Here we analyzed the distribution of long-chain diols in surface-sediment samples from 38 East African lakes and compare them to climatic and limnological parameters, including mean annual air temperature (MAAT), lake water conductivity, pH, nutrient content, and morphometry. Fractional abundances of C32 1,15-diols showed the strongest correlation with MAAT across the entire dataset. Strong correlations were also found between individual diol fractional abundances and pH and phosphorus, but correlation between the LDI and temperature was low (r2 = 0.193, p = 0.012). We used stepwise forward selection (SFS) to develop a multivariate linear regression between the fractional abundances of a combination of long-chain diols and MAAT (r2 = 0.8, p < 0.001). Application of the LDI as well as this new temperature calibration to a sediment core from Lake Tanganyika indicate a cooling of 4°C from LGM to present, suggesting that long-chain diols may not provide accurate temperature reconstructions in large, warm, tropical lakes. However, by splitting the dataset into 'cold' and 'warm' lakes and developing SFS regressions for these lake subsets, we found a strong linear correlation between diol relative abundances and temperature in the 'cold' lakes subset, suggesting diols may be a valuable temperature proxy in cold, high elevation tropical lakes.

  1. Benzo(a)pyrene in Brazilian vegetable oils.

    PubMed

    Pupin, A M; Toledo, M C

    1996-01-01

    Samples of vegetable oils on the Brazilian market including rape seed, corn, soybean, sunflower, rice, palm and garlic were analysed for benzo(a)pyrene (B(a)P). The analytical method involved liquid-liquid extraction, clean-up on silica gel column and determination by high performance liquid chromatography using fluorescence detection. The limit of detection was 0.5 microgram/kg. Benzo(a)pyrene was detected in almost all samples, at levels up to 58.9 micrograms/kg. The mean levels of B(a)P in rice, sunflower, soybean, corn and palm oils were 1.8, 0.2, 2.2, 10.8 and 2.1 micrograms/kg respectively. No B(a)P was detected in garlic and rape seed oils. The data indicate that the levels of B(a)P found in Brazilian corn oils are relatively higher than those published in the literature for European corn oils. PMID:8871121

  2. Stereochemical features of the hydrolysis of 9,10-epoxystearic acid catalysed by plant and mammalian epoxide hydrolases.

    PubMed Central

    Summerer, Stephan; Hanano, Abdulsamie; Utsumi, Shigeru; Arand, Michael; Schuber, Francis; Blée, Elizabeth

    2002-01-01

    cis-9,10-epoxystearic acid was used as a tool to probe the active sites of epoxide hydrolases (EHs) of mammalian and plant origin. We have compared the stereochemical features of the hydrolysis of this substrate catalysed by soluble and membrane-bound rat liver EHs, by soluble EH (purified to apparent homogeneity) obtained from maize seedlings or celeriac roots, and by recombinant soybean EH expressed in yeast. Plant EHs were found to differ in their enantioselectivity, i.e. their ability to discriminate between the two enantiomers of 9,10-epoxystearic acid. For example, while the maize enzyme hydrated both enantiomers at the same rate, the EH from soybean exhibited very high enantioselectivity in favour of 9R,10S-epoxystearic acid. This latter enzyme also exhibited a strict stereoselectivity, i.e. it hydrolysed the racemic substrate with a very high enantioconvergence, yielding a single chiral diol product, threo-9R,10R-dihydroxystearic acid. Soybean EH shared these distinctive stereochemical features with the membrane-bound rat liver EH. The stereochemical outcome of these enzymes probably results from a stereoselective attack by the nucleophilic residue on the oxirane ring carbon having the (S)-configuration, leading to the presumed (in plant EH) covalent acyl-enzyme intermediate. In sharp contrast, the reactions catalysed by cytosolic rat liver EH exhibited a complete absence of enantioselectivity and enantioconvergence; this latter effect might be ascribed to a regioselective formation of the acyl-enzyme intermediate involving C-10 of 9,10-epoxystearic acid, independent of its configuration. Thus, compared with soybean EH, the active site of rat liver soluble EH displays a very distinct means of anchoring the oxirane ring of the fatty acid epoxides, and therefore appears to be a poor model for mapping the catalytic domain of plant EHs. PMID:12020347

  3. Stereochemical features of the hydrolysis of 9,10-epoxystearic acid catalysed by plant and mammalian epoxide hydrolases.

    PubMed

    Summerer, Stephan; Hanano, Abdulsamie; Utsumi, Shigeru; Arand, Michael; Schuber, Francis; Blée, Elizabeth

    2002-09-01

    cis-9,10-epoxystearic acid was used as a tool to probe the active sites of epoxide hydrolases (EHs) of mammalian and plant origin. We have compared the stereochemical features of the hydrolysis of this substrate catalysed by soluble and membrane-bound rat liver EHs, by soluble EH (purified to apparent homogeneity) obtained from maize seedlings or celeriac roots, and by recombinant soybean EH expressed in yeast. Plant EHs were found to differ in their enantioselectivity, i.e. their ability to discriminate between the two enantiomers of 9,10-epoxystearic acid. For example, while the maize enzyme hydrated both enantiomers at the same rate, the EH from soybean exhibited very high enantioselectivity in favour of 9R,10S-epoxystearic acid. This latter enzyme also exhibited a strict stereoselectivity, i.e. it hydrolysed the racemic substrate with a very high enantioconvergence, yielding a single chiral diol product, threo-9R,10R-dihydroxystearic acid. Soybean EH shared these distinctive stereochemical features with the membrane-bound rat liver EH. The stereochemical outcome of these enzymes probably results from a stereoselective attack by the nucleophilic residue on the oxirane ring carbon having the (S)-configuration, leading to the presumed (in plant EH) covalent acyl-enzyme intermediate. In sharp contrast, the reactions catalysed by cytosolic rat liver EH exhibited a complete absence of enantioselectivity and enantioconvergence; this latter effect might be ascribed to a regioselective formation of the acyl-enzyme intermediate involving C-10 of 9,10-epoxystearic acid, independent of its configuration. Thus, compared with soybean EH, the active site of rat liver soluble EH displays a very distinct means of anchoring the oxirane ring of the fatty acid epoxides, and therefore appears to be a poor model for mapping the catalytic domain of plant EHs. PMID:12020347

  4. Ovarian expressed microsomal epoxide hydrolase: role in detoxification of 4-vinylcyclohexene diepoxide and regulation by phosphatidylinositol-3 kinase signaling.

    PubMed

    Bhattacharya, Poulomi; Sen, Nivedita; Hoyer, Patricia B; Keating, Aileen F

    2012-01-01

    4-vinylcyclohexene diepoxide (VCD) is a metabolite of 4-vinylcyclohexene (VCH) which has the potential to be formed in the ovary through CYP2E1 activity. VCD specifically destroys primordial and small primary follicles in the rodent ovary. Mouse ovaries exposed to VCD demonstrate increased mRNA and protein expression of microsomal epoxide hydrolase (mEH), and an inactive tetrol metabolite (4-(1,2-dihydroxy)ethyl-1,2-dihydroxycyclohexane) can be formed in mouse ovarian follicles, potentially through detoxification action of mEH. In contrast, mEH can bioactivate another ovotoxic chemical, 7,12-dimethylbenz[a]anthracene (DMBA) to a more toxic compound, DMBA-3,4-diol-1,2-epoxide. Thus, the present study evaluated a functional role for mEH during detoxification of VCD. Additionally, because inhibition of the phosphatidyinositol-3 kinase (PI3K) signaling pathway in a previous study protected primordial follicles from VCD-induced destruction, but accelerated DMBA-induced ovotoxicity, a role for PI3K in ovarian mEH regulation was evaluated. Using a post-natal day (PND) 4 Fischer 344 rat whole ovary culture system inhibition of mEH using cyclohexene oxide during VCD exposure resulted in a greater (P<0.05) loss of primordial and small primary follicles relative to VCD-treated ovaries. Also, relative to controls, meh mRNA was increased (P<0.05) on day 4 of VCD (30 μM) exposure, followed by increased (P<0.05) mEH protein after 6 days. Furthermore, inhibition of PI3K signaling increased mEH mRNA and protein expression. Thus, these results support a functional role for mEH in the rat ovary, and demonstrate the involvement of PI3K signaling in regulation of ovarian xenobiotic metabolism by mEH. PMID:22061827

  5. Ovarian expressed microsomal epoxide hydrolase: role in detoxification of 4-vinylcyclohexene diepoxide and regulation by phosphatidylinositol-3 kinase signaling

    PubMed Central

    Bhattacharya, Poulomi; Sen, Nivedita; Hoyer, Patricia B.; Keating, Aileen F.

    2011-01-01

    4-vinylcyclohexene diepoxide (VCD) is a metabolite of 4-vinylcyclohexene (VCH) which has the potential to be formed in the ovary through CYP2E1 activity. VCD specifically destroys primordial and small primary follicles in the rodent ovary. Mouse ovaries exposed to VCD demonstrate increased mRNA and protein expression of microsomal epoxide hydrolase (mEH), and an inactive tetrol metabolite (4-(1,2-dihydroxy)ethyl-1,2-dihydroxycyclohexane) can be formed in mouse ovarian follicles, potentially through detoxification action of mEH. In contrast, mEH can bioactivate another ovotoxic chemical, 7,12-dimethylbenz[a]anthracene (DMBA) to a more toxic compound, DMBA-3,4-diol-1,2-epoxide. Thus, the present study evaluated a functional role for mEH during detoxification of VCD. Additionally, because inhibition of the phosphatidyinositol-3 kinase (PI3K) signaling pathway in a previous study protected primordial follicles from VCD-induced destruction, but accelerated DMBA-induced ovotoxicity, a role for PI3K in ovarian mEH regulation was evaluated. Using a post-natal day (PND) 4 Fischer 344 rat whole ovary culture system inhibition of mEH using cyclohexene oxide during VCD exposure resulted in a greater (P < 0.05) loss of primordial and small primary follicles relative to VCD-treated ovaries. Also, relative to controls, meh mRNA was increased (P < 0.05) on day 4 of VCD (30 μM) exposure, followed by increased (P < 0.05) mEH protein after 6 days. Furthermore, inhibition of PI3K signaling increased mEH mRNA and protein expression. Thus, these results support a functional role for mEH in the rat ovary, and demonstrate the involvement of PI3K signaling in regulation of ovarian xenobiotic metabolism by mEH. PMID:22061827

  6. Inflammatory mediators accelerate metabolism of benzo[a]pyrene in rat alveolar type II cells: the role of enhanced cytochrome P450 1B1 expression.

    PubMed

    Smerdová, Lenka; Neča, Jiří; Svobodová, Jana; Topinka, Jan; Schmuczerová, Jana; Kozubík, Alois; Machala, Miroslav; Vondráček, Jan

    2013-12-01

    Long-term deregulated inflammation represents one of the key factors contributing to lung cancer etiology. Previously, we have observed that tumor necrosis factor-α (TNF-α), a major pro-inflammatory cytokine, enhances genotoxicity of benzo[a]pyrene (B[a]P), a highly carcinogenic polycyclic aromatic hydrocarbon, in rat lung epithelial RLE-6TN cells, a model of alveolar type II cells. Therefore, we analyzed B[a]P metabolism in RLE-6TN cells under inflammatory conditions, simulated using either recombinant TNF-α, or a mixture of inflammatory mediators derived from activated alveolar macrophage cell line. Inflammatory conditions significantly accelerated BaP metabolism, as evidenced by decreased levels of both parent B[a]P and its metabolites. TNF-α altered production of the metabolites associated with dihydrodiol-epoxide and radical cation pathways of B[a]P metabolism, especially B[a]P-dihydrodiols, and B[a]P-diones. We then evaluated the role of cytochrome P450 1B1 (CYP1B1), which is strongly up-regulated in cells treated with B[a]P under inflammatory conditions, in the observed effects. The siRNA-mediated CYP1B1 knock-down increased levels of B[a]P and reduced formation of stable DNA adducts, thus confirming the essential role of CYP1B1 in B[a]P metabolism under inflammatory conditions. TNF-α also reduced expression of aldo-keto reductase 1C14, which may compete with CYP1B1 for B[a]P-7,8-dihydrodiol and divert it from the formation of ultimate B[a]P dihydrodiol epoxide. Together, the present data suggests that the CYP1B1-catalyzed metabolism of polycyclic aromatic hydrocarbons might contribute to their enhanced bioactivation and genotoxic effects under inflammatory conditions. PMID:24025706

  7. Effects of inhaled ammonium sulfate on benzo(a)pyrene carcinogenesis. [Hamster

    SciTech Connect

    Godleski, J.J.; Melnicoff, M.J.; Sadri, S.; Garbeil, P.

    1984-01-01

    The effect of inhaled ammonium sulfate on benzo(a)pyrene carcinogenesis in the lungs of Syrian golden hamsters was studied. Exposure to ammonium sulfate at an airborne concentration 20 times average United States ambient levels resulted in a significant depression of benzo(a)pyrene carcinogenesis in the first 6 mo of the study. However, at 2 yr, the termination of the study, there were no differences in cancer incidence between groups receiving benzo(a)pyrene and benzo(a)pyrene plus ammonium sulfate. In addition, at the concentration studied, inhaled ammonium sulfate did not significantly increase the incidence or severity of pneumonitis or pulmonary fibrosis in the hamster. However, this inhalation did increase the incidence of emphysema but not the severity. The decreased incidence of cancer during the first 6 mo of this study in animals receiving both benzo(a)pyrene and ammonium sulfate suggests that interaction between sulfate and benzo(a)pyrene does occur, but is insufficient to afford long-term protection against the development of cancer. No enhancement of carcinogenesis by benzo(a)pyrene occurs in the presence of inhaled sulfate. 31 references, 5 tables, 2 figures.

  8. Opposite Effects of Gene Deficiency and Pharmacological Inhibition of Soluble Epoxide Hydrolase on Cardiac Fibrosis

    PubMed Central

    Zhang, Xu; Hammock, Bruce D.; Ai, Ding; Zhu, Yi

    2014-01-01

    Arachidonic acid-derived epoxyeicosatrienoic acids (EETs) are important regulators of cardiac remodeling; manipulation of their levels is a potentially useful pharmacological strategy. EETs are hydrolyzed by soluble epoxide hydrolase (sEH) to form the corresponding diols, thus altering and reducing the activity of these oxylipins. To better understand the phenotypic impact of sEH disruption, we compared the effect of EPHX2 gene knockout (EPHX2−/−) and sEH inhibition in mouse models. Measurement of plasma oxylipin profiles confirmed that the ratio of EETs/DHETs was increased in EPHX2−/− and sEH-inhibited mice. However, plasma concentrations of 9, 11, 15, 19-HETE were elevated in EPHX2−/− but not sEH-inhibited mice. Next, we investigated the role of this difference in cardiac dysfunction induced by Angiotensin II (AngII). Both EPHX2 gene deletion and inhibition protected against AngII-induced cardiac hypertrophy. Interestingly, cardiac dysfunction was attenuated by sEH inhibition rather than gene deletion. Histochemical staining revealed that compared with pharmacological inhibition, EPHX2 deletion aggravated AngII-induced myocardial fibrosis; the mRNA levels of fibrotic-related genes were increased. Furthermore, cardiac inflammatory response was greater in EPHX2−/− than sEH-inhibited mice with AngII treatment, as evidenced by increased macrophage infiltration and expression of MCP-1 and IL-6. In vitro, AngII-upregulated MCP-1 and IL-6 expression was significantly attenuated by sEH inhibition but promoted by EPHX2 deletion in cardiofibroblasts. Thus, compared with pharmacological inhibition of sEH, EPHX2 deletion caused the shift in arachidonic acid metabolism, which may led to pathological cardiac remodeling, especially cardiac fibrosis. PMID:24718617

  9. Epoxygenase Eicosanoids: Synthesis of Tetrahydrofuran-Diol Metabolites and Their Vasoactivity

    PubMed Central

    Falck, J. R.; Reddy, L. Manmohan; Byun, Kihwan; Campbell, William B.; Yi, Xiu-Yu

    2007-01-01

    Eight members of a recently identified family of tetrahydrofuran-diols (THFDs), originating from epoxyeicosatrienoic acids (EETs), were prepared stereospecifically from D-(+)-glucose. The THFDs potently induced relaxation of pre-contracted bovine arteries. PMID:17293113

  10. Organocatalytic asymmetric epoxidation and tandem epoxidation/Passerini reaction under eco-friendly reaction conditions.

    PubMed

    Deobald, Anna Maria; Corrêa, Arlene G; Rivera, Daniel G; Paixão, Márcio Weber

    2012-10-14

    An eco-friendly synthesis of highly functionalized epoxides and their incorporation into an organocatalytic multicomponent approach are reported. For this, a modified class of diarylprolinol silyl ethers was designed to enable high catalytic activity in an environmentally benign solvent system. The one-pot procedure showed great efficiency in promoting stereoselective multicomponent transformations in a tandem, 'green' fashion. Because of its non-residual, efficient and selective character, this synthetic design shows promise for large-scale applications in both diversity and target-oriented syntheses. PMID:22918441

  11. Review on proteomic analyses of benzo[a]pyrene toxicity.

    PubMed

    Verma, Nisha; Pink, Mario; Rettenmeier, Albert W; Schmitz-Spanke, Simone

    2012-06-01

    Benzo[a]pyrene (BaP), a five-ring polycyclic aromatic hydrocarbon, is a well-recognized environmental pollutant. Coal-processing waste products, petroleum sludge, asphalt, creosote, and tobacco smoke, all contain high levels of BaP. Exposure to BaP elicits many adverse biological effects, including tumor formation, immunosuppression, teratogenicity, and hormonal effects. In addition to the genetic damage caused by BaP exposure, several studies have indicated the disruption of protein-protein signaling pathways. However, contrary to the large number of studies on BaP-induced DNA damage, only few data have been gathered on its effects at the protein level. This review highlights all proteomic studies to date used for assessing the toxicity of BaP and its metabolites in various organ systems. It will also give an overview on the role proteomics may play to elucidate the mechanisms underlying BaP toxicity. PMID:22623321

  12. BENZO(A)PYRENE CONCENTRATIONS IN SOMATIC AND GONAD TISSUES OF BAY MUSSELS, 'MYTILUS EDULIS'

    EPA Science Inventory

    The purposes of the present study were to measure benzo(a)pyrene concentrations in the somatic and gonadal tissues of mytilus edulis and determine whether or not variations in those two tissue compartments could be related to seasonal fluctuations.

  13. IRIS Toxicological Review of Benzo[a]pyrene (Public Comment Draft)

    EPA Science Inventory

    EPA is developing an Integrated Risk Information System (IRIS) assessment of benzo[a]pyrene and has released the draft assessment for public comment and external peer review. When final, the assessment will appear on the IRIS database.

  14. Photopolymerizations of multicomponent epoxide and acrylate/epoxide hybrid systems for controlled kinetics and enhanced material properties

    NASA Astrophysics Data System (ADS)

    Eom, Ho Seop

    2011-12-01

    Cationic photopolymerization of multifunctional epoxides is very useful for efficient cure at room temperature and has been widely used in coatings and adhesives. Despite excellent properties of the final cured polymers, cationic photopolymerizations of epoxides have seen limited application due to slow reactions (relative to acrylates) and brittleness associated with a highly crosslinked, rigid network. To address these issues, two reaction systems were studied in this thesis: photoinitiated cationic copolymerizations of a cycloaliphatic diepoxide with epoxidized elastomers and acrylate/epoxide hybrid photopolymerizations. Oligomer/monomer structures, viscosity, compositions, and photoinitiator system were hypothesized to play important roles in controlling photopolymerizations of the epoxide-based mixtures. A fundamental understanding of the interplay between these variables for the chosen systems will provide comprehensive guidelines for the future development of photopolymerization systems comparable to the epoxide-based mixtures in this research. For diepoxide/oligomer mixtures, the observed overall enhancement in polymerization rate and ultimate conversion of the cycloaliphatic diepoxide was attributed to the activated monomer mechanism associated with hydroxyl terminal groups in the epoxidized oligomers. This enhancement increased with increasing oligomer content. The mixture viscosity influenced the initial reactivity of the diepoxide for oligomer content above 50 wt.%. Real-time consumption of internal epoxides in the oligomers was successfully determined using Raman spectroscopy. Initial reactivity and ultimate conversion of the internal epoxides decreased with increasing the diepoxide content. This trend was more pronounced for the oligomer containing low internal epoxide content. These results indicate that the reactivity of the hydroxyl groups is higher toward cationic active centers of the diepoxide than those of the internal epoxides in the oligomers

  15. 40 CFR 721.10210 - Soybean oil, epoxidized, reaction products with diethanolamine.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Significant New Uses for Specific Chemical Substances § 721.10210 Soybean oil, epoxidized, reaction products... chemical substance identified as soybean oil, epoxidized, reaction products with diethanolamine (PMN P-09... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Soybean oil, epoxidized,...

  16. 40 CFR 721.10210 - Soybean oil, epoxidized, reaction products with diethanolamine.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... Significant New Uses for Specific Chemical Substances § 721.10210 Soybean oil, epoxidized, reaction products... chemical substance identified as soybean oil, epoxidized, reaction products with diethanolamine (PMN P-09... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Soybean oil, epoxidized,...

  17. 40 CFR 721.10210 - Soybean oil, epoxidized, reaction products with diethanolamine.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... Significant New Uses for Specific Chemical Substances § 721.10210 Soybean oil, epoxidized, reaction products... chemical substance identified as soybean oil, epoxidized, reaction products with diethanolamine (PMN P-09... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Soybean oil, epoxidized,...

  18. 40 CFR 721.10210 - Soybean oil, epoxidized, reaction products with diethanolamine.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... Significant New Uses for Specific Chemical Substances § 721.10210 Soybean oil, epoxidized, reaction products... chemical substance identified as soybean oil, epoxidized, reaction products with diethanolamine (PMN P-09... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Soybean oil, epoxidized,...

  19. Formation of furan fatty alkyl esters from their bis-epoxide fatty esters

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Epoxidation of vegetable oils and consecutive epoxide ring-opening reaction is a widely investigated path for producing biobased lubricants and polymers. The reaction mechanism and products are considered well-studied and known. In the current study, the reactions of epoxidized alkyl soyate with fou...

  20. Sulfuric acid as a catalyst for ring-opening of biobased bis-epoxides

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Vegetable oils can be relatively and easily transformed into bio-based epoxides. Because of this, the acid-catalyzed epoxide ring-opening has been explored for the preparation of bio-based lubricants and polymers. Detailed model studies are carried out only with mono-epoxide made from methyl oleate,...

  1. Epoxide Chemistry: Guided Inquiry Experiment Emphasizing Structure Determination and Mechanism

    NASA Astrophysics Data System (ADS)

    Krishnamurty, H. G.; Jain, Niveta; Samby, Kiran

    2000-04-01

    This paper presents an operationally simple three-step synthesis of an a-hydroxy acid based on epoxide chemistry. The focus of the experiment is on the preparation of the chalcone epoxide and its reaction with hot alcoholic alkali. The experiment leads to an unpredicted reaction product. Its structure is established as 2-benzyl-2-phenylglycollic acid by chemical and spectroscopic analysis. The hydroxyacid is a good example to bring home an important NMR principle: the nonequivalence of hydrogens adjacent to a stereogenic center. The formation of the alpha-hydroxy acid is a mechanistic puzzle. A stepwise mechanism can be developed applying lecture-based organic chemistry concepts. On the other hand, acid-catalyzed (H2SO4, BF3) reaction of the chalcone epoxide gives benzoylphenylacetaldehyde. The exercise can be used as a multistep organic chemistry experiment. It also gives students a research-type experience.

  2. Epoxidation of propylene dimers and isomerization of mixtures obtained

    SciTech Connect

    Dobrev, D.M.; Kurtev, K.S.

    1988-05-10

    Mixtures of hexenes are obtained in the dimerization of propylene on a Ziegler catalyst. By the epoxidation of this mixture by organic peroxides, followed by isomerization of the oxides, C/sub 6/ ketones, which are used as solvents, can be obtained. The hexenes were obtained by dimerization of propylene in the presence of a Ni(C/sub 5/H/sub 7/O/sub 2/)/sub 2/-P(C/sub 6/H/sub 5/)/sub 3/-(C/sub 3/H/sub 5/)/sub 2/AlCl catalytic system. The epoxidation was carried with technical grade isopropylbenzyl hydroperoxide (IPBHP). MoO/sub 2/(C/sub 5/H/sub 7/O/sub 2/)/sub 2/ was used as the catalyst. The relative rates of epoxidation of different isomers contained in the dimeric fraction, with respect to 2-methyl-1-pentene, was determined by means of competing reactions.

  3. The oxidation of copper catalysts during ethylene epoxidation.

    PubMed

    Greiner, M T; Jones, T E; Johnson, B E; Rocha, T C R; Wang, Z J; Armbrüster, M; Willinger, M; Knop-Gericke, A; Schlögl, R

    2015-10-14

    The oxidation of copper catalysts during ethylene epoxidation was characterized using in situ photoemission spectroscopy and electron microscopy. Gas chromatography, proton-transfer reaction mass spectrometry and electron-ionization mass spectrometry were used to characterize the catalytic properties of the oxidized copper. We find that copper corrodes during epoxidation in a 1 : 1 mixture of oxygen and ethylene. The catalyst corrosion passes through several stages, beginning with the formation of an O-terminated surface, followed by the formation of Cu2O scale and eventually a CuO scale. The oxidized catalyst exhibits measurable activity for ethylene epoxidation, but with a low selectivity of <3%. Tests on pure Cu2O and CuO powders confirm that the oxides intrinsically exhibit partial-oxidation activity. Cu2O was found to form acetaldehyde and ethylene epoxide in roughly equal amounts (1.0% and 1.2% respectively), while CuO was found to form much less ethyl aldehyde than ethylene epoxide (0.1% and 1.0%, respectively). Metallic copper catalysts were examined in extreme dilute-O2 epoxidation conditions to try and keep the catalyst from oxidizing during the reaction. It was found that in feed of 1 part O2 to 2500 parts C2H4 (PO2 = 1.2 × 10(-4) mbar) the copper surface becomes O-terminated. The O-terminated surface was found to exhibit partial-oxidation selectivity similar to that of Cu2O. With increasing O2 concentration (>8/2500) Cu2O forms and eventually covers the surface. PMID:26345450

  4. A role for the androgen metabolite, 5alpha androstane 3beta, 17beta diol (3β-diol) in the regulation of the hypothalamo-pituitary-adrenal axis.

    PubMed

    Handa, Robert J; Sharma, Dharmendra; Uht, Rosalie

    2011-01-01

    Activation of the hypothalamo-pituitary-adrenal (HPA) axis is a basic reaction of animals to environmental perturbations that threaten homeostasis. These responses are ultimately regulated by neurons residing within the paraventricular nucleus (PVN) of the hypothalamus. Within the PVN, corticotrophin-releasing hormone (CRH), vasopressin (AVP), and oxytocin (OT) expressing neurons are critical as they can regulate both neuroendocrine and autonomic responses. Estradiol (E2) and testosterone (T) are well known reproductive hormones; however, they have also been shown to modulate stress reactivity. In rodent models, evidence shows that under some conditions E2 enhances stress activated adrenocorticotropic hormone (ACTH) and corticosterone secretion. In contrast, T decreases the gain of the HPA axis. The modulatory role of testosterone was originally thought to be via 5 alpha reduction to the potent androgen dihydrotestosterone (DHT) and its subsequent binding to the androgen receptor, whereas E2 effects were thought to be mediated by estrogen receptors alpha (ERalpha) and beta (ERbeta). However, DHT has been shown to be metabolized to the ERbeta agonist, 5α- androstane 3β, 17β Diol (3β-Diol). The actions of 3β-Diol on the HPA axis are mediated by ERbeta which inhibits the PVN response to stressors. In gonadectomized rats, ERbeta agonists reduce CORT and ACTH responses to restraint stress, an effect that is also present in wild-type but not ERbeta-knockout mice. The neurobiological mechanisms underlying the ability of ERbeta to alter HPA reactivity are not currently known. CRH, AVP, and OT have all been shown to be regulated by estradiol and recent studies indicate an important role of ERbeta in these regulatory processes. Moreover, activation of the CRH and AVP promoters has been shown to occur by 3β-Diol binding to ERbeta and this is thought to occur through alternate pathways of gene regulation. Based on available data, a novel and important role of 3β-Diol in

  5. A Role for the Androgen Metabolite, 5alpha Androstane 3beta, 17beta Diol (3β-Diol) in the Regulation of the Hypothalamo-Pituitary–Adrenal Axis

    PubMed Central

    Handa, Robert J.; Sharma, Dharmendra; Uht, Rosalie

    2011-01-01

    Activation of the hypothalamo-pituitary–adrenal (HPA) axis is a basic reaction of animals to environmental perturbations that threaten homeostasis. These responses are ultimately regulated by neurons residing within the paraventricular nucleus (PVN) of the hypothalamus. Within the PVN, corticotrophin-releasing hormone (CRH), vasopressin (AVP), and oxytocin (OT) expressing neurons are critical as they can regulate both neuroendocrine and autonomic responses. Estradiol (E2) and testosterone (T) are well known reproductive hormones; however, they have also been shown to modulate stress reactivity. In rodent models, evidence shows that under some conditions E2 enhances stress activated adrenocorticotropic hormone (ACTH) and corticosterone secretion. In contrast, T decreases the gain of the HPA axis. The modulatory role of testosterone was originally thought to be via 5 alpha reduction to the potent androgen dihydrotestosterone (DHT) and its subsequent binding to the androgen receptor, whereas E2 effects were thought to be mediated by estrogen receptors alpha (ERalpha) and beta (ERbeta). However, DHT has been shown to be metabolized to the ERbeta agonist, 5α- androstane 3β, 17β Diol (3β-Diol). The actions of 3β-Diol on the HPA axis are mediated by ERbeta which inhibits the PVN response to stressors. In gonadectomized rats, ERbeta agonists reduce CORT and ACTH responses to restraint stress, an effect that is also present in wild-type but not ERbeta-knockout mice. The neurobiological mechanisms underlying the ability of ERbeta to alter HPA reactivity are not currently known. CRH, AVP, and OT have all been shown to be regulated by estradiol and recent studies indicate an important role of ERbeta in these regulatory processes. Moreover, activation of the CRH and AVP promoters has been shown to occur by 3β-Diol binding to ERbeta and this is thought to occur through alternate pathways of gene regulation. Based on available data, a novel and important role of 3β-Diol

  6. The generation of oxidation products of benzo(a)pyrene by lipid peroxidation: a study using gamma-irradiation

    SciTech Connect

    Gower, J.D.; Wills, E.D.

    1984-09-01

    The role which active oxygen and radicals generated by the peroxidation of unsaturated fatty acids could play in the oxidation of benzo(a)pyrene has been studied using gamma-irradiation. Irradiation of benzo(a)pyrene resulted in the formation of benzo(a)pyrene 1,6-, 3,6- and 6,12-quinones and other more polar products which were analysed by h.p.l.c. OH. radicals are believed to be involved in this oxidation. The presence of polyunsaturated fatty acids and polyunsaturated lipids stimulated the formation of benzo(a)pyrene products following gamma-irradiation. Oxidation of benzo(a)pyrene also occurred over a period of days in the presence of autoxidising mackerel oil. The rate of benzo(a)pyrene oxidation was related to the extent of lipid peroxidation as determined by malonaldehyde formation. Malonaldehyde production as a result of peroxidising lipids was inhibited by benzo(a)pyrene which suggested that benzo(a)pyrene reacted directly with lipid peroxy radicals or hydroperoxides generated in the process of lipid peroxidation. These results demonstrate that oxidation products of the peroxidation of lipids and fatty acids are able to react directly with benzo(a)pyrene to form products including benzo(a)pyrene quinones without the presence of enzymes such as the cytochrome P-450 mixed function oxidase system and prostaglandin synthetase. It is possible that benzo(a)pyrene may be activated by these types of reactions in vivo or in vitro when benzo(a)pyrene is in contact with polyunsaturated lipids in foodstuffs or the intestinal lumen and peroxidation of unsaturated fats may play an important role in human carcinogenesis.

  7. Experimental and DFT study of cyclodehydration and acetylation of ferrocenyl diols

    NASA Astrophysics Data System (ADS)

    Lapić, Jasmina; Višnjevac, Aleksandar; Cetina, Mario; Djaković, Senka; Vrček, Valerije; Rapić, Vladimir

    2012-07-01

    Racemic ferrocenyl diols, i.e. ferrocenyl(2-hydroxymethylphenyl)methanol (2), ferrocenyl-2-(2-hydroxymethylphenyl)ethanol (7), and ferrocenyl(2-(2-hydroxyethyl)phenyl)methanol (9) have been prepared by reduction of corresponding ketoesters using NaBH4 in a mixture EtOH and Et2O. In the course of these reactions new cyclic ethers 1-ferrocenyl-2-oxaindane (3), 3-ferrocenylisochromane (8), and 1-ferrocenylisochromane (10) have been isolated as side-products. Intramolecular cyclizations of ferrocenyl diols occur in both acidic and neutral medium. Density functional theory (BP86) calculations were used to explain the mechanism of these cyclodehydrations. Acid catalyzed reaction follows the classical SN1 mechanism, whereas the cyclodehydration in neutral medium is described as an SN2 reaction. X-ray diffraction analysis of new cyclic ether products has been performed. Monoacetates 11, 13 and 15 have been obtained in the reaction of ferrocenyl diols 2, 7, and 9, respectively, and acetic anhydride. Stereoselective acylation of racemic diols by vinyl acetate have been catalyzed by various lipases, and the best stereoselectivity has been observed for the diol 2 in the presence of Penicillium camembertii lipase.

  8. Plasma oxylipin profiling identifies polyunsaturated vicinal diols as responsive to arachidonic acid and docosahexaenoic acid intake in growing piglets.

    PubMed

    Bruins, Maaike J; Dane, Adrie D; Strassburg, Katrin; Vreeken, Rob J; Newman, John W; Salem, Norman; Tyburczy, Cynthia; Brenna, J Thomas

    2013-06-01

    The dose-responsiveness of plasma oxylipins to incremental dietary intake of arachidonic acid (20:4n-6; ARA) and docosahexaenoic acid (22:6n-3; DHA) was determined in piglets. Piglets randomly received one of six formulas (n = 8 per group) from days 3 to 27 postnatally. Diets contained incremental ARA or incremental DHA levels as follows (% fatty acid, ARA/DHA): (A1) 0.1/1.0; (A2) 0.53/1.0; (A3-D3) 0.69/1.0; (A4) 1.1/1.0; (D1) 0.66/0.33; and (D2) 0.67/0.62, resulting in incremental intake (g/kg BW/day) of ARA: 0.07 ± 0.01, 0.43 ± 0.03, 0.55 ± 0.03, and 0.82 ± 0.05 at constant DHA intake (0.82 ± 0.05), or incremental intake of DHA: 0.27 ± 0.02, 0.49 ± 0.03, and 0.81 ± 0.05 at constant ARA intake (0.54 ± 0.04). Plasma oxylipin concentrations and free plasma PUFA levels were determined at day 28 using LC-MS/MS. Incremental dietary ARA intake dose-dependently increased plasma ARA levels. In parallel, ARA intake dose-dependently increased ARA-derived diols 5,6- and 14,15-dihydroxyeicosatrienoic acid (DiHETrE) and linoleic acid-derived 12,13-dihydroxyoctadecenoic acid (DiHOME), downstream metabolites of cytochrome P450 expoxygenase (CYP). The ARA epoxide products from CYP are important in vascular homeostatic maintenance. Incremental DHA intake increased plasma DHA and most markedly raised the eicosapentaenoic acid (EPA) metabolite 17,18-dihydroxyeicosatetraenoic acid (DiHETE) and the DHA metabolite 19,20-dihydroxydocosapentaenoic acid (DiHDPE). In conclusion, increasing ARA and DHA intake dose-dependently influenced endogenous n-6 and n-3 oxylipin plasma concentrations in growing piglets, although the biological relevance of these findings remains to be determined. PMID:23543770

  9. DEVELOPMENT OF METABOLICALLY STABLE INHIBITORS OF MAMMALIAN MICROSOMAL EPOXIDE HYDROLASE

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The microsomal epoxide hydrolase (mEH) plays a significant role in the metabolism of xenobiotics such as polyaromatic toxicants. Additionally, polymorphism studies have underlined a potential role of this enzyme in relation to a number of diseases, such as emphysema, spontaneous abortion, eclampsia ...

  10. Peptidyl-urea based inhibitors of soluble epoxide hydrolases

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We prepared a series of amino acid derived cyclohexyl and adamantyl ureas and tested them as inhibitors of the human soluble epoxide hydrolase, and obtained very potent compounds (K(I)=15nM) that are >10-fold more soluble than previously described sEH inhibitors. While our lead compound 2 showed low...

  11. Ring-opening Polymerization of Epoxidized Soybean Oil

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Ring opening polymerization of epoxidized soybean oil (ESO) initiated by boron trifluoride diethyl etherate, (BF3•OEt2), in methylene chloride was conducted in an effort to develop useful biodegradable polymers. The resulting polymers (PESO) were characterized using Infrared (IR), differential scan...

  12. Stability and friction reducing properties of epoxidized oleochemical methyl esters

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The use of oleochemicals as biobased replacements for petrochemical lubricants is an important area of study. Physical properties of the epoxidized fatty esters derived from vegetable oil are reported and compared to their olefinic counterparts. Overall the frictional behavior of epoxy methyl olea...

  13. ULTRASOUND-ASSISTED ORGANIC SYNTHESIS: ALCOHOL OXIDATION AND OLEFIN EPOXIDATION

    EPA Science Inventory

    Ultrasound-assisted Organic Synthesis: Alcohol Oxidation and Olefin Epoxidation

    Unnikrishnan R Pillai, Endalkachew Sahle-Demessie , Vasudevan Namboodiri, Quiming Zhao, Juluis Enriquez
    U.S. EPA , 26 W. Martin Luther King Dr. , Cincinnati, OH 45268
    Phone: 513-569-773...

  14. Persistence of urinary excretion products of benzo(a)pyrene

    SciTech Connect

    Uziel, M.; Haglund, R.; White, D.A.

    1988-01-01

    Persistence of DNA-adducts has been observed in a variety of experimental circumstances and has been suggested as one potential mechanism for explaining the long-term delay before expression of proliferative disease. In this concept, a stable DNA-adduct, which is a remnant of a prior exposure in a nondividing cell, would not express the genotoxic effect until the cells were stimulated to divide, and thus explain the long-term delay in expression of cancer. An alternative view of the observation of persistent DNA-adducts, described in this communication, is the continuing replenishment of DNA adducts by formation and turnover of these adducts from exposure to a constant supply of the ultimate carcinogenic species derived from a prior exposure. It is of interest to note that virtually all experiments where ''persistent'' adducts have been observed have been high dose exposures. During the course of experiments designed to develop improved methods for detection of DNA adducts and related derivatives derived from polynuclear aromatic hydrocarbons (PAH), we observed that there was a continuous excretion of urinary derivatives of the injected benzo(a)pyrene (BaP) beyond the initial burst of detoxification. This report describes the time dependent distribution of those derivatives in blood, urine, feces, and at the site of injection. 11 refs., 5 figs., 4 tabs.

  15. [Benzo(a)pyrene contamination of vegetable oils].

    PubMed

    Jedra, Małgorzata; Starski, Andrzej; Gawarska, Halina; Sawilska-Rautenstrauch, Dorota

    2008-01-01

    Benzo(a)pyrene (B(a)P) analysis was carried out with glass chromatographic column with alumina followed by reverse phase high-performance liquid chromatography (HPLC) and spectrofluorometric detection. B(a)P level in 40 vegetable oils were as follow: from 0.11 to 0.38 microg/kg in olive; from 0.92 to 3.74 microg/kg in rape seed oils; from 0.11 to 2.25 microg/kg in sunflower oils and from 0.33 to 1.26 microg/kg in soya oils. In another investigated oils: arachide (peanut) corn, safflower, linen, hempen, sesame, pumpkin seeds, grape seeds---values from 0.10 to 1.44 microg/kg and 3.83 microg/kg in sea buckthorn oil were detected. B(a)P concentration in 4 from 40 investigated oils exceed the 2 ppb limit proposed by the European Commission. Heating of sample of oils: olive, rape, soya, linen, corn, sesame, peanut, in temp. 240 degrees C for 30 min. has not influence on decreased of B(a)P level. PMID:18807910

  16. Species differences in biliary excretion of benzo(a)pyrene

    SciTech Connect

    Weyand, E.H.; Bevan, D.R.

    1986-05-01

    Biliary excretion of benzo(a)pyrene (B(a)P) was investigated in rats, hamsters, and guinea pigs following intratracheal administration. (/sup 3/H)-B(a)P, in amounts of approximately 150 ng or 350 ..mu..g, was instilled into lungs and amounts of radioactivity excreted in bile were monitored for six hrs following administration. Differences in biliary excretion of (/sup 3/H)-B(a)P and/or metabolites among species were observed at low doses but not at high doses. Six hours after instillation of a low dose of B(a)P, 70, 54, and 62% of the dose was excreted in bile of rats, hamsters, and guinea pigs, respectively. Upon administration of the higher dose of B(a)P, approximately 50% of the dose was excreted in bile in six hrs by all species. Thus, rats and guinea pigs exhibit differences in biliary excretion of low and high doses of B(a)P whereas hamsters do not. Profiles of phase II metabolites in rats and hamsters were similar at both low and high doses, with the majority of metabolites being glucuronides and thioether conjugates. However, differences in relative amounts of these conjugates were observed between the two doses, with a shift towards a greater proportion of glucuronides at the higher dose. Metabolites in bile from guinea pigs were primarily thioether conjugates, which accounted for 88% of metabolites at the low dose and 95% at the high dose.

  17. Gas-phase water-mediated equilibrium between methylglyoxal and its geminal diol

    PubMed Central

    Axson, Jessica L.; Takahashi, Kaito; De Haan, David O.; Vaida, Veronica

    2010-01-01

    In aqueous solution, aldehydes, and to a lesser extent ketones, hydrate to form geminal diols. We investigate the hydration of methylglyoxal (MG) in the gas phase, a process not previously considered to occur in water-restricted environments. In this study, we spectroscopically identified methylglyoxal diol (MGD) and obtained the gas-phase partial pressures of MG and MGD. These results, in conjunction with the relative humidity, were used to obtain the equilibrium constant, KP, for the water-mediated hydration of MG in the gas phase. The Gibbs free energy for this process, ΔG°, obtained as a result, suggests a larger than expected gas-phase diol concentration. This may have significant implications for understanding the role of organics in atmospheric chemistry. PMID:20142510

  18. Energy and chemicals from the selective electrooxidation of renewable diols by organometallic fuel cells.

    PubMed

    Bellini, Marco; Bevilacqua, Manuela; Filippi, Jonathan; Lavacchi, Alessandro; Marchionni, Andrea; Miller, Hamish A; Oberhauser, Werner; Vizza, Francesco; Annen, Samuel P; Grützmacher, H

    2014-09-01

    Organometallic fuel cells catalyze the selective electrooxidation of renewable diols, simultaneously providing high power densities and chemicals of industrial importance. It is shown that the unique organometallic complex [Rh(OTf)(trop2NH)(PPh3)] employed as molecular active site in an anode of an OMFC selectively oxidizes a number of renewable diols, such as ethylene glycol , 1,2-propanediol (1,2-P), 1,3-propanediol (1,3-P), and 1,4-butanediol (1,4-B) to their corresponding mono-carboxylates. The electrochemical performance of this molecular catalyst is discussed, with the aim to achieve cogeneration of electricity and valuable chemicals in a highly selective electrooxidation from diol precursors. PMID:25082272

  19. Acid-catalyzed reactions of a disecondary aromatic diol with alkanols

    SciTech Connect

    Zaitsev, B.A.; Dantsig, L.L.

    1986-07-10

    On heating a disecondary aromatic diol with an alkanol in an aromatic solvent in the presence of an acid catalyst, condensation telomerization takes place with the formation of oligomeric ethers, alcoholysis of which and condensation of hydroxylated intermediate products gives dialkyl ethers of the diol, followed by cleavage of these ethers to give vinyl- and divinylaromatic compounds, and cationic polyaddition of these monomers to give straight-chain unsaturated oligomers, giving mixtures of vinylaromatic compounds and unsaturated straight-chain oligomers. The rate of cleavage of dialkoxy-derivatives of the aromatic diol decreases as the reaction progresses as a result of the increasing concentration of the liberated alkanol, which modifies the activity of the catalyst.

  20. Synthesis of high molecular weight polyesters via in vacuo dehydrogenation polymerization of diols.

    PubMed

    Hunsicker, David M; Dauphinais, Brian C; Mc Ilrath, Sean P; Robertson, Nicholas J

    2012-02-13

    The Milstein catalyst has proven to be highly effective for the conversion of alcohols to esters, as well as alcohols and amines to amides and polyamides. We have recently found that the catalyst's range can be extended to very efficient in vacuo dehydrogenation polymerization of α,ω-diols to generate polyesters. The gaseous hydrogen byproduct that is produced is easily removed to drive the equilibrium toward product, which leads to the formation of high molecular weight polymer (M(n) up to 145,000 g mol(-1)). This optimized methodology works well to polymerize diols with a spacer of six carbons or more. Diols with fewer carbons are cyclized to lactone; the dividing point is the dehydrogenation of 1,5-pentanediol, which leads to a mixture of polyester and lactone. Reported herein is the synthesis and characterization of five aliphatic polyesters prepared via this novel dehydrogenation polymerization approach. PMID:22173989

  1. An ab initio study of three (ethane-1,2 diol/water) complexes

    NASA Astrophysics Data System (ADS)

    Manivet, Philippe; Masella, Michel

    1998-05-01

    Three (ethane-1,2 diol/water) complexes have been studied using ab initio calculations at the MP2 level. In two complexes, the ethane-1,2 diol structure is close to its gas phase experimental structure (presence of an intramolecular hydrogen bond HB and the O-C-C-O dihedral angle is gauche) while the intramolecular HB is disrupted by the presence of a water molecule in the third ( tGg'a). Computations have shown that most of the experimental observations regarding the solvation of ethane-1,2 diol in water may be reproduced only by considering the tGg'a complex (absence of intramolecular HB, O-C-C-O dihedral angle of 72-74°), which is also more stable than the other two by 2 kcal mol -1.

  2. Ruthenium(salen)-catalyzed aerobic oxidative desymmetrization of meso-diols and its kinetics.

    PubMed

    Shimizu, Hideki; Onitsuka, Satoaki; Egami, Hiromichi; Katsuki, Tsutomu

    2005-04-20

    Chiral (nitrosyl)ruthenium(salen) complexes were found to be efficient catalysts for aerobic oxidative desymmetrization of meso-diols under photoirradiation to give optically active lactols. The scope of the applicability of this reaction ranges widely from acyclic diols to mono-cyclic diols, although fine ligand-tuning of the ruthenium(salen) complexes was required to attain high enantioselectivity (up to 93% ee). In particular, the nature of the apical ligand was found to affect not only enantioselectivity but also kinetics of the desymmetrization reaction. Spectroscopic analysis of the oxidation disclosed that irradiation of visible light is indispensable not only for dissociation of the nitrosyl ligand but also for single electron transfer from the alcohol-bound ruthenium ion to dioxygen. PMID:15826178

  3. Practical asymmetric synthesis of the herbicide (S)-indanofan via lipase-catalyzed kinetic resolution of a diol and stereoselective acid-catalyzed hydrolysis of a chiral epoxide.

    PubMed

    Tanaka, Ken; Yoshida, Kenji; Sasaki, Chiduko; Osano, Yasuko T

    2002-05-01

    Racemic indanofan [(+/-)-1] was efficiently converted to enantiopure (S)-indanofan [(S)-1] by a combination of enzymatic resolution and chemical inversion techniques. An additional important technique is the use of an o-xylene complex of a hemiketal (S)-3c as a precursor, which can be quantitatively converted to (S)-indanofan and easily purified by recrystallization from o-xylene. PMID:11975580

  4. Effect of strand-specific excision repair on the spectra of mutations induced by benzo[a]pyrene-diol epoxide and ultraviolet radiation in diploid human cells

    SciTech Connect

    Ruey-Hwa, Chen.

    1991-01-01

    To study the effect of excision repair on the spectra of mutations induced in diploid human cells by UV and [plus minus]-7[beta], 8[alpha]-dihydroxy-9[alpha],10[alpha]-epoxy- 7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE), the author synchronized repair-proficient cells, treated them at the beginning of S phase or in G[sub 1] phase several hours prior to the onset of S phase, selected for thioguanine resistant cells, and determined the spectra of mutations in the coding region of the hyproxanthine(guanine)phosphoribosyl-transferase (HPRT) gene in the mutants. As a control, the spectra of mutations similarly induced in repair-deficient xeroderma pigmentosum (XP) cells were compared. There was no difference in the kinds of mutations observed in mutants derived from either cell strain treated with a particular mutagen either in S or in G[sub 1]. With BPDE, the majority were G.C[yields]T.A transversions; with UV, they were mainly G.C.[yields]A.T transitions. The strand distribution of premutagenic lesions in mutants from repair-proficient cells treated in S or G[sub 1] differed significantly. The results strongly support the hypothesis that human cells preferentially repair UV- and BPDE-induced lesions from the transcribed strand of the HPRT gene. To test this, the rate of repair of BPDE adducts from individual strands of the HPRT gene was measured, using the UvrABC exinuclease and Southern hybridizations with strand-specific probes to detect lesions remaining. BPDE lesions were removed from the transcribed strand at a significantly faster rate than from the nontranscribed strand, consistent with my hypothesis. It was found that BPDE adducts were removed faster from either strand of the HPRT gene than from a transcriptionally inactive locus, indicating preferential repair of active genes. The results of these studies provide biochemical and biological evidence of strand-specific DNA repair of BPDE adducts in human cells.

  5. Thermoresponsive Polymers and Inverse Opal Hydrogels for the Detection of Diols.

    PubMed

    Couturier, Jean-Philippe; Wischerhoff, Erik; Bernin, Robert; Hettrich, Cornelia; Koetz, Joachim; Sütterlin, Martin; Tiersch, Brigitte; Laschewsky, André

    2016-05-01

    Responsive inverse opal hydrogels functionalized by boroxole moieties were synthesized and explored as sensor platforms for various low molar mass as well as polymeric diols and polyols, including saccharides, glycopolymers and catechols, by exploiting the diol induced modulation of their structural color. The underlying thermoresponsive water-soluble copolymers and hydrogels exhibit a coil-to-globule or volume phase transition, respectively, of the LCST-type. They were prepared from oligoethylene oxide methacrylate (macro)monomers and functionalized via copolymerization to bear benzoboroxole moieties. The resulting copolymers represent weak polyacids, which can bind specifically to diols within an appropriate pH window. Due to the resulting modulation of the overall hydrophilicity of the systems and the consequent shift of their phase transition temperature, the usefulness of such systems for indicating the presence of catechols, saccharides, and glycopolymers was studied, exploiting the diol/polyol induced shifts of the soluble polymers' cloud point, or the induced changes of the hydrogels' swelling. In particular, the increased acidity of benzoboroxoles compared to standard phenylboronic acids allowed performing the studies in PBS buffer (phosphate buffered saline) at the physiologically relevant pH of 7.4. The inverse opals constructed of these thermo- and analyte-responsive hydrogels enabled following the binding of specific diols by the induced shift of the optical stop band. Their highly porous structure enabled the facile and specific optical detection of not only low molar mass but also of high molar mass diol/polyol analytes such as glycopolymers. Accordingly, such thermoresponsive inverse opal systems functionalized with recognition units represent attractive and promising platforms for the facile sensing of even rather big analytes by simple optical means, or even by the bare eye. PMID:27108735

  6. Leukotoxin diols from ground corncob bedding disrupt estrous cyclicity in rats and stimulate MCF-7 breast cancer cell proliferation.

    PubMed

    Markaverich, Barry M; Crowley, Jan R; Alejandro, Mary A; Shoulars, Kevin; Casajuna, Nancy; Mani, Shaila; Reyna, Andrea; Sharp, John

    2005-12-01

    Previous studies in our laboratory demonstrated that high-performance liquid chromatography (HPLC) analysis of ground corncob bedding extracts characterized two components (peak I and peak II) that disrupted endocrine function in male and female rats and stimulated breast and prostate cancer cell proliferation in vitro and in vivo. The active substances in peak I were identified as an isomeric mixture of 9,12-oxy-10,13-dihydroxyoctadecanoic acid and 10,13-oxy-9,12-dihydroxyoctadecanoic acid, collectively designated tetrahydrofurandiols (THF-diols). Studies presented here describe the purification and identification of the HPLC peak II component as 9,10-dihydroxy-12-octadecenoic acid (leukotoxin diol; LTX-diol), a well-known leukotoxin. A synthetic mixture of LTX-diol and 12,13-dihydroxy-9-octadecenoic acid (iso-leukotoxin diol; i-LTX-diol) isomers was separated by HPLC, and each isomer stimulated (p < 0.001) MCF-7 cell proliferation in an equivalent fashion. The LTX-diol isomers failed to compete for [3H]estradiol binding to the estrogen receptor or nuclear type II sites, even though oral administration of very low doses of these compounds (> 0.8 mg/kg body weight/day) disrupted estrous cyclicity in female rats. The LTX-diols did not disrupt male sexual behavior, suggesting that sex differences exist in response to these endocrine-disruptive agents. PMID:16330350

  7. Demonstration of Redox Potential of Metschnikowia koreensis for Stereoinversion of Secondary Alcohols/1,2-Diols

    PubMed Central

    Meena, Vachan Singh; Banoth, Linga; Banerjee, U. C.

    2014-01-01

    The present work reports the Metschnikowia koreensis-catalyzed one-pot deracemization of secondary alcohols/1,2-diols and their derivatives with in vivo cofactor regeneration. Reaction is stereoselective and proceeds with sequential oxidation of (R)-secondary alcohols to the corresponding ketones and the reduction of the ketones to (S)-secondary alcohols. Method is applicable to a repertoire of racemic aryl secondary alcohols and 1,2-diols establishing a wide range of substrate specificity of M. koreensis. This ecofriendly method afforded the product in high yield (88%) and excellent optical purity (>98% ee), minimizing the requirement of multistep reaction and expensive cofactor. PMID:24592389

  8. Regioselective Benzoylation of Diols and Carbohydrates by Catalytic Amounts of Organobase.

    PubMed

    Lu, Yuchao; Hou, Chenxi; Ren, Jingli; Xin, Xiaoting; Xu, Hengfu; Pei, Yuxin; Dong, Hai; Pei, Zhichao

    2016-01-01

    A novel metal-free organobase-catalyzed regioselective benzoylation of diols and carbohydrates has been developed. Treatment of diol and carbohydrate substrates with 1.1 equiv. of 1-benzoylimidazole and 0.2 equiv. of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) in MeCN under mild conditions resulted in highly regioselective benzoylation for the primary hydroxyl group. Importantly, compared to most commonly used protecting bulky groups for primary hydroxyl groups, the benzoyl protective group offers a new protection strategy. PMID:27196888

  9. Effect of epoxidation level on thermal properties and ionic conductivity of epoxidized natural rubber solid polymer nanocomposite electrolytes

    NASA Astrophysics Data System (ADS)

    Harun, Fatin; Chan, Chin Han; Sim, Lai Har; Winie, Tan; Zainal, Nurul Fatahah Asyqin

    2015-08-01

    Effect of epoxide content on the thermal and conductivity properties of epoxidized natural rubber (ENR) solid polymer nanocomposite electrolytes was investigated. Commercial available epoxidized natural rubber having 25 (ENR25) and 50 mole% (ENR50) epoxide, respectively were incorporated with lithium perchlorate (LiClO4) salt and titanium dioxide (TiO2) nanofiller via solution casting method. The solid polymer nanocomposite electrolytes were characterized by differential scanning calorimetry (DSC) and impedance spectroscopy (IS) for their thermal properties and conductivity, respectively. It was evident that introduction of LiClO4 causes a greater increase in glass transition temperature (Tg) and ionic conductivity of ENR50 as compared to ENR25. Upon addition of TiO2 in ENR/LiClO4 system, a remarkable Tg elevation was observed for both ENRs where ENR50 reveals a more pronounced changes. It is interesting to note that they exhibit different phenomenon in ionic conductivity with TiO2 loading where ENR25 shows enhancement of conductivity while ENR50 shows declination.

  10. Effect of epoxidation level on thermal properties and ionic conductivity of epoxidized natural rubber solid polymer nanocomposite electrolytes

    SciTech Connect

    Harun, Fatin; Chan, Chin Han; Winie, Tan; Sim, Lai Har; Zainal, Nurul Fatahah Asyqin

    2015-08-28

    Effect of epoxide content on the thermal and conductivity properties of epoxidized natural rubber (ENR) solid polymer nanocomposite electrolytes was investigated. Commercial available epoxidized natural rubber having 25 (ENR25) and 50 mole% (ENR50) epoxide, respectively were incorporated with lithium perchlorate (LiClO{sub 4}) salt and titanium dioxide (TiO{sub 2}) nanofiller via solution casting method. The solid polymer nanocomposite electrolytes were characterized by differential scanning calorimetry (DSC) and impedance spectroscopy (IS) for their thermal properties and conductivity, respectively. It was evident that introduction of LiClO{sub 4} causes a greater increase in glass transition temperature (T{sub g}) and ionic conductivity of ENR50 as compared to ENR25. Upon addition of TiO{sub 2} in ENR/LiClO{sub 4} system, a remarkable T{sub g} elevation was observed for both ENRs where ENR50 reveals a more pronounced changes. It is interesting to note that they exhibit different phenomenon in ionic conductivity with TiO{sub 2} loading where ENR25 shows enhancement of conductivity while ENR50 shows declination.

  11. The impact of individual cytochrome P450 enzymes on oxidative metabolism of benzo[a]pyrene in human livers

    PubMed Central

    Šulc, Miroslav; Indra, Radek; Moserová, Michaela; Schmeiser, Heinz H.; Frei, Eva; Arlt, Volker M.; White, P.

    2016-01-01

    Benzo[a]pyrene (BaP) is a human carcinogen that covalently binds to DNA after metabolic activation by cytochrome P450 (CYP) enzymes. In this study human recombinant CYPs (CYP1A1, 1A2, 1B1, 2A6, 2B6, 2C8, 2C9, 2C19, 2E1, 3A4, and 3A5) were expressed in Supersomes™ together with their reductases, NADPH:CYP oxidoreductase, epoxide hydrolase and cytochrome b5, to investigate BaP metabolism. Human CYPs produced up to eight BaP metabolites. Among these, BaP‐7,8‐dihydrodiol and BaP‐9‐ol, which are intermediates in BaP‐derived DNA adduct formation, were mainly formed by CYP1A1 and 1B1, and to a lesser extent by CYP2C19 and 3A4. BaP‐3‐ol, a metabolite that is a ‘detoxified’ product of BaP, was formed by most human CYPs tested, although CYP1A1 and 1B1 produced it the most efficiently. Based on the amounts of the individual BaP metabolites formed by these CYPs and their expression levels in human liver, we determined their contributions to BaP metabolite formation in this organ. Our results indicate that hepatic CYP1A1 and CYP2C19 are most important in the activation of BaP to BaP‐7,8‐dihydrodiol, whereas CYP2C19, 3A4, and 1A1 are the major enzymes contributing to the formation of BaP‐9‐ol. BaP‐3‐ol is predominantly formed by hepatic CYP3A4, while CYP1A1 and 2C19 are less active. Environ. Mol. Mutagen. 57:229–235, 2016. © 2016 The Authors. Environmental and Molecular Mutagenesis Published by Wiley Periodicals, Inc. PMID:26919089

  12. Modeling Epoxidation of Drug-like Molecules with a Deep Machine Learning Network.

    PubMed

    Hughes, Tyler B; Miller, Grover P; Swamidass, S Joshua

    2015-07-22

    Drug toxicity is frequently caused by electrophilic reactive metabolites that covalently bind to proteins. Epoxides comprise a large class of three-membered cyclic ethers. These molecules are electrophilic and typically highly reactive due to ring tension and polarized carbon-oxygen bonds. Epoxides are metabolites often formed by cytochromes P450 acting on aromatic or double bonds. The specific location on a molecule that undergoes epoxidation is its site of epoxidation (SOE). Identifying a molecule's SOE can aid in interpreting adverse events related to reactive metabolites and direct modification to prevent epoxidation for safer drugs. This study utilized a database of 702 epoxidation reactions to build a model that accurately predicted sites of epoxidation. The foundation for this model was an algorithm originally designed to model sites of cytochromes P450 metabolism (called XenoSite) that was recently applied to model the intrinsic reactivity of diverse molecules with glutathione. This modeling algorithm systematically and quantitatively summarizes the knowledge from hundreds of epoxidation reactions with a deep convolution network. This network makes predictions at both an atom and molecule level. The final epoxidation model constructed with this approach identified SOEs with 94.9% area under the curve (AUC) performance and separated epoxidized and non-epoxidized molecules with 79.3% AUC. Moreover, within epoxidized molecules, the model separated aromatic or double bond SOEs from all other aromatic or double bonds with AUCs of 92.5% and 95.1%, respectively. Finally, the model separated SOEs from sites of sp(2) hydroxylation with 83.2% AUC. Our model is the first of its kind and may be useful for the development of safer drugs. The epoxidation model is available at http://swami.wustl.edu/xenosite. PMID:27162970

  13. Modeling Epoxidation of Drug-like Molecules with a Deep Machine Learning Network

    PubMed Central

    2015-01-01

    Drug toxicity is frequently caused by electrophilic reactive metabolites that covalently bind to proteins. Epoxides comprise a large class of three-membered cyclic ethers. These molecules are electrophilic and typically highly reactive due to ring tension and polarized carbon–oxygen bonds. Epoxides are metabolites often formed by cytochromes P450 acting on aromatic or double bonds. The specific location on a molecule that undergoes epoxidation is its site of epoxidation (SOE). Identifying a molecule’s SOE can aid in interpreting adverse events related to reactive metabolites and direct modification to prevent epoxidation for safer drugs. This study utilized a database of 702 epoxidation reactions to build a model that accurately predicted sites of epoxidation. The foundation for this model was an algorithm originally designed to model sites of cytochromes P450 metabolism (called XenoSite) that was recently applied to model the intrinsic reactivity of diverse molecules with glutathione. This modeling algorithm systematically and quantitatively summarizes the knowledge from hundreds of epoxidation reactions with a deep convolution network. This network makes predictions at both an atom and molecule level. The final epoxidation model constructed with this approach identified SOEs with 94.9% area under the curve (AUC) performance and separated epoxidized and non-epoxidized molecules with 79.3% AUC. Moreover, within epoxidized molecules, the model separated aromatic or double bond SOEs from all other aromatic or double bonds with AUCs of 92.5% and 95.1%, respectively. Finally, the model separated SOEs from sites of sp2 hydroxylation with 83.2% AUC. Our model is the first of its kind and may be useful for the development of safer drugs. The epoxidation model is available at http://swami.wustl.edu/xenosite. PMID:27162970

  14. Evaluation of Benzo[a]pyrene in Food from China by High-Performance Liquid Chromatography-Fluorescence Detection

    PubMed Central

    Chen, Yong-Hong; Xia, En-Qin; Xu, Xiang-Rong; Li, Sha; Ling, Wen-Hua; Wu, Shan; Deng, Gui-Fang; Zou, Zhi-Fei; Zhou, Jing; Li, Hua-Bin

    2012-01-01

    The occurrence and levels of benzo[a]pyrene in various heat-treated foods from China were evaluated by high-performance liquid chromatography-fluorescence detection. In a total of 119 samples, 105 were found to contain benzo[a]pyrene at levels of 0.03 to 19.75 µg/kg. The benzo[a]pyrene contents in 12 animal source foods were higher than the Chinese maximum permissible level in food (5 µg/kg) and the highest level was 19.75 µg/kg, nearly four times the maximum permissible level. The results revealed a widespread carinogenic public health risk from benzo[a]pyrene in heat-treated foods. The highest benzo[a]pyrene levels were found in animal source samples such as charcoal-grilled and smoked meats, especially pork, beef and sausage, while trace levels of benzo[a]pyrene were present in grain food. Charcoal-grilled vegetables were found to also contain certain levels of benzo[a]pyrene. This study provided new information on benzo[a]pyrene content of a variety of heat-treated foods from China. PMID:23202838

  15. Soluble epoxide hydrolase deficiency inhibits dextran sulfate sodium-induced colitis and carcinogenesis in mice.

    PubMed

    Zhang, Wanying; Li, Haonan; Dong, Hua; Liao, Jie; Hammock, Bruce D; Yang, Guang-Yu

    2013-12-01

    Soluble epoxide hydrolase (sEH) hydrolyses/inactivates anti-inflammatory epoxyeicosatrienoic acids (EETs) to their corresponding diols, and targeting sEH leads to strong anti-inflammatory effects. In the present study, using a tissue microarray and immunohistochemical approach, a significant increase of sEH expression was identified in ulcerative colitis (UC)-associated dysplasia and adenocarcinoma. The effects of deficiency in the sEH gene were determined on dextran sulfate sodium (DSS) colitis-induced carcinogenesis. The effects of EETs on lipopolysaccharide (LPS)-activated macrophages were analyzed in vitro. With extensive histopathological and immunohistochemical analyses, compared to wild-type mice, sEH(-/-) mice exhibited a significant decrease in tumor incidence (13/20 vs. 6/19, p<0.05) and a markedly reduced average tumor size (59.62±20.91 mm(3) vs. 22.42±11.22 mm(3)), and a significant number of pre-cancerous dysplasia (3±1.18 vs. 2±0.83, p<0.01). The inflammatory activity, as measured by the extent/proportion of erosion/ulceration/dense lymphoplasmacytosis (called active colitis index) in the colon, was significantly lower in sEH(-/-) mice (44.7%±24.9% vs. 20.2%±16.2%, p<0.01). The quantitative polymerase chain reaction (qPCR) assays demonstrated significantly low levels of cytokines/chemokines including monocyte chemoattractant protein (MCP-1), inducible nitric oxide synthase (iNOS), vasopressin-activated calcium-mobilizing (VCAM-1), interleukin-1 beta (IL-1β) and tumor necrosis factor-alpha (TNF-α). In vitro, LPS-activated macrophages treated with 14,15-EET showed a significant reduction of LPS-triggered IL-1β and TNF-α expression. Eicosanoic acid metabolic profiling revealed a significant increase of the ratios of EETs/ dihydroeicosatrienoic acids (DHETs) and epoxyoctadecennoic acid/dihydroxyoctadecenoic acid (EpOMEs/DiHOMEs). These results indicate that sEH plays an important role in the development of colitis and in inducing carcinogenesis

  16. Dietary cadmium and benzo(a)pyrene increased intestinal metallothionein expression in the fish Fundulus heteroclitus

    SciTech Connect

    Roesijadi, Guritno; Rezvankhah, Saeid; Perez-Matus, Alejandro; Mitelberg, A.; Torruellas, K.; Van Veld, P. A.

    2008-10-17

    To test the effect of dietary exposure to cadmium and benzo(a)pyrene on induction of metallothionein mRNA in the Fundulus heteroclitus, fish were individually fed a pelletized gel food containing cadmium, benzo(a)pyrene, or a combination of the two over a period of seven days, then analyzed for relative levels of metallothionein mRNA in the intestine, liver, and gill using real-time RT-qPCR. An initial experiment with only cadmium exposure showed an apparent 10-fold induction in the intestine, but no induction in liver or gill. Ingestion of contaminated pellets varied in individual fish, and because it was possible to monitor individual ingestion rates with our method, individual cadmium doses were estimated from the amount of ingested cadmium. When the levels of metallothionein mRNA were related to the dose to each fish, a linear dose-response relationship was observed for the intestine, but not the other organs, which showed no induction. In a second experiment, dose was controlled by placing the entire daily cadmium dose into a single contaminated pellet that was fed first (thereby, effectively controlling the effect of variable ingestion rates), and the interaction between cadmium and benzo(a)pyrene was also investigated. The intestine was again the primary organ for metallothionein induction by cadmium, with a 20-fold increase in metallothionein mRNA over control levels. When benzo(a)pyrene was administered together with cadmium, induction of metallothionein was potentiated by the presence of benzo(a)pyrene, with the main effect seen in the intestine, where already high levels of induction by cadmium alone increased by 1.74-fold when benzo(a)pyrene was present.

  17. Topological, functional, and dynamic properties of the protein interaction networks rewired by benzo(a)pyrene

    SciTech Connect

    Ba, Qian; Li, Junyang; Huang, Chao; Li, Jingquan; Chu, Ruiai; Wu, Yongning; Wang, Hui

    2015-03-01

    Benzo(a)pyrene is a common environmental and foodborne pollutant that has been identified as a human carcinogen. Although the carcinogenicity of benzo(a)pyrene has been extensively reported, its precise molecular mechanisms and the influence on system-level protein networks are not well understood. To investigate the system-level influence of benzo(a)pyrene on protein interactions and regulatory networks, a benzo(a)pyrene-rewired protein interaction network was constructed based on 769 key proteins derived from more than 500 literature reports. The protein interaction network rewired by benzo(a)pyrene was a scale-free, highly-connected biological system. Ten modules were identified, and 25 signaling pathways were enriched, most of which belong to the human diseases category, especially cancer and infectious disease. In addition, two lung-specific and two liver-specific pathways were identified. Three pathways were specific in short and medium-term networks (< 48 h), and five pathways were enriched only in the medium-term network (6 h–48 h). Finally, the expression of linker genes in the network was validated by Western blotting. These findings establish the overall, tissue- and time-specific benzo(a)pyrene-rewired protein interaction networks and provide insights into the biological effects and molecular mechanisms of action of benzo(a)pyrene. - Highlights: • Benzo(a)pyrene induced scale-free, highly-connected protein interaction networks. • 25 signaling pathways were enriched through modular analysis. • Tissue- and time-specific pathways were identified.

  18. Ovarian expressed microsomal epoxide hydrolase: Role in detoxification of 4-vinylcyclohexene diepoxide and regulation by phosphatidylinositol-3 kinase signaling

    SciTech Connect

    Bhattacharya, Poulomi; Sen, Nivedita; Hoyer, Patricia B.; Keating, Aileen F.

    2012-01-01

    4-vinylcyclohexene diepoxide (VCD) is a metabolite of 4-vinylcyclohexene (VCH) which has the potential to be formed in the ovary through CYP2E1 activity. VCD specifically destroys primordial and small primary follicles in the rodent ovary. Mouse ovaries exposed to VCD demonstrate increased mRNA and protein expression of microsomal epoxide hydrolase (mEH), and an inactive tetrol metabolite (4-(1,2-dihydroxy)ethyl-1,2-dihydroxycyclohexane) can be formed in mouse ovarian follicles, potentially through detoxification action of mEH. In contrast, mEH can bioactivate another ovotoxic chemical, 7,12-dimethylbenz[a]anthracene (DMBA) to a more toxic compound, DMBA-3,4-diol-1,2-epoxide. Thus, the present study evaluated a functional role for mEH during detoxification of VCD. Additionally, because inhibition of the phosphatidyinositol-3 kinase (PI3K) signaling pathway in a previous study protected primordial follicles from VCD-induced destruction, but accelerated DMBA-induced ovotoxicity, a role for PI3K in ovarian mEH regulation was evaluated. Using a post-natal day (PND) 4 Fischer 344 rat whole ovary culture system inhibition of mEH using cyclohexene oxide during VCD exposure resulted in a greater (P < 0.05) loss of primordial and small primary follicles relative to VCD-treated ovaries. Also, relative to controls, meh mRNA was increased (P < 0.05) on day 4 of VCD (30 μM) exposure, followed by increased (P < 0.05) mEH protein after 6 days. Furthermore, inhibition of PI3K signaling increased mEH mRNA and protein expression. Thus, these results support a functional role for mEH in the rat ovary, and demonstrate the involvement of PI3K signaling in regulation of ovarian xenobiotic metabolism by mEH. -- Highlights: ► Ovarian mEH functions to metabolize VCD to a less toxic compound. ► mEH expression is increased in a temporal pattern in response to VCD exposure. ► PI3K signaling is involved in regulation of ovarian mEH expression.

  19. Carcinogenicity of airborne fine particulate benzo(a)pyrene: an appraisal of the evidence and the need for control.

    PubMed Central

    Perera, F

    1981-01-01

    Benzo(a)pyrene(BaP) originating from fossil fuel and other organic combustion processes is largely adsorbed on fine particulate and hence is a widespread atmospheric pollutant. Available emissions and air quality data are based on the total weight of particulate matter without reference to size and give little information on trends and concentrations of fine particulate BaP. Greater reliance on coal, synfuels and diesel fuel for energy production and transportation will significantly increase ambient levels of BaP. Because of the particulate size, BaP is substantially deposited in the lower lung and readily eluted into surrounding tissue. After elution in the lung, BaP is metabolically activated to its electrophilic, carcinogenic from by a complex enzyme system whose activity is increased by prior exposure to air pollutants, cigarette smoke and certain drugs. The resultant diol epoxide metabolite has been shown to bind covalently with the DNA of the lung. In experimental animals, BaP is a potent initiating carcinogen whose action is enhanced by sulfur dioxide, promoting agents and carrier fine particles. The effect of small, divided doses of BaP has been shown to be greater than that of a single high dose; no threshold has been established. Epidemiological studies show that mixtures containing BaP (such as urban air, industrial emissions and cigarette smoke) are carcinogenic and may interact synergistically. Occupational studies indicate that the action of BaP-containing mixtures is enhanced in the presence of SO2. However, quantitative risk assessment for BaP is precluded by problems in extrapolating to the general population from small-scale animal studies; uncertainties in findings of epidemiology; and imprecise exposure data. Existing stationary and mobile controls preferentially remove coarse particulate matter and are inefficient collectors of the particulate BaP. In the current absence of health and environmental standards for BaP, there is little incentive

  20. 40 CFR 721.10662 - Acetaldehyde, substituted-, reaction products with 2-butyne-1, 4-diol (generic).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...-, reaction products with 2-butyne-1, 4-diol (generic). (a) Chemical substance and significant new uses... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Acetaldehyde, substituted-, reaction... ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT SIGNIFICANT NEW USES OF...

  1. 40 CFR 721.10662 - Acetaldehyde, substituted-, reaction products with 2-butyne-1, 4-diol (generic).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...-, reaction products with 2-butyne-1, 4-diol (generic). (a) Chemical substance and significant new uses... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Acetaldehyde, substituted-, reaction... ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT SIGNIFICANT NEW USES OF...

  2. 40 CFR 721.8085 - Reaction product of substituted aromatic diol, formaldehyde and alkanolamine, propoxylated...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Reaction product of substituted... NEW USES OF CHEMICAL SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.8085 Reaction product of substituted aromatic diol, formaldehyde and alkanolamine, propoxylated (generic)....

  3. 40 CFR 721.8085 - Reaction product of substituted aromatic diol, formaldehyde and alkanolamine, propoxylated...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Reaction product of substituted... NEW USES OF CHEMICAL SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.8085 Reaction product of substituted aromatic diol, formaldehyde and alkanolamine, propoxylated (generic)....

  4. 40 CFR 721.8085 - Reaction product of substituted aromatic diol, formaldehyde and alkanolamine, propoxylated...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Reaction product of substituted... NEW USES OF CHEMICAL SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.8085 Reaction product of substituted aromatic diol, formaldehyde and alkanolamine, propoxylated (generic)....

  5. 40 CFR 721.8085 - Reaction product of substituted aromatic diol, formaldehyde and alkanolamine, propoxylated...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Reaction product of substituted... NEW USES OF CHEMICAL SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.8085 Reaction product of substituted aromatic diol, formaldehyde and alkanolamine, propoxylated (generic)....

  6. 40 CFR 721.8085 - Reaction product of substituted aromatic diol, formaldehyde and alkanolamine, propoxylated...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Reaction product of substituted... NEW USES OF CHEMICAL SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.8085 Reaction product of substituted aromatic diol, formaldehyde and alkanolamine, propoxylated (generic)....

  7. Analysis of benzo(a)pyrene in airborne particulates by gas chromatography

    NASA Technical Reports Server (NTRS)

    Luedecke, E.

    1976-01-01

    A routine method was developed to measure benzo(a)pyrene in airborne particulates. Samples were collected on a filter and the organic portion was extracted with cyclohexane. The polynuclear hydrocarbon (PNHC) fraction was separated from the aliphatics by column chromatography. An internal standard was added to the extract and a portion of it was injected into a gas chromatograph. Although the gas chromatographic method has often been reported in the literature, satisfactory separation of benzo(a)pyrene and benzo(e)pyrene has not been achieved. With the introduction of a nematic liquid crystal as the stationary phase good separation is now possible.

  8. Studies on the mechanism of activation of microsomal benzo(a)pyrene hydroxylation by flavonoids

    SciTech Connect

    Huang, M.T.; Chang, R.L.; Fortner, J.G.; Conney, A.H.

    1981-07-10

    7,8-benzoflavone or flavone stimulates the hydroxylation of benzo(a)pyrene by liver microsomes from rabbit, hamster, and man severalfold. Little or no activation by the flavonoid occurs in liver microsomes from rat or guinea pig. Intact liver microsomal membranes are not required for the activation. Although 7,8-benzoflavone does not stimulate the NADPH-dependent reduction of cytochrome c by rabbit liver microsomes, the NADPH-dependent reduction of cytochrome P-450 is stimulated by 7,8-benzoflavone either in the presence or absence of benzo(a)pyrene. Purified cytochrome P-450 reductase causes an increase in the rate of benzo(a)pyrene hydroxylation in cholate-solubilized liver microsomes from all of the species studied. In cholate-solubilized microsomes from all of the species susceptible for flavonoid activation, 7,8-benzoflavone decreases the K/sub m/ for cytochrome P-450 reductase and increases the V/sub max/ for benzo(a)pyrene hydroxylation. With cholate-solubilized human liver microsomes, the K/sub m/ for cytochrome P-450 reductase in the absence of flavonoids was about 3-fold higher than in the presence of 100 ..mu..M 7,8-benzoflavone or 500 ..mu..M flavone. 7,8-benzoflavone and flavone stimulate the hydroxylation of benzo(a)pyrene in liver microsomes at least in part by enhancing the interaction between cytochrome P-450 and cytochrome P-450 reductase. 7,8-benzoflavone does not influence the K/sub m/ for benzo(a)pyrene or NADPH, but the V/sub max/ values for benzo(a)pyrene are increased from 2.5- to 4-fold in rabbit liver microsomes. 7,8-benzoflavone does not stimulate the cumene hydroperoxide-dependent hydroxylation of benzo(a)pyrene by rabbit liver microsomes. In two partially purified cytochrome P-450 fractions from rabbit liver microsomes, flavone has a specific stimulatory effect on one of the reconstituted partially purified cytochrome P-450 systems, but an inhibitory effect on the other.

  9. Inhibition of aryl hydrocarbon receptor transactivation and DNA adduct formation by CYP1 isoform-selective metabolic deactivation of benzo[a]pyrene

    SciTech Connect

    Endo, Kaori; Uno, Shigeyuki; Seki, Taiichiro; Ariga, Toyohiko; Kusumi, Yoshiaki; Mitsumata, Masako; Yamada, Sachiko; Makishima, Makoto

    2008-07-15

    Benzo[a]pyrene (BaP), a polyaromatic hydrocarbon produced by the combustion of cigarettes and coke ovens, is a known procarcinogen. BaP activates the aryl hydrocarbon receptor (AhR) and induces the expression of a battery of genes, including CYP1A1, which metabolize BaP to toxic compounds. The possible role of CYP1 enzymes in mediating BaP detoxification or metabolic activation remains to be elucidated. In this study, we assessed the effects of CYP1 enzymes (CYP1A1, CYP1A2 and CYP1B1) on BaP-induced AhR transactivation and DNA adduct formation in HEK293 cells and HepG2 cells. Transfection of CYP1A1 and CYP1B1, but not CYP1A2, suppressed BaP-induced activation of AhR. Expression of CYP1A1 and CYP1A2, but not CYP1B1, inhibited DNA adduct formation in BaP-treated HepG2 cells. These results indicate that CYP1A1 and CYP1B1 play a role in deactivation of BaP on AhR and that CYP1A1 and CYP1A2 are involved in BaP detoxification by suppressing DNA adduct formation. BaP treatment did not induce DNA adduct formation in HEK293 cells, even after transfection of CYP1 enzymes, suggesting that expression of CYP1 enzymes is not sufficient for DNA adduct formation. Lower expression of epoxide hydrolase and higher expression of glutathione S-transferase P1 (GSTP1) and GSTM1/M2 were observed in HEK293 cells compared with HepG2 cells. Dynamic expression of CYP1A1, CYP1A2 and CYP1B1 along with expression of other enzymes such as epoxide hydrolase and phase II enzymes may determine the detoxification or metabolic activation of BaP.

  10. Toughening of epoxy resins by epoxidized soybean oil

    SciTech Connect

    Frischinger, I.; Dirlikov, S.

    1993-12-31

    Homogeneous mixtures of a liquid rubber based on prepolymers of epoxidized soybean oil with amines, diglycidyl ether of bisphenol A epoxy resins, and commercial diamines form, under certain conditions, two-phase thermosetting materials that consist of a rigid epoxy matrix and randomly distributed small rubbery soybean particles (0.1-5 {mu}m). These two-phase thermosets have improved toughness, similar to that of other rubber-modified epoxies, low water absorption, and low sodium content. In comparison to the unmodified thermosets, the two-phase thermosets exhibit slightly lower glass-transition temperatures and Young`s moduli, but their dielectric properties do not change. The epoxidized soybean oil is available at a price below that of commercial epoxy resins and appears very attractive for epoxy toughening on an industrial scale. 15 refs., 17 figs., 6 tabs.

  11. Direct epoxidation of propylene over stabilized Cu(+) surface sites on titanium-modified Cu2O.

    PubMed

    Yang, Xiaofang; Kattel, Shyam; Xiong, Ke; Mudiyanselage, Kumudu; Rykov, Sergei; Senanayake, Sanjaya D; Rodriguez, José A; Liu, Ping; Stacchiola, Dario J; Chen, Jingguang G

    2015-10-01

    Direct propylene epoxidation by O2 is a challenging reaction because of the strong tendency for complete combustion. Results from the current study demonstrate that by generating highly dispersed and stabilized Cu(+) active sites in a TiCuOx mixed oxide the epoxidation selectivity can be tuned. The TiCuOx surface anchors the key surface intermediate, an oxametallacycle, leading to higher selectivity for epoxidation of propylene. PMID:26215635

  12. Markedly Elevated Carbamazepine-10,11-epoxide/Carbamazepine Ratio in a Fatal Carbamazepine Ingestion

    PubMed Central

    Russell, Jason L.; Spiller, Henry A.; Baker, Daniel D.

    2015-01-01

    Carbamazepine is a widely used anticonvulsant. Its metabolite, carbamazepine-10,11-epoxide, has been found to display similar anticonvulsant and neurotoxic properties. While the ratio of parent to metabolite concentration varies significantly, at therapeutic doses the epoxide concentration is generally about 20% of the parent. We report a case of fatal carbamazepine overdose in which the epoxide metabolite concentration was found to be 450% higher than the parent compound, suggesting a potential role for metabolite quantification in severe toxicity. PMID:26550016

  13. Direct Epoxidation of Propylene over Stabilized Cu+ Surface Sites on Ti Modified Cu2O

    DOE PAGESBeta

    Yang, X.; Kattel, S.; Xiong, K.; Mudiyanselage, K.; Rykov, S.; Senanayake, S. D.; Rodriguez, J. A.; Liu, P.; Stacchiola, D. J.; Chen, J. G.

    2015-07-17

    Direct propylene epoxidation by O2 is a challenging reaction because of the strong tendency for complete combustion. Results from the current study demonstrate the feasibility to tune the epoxidation selectivity by generating highly dispersed and stabilized Cu+ active sites in a TiCuOx mixed oxide. The TiCuOx surface anchors the key surface intermediate, oxametallacycle, leading to higher selectivity for epoxidation of propylene.

  14. Isolation and characterization of Xenopus soluble epoxide hydrolase.

    PubMed

    Purba, Endang R; Oguro, Ami; Imaoka, Susumu

    2014-07-01

    Soluble epoxide hydrolase (sEH) contributes to cell growth, but the contribution of sEH to embryonic development is not well understood. In this study, Xenopus sEH cDNA was isolated from embryos of Xenopus laevis. The Xenopus sEH was expressed in Escherichia coli and was purified. The epoxide hydrolase and phosphatase activities of purified sEH were investigated. The Xenopus sEH did not show phosphatase activity toward 4-methylumbelliferyl phosphate or several lysophosphatidic acids although it had EH activity. The amino acid sequence of Xenopus sEH was compared with that reported previously. We found amino acid substitutions of the 29th Thr to Asn and the 146th Arg to His and prepared a sEH mutant (N29T/H146R), designed as mutant 1. Neither wild-type sEH nor mutant 1 had phosphatase activity. Additional substitution of the 11th Gly with Asp was found by comparison with human sEH which has phosphatase activity, but the Xenopus sEH mutant G11D prepared as mutant 2 did not have phosphatase activity. The epoxide hydrolase activity of sEH seemed to be similar to that of human sEH, while Xenopus sEH did not have phosphatase activity toward several substrates that human sEH metabolizes. PMID:24681163

  15. Acid-Catalyzed Reaction of Epoxides on Atmospheric Nanoparticles

    NASA Astrophysics Data System (ADS)

    Xu, W.; Gomez-Hernandez, M.; Lal, V.; Qiu, C.; Khalizov, A. F.; Wang, L.; Zhang, R.

    2013-12-01

    Aerosol plays an important role in affecting the earth climate and harming human health. Atmospheric aerosols can be formed from either primary emissions or gas-to-particle conversion process. Numerous studies, including both experimental and theoretical, have been carried out to elucidate the mechanism of gas-to-particle conversion process (a.k.a. nucleation) and the later growth stage of newly formed nanoparticles. However, a complete list of species involving in the nucleation and growth processes of nanoparticles is still poorly understood. The growth of newly formed sulfuric acid - water nanoparticles has been suggested to involve several potential organic vapors, such as amines, glyoxal, 2-4 hexadienal, and epoxides. In the present study, new formed sulfuric acid -water nanoparticles were size selected by a differential mobility analyzer and exposed to epoxide vapors. The size-change after exposure was detected using the second differential mobility analyzer. The size-enlarged particles were then collected by an electrostatic precipitator, thermal vaporized, and analyzed by an ion drift chemical ionization mass spectrometer. Our results show that the sizes of nanoparticles are increased considerably and the magnitude of the increment in size is size-dependent. Mass spectrometry analysis of the nanoparticles after exposure demonstrates that low volatile organosulfate and oligomers are formed in nanoparticles upon their exposure to epoxide vapors.

  16. Metabolic enzyme activities, metabolism-related genes expression and bioaccumulation in juvenile white shrimp Litopenaeus vannamei exposed to benzo[a]pyrene.

    PubMed

    Ren, Xianyun; Pan, Luqing; Wang, Lin

    2014-06-01

    The purpose of this study was to investigate the impact of benzo[a]pyrene (BaP) on metabolic detoxification system and bioaccumulation of white shrimp Litopenaeus vannamei. In this study, juvenile white shrimp L. vannamei were exposed for 21 days at four different concentrations of 0, 0.03, 0.3 and 3μg/L. Detoxification enzyme activities of phase I (aryl hydrocarbon hydroxylase (AHH), 7-ethoxyresorufin O-deethylase (EROD), epoxide hydrolase (EH)) and phase II (glutathione-S-transferase (GST), sulfotransferase (SULT), uridine diphosphate glucuronyl transferase (UGT)) were determined, and results showed that all the detoxification enzyme activities increased in a dose-dependent manner except for the low BaP exposure. Transcription of genes was detected and measured by real-time RT-PCR. It showed that at day six BaP increased cytochrome P450 (CYP) 1A1, GST, SULT visa aryl hydrocarbon receptor (AhR) mRNA expression in a dose-dependent manner, which suggests that they could be potential targets of BaP that disrupt the detoxification system. The consistency of their responses to BaP exposure implies that AhR action may be involved in invertebrate CYP regulation. Additionally, BaP bioaccumulation increased rapidly first and showed an incoming plateau. Besides, the enzyme activities and bioaccumulation in the hepatopancreas were higher than those in the gills. These results will not only provide information on BaP metabolic mechanism for this species, but also scientific data for pollution monitoring. PMID:24636950

  17. Transcriptomic changes in zebrafish embryos and larvae following benzo[a]pyrene exposure

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Benzo[a]pyrene (BaP) is an environmentally relevant carcinogenic and endocrine disrupting compound that causes immediate, long-term, and multigenerational health deficits in mammals and fish. Previously, we found that BaP alters DNA methylation patterns in developing zebrafish, which may affect gene...

  18. Benzo(A)pyrene Decreases Brain and Ovarian Aromatase mRNA Expression

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The higher molecular weight polycyclic aromatic hydrocarbons (PAHs) such as benzo(a)pyrene (BaP) are typically associated with genotoxicity, however newer evidence suggests that these compounds may also act as endocrine system disruptors. We hypothesized that a target for reproductive or development...

  19. SYNTHESIS OF A NOVEL FLUORINATED BENZO(A)PYRENE: 4,5-DIFLUOROBENZO(A)PYRENE

    EPA Science Inventory

    The synthesis of difluorobenzo(a)pyrene, as a fluorinated probe to investigate the involvement of the K-region in the further metabolic activation of benzo(a)pyrene metabolites is described. enzo(a)pyrene-,5-dione obtained from 3-dichloro-5,6-dicyano-1,4-benzoquinone oxidation of...

  20. IRIS Toxicological Review of Benzo[a]pyrene (Interagency Science Consultation Draft)

    EPA Science Inventory

    On August 21, 2013, the draft Toxicological Review of Benzo[a]pyrene and the draft charge to external peer reviewers were released for public review and comment. The Toxicological Review and charge were reviewed internally by EPA and by other federal agencies and White House Offi...

  1. BENZO(A)PYRENE METABOLISM IN THE AMERICA OYSTER 'CRASSOSTREA VIRGINICA'

    EPA Science Inventory

    The research program was initiated with the overall objective of determining the role of NADPH-dependent microsomal mono-oxygenase in the metabolism of the widespread environmental carcinogen benzo(a)pyrene (BP) by the oyster Crassostrea virginica. This enzyme system is important...

  2. Mechanism-based inactivation of benzo(a)pyrene hydroxylase by aryl acetylenes and aryl olefins

    SciTech Connect

    Gan, L.S.; Lu, J.Y.L.; Alworth, W.L.

    1986-05-01

    A series of aryl acetylenes and aryl olefins have been examined as substrates and inhibitors of cytochrome P-450 dependent monooxgenases in liver microsomes from 5,6-benzoflavone or phenobarbital pretreated rats. 1-Ethynylpyrene, 3-ethynylperylene, 2-ethynylfluorene, methyl 1-pyrenyl acetylene, cis- and trans-1-(2-bromovinyl)pyrene, and 1-allylpyrene serve as mechanism-based irreversible inactivators (suicide inhibitors) of benzo(a)pyrene hydroxylase, while 1-vinylpyrene and phenyl 1-pyrenyl acetylene do not cause a detectable suicide inhibition of benzo(a)pyrene hydroxylase. The mechanism-based loss of benzo(a)pyrene hydroxylase caused by the aryl acetylenes is not accompanied by a corresponding loss of the P-450 content of the microsomes (suicide destruction). The suicide inhibition by these aryl acetylenes therefore does not involve covalent binding to the heme moiety of the monooxygenase. Nevertheless, in the presence of NADPH, /sup 3/H-labeled 1-ethynylpyrene becomes covalently attached to the cytochrome P-450 protein; the measured stoichiometry of binding is one 1-ethynylpyrene per P-450 heme unit. The authors conclude that the inhibition of benzo(a)pyrene hydroxylase produced by 1-ethynylpyrene may be related to the mechanism of suicide inhibition of P-450 activity by chloramphenicol rather than the mechanism of suicide destruction of P-450 previously described for acetylene and propyne.

  3. On the carcinogenic polycyclic aromatic hydrocarbon benzo(a)pyrene in volcano exhausts.

    PubMed

    Ilnitsky, A P; Belitsky, G A; Shabad, L M

    1976-05-01

    The content of benzo(a)pyrene in the juvenile ashes of the volcano Tyatya (Kunashir Island, Kuriles) and in the soil, vegetation and volcanic mud collected near volcanos in Kamchatka was studied. It was concluded that volcanic activity does not play a large role in forming the background level of this carcinogen in the human environment. PMID:1016954

  4. Benzo[a]pyrene decreases global and gene specific DNA methylation during zebrafish development

    Technology Transfer Automated Retrieval System (TEKTRAN)

    DNA methylation is important for gene regulation and is vulnerable to early-life exposure to environmental contaminants. We found that direct waterborne benzo[a]pyrene (BaP) exposure at 24 'g/L from 2.5 to 96 hours post fertilization (hpf) to zebrafish embryos significantly decreased global cytosine...

  5. Impacts of Anthropogenic Emissions in the Southeastern U.S. on Heterogeneous Chemistry of Isoprene-Derived Epoxides Leading to Secondary Organic Aerosol Formation (Invited)

    NASA Astrophysics Data System (ADS)

    Surratt, J. D.; Pye, H.; Lin, Y.; Budisulistiorini, S.; Zhang, H.; Marth, W.; Cui, T.; Arashiro, M.; Chu, K.; Zhang, Z.; Sexton, K.; Piletic, I.; Xie, Y.; Capps, S. L.; Luecken, D.; Hutzell, W. T.; Jaoui, M.; Canagaratna, M. R.; Croteau, D.; Jayne, J. T.; Worsnop, D. R.; Offenberg, J.; Kleindienst, T. E.; Lewandowski, M.; Edney, E.; Pinder, R. W.; Bartolotti, L.; Gold, A.

    2013-12-01

    Isoprene is a major source of secondary organic aerosol (SOA); however, the exact manner in which it forms SOA remains unclear. Improving our fundamental understanding of isoprene-derived SOA is key to improving existing air quality models, especially in the southeastern U.S. where models currently underestimate observations. By combining organic synthesis, computational calculations, mass spectrometry, smog chamber studies, and field measurements, we show that reactive epoxides, which include methacrylic acid epoxide (MAE) and isomeric isoprene epoxydiols (IEPOX), produced from the photochemical oxidation of isoprene are key to SOA formation. Furthermore, anthropogenic pollutants (NOx and SO2) enhance isoprene-derived epoxides as an SOA source. In the laboratory, we find that the reactive uptake of synthetic IEPOX and MAE standards onto acidified sulfate aerosol yields known isoprene-derived SOA tracers (2-methlytetrols, 2-methylglyceric acid, C5-alkene triols, 3-methyltetrahydrofuran-3,4-diols, dimers and organosulfates) that we measure in fine aerosol collected from multiple sites across the southeastern U.S. using gas chromatography/mass spectrometry (GC/MS) and liquid chromatography coupled to diode array detection and electrospray ionization high-resolution quadrupole time-of-flight mass spectrometry (LC/DAD-ESI-QTOFMS). Notably, IEPOX- and MAE-derived SOA tracers account for ~19% of the organic aerosol mass in Yorkville, GA. Moreover, real-time continuous chemical measurements of fine aerosol made using an Aerodyne Aerosol Chemical Speciation Monitor (ACSM) during summer 2011 and summer 2013 in Atlanta, GA, and Look Rock, TN, respectively, resolved an IEPOX-oxygenated organic aerosol (IEPOX-OOA) factor when applying positive matrix factorization (PMF) to the organic mass spectral time series. In Atlanta, this factor is found to account for ~33% of the fine OA mass and is correlated with IEPOX-derived SOA tracers (r2 = 0.6), sulfate (r2 = 0.5), and to some

  6. Effect of CYP2E1 gene deletion in mice on expression of microsomal epoxide hydrolase in response to VCD exposure.

    PubMed

    Keating, Aileen F; Rajapaksa, Kathila S; Sipes, I Glenn; Hoyer, Patricia B

    2008-10-01

    Females are born with a finite number of primordial follicles. 4-Vinylcyclohexene diepoxide (VCD) is a metabolite formed by epoxidation of 4-vinylcyclohexene (VCH) via its two monoepoxides 1,2- and 7,8-4-vinylcyclohexene monoepoxide (VCM). VCD specifically destroys small preantral (primordial and small primary) follicles in the rodent ovary. The phase I enzyme, cytochrome P450 isoform 2E1 (CYP2E1) is involved in ovarian metabolism of VCM to VCD. Further, microsomal epoxide hydrolase (mEH) can detoxify VCD to an inactive tetrol (4-(1,2-dihydroxy)ethyl-1,2-dihydroxycyclohexane). This study evaluated the effects of VCD-induced ovotoxicity on mEH in CYP2E1+/+ and -/- mice (129S(1)/SvImJ background strain) using a postnatal day 4 mouse whole ovary culture system. The hypothesis of our study is that there is a relationship between CYP2E1 and mEH gene expression in the mouse ovary. Relative to control, VCD exposure caused follicle loss (p < 0.05) in ovaries from both genotypes; however, after 15 days, this loss was greater (p < 0.05) in CYP2E1+/+ ovaries. In a time course (2-15 days), relative to control, VCD (5 microM) caused an increase (p < 0.05) in mEH mRNA by 0.5-fold (day 10) and 1.84-fold (day 15) in CYP2E1-/- but not +/+ ovaries. 7,12-Dimethylbenz[a]anthracene (DMBA) also destroys ovarian follicles but, unlike VCD, is bioactivated by mEH to an ovotoxic 3,4-diol-1,2-epoxide metabolite. Incubation of ovaries in increasing concentrations of DMBA (0.5-1 microM, 15 days) resulted in greater (p < 0.05) follicle loss in CYP2E1-/-, relative to +/+ ovaries. With greater mEH (CYP2E1-/-), increased follicle loss with DMBA (bioactivation) and decreased follicle loss with VCD (detoxification) support that ovarian expression of CYP2E1 and mEH may be linked. PMID:18622027

  7. The mixed diol-dithiol 2,2-bis(sulfanylmethyl)propane-1,3-diol: characterization of key intermediates on a new synthetic pathway.

    PubMed

    Simmons, Trevor R; Pickett, Christopher J; Wright, Joseph A

    2011-01-01

    A new synthetic route to 2,2-bis(sulfanylmethyl)propane-1,3-diol, (II), is described starting from the commercially available 2,2-bis(hydroxymethyl)propane-1,3-diol. The structures of two intermediates on this route are described. 5,5-Dimethenyl-2,2-dimethyl-1,3-dioxane bis(thiocyanate) (systematic name: {[5-(cyanosulfanyl)-2,2-dimethyl-1,3-dioxan-5-yl]sulfanyl}formonitrile), C(10)H(14)N(2)O(2)S(2), (X), crystallizes in the space group P2(1)/c with no symmetry relationship between the two thiocyanate groups. There is a short intramolecular N...S contact for one thiocyanate group, while the second group is positioned such that this type of interaction is not possible. 1,3-(Hydroxymethyl)propane-1,3-diyl bis(thiocyanate), C(7)H(10)N(2)O(2)S(2), (XI), also features a single short N···S contact in the solid state. Hydrogen bonding between two molecules of compound (XI) results in the formation of dimers in the crystal, which are then linked together by a second hydrogen-bond interaction between the dimers. In addition, the structures of two intermediates from an unsuccessful alternative synthesis of (II) are reported. 2,2-Bis(chloromethyl)propane-1,3-diol, C(5)H(10)Cl(2)O(2), (VI), crystallized as an inversion twin with a minor twin fraction of 0.43 (6). It forms a zigzag structure as a result of intermolecular hydrogen bonding. The structure of 9,9-dimethyl-2,4,8,10-tetraoxa-3λ(4)-thiaspiro[5.5]undecan-3-one, C(8)H(14)O(5)S, (VII), shows evidence for a weak S···O contact with a distance of 3.2529 (11) Å. PMID:21206075

  8. Sources and proxy potential of long chain alkyl diols in lacustrine environments

    NASA Astrophysics Data System (ADS)

    Rampen, Sebastiaan W.; Datema, Mariska; Rodrigo-Gámiz, Marta; Schouten, Stefan; Reichart, Gert-Jan; Sinninghe Damsté, Jaap S.

    2014-11-01

    Long chain 1,13- and 1,15-alkyl diols form the base of a number of recently proposed proxies used for climate reconstruction. However, the sources of these lipids and environmental controls on their distribution are still poorly constrained. We have analyzed the long chain alkyl diol (LCD) composition of cultures of ten eustigmatophyte species, with three species from different families grown at various temperatures, to identify the effect of species composition and growth temperature on the LCD distribution. The results were compared with the LCD distribution of sixty-two lake surface sediments, and with previously reported LCD distributions from marine environments. The different families within the Eustigmatophyceae show distinct LCD patterns, with the freshwater family Eustigmataceae most closely resembling LCD distributions in both marine and lake environments. Unlike the other two eustigmatophyte families analyzed (Monodopsidaceae and Goniochloridaceae), C28 and C30 1,13-alkyl diols and C30 and C32 1,15-alkyl diols are all relatively abundant in the family Eustigmataceae, while the mono-unsaturated C32 1,15-alkyl diol was below detection limit. In contrast to the marine environment, LCD distributions in lakes did not show a clear relationship with temperature. The Long chain Diol Index (LDI), a proxy previously proposed for sea surface temperature reconstruction, showed a relatively weak correlation (R2 = 0.33) with mean annual air temperature used as an approximation for annual mean surface temperature of the lakes. A much-improved correlation (R2 = 0.74, p-value <0.001) was observed applying a multiple linear regression analysis between LCD distributions and lake temperatures reconstructed using branched tetraether lipid distributions. The obtained regression model provides good estimates of temperatures for cultures of the family Eustigmataceae, suggesting that algae belonging to this family have an important role as a source for LCDs in lacustrine

  9. Bispidin-9,9-diol Analogues of Cisplatin, Carboplatin, and Oxaliplatin: Synthesis, Structures, and Cytotoxicity.

    PubMed

    Cui, Huiling; Goddard, Richard; Pörschke, Klaus-Richard; Hamacher, Alexandra; Kassack, Matthias U

    2016-03-21

    3,7-Diallyl-bispidin-9-one (6) (bispidin-9-one = 3,7-diazabicyclo[3.3.1]nonan-9-one) is converted to N-unsubstituted spiro[bispidin-9,2'-[1,3]dioxolane] (12; 35%). The ketal crystallizes in the forms of anhydrous 12a and the dihydrate 12b. The molecules in anhydrous 12a are linked to each other, forming N1-H1···N2-H2···N1* hydrogen-bond chiral helices of alternating chirality. In the dihydrate 12b, the ketal molecules are connected to a central string of water molecules by O3-H···O1 and O4-H···N1 hydrogen bonds, but not to themselves. Reaction of 12 with (1,5-hexadiene)PtCl2 affords almost quantitatively spiro[bispidin-9,2'-[1,3]dioxolane]PtCl2 (13). Cleavage of the ketal to retrieve the ketone produces the geminal diol (bispidin-9,9-diol)PtCl2 (14; 85%). Compound 14 reacts with Ag2cbdca (cbdca = 1,1-cyclobutanedicarboxylate) to give the dihydrate (bispidin-9,9-diol)Pt(cbdca)·2H2O (15b), which can be dehydrated to obtain anhydrous (bispidin-9,9-diol)Pt(cbdca) (15a). Similarly, anhydrous (bispidin-9,9-diol)Pt(oxalate) (16) is obtained. Crystal structures of 14 and 15b reveal association by various forms of O-H···O, O-H···Cl, N-H···Cl, and N-H···O hydrogen bonds. Biological studies showed a moderate cytotoxic activity of the bispidin-9,9-diol complexes 14-16, compared to the 9,9-unsubstituted bispidine complexes. No unspecific cytotoxicity of 14-16 up to 316 μM was found against the noncancer cell line HEK293. PMID:26918619

  10. Variants of mouse DNA polymerase κ reveal a mechanism of efficient and accurate translesion synthesis past a benzo[a]pyrene dG adduct

    PubMed Central

    Liu, Yang; Yang, Yeran; Tang, Tie-Shan; Zhang, Hui; Wang, Zhifeng; Friedberg, Errol; Yang, Wei; Guo, Caixia

    2014-01-01

    DNA polymerase κ (Polκ) is the only known Y-family DNA polymerase that bypasses the 10S (+)-trans-anti-benzo[a]pyrene diol epoxide (BPDE)-N2-deoxyguanine adducts efficiently and accurately. The unique features of Polκ, a large structure gap between the catalytic core and little finger domain and a 90-residue addition at the N terminus known as the N-clasp, may give rise to its special translesion capability. We designed and constructed two mouse Polκ variants, which have reduced gap size on both sides [Polκ Gap Mutant (PGM) 1] or one side flanking the template base (PGM2). These Polκ variants are nearly as efficient as WT in normal DNA synthesis, albeit with reduced accuracy. However, PGM1 is strongly blocked by the 10S (+)-trans-anti-BPDE-N2-dG lesion. Steady-state kinetic measurements reveal a significant reduction in efficiency of dCTP incorporation opposite the lesion by PGM1 and a moderate reduction by PGM2. Consistently, Polκ-deficient cells stably complemented with PGM1 GFP-Polκ remained hypersensitive to BPDE treatment, and complementation with WT or PGM2 GFP-Polκ restored BPDE resistance. Furthermore, deletion of the first 51 residues of the N-clasp in mouse Polκ (mPolκ52–516) leads to reduced polymerization activity, and the mutant PGM252–516 but not PGM152–516 can partially compensate the N-terminal deletion and restore the catalytic activity on normal DNA. However, neither WT nor PGM2 mPolκ52–516 retains BPDE bypass activity. We conclude that the structural gap physically accommodates the bulky aromatic adduct and the N-clasp is essential for the structural integrity and flexibility of Polκ during translesion synthesis. PMID:24449898

  11. Percutaneous absorption of an insect repellent p-menthane-3,8-DIOL: a model for human dermal absorption.

    PubMed

    Reifenrath, William G; Olson, James J; Vedula, Usha; Osimitz, Thomas G

    2009-01-01

    p-Menthane-3,8-diol(38DIOL) was recently introduced as a natural topical insect repellent in the commercial product "OFF! Botanicals" lotion. The objective of this study was to provide an estimate of the potential for 38DIOL systemic absorption in humans. Carbon-14-labeled 38DIOL formulated in the lotion and in an ethanol solution was applied to excised pig skin in an in vitro flow-through test system predictive of skin absorption in humans. Twenty-four hours after application, radiolabel recovered from the dermis and receptor fluid was summed to determine percent absorption. At a dose of approximately 80 microg/cm(2) of 38DIOL in the lotion, a value of 3.5 +/- 0.8% of applied dose was obtained with pig skin. The corresponding value for 38DIOL in ethanol (90 microg/cm(2)) was not significantly different (3.0 +/- 1.2%). Most of the applied dose of 38DIOL was found to evaporate from pig skin (77 +/- 8% for the lotion and 87 +/- 1% for ethanol solution), thus limiting percutaneous absorption values. For reference purposes, the pig skin absorptions of piperonyl butoxide (PBO) at 100 microg/cm(2) in isopropanol, N,N-diethyl-m-toluamide (DEET) at 500 microg/cm(2) in ethanol, and neat isododecane at 650 microg/cm(2) (in order of increasing volatility) were 15 +/- 6%, 23 +/- 3%, and 0.09 +/- 0.05% of applied dose respectively. Isododecane was lost almost exclusively from the skin surface by evaporation. For additional reference, absorptions of PBO, DEET, and 38DIOL were found to be higher with excised rat skin. PMID:19557607

  12. (S)-(+)-N-acetylphenylglycineboronic acid: a chiral derivatizing agent for Ee determination of 1,2-diols.

    PubMed

    Caselli, Emilia; Danieli, Chiara; Morandi, Stefania; Bonfiglio, Beatrice; Forni, Arrigo; Prati, Fabio

    2003-12-11

    A new chiral derivatizing agent for ee determination of 1,2-diols via (1)H NMR is described. (S)-(+)-N-acetylphenylglycineboronic acid (1) is synthesized in enantiomerically pure form; its reaction with chiral diols quantitatively yields cyclic boronic esters 5a-g. The latter show a remarkably high diastereodifferentiation of proton NMR signals useful for de determination. [reaction: see text] PMID:14653693

  13. Voltammetric response of ferroceneboronic acid to diol and phenolic compounds as possible pollutants.

    PubMed

    Takahashi, Shigehiro; Abiko, Naoyuki; Haraguchi, Nobuhiro; Fujita, Hiroyuki; Seki, Eriko; Ono, Tetsuya; Yoshida, Kentaro; Anzai, Jun-ichi

    2011-01-01

    A voltammetric determination of possible organic pollutants such as diol and phenolic compounds in water was studied using ferroceneboronic acid (FBA) as a redox-active marker. A cyclic voltammogram of FBA exhibited a pair of oxidation and reduction peaks at 230 and 170 mV at pH 7.0, respectively, while another pair of redox peaks was observed in the presence of diol or phenolic compounds tested. The results were rationalized based on the formation of boronate esters of FBA with the added compounds. The changes in the redox peak currents were dependent on the concentration of the additives, suggesting a usefulness of FBA in the electrochemical determination of these compounds in water. PMID:22066227

  14. Towards a General Understanding of Carbonyl-Stabilised Ammonium Ylide-Mediated Epoxidation Reactions.

    PubMed

    Novacek, Johanna; Roiser, Lukas; Zielke, Katharina; Robiette, Raphaël; Waser, Mario

    2016-08-01

    The key factors for carbonyl-stabilised ammonium ylide-mediated epoxidation reactions were systematically investigated by experimental and computational means and the hereby obtained energy profiles provide explanations for the observed experimental results. In addition, we were able to identify the first tertiary amine-based chiral auxiliary that allows for high enantioselectivities and high yields for such epoxidation reactions. PMID:27381752

  15. Asymmetric Epoxidation: A Twinned Laboratory and Molecular Modeling Experiment for Upper-Level Organic Chemistry Students

    ERIC Educational Resources Information Center

    Hii, King Kuok; Rzepa, Henry S.; Smith, Edward H.

    2015-01-01

    The coupling of a student experiment involving the preparation and use of a catalyst for the asymmetric epoxidation of an alkene with computational simulations of various properties of the resulting epoxide is set out in the form of a software toolbox from which students select appropriate components. At the core of these are the computational…

  16. 40 CFR 721.7210 - Epoxidized copolymer of phenol and substituted phenol.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Epoxidized copolymer of phenol and substituted phenol. 721.7210 Section 721.7210 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... Specific Chemical Substances § 721.7210 Epoxidized copolymer of phenol and substituted phenol. (a)...

  17. 40 CFR 721.7210 - Epoxidized copolymer of phenol and substituted phenol.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Epoxidized copolymer of phenol and substituted phenol. 721.7210 Section 721.7210 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... Specific Chemical Substances § 721.7210 Epoxidized copolymer of phenol and substituted phenol. (a)...

  18. 40 CFR 721.7210 - Epoxidized copolymer of phenol and substituted phenol.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Epoxidized copolymer of phenol and substituted phenol. 721.7210 Section 721.7210 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... Specific Chemical Substances § 721.7210 Epoxidized copolymer of phenol and substituted phenol. (a)...

  19. 40 CFR 721.7210 - Epoxidized copolymer of phenol and substituted phenol.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Epoxidized copolymer of phenol and substituted phenol. 721.7210 Section 721.7210 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... Specific Chemical Substances § 721.7210 Epoxidized copolymer of phenol and substituted phenol. (a)...

  20. 40 CFR 721.7210 - Epoxidized copolymer of phenol and substituted phenol.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Epoxidized copolymer of phenol and substituted phenol. 721.7210 Section 721.7210 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... Specific Chemical Substances § 721.7210 Epoxidized copolymer of phenol and substituted phenol. (a)...

  1. General, Highly Selective Synthesis of 1,3- and 1,4-Difunctionalized Building Blocks by Regiodivergent Epoxide Opening.

    PubMed

    Funken, Nico; Mühlhaus, Felix; Gansäuer, Andreas

    2016-09-19

    We describe a regiodivergent epoxide opening (REO) featuring a catalyst-controlled synthesis of enantiomerically and diastereomerically highly enriched or pure syn- and anti- 1,3- and 1,4-difunctionalized building blocks from a common epoxide precursor. The REO is attractive for natural product synthesis and as a branching reaction for diversity-oriented synthesis with epoxides. PMID:27600090

  2. Carbene-catalyzed desymmetrization of 1,3-diols: access to optically enriched tertiary alkyl chlorides.

    PubMed

    Li, Bao-Sheng; Wang, Yuhuang; Proctor, Rupert S J; Jin, Zhichao; Chi, Yonggui Robin

    2016-07-01

    The introduction of a chlorine atom to a carbon center in an enantioselective manner via conventional C-Cl bond formation is difficult. Here we report a new approach to this class of tertiary alkyl chlorides with high optical purities. Instead of forming a new C-Cl bond, our approach involves carbene-catalyzed desymmetrization of 2-chloro-1,3-diols as the key step to set up the chiral carbon center with excellent enantiomeric excess. PMID:27298081

  3. Pyrolytic transformations of the vinyl monoethers of diols in the presence of alkalis

    SciTech Connect

    Trofimov, B.A.; Oparina, L.A.; Parshina, L.N.; Lavrov, V.I.; Grigorenko, V.I.; Zhumabekov, M.K.

    1987-01-10

    The alkaline pyrolysis of the vinyl monoethers of diols takes place at 170-250/sup 0/C and is accompanied by cycloacetalization (ethylene glycol, 1,3-propanediol), by processes involving cleavage of the C-O bonds (diethylene glycol, 1,4-butanediol), and also by the release of hydrogen, carbon dioxide, methane, ethane, acetylene, potassium hydroxide, sodium hydroxide, and lithium hydroxide can result in explosion as a result of the vigorous and exothermic release of gas.

  4. Zirconium-doped magnetic microspheres for the selective enrichment of cis-diol-containing ribonucleosides.

    PubMed

    Fan, Hua; Chen, Peihong; Wang, Chaozhan; Wei, Yinmao

    2016-05-27

    Zirconium-doped magnetic microspheres (Zr-Fe3O4) for the selective enrichment of cis-diol-containing biomolecules were easily synthesized via a one-step hydrothermal method. Characterization of the microspheres revealed that zirconium was successfully doped into the lattice of Fe3O4 at a doping level of 4.0 at%. Zr-Fe3O4 possessed good magnetic properties and high specificity towards cis-diol molecules, as shown using 28 compounds. For ribonucleosides, the adsorbent not only has favorable anti-interferential abilities but also has a high adsorption capacity up to 159.4μmol/g. As an example of a real application, four ribonucleosides in urine were efficiently enriched and detected via magnetic solid-phase extraction coupled with high-performance liquid chromatography. Under the optimized extraction conditions, the detection limits were determined to be between 0.005 and 0.017μg/mL, and the linearities ranged from 0.02 to 5.00μg/mL (R≥0.996) for these analytes. The accuracy of the analytical method was examined by studying the relative recoveries of the analytes in real urine samples, with recoveries varying from 77.8% to 119.6% (RSDs<10.6%, n=6). The results indicate that Zr-Fe3O4 is a suitable adsorbent for the analysis of cis-diol-containing biomolecules in practical applications. PMID:27130580

  5. Photoaffinity labeling of opioid receptor with morphine-7,8-oxide (morphine epoxide)

    SciTech Connect

    Takayanagi, I.; Shibata, R.; Miyata, N.; Hirobe, M.

    1982-05-01

    The opioid receptor mediating inhibitory action of morphine in the electrically stimulated guinea pig ileum was irreversibly photoinactivated by morphine epoxide (3 X 10(-6) M). Morphine epoxide (up to 3 X 10(-5) M) did not influence the responses of rat vas deferens (epsilon-receptor) or rabbit vas deferens (kappa-receptor) to electrical stimulation. Effective concentrations of morphine epoxide were much lower in the guinea pig ileum (mu-receptor) than in the mouse vas deference (delta-receptor). The inhibitory action of (Met)-enkephalin on the twitch responses of the rat vas deferens and mouse vas deferens to electrical stimulation were not influenced after irradiation in the presence of morphine epoxide (3 X 10(-6) M). Therefore, morphine epoxide is probably a useful probe for photoaffinity labeling of the mu-receptor in vitro.

  6. Iron-catalysed propylene epoxidation by nitrous oxide: dramatic shift of allylic oxidation to epoxidation by the modification with alkali metal salts.

    PubMed

    Wang, Xiaoxing; Zhang, Qinghong; Guo, Qian; Lou, Yinchuan; Yang, Lujuan; Wang, Ye

    2004-06-21

    A dramatic shift of allylic oxidation to epoxidation has been observed during the oxidation of propylene by N(2)O when the FeO(x)/SBA-15 catalyst is modified with alkali metal salts, and the roles of alkali metal salts are to suppress the reactivity of lattice oxygen and to induce an iron coordination structure effective for epoxidation with N(2)O. PMID:15179482

  7. An enzyme catalysing the conjugation of epoxides with glutathione

    PubMed Central

    Boyland, E.; Williams, K.

    1965-01-01

    1. Liver supernatant preparations from rats and ferrets catalyse the conjugation of some epoxides with glutathione. The enzyme involved might be called `glutathione S-epoxidetransferase', as it is different from glutathione S-aryltransferase, the enzyme catalysing the conjugation of 1,2-dichloro-4-nitrobenzene, 4-nitro-pyridine N-oxide and other cyclic compounds with glutathione and from the enzyme catalysing the conjugation of iodomethane and glutathione. 2. The enzyme does not catalyse the reaction with cysteine. It is not inactivated by dialysis but is unstable at pH 5·0. 3. The role of the enzyme in metabolism of foreign compounds is discussed. PMID:14342229

  8. Catalysts for CO2/epoxide ring-opening copolymerization

    PubMed Central

    Trott, G.; Saini, P. K.; Williams, C. K.

    2016-01-01

    This article summarizes and reviews recent progress in the development of catalysts for the ring-opening copolymerization of carbon dioxide and epoxides. The copolymerization is an interesting method to add value to carbon dioxide, including from waste sources, and to reduce pollution associated with commodity polymer manufacture. The selection of the catalyst is of critical importance to control the composition, properties and applications of the resultant polymers. This review highlights and exemplifies some key recent findings and hypotheses, in particular using examples drawn from our own research. PMID:26755758

  9. Catalysts for CO2/epoxide ring-opening copolymerization.

    PubMed

    Trott, G; Saini, P K; Williams, C K

    2016-02-28

    This article summarizes and reviews recent progress in the development of catalysts for the ring-opening copolymerization of carbon dioxide and epoxides. The copolymerization is an interesting method to add value to carbon dioxide, including from waste sources, and to reduce pollution associated with commodity polymer manufacture. The selection of the catalyst is of critical importance to control the composition, properties and applications of the resultant polymers. This review highlights and exemplifies some key recent findings and hypotheses, in particular using examples drawn from our own research. PMID:26755758

  10. Electroless copper coating of epoxide plates in an ultrasonic field.

    PubMed

    Touyeras, F; Hihn, J Y; Doche, M L; Roizard, X

    2001-07-01

    This paper reports the study of ultrasonic irradiation effects on electroless copper coating on an epoxide resin. Several parameters were monitored, such as plating rates, practical adhesion and internal stress, versus varying acoustic powers at a constant frequency of 530 kHz. Exposure conditions were characterised by both transmitted power and interfacial mass transfer coefficients. Optimum conditions expressed in irradiation time and power were determined. The use of ultrasound during electroless copper plating affects the plating rates and the deposits properties, particularly the practical adhesion which increases whereas the internal stress decreases. Then, the changes in the coating mechanisms are discussed. PMID:11441612

  11. A 90 kyr upwelling record from the northwestern Indian Ocean using a novel long-chain diol index

    NASA Astrophysics Data System (ADS)

    Rampen, Sebastiaan W.; Schouten, Stefan; Koning, Erica; Brummer, Geert-Jan A.; Sinninghe Damsté, Jaap S.

    2008-11-01

    Presently, upwelling is of major importance for driving primary productivity in the Arabian Sea but its intensity in the past is not well constrained. Here we used long-chain 1,14-alkane diols, specific lipids of diatoms of the genus Proboscia, as new proxies to reconstruct upwelling conditions in the Arabian Sea. Variations in the seasonal lipid fluxes were determined using sediment traps in the Somalia upwelling system deployed 80 km off the coast on the Somali continental slope (NIOP 905, 10°45.444'N / 51°56.655'E) at 1265 m water depth, 268 m above the sea floor and 270 km off the coast in the deep Somali Basin south of Socotra (NIOP 915, 10°43.068'N / 53°34.422'E), at 3047 m depth, 1000 m above the sea floor. Highest fluxes of C 28 and C 30 1,14-diols (up to almost 600 µg m - 2 day - 1 ) were only observed during nutricline shoaling at the onset of the Southwest monsoon (SWM), prior to massive upwelling. By contrast, fluxes of C 30 1,15-diols, derived from as yet undefined biological sources, only increased marginally during the SWM and also during the Northeast monsoon (NEM), when, instead of upwelling, enhanced vertical mixing led to a second productivity pulse. Sediment core NIOP 905 taken at the continental slope site showed strong fluctuations in relative concentrations of long-chain 1,14- and 1,15-diols with time, which we quantified as the summed concentrations of C 28 and C 30 1,14-diols divided by the summed concentrations of C 28 and C 30 1,14-diols and C 30 1,15-diols. This diol index follows the same trend as other upwelling intensity records from the Arabian Sea that are based on sea surface temperature reconstructions, organic carbon content, barium/aluminium ratios, and abundance and stable isotope composition of specific foraminiferal species. The diol index was relatively high during the Holocene (ca. 0.7) but much lower during the Late Glacial Maximum (ca. 0.2). It was generally low during the last Glacial but elevated values were found

  12. Integrated process and dual-function catalyst for olefin epoxidation

    DOEpatents

    Zhou, Bing; Rueter, Michael

    2003-01-01

    The invention discloses a dual-functional catalyst composition and an integrated process for production of olefin epoxides including propylene oxide by catalytic reaction of hydrogen peroxide from hydrogen and oxygen with olefin feeds such as propylene. The epoxides and hydrogen peroxide are preferably produced simultaneously in situ. The dual-functional catalyst comprises noble metal crystallites with dimensions on the nanometer scale (on the order of <1 nm to 10 nm), specially dispersed on titanium silicalite substrate particles. The dual functional catalyst catalyzes both the direct reaction of hydrogen and oxygen to generate hydrogen peroxide intermediate on the noble metal catalyst surface and the reaction of the hydrogen peroxide intermediate with the propylene feed to generate propylene oxide product. Combining both these functions in a single catalyst provides a very efficient integrated process operable below the flammability limits of hydrogen and highly selective for the production of hydrogen peroxide to produce olefin oxides such as propylene oxide without formation of undesired co-products.

  13. Catalysis of potato epoxide hydrolase, StEH1

    PubMed Central

    Elfström, Lisa T.; Widersten, Mikael

    2005-01-01

    The kinetic mechanism of epoxide hydrolase (EC 3.3.2.3) from potato, StEH1 (Solanum tuberosum epoxide hydrolase 1), was studied by presteady-state and steady-state kinetics as well as by pH dependence of activity. The specific activities towards the different enantiomers of TSO (trans-stilbene oxide) as substrate were 43 and 3 μmol·min−1·mg−1 with the R,R- or S,S-isomers respectively. The enzyme was, however, enantioselective in favour of the S,S enantiomer due to a lower Km value. The pH dependences of kcat with R,R or S,S-TSO were also distinct and supposedly reflecting the pH dependences of the individual kinetic rates during substrate conversion. The rate-limiting step for TSO and cis- and trans-epoxystearate was shown by rapid kinetic measurements to be the hydrolysis of the alkylenzyme intermediate. Functional characterization of point mutants verified residues Asp105, Tyr154, Tyr235 and His300 as crucial for catalytic activity. All mutants displayed drastically decreased enzymatic activities during steady state. Presteady-state measurements revealed the base-deficient H300N (His300→Asn) mutant to possess greatly reduced efficiencies in catalysis of both chemical steps (alkylation and hydrolysis). PMID:15882148

  14. Determination of benzo(a)pyrene in the total particulate matter of cigarette smoke

    SciTech Connect

    Risner, C.H.

    1988-03-01

    A procedure for the isolation and determination of benzo(a)pyrene in the total particulate matter of cigarette smoke is described. Two high-pressure liquid chromatographic (HPLC) techniques are employed: a normal-phase, mu Bondapak-NH2, amino column is used for isolation of the benzo(a)pyrene fraction and a reversed-phase, Vydac 201TP54, polymeric octadecyl silane column is used for quantitation. Fluorescence detection is used in both modes of chromatography. The wavelengths of excitation and emission are evaluated for analytical detection. Extraction media and various isolation techniques are compared for their extraction efficiency and isolation from interferences, respectively. The procedure is efficient, reproducible, sensitive (3 pg), and gives results that compare favorably with other techniques reported in the literature for the B(a)P content of reference cigarettes, 1R1 and 1R4F.

  15. Metabolism of benzo(a)pyrene by isolated perfused testis and testicular homogenate

    SciTech Connect

    Dixon, R.L.; Lee, I.P.

    1980-12-01

    In an effort to improve the extrapolation of laboratory data to man and estimate risk of human reproductive toxicity associated with environmental exposure, the pharmacokinetic parameters of the testicular compartment are being studied. Of particular interest is the variety of enzyme systems capable of activating and detoxicating environmental chemicals and drugs. This report compares the metabolism of benzo(a)pyrene by the isolated perfused testis and testicular homogenates in vitro. The cell free in vitro system metabolized benzo(a)pyrene at a much greater rate than the perfused testis and produced a different spectrum of metabolites. Reliable laboratory prediction of biotransformation by the whole organ or intact animal is an essential aspect of reproductive toxicology.

  16. Biotin-mediated epigenetic modifications: Potential defense against the carcinogenicity of benzo[a]pyrene.

    PubMed

    Xia, Bo; Pang, Li; Zhuang, Zhi-xiong; Liu, Jian-jun

    2016-01-22

    Environmental pollution and an unhealthy lifestyle result in direct exposure to dangerous chemicals that can modify endogenous pathways and induce malignant transformation of human cells. Although the molecular mechanisms of tumorigenesis are still not well understood, epigenetic alteration may be associated with exogenous chemical-induced carcinogenicity. Given the association between nutrition and cancer, nutrient supplementation may reduce aberrant epigenetic modifications induced by chemicals, thus decreasing carcinogenesis. This paper provides an overview of the epigenetic events caused by benzo[a]pyrene, a procarcinogenic and environmental pollutant, and biotin, an essential water-soluble vitamin, and investigates potential connections between them. This paper also discusses the potential inhibitory effect of biotin-related epigenetic modifications on the carcinogenicity of benzo[a]pyrene. The effect of nutritional supplementation on tumorigenesis involving epigenetic modifications is also discussed. PMID:26569572

  17. Occurrence of benzo(a)pyrene in combustion effluents of kerosene and diesel burners

    SciTech Connect

    Gharaibeh, S.H.; Abuirjeie, M.A.; Hunaiti, A.A.

    1988-09-01

    Due to limited Jordanian resources, kerosene and diesel burners have been widely used for heating homes and water, warming bread, grilling meat and cooking food. Jordan annually imports and average of 204 tons of burners which corresponds to approximately 20,400 burners. Considerable amounts of combustion products are produced such as gases, aerosols and polycyclic aromatic hydrocarbons (PAH), especially benzo(a)pyrene (Bp), the well known carcinogen for man and animal. Since most Jordanians use burners more than five months a year, a considerable amount of combustion effluents accumulate indoors. Some of these materials can enter the human body via various routes, and are potential health hazards. Little information is available about the chemical nature and amount of the combustion effluents produced by these burners; therefore the present study was designed to screen for benzo(a)pyrene in the indoor-accumulated combustion effluent.

  18. Benzo(a)pyrene inhibits the role of the bioturbator Tubifex tubifex in river sediment biogeochemistry.

    PubMed

    Mermillod-Blondin, F; Foulquier, A; Gilbert, F; Navel, S; Montuelle, B; Bellvert, F; Comte, G; Grossi, V; Fourel, F; Lecuyer, C; Simon, L

    2013-04-15

    The interactions between invertebrates and micro-organisms living in streambed sediments often play key roles in the regulation of nutrient and organic matter fluxes in aquatic ecosystems. However, benthic sediments also constitute a privileged compartment for the accumulation of persistent organic pollutants such as PAHs or PCBs that may affect the diversity, abundance and activity of benthic organisms. The objective of this study was to quantify the impact of sediment contamination with the PAH benzo(a)pyrene on the interaction between micro-organisms and the tubificid worm, Tubifex tubifex, which has been recognized as a major bioturbator in freshwater sediments. Sedimentary microcosms (slow filtration columns) contaminated or not with benzo(a)pyrene (3 tested concentrations: 0, 1 and 5 mg kg(-1)) at the sediment surface were incubated under laboratory conditions in the presence (100 individuals) or absence of T. tubifex. Although the surface sediment contaminations with 1 mg kg(-1) and 5 mg kg(-1) of benzo(a)pyrene did not affect tubificid worm survival, these contaminations significantly influenced the role played by T. tubifex in biogeochemical processes. Indeed, tubificid worms stimulated aerobic respiration, denitrification, dehydrogenase and hydrolytic activities of micro-organisms in uncontaminated sediments whereas such effects were inhibited in sediments polluted with benzo(a)pyrene. This inhibition was due to contaminant-induced changes in bioturbation (and especially bio-irrigation) activities of worms and their resulting effects on microbial processes. This study reveals the importance of sublethal concentrations of a contaminant on ecological processes in river sediments through affecting bioturbator-microbe interactions. Since they affect microbial processes involved in water purification processes, such impacts of sublethal concentrations of pollutants should be more often considered in ecosystem health assessment. PMID:23500821

  19. Vitamin K as a regulator of benzo(a)pyrene metabolism, mutagenesis, and carcinogenesis. Studies with rat microsomes and tumorigenesis in mice.

    PubMed Central

    Israels, L G; Walls, G A; Ollmann, D J; Friesen, E; Israels, E D

    1983-01-01

    Vitamin K3 inhibits the conversion of benzo(a)pyrene to its more polar metabolites in an in vitro rat liver microsomal system. Vitamin K3 also inhibits benzo(a)pyrene metabolism in rat liver fragments and reduces its mutagenicity in the Ames test. Higher concentrations of vitamin K3 are required to comparably reduce benzo(a)pyrene metabolism when the microsomal system has been induced with 3-methylcholanthrene. High pressure liquid chromatography analysis of the products of benzo(a)pyrene metabolism shows a uniform reduction of all the metabolic products. When tumors were induced in ICR/Ha female mice by the intraperitoneal injection of benzo(a)pyrene, those mice given vitamin K3 before or both before and after benzo(a)pyrene had a slower rate of tumor appearance and tumor death rate as compared with those receiving benzo(a)pyrene alone. However, vitamin K1 increased the rate of tumor death while vitamin K deprivation and warfarin decreased the rate of tumor appearance and death in benzo(a)pyrene-injected mice. These studies indicate that vitamin K3 is an inhibitor of aryl hydrocarbon hydroxylase and reduces the carcinogenic and mutagenic metabolites in vitro, and inhibits benzo(a)pyrene tumorigenesis in vivo. That vitamin K1 enhances the benzo(a)pyrene effect while warfarin and vitamin K deficiency inhibit benzo(a)pyrene tumorigenesis indicates that vitamin K1, vitamin K deprivation, or possibly blockade of its metabolic cycle also modulates benzo(a)pyrene metabolism in vivo but by a mechanism or at a site different from the vitamin K3 effect. The vitamin K series should be considered as capable of serving a regulatory function in the metabolism of benzo(a)pyrene and possibly other compounds metabolized through the mixed function oxidase system. PMID:6304144

  20. Aminoacylase 1-catalysed deacetylation of bioactives epoxides mycotoxin-derived mercapturates; 3,4-epoxyprecocenes as models of cytotoxic epoxides.

    PubMed

    Stocker, Pierre; Brunel, Jean Michel; de Rezende, Leandro; do Amaral, Antonia Tavares; Morelli, Xavier; Roche, Phillipe; Vidal, Nicolas; Giardina, Thierry; Perrier, Josette

    2012-08-01

    The mycotoxin aflatoxin B1 (AFB1) is a carcinogenic food contaminant which is metabolically activated by epoxydation. The metabolism of mycotoxins via the mercapturate metabolic pathway was shown, in general, to lead to their detoxication. Mercapturic acids thus formed (S-substitued-N-acetyl-l-cysteines) may be accumulated in the kidney and either excreted in the urine or desacetylated by Acylase 1 (ACY1) to yield cysteine S-conjugates. To be toxic, the N-acetyl-l-cysteine-S-conjugates first have to undergo deacetylation by ACY 1. The specificity and rate of mercapturic acid deacetylation may determine the toxicity, however the exact deacetylation processes involved are not well known. The aim of this study was to investigate the role of ACY1 in the toxicity of some bioactive epoxides from Aflatoxin B1. We characterized the kinetic parameters of porcine kidney and human recombinant aminoacylase-1 towards some aromatic and aliphatic-derived mercapturates analogue of mycotoxin-mercapturic acids and 3,4-epoxyprecocene, a bioactive epoxide derivated from aflatoxin. The deacetylation of mercapturated substrates was followed both by reverse phase HPLC and by TNBS method. Catalytic activity was discussed in a structure-function relationship. Ours results indicate for the first time that aminoacylase-1 could play an important role in deacetylating mercapturate metabolites of aflatoxin analogues and this process may be in relation with their cyto- and nephrotoxicity in human. PMID:22349737

  1. Role of induction of specific hepatic cytochrome P450 isoforms in epoxidation of 4-vinylcyclohexene.

    PubMed

    Fontaine, S M; Hoyer, P B; Halpert, J R; Sipes, I G

    2001-09-01

    4-Vinyl-1-cyclohexene (VCH) is ovotoxic in B6C3F(1) mice but not in Fischer-344 rats, which can be partially attributed to greater formation of toxic epoxides from VCH in mice compared with rats. Since repeated exposure to VCH is necessary to cause ovotoxicity in mice, it is important to determine whether repeated exposure results in induction of cytochrome P450 (CYP) enzymes involved in its bioactivation. Hepatic microsomes prepared from mice or rats treated repeatedly with VCH demonstrated significantly increased VCH bioactivation in vitro, as assessed by VCH-1,2-epoxide, VCH-7,8-epoxide, or vinylcyclohexene diepoxide (VCD) formation. Mice and rats were then dosed with VCH, VCH-1,2-epoxide, or VCD for 10 days and measured for increases in hepatic microsomal CYP levels or activities. Total hepatic CYP levels were elevated only in microsomes from mice pretreated with VCH or VCH-1,2-epoxide. Immunoblotting analysis of microsomes from VCH-treated rodents revealed elevated levels of CYP2A and CYP2B in mice but not rats. VCH-1,2-epoxide pretreatment also increased CYP2B levels in the mouse. Activities toward specific substrates for CYP2A and CYP2B (coumarin and pentoxyresorufin, respectively) confirmed that VCH and VCH-1,2-epoxide pretreatments resulted in increased catalytic activities of CYP2A and CYP2B in the mouse but not the rat. Pretreatment with phenobarbital, a known inducer of CYP2A and CYP2B, increased VCH bioactivation in both species. Interestingly, metabolism studies with human CYP "Supersomes" reveal that, of eight isoforms tested, only human CYP2E1 and CYP2B6 were capable of significantly catalyzing VCH epoxidation, whereas CYP2B6, CYP2A6, CYP2E1, and CYP3A4 were capable of catalyzing the epoxidation of the monoepoxides. PMID:11502734

  2. Cyclic interconversion of vitamin K1 and vitamin K1 2,3-epoxide in man.

    PubMed Central

    Bechtold, H; Trenk, D; Meinertz, T; Rowland, M; Jähnchen, E

    1983-01-01

    The disposition of a single intravenous bolus dose of 10 mg vitamin K1 and vitamin K1-2,3-epoxide were studied in two healthy subjects without and with 12 h pretreatment dose of phenprocoumon (0.4 mg/kg). For each compound administered alone the plasma concentration-time profile was adequately fitted by a biexponential equation, with an average terminal half-life of 2.0 and 1.15 h for the administered vitamin K and its 2,3-epoxide respectively. While vitamin K1 was measurable in plasma following administration of vitamin K1-2,3-epoxide, the epoxide was not detectable following administration of vitamin K1. Following pretreatment with phenprocoumon and after intravenous administration of vitamin K1, both the average half-life and area under the plasma concentration-time profile of vitamin K1 were marginally reduced to 1.5 h and 1.76 mg l-1 h respectively, while the plasma concentration of vitamin K1-2,3-epoxide was readily measurable and its half-life markedly prolonged to 14.7 h. Following pretreatment with phenprocoumon and after oral administration of vitamin K1-2,3-epoxide, no vitamin K1 was detectable in plasma and the half-life of the epoxide was 13.8 h. Based on area considerations the data suggest that either phenprocoumon does more than just inhibit the reduction of vitamin K1-2,3-epoxide to vitamin K1, or that the simple model describing the interconversion between vitamin K1 and its epoxide is inadequate. The same conclusion is drawn from the analysis of comparable data in dogs, obtained by Carlisle & Blaschke (1981). PMID:6661354

  3. Biosynthesis of unnatural bacteriochlorophyll c derivatives esterified with α,ω-diols in the green sulfur photosynthetic bacterium Chlorobaculum tepidum.

    PubMed

    Nishimori, Risato; Mizoguchi, Tadashi; Tamiaki, Hitoshi; Kashimura, Shigenori; Saga, Yoshitaka

    2011-09-13

    Unnatural bacteriochlorophyll (BChl) c derivatives possessing a hydroxy group at the terminus of a hydrocarbon chain at the 17-propionate were biosynthesized in the green sulfur photosynthetic bacterium Chlorobaculum tepidum. Addition of exogenous 1,8-octanediol, 1,12-dodecanediol, and 1,16-hexadecanediol in acetone to liquid cultures resulted in accumulation of BChl c monoesterified with the corresponding diols. The relative ratios of the novel BChl c derivatives esterified with 1,8-, 1,12-, and 1,16-diols to totally producing BChl c were 8.2, 50.2, and 57.6% in the cells grown with additive α,ω-diols at concentrations of 1.5, 0.06, and 0.06 mM, respectively, at the final concentration. The homologue composition of BChl c derivatives esterified with these α,ω-diols was similar to that of original, coexisting BChl c esterified with farnesol (BChl c(F)), suggesting that esterification of α,ω-diols occurred at the last step of the BChl c biosynthetic pathway by BChl c synthase, BchK, in the same manner as in BChl c(F). Chlorosomes, which were isolated from cells grown in the presence of exogenous α,ω-diols, contained a ratio and a composition of BChl c derivatives esterified with the diols similar to those in the whole cells, indicating that these BChl c derivatives were actually present in chlorosomes. Q(y) absorption bands of C. tepidum cells containing the novel BChl c derivatives were shifted to a shorter wavelength, although their bandwidths were analogous to those of cells obtained by normal cultivation. Circular dichroism spectra of cells that had BChl c derivatives esterified with α,ω-diols exhibited S-shaped signals in the Q(y) region, whose polarities were the reverse of those of cells grown in the normal medium and by supplementation with neat acetone as a control experiment. These spectral features of C. tepidum possessing BChl c derivatives esterified with α,ω-diols imply that the novel BChl c derivatives possessing a hydroxy group at the

  4. Methods of producing epoxides from alkenes using a two-component catalyst system

    DOEpatents

    Kung, Mayfair C.; Kung, Harold H.; Jiang, Jian

    2013-07-09

    Methods for the epoxidation of alkenes are provided. The methods include the steps of exposing the alkene to a two-component catalyst system in an aqueous solution in the presence of carbon monoxide and molecular oxygen under conditions in which the alkene is epoxidized. The two-component catalyst system comprises a first catalyst that generates peroxides or peroxy intermediates during oxidation of CO with molecular oxygen and a second catalyst that catalyzes the epoxidation of the alkene using the peroxides or peroxy intermediates. A catalyst system composed of particles of suspended gold and titanium silicalite is one example of a suitable two-component catalyst system.

  5. Mechanism of olefin epoxidation in the presence of a titanium-containing zeolite

    NASA Astrophysics Data System (ADS)

    Danov, S. M.; Krasnov, V. L.; Sulimov, A. V.; Ovcharova, A. V.

    2013-11-01

    The effect of the nature of a solvent on the liquid-phase epoxidation of olefins with an aqueous solution of hydrogen peroxide over a titanium-containing zeolite is studied. Butanol-1, butanol-2, propanol-1, isopropanol, methanol, ethanol, water, acetone, methyl ethyl ketone, isobutanol, and tert-butanol are examined as solvents. A mechanism of olefin epoxidation with hydrogen peroxide in an alcohol medium over a titanium-containing zeolite is proposed. Epoxidation reactions involving hydrogen peroxide and different olefins are studied experimentally.

  6. Crystal structures and fungicidal activities of anti-2,4-bis(X-phenyl)pentane-2,4-diols

    NASA Astrophysics Data System (ADS)

    Jiao, Yinchun; Cao, Chenzhong; Zhao, Xiaolin

    2012-11-01

    The 1,3-diol moiety is present in a number of natural products and has some biological activity. Four symmetric anti-2,4-bis(X-phenyl)pentane-2,4-diols (a, X = p-F; b, X = p-CF3; c, X = m-OMe; d, X = m-CF3) have been characterized by X-ray diffraction, and the results indicated that the dihedral angles between the every two benzene rings in the systems are 34.38(10)°, 39.46(13)°, 23.42(7)°(A), 30.42(7)°(B) and 44.74(9)°, respectively. All of the structures were stabilized by classical intra- and intermolecular hydrogen bonding and some other weak interactions. It was observed that the hydrogen bonding patterns were formed between each single-molecule in compounds a-d, whereas H-bonding dimers were formed in the crystal lattices of both the anti- and syn-2,4-bisphenylpentane-2,4-diols. The four symmetric diaryl 1,3-diols were evaluated alongside several other 1,3-diols as potential antifungal agents, and their in vitro antifungal activities were measured against several fungal species, including Gibberella zeae, Botrytis cinerea, Alternaria alternata and Sclerotonia sclerotiorum.

  7. Analyses of effects of α-cembratrien-diol on cell morphology and transcriptome of Valsa mali var. mali.

    PubMed

    Yan, Ning; Du, Yongmei; Liu, Xinmin; Zhang, Hongbo; Liu, Yanhua; Shi, John; Xue, Sophia Jun; Zhang, Zhongfeng

    2017-01-01

    The objective of this work was to study the underlying mechanisms of growth inhibition of Valsa mali var. mali, the causative pathogen of apple tree canker disease, by α-cembratrien-diol. The half maximal inhibitory concentration of α-cembratrien-diol against V. mali var. mali is 18.0mg/L. Treatment of V. mali var. mali with α-cembratrien-diol resulted in various mycelial and cellular abnormalities, and the up- and down-regulation of 94 and 170 differentially expressed genes, respectively. Gene Ontology term enrichment analysis revealed that α-cembratrien-diol substantially altered the expression of genes involved in the redox process, tetrapyrrole binding, coenzyme binding, heme binding, and iron binding. Kyoto Encyclopedia of Genes and Genomes enrichment analysis also showed significant enrichment of specific metabolic pathways involving the set of differentially expressed genes. The present study will assist in the development of alternative α-cembratrien-diol-based biological control agents and ultimately facilitate organic apple production. PMID:27507455

  8. Impact of Large Aggregated Uricases and PEG Diol on Accelerated Blood Clearance of PEGylated Canine Uricase

    PubMed Central

    Zhang, Chun; Fan, Kai; Ma, Xuefeng; Wei, Dongzhi

    2012-01-01

    Background Uricase has proven therapeutic value in treating hyperuricemia but sufficient reduction of its immunogenicity may be the largest obstacle to its chronic use. In this study, canine uricase was modified with 5 kDa mPEG-SPA and the impact of large aggregated uricases and cross-linked conjugates induced by difunctional PEG diol on immunogenicity was investigated. Methods and Findings Recombinant canine uricase was first expressed and purified to homogeneity. Source 15Q anion-exchange chromatography was used to separate tetrameric and aggregated uricase prior to pegylation, while DEAE anion-exchange chromatography was used to remove Di-acid PEG (precursor of PEG diol) from unfractionated 5 kDa mPEG-propionic acid. Tetrameric and aggregated uricases were separately modified with the purified mPEG-SPA. In addition, tetrameric uricases was modified with unfractionated mPEG-SPA, resulting in three types of 5 kDa mPEG-SPA modified uricase. The conjugate size was evaluated by dynamic light scattering and transmission electron microscope. The influence of differently PEGylated uricases on pharmacokinetics and immunogenicity were evaluated in vivo. The accelerated blood clearance (ABC) phenomenon previously identified for PEGylated liposomes occurred in rats injected with PEGylated uricase aggregates. Anti-PEG IgM antibodies, rather than neutralizing antibodies, were found to mediate the ABC. Conclusions The size of conjugates is important for triggering such phenomena and we speculate that 40–60 nm is the lower size limit that can trigger ABC. Removal of the uricase aggregates and the PEG diol contaminant and modifying with small PEG reagents enabled ABC to be successfully avoided and sufficient reduction in the immunogenicity of 5 kDa mPEG-modified tetrameric canine uricase. PMID:22745806

  9. Immunogenicity of a Promiscuous T Cell Epitope Peptide Based Conjugate Vaccine against Benzo[a]pyrene: Redirecting Antibodies to the Hapten

    PubMed Central

    Schellenberger, Mario T.; Grova, Nathalie; Farinelle, Sophie; Willième, Stéphanie; Revets, Dominique; Muller, Claude P.

    2012-01-01

    The prototype polycyclic aromatic hydrocarbon benzo[a]pyrene (B[a]P) is an environmental pollutant and food contaminant of epidemiological importance. To protect against adverse effects of this ubiquitous carcinogen, we developed an immunoprophylactic strategy based on a B[a]P-protein conjugate vaccine to induce B[a]P specific antibodies (Grova et al., Vaccine. 2009;27:4142–51). Here, we investigated in mice the efficacy of B[a]P-peptide conjugates based on promiscuous T cell epitopes (TCE) into further improve this approach. We showed that B[a]P-peptide conjugates induced very different levels of hapten-specific antibodies with variable functional efficacy, depending on the carrier. In some cases peptide carriers induced a more efficient antibody response against B[a]P than tetanus toxoid as a protein carrier, with the capacity to sequester more B[a]P in the blood. Reducing the carrier size to a single TCE can dramatically shift the antibody bias from the carrier to the B[a]P. Conjugates based on the TCE FIGITEL induced the best anti-hapten response and no antibodies against the carrier peptide. Some peptide conjugates increased the selectivity of the antibodies for the activated metabolite 7,8-diol-B[a]P and B[a]P by one or two orders of magnitude. The antibody efficacy was also demonstrated in their ability to sequester B[a]P in the blood and modulate its faecal excretion (15–56%). We further showed that pre-existing immunity to the carrier from which the TCE was derived did not reduce the immunogenicity of the peptide conjugate. In conclusion, we showed that a vaccination against B[a]P using promiscuous TCEs of tetanus toxin as carriers is feasible even in case of a pre-existing immunity to the toxoid and that some TCE epitopes dramatically redirect the antibody response to the hapten. Further studies to demonstrate a long-term protection of an immunoprophylactic immunisation against B[a]P are warranted. PMID:22666501

  10. Immunogenicity of a promiscuous T cell epitope peptide based conjugate vaccine against benzo[a]pyrene: redirecting antibodies to the hapten.

    PubMed

    Schellenberger, Mario T; Grova, Nathalie; Farinelle, Sophie; Willième, Stéphanie; Revets, Dominique; Muller, Claude P

    2012-01-01

    The prototype polycyclic aromatic hydrocarbon benzo[a]pyrene (B[a]P) is an environmental pollutant and food contaminant of epidemiological importance. To protect against adverse effects of this ubiquitous carcinogen, we developed an immunoprophylactic strategy based on a B[a]P-protein conjugate vaccine to induce B[a]P specific antibodies (Grova et al., Vaccine. 2009;27:4142-51). Here, we investigated in mice the efficacy of B[a]P-peptide conjugates based on promiscuous T cell epitopes (TCE) into further improve this approach. We showed that B[a]P-peptide conjugates induced very different levels of hapten-specific antibodies with variable functional efficacy, depending on the carrier. In some cases peptide carriers induced a more efficient antibody response against B[a]P than tetanus toxoid as a protein carrier, with the capacity to sequester more B[a]P in the blood. Reducing the carrier size to a single TCE can dramatically shift the antibody bias from the carrier to the B[a]P. Conjugates based on the TCE FIGITEL induced the best anti-hapten response and no antibodies against the carrier peptide. Some peptide conjugates increased the selectivity of the antibodies for the activated metabolite 7,8-diol-B[a]P and B[a]P by one or two orders of magnitude. The antibody efficacy was also demonstrated in their ability to sequester B[a]P in the blood and modulate its faecal excretion (15-56%). We further showed that pre-existing immunity to the carrier from which the TCE was derived did not reduce the immunogenicity of the peptide conjugate. In conclusion, we showed that a vaccination against B[a]P using promiscuous TCEs of tetanus toxin as carriers is feasible even in case of a pre-existing immunity to the toxoid and that some TCE epitopes dramatically redirect the antibody response to the hapten. Further studies to demonstrate a long-term protection of an immunoprophylactic immunisation against B[a]P are warranted. PMID:22666501

  11. Exploiting Acid Phosphatases in the Synthesis of Phosphorylated Monoalcohols and Diols

    PubMed Central

    Tasnádi, Gábor; Lukesch, Michael; Zechner, Michaela; Jud, Wolfgang; Hall, Mélanie; Ditrich, Klaus; Baldenius, Kai; Hartog, Aloysius F.; Wever, Ron

    2015-01-01

    Abstract A set of phosphatases was evaluated for their potential to catalyze the regio‐ and stereoselective phosphorylation of alcohols using a high‐energy inorganic phosphate donor, such as di‐, tri‐ and polyphosphate. Parameters such as type and amount of phosphate donor and pH of the reaction were investigated in order to minimize the thermodynamically favored hydrolysis of the phosphate donor and the formed phosphate ester. Diols were monophosphorylated with high selectivities. This biocatalytic phosphorylation method provides selectively activated and/or protected synthetic intermediates for further chemical and/or enzymatic transformations and is applicable to a large scale (6.86 g) in a flow setup with immobilized phosphatase.

  12. Synthesis and characterization of segmented polyurethanes based on amphiphilic polyether diols.

    PubMed

    Lan, P N; Corneillie, S; Schacht, E; Davies, M; Shard, A

    1996-12-01

    Segmented polyurethanes (SPUs) based on polyethylene glycol (PEG), polypropylene glycol (PPG) and a series of Pluronics with different ethylene oxide/propylene oxide ratios (EO/PO) and molecular weights were prepared. Different diisocyanates were used for making SPUs: 4,4-diphenylmethane diisocyanate (MDI), 4,4-dicyclohexylmethane diisocyanate (MDCI), hexamethylene diisocyanate (HMDI) and isophorone diisocyanate (IPDI). 1,4-Butane diol (BD) and ethylene diamine (ED) were used as chain extenders. The polymers obtained were characterized by infrared spectroscopy (IR), nuclear magnetic resonance (NMR) and differential scanning calorimetry (DSC). The microphase morphology (phase separation and phase mixing) is discussed in more detail. PMID:8968523

  13. Renewable non-isocyanate based thermoplastic polyurethanes via polycondensation of dimethyl carbamate monomers with diols.

    PubMed

    Unverferth, Maike; Kreye, Oliver; Prohammer, Alexander; Meier, Michael A R

    2013-10-01

    1,5,7-Triazabicyclo[4.4.0]dec-5-ene (TBD)-catalyzed polycondensation reactions of fatty acid derived dimethyl dicarbamates and diols are introduced as a versatile, non-isocyanate route to renewable polyurethanes. The key step for the synthesis of dimethyl carbamate monomers from plant-oil-derived dicarboxylic acids is based on a sustainable base-catalyzed Lossen rearrangement. The formed polyurethanes with molecular weights up to 25 kDa are characterized by SEC, DSC, and NMR analysis. PMID:23996909

  14. Olefin Epoxidation in Aqueous Phase Using Ionic-Liquid Catalysts.

    PubMed

    Cokoja, Mirza; Reich, Robert M; Wilhelm, Michael E; Kaposi, Marlene; Schäffer, Johannes; Morris, Danny S; Münchmeyer, Christian J; Anthofer, Michael H; Markovits, Iulius I E; Kühn, Fritz E; Herrmann, Wolfgang A; Jess, Andreas; Love, Jason B

    2016-07-21

    Hydrophobic imidazolium-based ionic liquids (IL) act as catalysts for the epoxidation of unfunctionalized olefins in water using hydrogen peroxide as oxidant. Although the catalysts are insoluble in both the substrate and in water, surprisingly, they are very well soluble in aqueous H2 O2 solution, owing to perrhenate-H2 O2 interactions. Even more remarkably, the presence of the catalyst also boosts the solubility of substrate in water. This effect is crucially dependent on the cation design. Hence, the imidazolium perrhenates enable both the transfer of hydrophobic substrate into the aqueous phase, and serve as actual catalysts, which is unprecedented. At the end of the reaction and in absence of H2 O2 the IL catalyst forms a third phase next to the lipophilic product and water and can easily be recycled. PMID:27219852

  15. Structure of a bacterial homologue of vitamin K epoxide reductase

    SciTech Connect

    Li, Weikai; Schulman, Sol; Dutton, Rachel J.; Boyd, Dana; Beckwith, Jon; Rapoport, Tom A.

    2010-03-19

    Vitamin K epoxide reductase (VKOR) generates vitamin K hydroquinone to sustain {gamma}-carboxylation of many blood coagulation factors. Here, we report the 3.6 {angstrom} crystal structure of a bacterial homologue of VKOR from Synechococcus sp. The structure shows VKOR in complex with its naturally fused redox partner, a thioredoxin-like domain, and corresponds to an arrested state of electron transfer. The catalytic core of VKOR is a four transmembrane helix bundle that surrounds a quinone, connected through an additional transmembrane segment with the periplasmic thioredoxin-like domain. We propose a pathway for how VKOR uses electrons from cysteines of newly synthesized proteins to reduce a quinone, a mechanism confirmed by in vitro reconstitution of vitamin K-dependent disulphide bridge formation. Our results have implications for the mechanism of the mammalian VKOR and explain how mutations can cause resistance to the VKOR inhibitor warfarin, the most commonly used oral anticoagulant.

  16. Preparation of Rh[16aneS4-diol]211 At and Ir[16aneS4-diol]211 At Complexes as Potential Precursors for Astatine Radiopharmaceuticals. Part I: Synthesis

    PubMed Central

    Pruszyński, Marek; Bilewicz, Aleksander; Zalutsky, Michael R.

    2010-01-01

    The goal of this study was to evaluate a new approach that can be applied for labeling biomolecules with 211At. Many astatine compounds that have been synthesized are unstable in vivo, providing motivation for seeking different 211At labeling strategies. The approach evaluated in this study was to attach astatide anions to soft metal cations, which are also complexed by a bifunctional ligand. Ultimately, this complex could in principle be subsequently conjugated to a biomolecule with the proper selection of ligand functionality. We report here the attachment of 211At− and *I− (*I = 131I or 125I) anions to the soft metal cations Rh(III) and Ir(III), which are complexed by the 1,5,9,13-tetrathiacyclohexadecane-3,11-diol (16aneS4-diol) ligand. Radioactive *I− anions were used for preliminary studies directed at the optimization of reaction conditions and to provide a baseline for comparison of results with 211At. Four complexes Rh[16aneS4-diol]*I/211At and Ir[16aneS4-diol]*I/211 At were synthesized in high yield in a one-step procedure, and the products were characterized mainly by paper electrophoresis and reversed-phase HPLC. The influences of time and temperature of heating and concentrations of metal cations and sulfur ligand 16aneS4-diol, as well as pH on the reaction yields were determined. Yields of about 80% were obtained when the quantities of Rh(III) or Ir(III) cations and 16aneS4-diol ligand in the solutions were 62.5 nmol and 250 nmol, respectively, and the pH ranged 3.0–4.0. Syntheses required heating for 1–1.5 h at 75–80 °C. The influence of microwave heating on the time and completeness of the complexation reaction was evaluated and compared with the conventional method of heating in an oil bath. Microwave synthesis accelerates reactions significantly. With microwave heating, yields of about 75% for Rh[16aneS4-diol]131I and Ir[16aneS4-diol]131I complexes were obtained after only 20 min exposure of the reaction mixtures to microwave

  17. Preparation of Rh[16aneS4-diol](211)At and Ir[16aneS4-diol](211)At complexes as potential precursors for astatine radiopharmaceuticals. Part I: Synthesis.

    PubMed

    Pruszyński, Marek; Bilewicz, Aleksander; Zalutsky, Michael R

    2008-04-01

    The goal of this study was to evaluate a new approach that can be applied for labeling biomolecules with (211)At. Many astatine compounds that have been synthesized are unstable in vivo, providing motivation for seeking different (211)At labeling strategies. The approach evaluated in this study was to attach astatide anions to soft metal cations, which are also complexed by a bifunctional ligand. Ultimately, this complex could in principle be subsequently conjugated to a biomolecule with the proper selection of ligand functionality. We report here the attachment of (211)At(-) and *I(-) (*I = (131)I or (125)I) anions to the soft metal cations Rh(III) and Ir(III), which are complexed by the 1,5,9,13-tetrathiacyclohexadecane-3,11-diol (16aneS4-diol) ligand. Radioactive *I(-) anions were used for preliminary studies directed at the optimization of reaction conditions and to provide a baseline for comparison of results with (211)At. Four complexes Rh[16aneS4-diol]*I/(211)At and Ir[16aneS4-diol]*I/(211)At were synthesized in high yield in a one-step procedure, and the products were characterized mainly by paper electrophoresis and reversed-phase HPLC. The influences of time and temperature of heating and concentrations of metal cations and sulfur ligand 16aneS4-diol, as well as pH on the reaction yields were determined. Yields of about 80% were obtained when the quantities of Rh(III) or Ir(III) cations and 16aneS4-diol ligand in the solutions were 62.5 nmol and 250 nmol, respectively, and the pH ranged 3.0-4.0. Syntheses required heating for 1-1.5 h at 75-80 degrees C. The influence of microwave heating on the time and completeness of the complexation reaction was evaluated and compared with the conventional method of heating in an oil bath. Microwave synthesis accelerates reactions significantly. With microwave heating, yields of about 75% for Rh[16aneS4-diol](131)I and Ir[16aneS4-diol](131)I complexes were obtained after only 20 min exposure of the reaction mixtures to

  18. Conformational diversity and enantioconvergence in potato epoxide hydrolase 1.

    PubMed

    Bauer, P; Carlsson, Å Janfalk; Amrein, B A; Dobritzsch, D; Widersten, M; Kamerlin, S C L

    2016-06-28

    Potato epoxide hydrolase 1 (StEH1) is a biocatalytically important enzyme that exhibits rich enantio- and regioselectivity in the hydrolysis of chiral epoxide substrates. In particular, StEH1 has been demonstrated to enantioconvergently hydrolyze racemic mixes of styrene oxide (SO) to yield (R)-1-phenylethanediol. This work combines computational, crystallographic and biochemical analyses to understand both the origins of the enantioconvergent behavior of the wild-type enzyme, as well as shifts in activities and substrate binding preferences in an engineered StEH1 variant, R-C1B1, which contains four active site substitutions (W106L, L109Y, V141K and I155V). Our calculations are able to reproduce both the enantio- and regioselectivities of StEH1, and demonstrate a clear link between different substrate binding modes and the corresponding selectivity, with the preferred binding modes being shifted between the wild-type enzyme and the R-C1B1 variant. Additionally, we demonstrate that the observed changes in selectivity and the corresponding enantioconvergent behavior are due to a combination of steric and electrostatic effects that modulate both the accessibility of the different carbon atoms to the nucleophilic side chain of D105, as well as the interactions between the substrate and protein amino acid side chains and active site water molecules. Being able to computationally predict such subtle effects for different substrate enantiomers, as well as to understand their origin and how they are affected by mutations, is an important advance towards the computational design of improved biocatalysts for enantioselective synthesis. PMID:27049844

  19. Expanding the Catalytic Triad in Epoxide Hydrolases and Related Enzymes

    PubMed Central

    2015-01-01

    Potato epoxide hydrolase 1 exhibits rich enantio- and regioselectivity in the hydrolysis of a broad range of substrates. The enzyme can be engineered to increase the yield of optically pure products as a result of changes in both enantio- and regioselectivity. It is thus highly attractive in biocatalysis, particularly for the generation of enantiopure fine chemicals and pharmaceuticals. The present work aims to establish the principles underlying the activity and selectivity of the enzyme through a combined computational, structural, and kinetic study using the substrate trans-stilbene oxide as a model system. Extensive empirical valence bond simulations have been performed on the wild-type enzyme together with several experimentally characterized mutants. We are able to computationally reproduce the differences between the activities of different stereoisomers of the substrate and the effects of mutations of several active-site residues. In addition, our results indicate the involvement of a previously neglected residue, H104, which is electrostatically linked to the general base H300. We find that this residue, which is highly conserved in epoxide hydrolases and related hydrolytic enzymes, needs to be in its protonated form in order to provide charge balance in an otherwise negatively charged active site. Our data show that unless the active-site charge balance is correctly treated in simulations, it is not possible to generate a physically meaningful model for the enzyme that can accurately reproduce activity and selectivity trends. We also expand our understanding of other catalytic residues, demonstrating in particular the role of a noncanonical residue, E35, as a “backup base” in the absence of H300. Our results provide a detailed view of the main factors driving catalysis and regioselectivity in this enzyme and identify targets for subsequent enzyme design efforts. PMID:26527505

  20. Toluene dioxygenase-catalyzed synthesis and reactions of cis-diol metabolites derived from 2- and 3-methoxyphenols.

    PubMed

    Boyd, Derek R; Sharma, Narain D; Malone, John F; McIntyre, Peter B A; McRoberts, Colin; Floyd, Stewart; Allen, Christopher C R; Gohil, Amit; Coles, Simon J; Horton, Peter N; Stevenson, Paul J

    2015-04-01

    Using toluene dioxygenase as biocatalyst, enantiopure cis-dihydrodiol and cis-tetrahydrodiol metabolites, isolated as their ketone tautomers, were obtained from meta and ortho methoxyphenols. Although these isomeric phenol substrates are structurally similar, the major bioproducts from each of these biotransformations were found at different oxidation levels. The relatively stable cyclohexenone cis-diol metabolite from meta methoxyphenol was isolated, while the corresponding metabolite from ortho methoxyphenol was rapidly bioreduced to a cyclohexanone cis-diol. The chemistry of the 3-methoxycyclohexenone cis-diol product was investigated and elimination, aromatization, hydrogenation, regioselective O-exchange, Stork-Danheiser transposition and O-methylation reactions were observed. An offshoot of this technology provided a two-step chemoenzymatic synthesis, from meta methoxyphenol, of a recently reported chiral fungal metabolite; this synthesis also established the previously unassigned absolute configuration. PMID:25756661

  1. Vibrational Excitations and Low Energy Electronic Structure of Epoxide-decorated Graphene

    PubMed Central

    Mattson, E.C.; Johns, J.E.; Pande, K.; Bosch, R.A.; Cui, S.; Gajdardziska-Josifovska, M.; Weinert, M.; Chen, J.H.; Hersam, M.C.; Hirschmugl, C.J.

    2014-01-01

    We report infrared studies of adsorbed atomic oxygen (epoxide functional groups) on graphene. Two different systems are used as a platform to explore these interactions, namely, epitaxial graphene/SiC(0001) functionalized with atomic oxygen (graphene epoxide, GE) and chemically reduced graphene oxide (RGO). In the case of the model GE system, IR reflectivity measurements show that epoxide groups distort the graphene π bands around the K-point, imparting a finite effective mass and contributing to a band gap. In the case of RGO, epoxide groups are found to be present following the reduction treatment by a combination of polarized IR reflectance and transmittance measurements. Similar to the GE system, a band gap in the RGO sample is observed as well. PMID:24563725

  2. The Role of Long Chain Fatty Acids and Their Epoxide Metabolites in Nociceptive Signaling

    PubMed Central

    Wagner, Karen; Vito, Steve; Inceoglu, Bora; Hammock, Bruce D.

    2014-01-01

    Lipid derived mediators contribute to inflammation and the sensing of pain. The contributions of omega-6 derived prostanoids in enhancing inflammation and pain sensation are well known. Less well explored are the opposing anti-inflammatory and analgesic effects of the omega-6 derived epoxyeicosatrienoic acids. Far less has been described about the epoxidized metabolites derived from omega-3 long chain fatty acids. The epoxide metabolites are turned over rapidly with enzymatic hydrolysis by the soluble epoxide hydrolase being the major elimination pathway. Despite this, the overall understanding of the role of lipid mediators in the pathology of chronic pain is growing. Here we review the role of long chain fatty acids and their metabolites in alleviating both acute and chronic pain conditions. We focus specifically on the epoxidized metabolites of omega-6 and omega-3 long chain fatty acids as well as a novel strategy to modulate their activity in vivo. PMID:25240260

  3. Regio- and Stereoselective Monoepoxidation of Dienes using Methyltrioxorhenium: Synthesis of Allylic Epoxides

    PubMed Central

    2015-01-01

    Methyltrioxorhenium (MTO) complexed with pyridine was shown to be a highly effective catalyst for the regioselective monoepoxidation of conjugated di- and trienes using 30% H2O2 at or below room temperature. The resultant allylic epoxides, and the triols derived from them, are versatile synthetic intermediates as well as substructures present in many bioactive natural products. The site of epoxidation was dependent upon olefin substitution, olefin geometry (Z vs E), and the presence of electron-withdrawing substituents on adjacent carbons. For 1-acyl(silyl)oxypenta-2,4-dienes, epoxidation of the distal olefin was generally favored in contrast to the adjacent regioselectivity characteristic of Sharpless, peracid, and other directed epoxidations of hydroxylated dienes. PMID:25321319

  4. Biobased composites from thermoplastic polyurethane elastomer and cross-linked acrylated-epoxidized soybean oil

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Soybean oil is an important sustainable material. Crosslinked acrylated epoxidized soybean oil (AESO) is brittle without flexibility and the incorporation of thermoplastic polyurethane improves its toughness for industrial applications. The hydrophilic functional groups from both oil and polyurethan...

  5. A Computational Study of Acid Catalyzed Aerosol Reactions of Atmospherically Relevant Epoxides

    EPA Science Inventory

    Epoxides are important intermediates of atmospheric isoprene oxidation. Their subsequent reactions in the particle phase lead to the production of organic compounds detected in ambient aerosols. We apply density functional theory to determine the important kinetic factors that ...

  6. Chemoenzymatic Epoxidation of Alkenes and Reusability Study of the Phenylacetic Acid

    PubMed Central

    Abdulmalek, Emilia; Mizan, Hanis Nabillah; Abdul Rahman, Mohd. Basyaruddin; Basri, Mahiran; Salleh, Abu Bakar

    2014-01-01

    Here, we focused on a simple enzymatic epoxidation of alkenes using lipase and phenylacetic acid. The immobilised Candida antarctica lipase B, Novozym 435 was used to catalyse the formation of peroxy acid instantly from hydrogen peroxide (H2O2) and phenylacetic acid. The peroxy phenylacetic acid generated was then utilised directly for in situ oxidation of alkenes. A variety of alkenes were oxidised with this system, resulting in 75–99% yield of the respective epoxides. On the other hand, the phenylacetic acid was recovered from the reaction media and reused for more epoxidation. Interestingly, the waste phenylacetic acid had the ability to be reused for epoxidation of the 1-nonene to 1-nonene oxide, giving an excellent yield of 90%. PMID:24587751

  7. Cultured mouse embryos metabolize benzo[a]pyrene during early gestation: genetic differences detectable by sister chromatid exchange.

    PubMed Central

    Galloway, S M; Perry, P E; Meneses, J; Nebert, D W; Pedersen, R A

    1980-01-01

    Mouse embryos explanted at 7 1/2 or 8 1/2 days of gestation were cultured in medium containing benzo[a]pyrene and supplemented with 5-bromodeoxyuridine to allow detection of sister chromatid exchanges. The murine Ah locus regulates the inducible metabolism of polycyclic hydrocarbons such as benzo[a]pyrene. A high frequency of sister chromatid exchange was induced by benzo[a]pyrene in embryos from three Ah-"responsive" inbred strains (BALB/cDub, C3H/AnfCum, and C57BL/6N); there was little or no increase in two Ah-"nonresponsive" inbred strains (AKR/J and DBA/2J). Benzo[a]pyrene also induced sister chromatid exchanges in the Ah-responsive recombinant inbred line B6NXAKN-12 but not in the Ah-nonresponsive recombinant inbred line B6NXAKN-3. Sister chromatid exchange in cultured Ah-responsive mouse embryos was thus shown to be a sensitive assay. These data provide direct evidence that genetically responsive mouse embryos (early postimplantation stage) possess the subcellular processes necessary for induction of enzymes that metabolize benzo[a]pyrene to its chemically active forms(s). Both the Ah regulatory gene product (a cytoslic receptor) and the structural gene product (inducible cytochrome P1-450) therefore appear to be functional at an early embryonic age. Furthermore, this metabolic capacity may play an important role in the damage to embryonic cells by polycyclic hydracarbons. PMID:6932035

  8. Hydroxyl-Substituted Ladder Polyethers via Selective Tandem Epoxidation/Cyclization Sequence

    PubMed Central

    Czabaniuk, Lara C.; Jamison, Timothy F.

    2015-01-01

    A new and highly selective method for the synthesis of hydroxyl-substituted tetrahydropyrans is described. This method utilizes titanium(IV) iso-propoxide and diethyl tartrate to perform a diastereoselective epoxidation followed by in situ epoxide activation and highly selective endo-cyclization to form the desired tetrahydropyran ring. The HIJ ring fragment of the marine ladder polyether yessotoxin was synthesized using this two-stage tactic that proceeds with high efficiency and excellent regioselectivity. PMID:25647091

  9. Highly Active Titanocene Catalysts for Epoxide Hydrosilylation: Synthesis, Theory, Kinetics, EPR Spectroscopy.

    PubMed

    Henriques, Dina Schwarz G; Zimmer, Katharina; Klare, Sven; Meyer, Andreas; Rojo-Wiechel, Elena; Bauer, Mirko; Sure, Rebecca; Grimme, Stefan; Schiemann, Olav; Flowers, Robert A; Gansäuer, Andreas

    2016-06-27

    A catalytic system for titanocene-catalyzed epoxide hydrosilylation is described. It features a straightforward preparation of titanocene hydrides that leads to a reaction with low catalyst loading, high yields, and high selectivity of radical reduction. The mechanism was studied by a suite of methods, including kinetic studies, EPR spectroscopy, and computational methods. An unusual resting state leads to the observation of an inverse rate order with respect to the epoxide. PMID:27125466

  10. The Epoxidation of Carbonyl Compounds with a Benzyne-Triggered Sulfur Ylide.

    PubMed

    Lou, Mei-Mei; Wang, Han; Song, Li; Liu, Hong-Yi; Li, Zhong-Qiu; Guo, Xiao-Shuang; Zhang, Fu-Geng; Wang, Bin

    2016-07-15

    An efficient method for the synthesis of epoxides from carbonyl compounds, sulfoxides, and benzyne is presented. The strategy involved an epoxidation by a sulfur ylide which is formed in situ from sulfoxide and benzyne through the S-O bond insertion and deprotonation. This one-pot reaction proceeds under mild and base-free conditions, providing a convenient way to introduce the substituted methylene groups onto the carbonyl carbon. PMID:27337065

  11. Fluorinated Boronic Acid-Appended Bipyridinium Salts for Diol Recognition and Discrimination via (19)F NMR Barcodes.

    PubMed

    Axthelm, Jörg; Görls, Helmar; Schubert, Ulrich S; Schiller, Alexander

    2015-12-16

    Fluorinated boronic acid-appended benzyl bipyridinium salts, derived from 4,4'-, 3,4'-, and 3,3'-bipyridines, were synthesized and used to detect and differentiate diol-containing analytes at physiological conditions via (19)F NMR spectroscopy. An array of three water-soluble boronic acid receptors in combination with (19)F NMR spectroscopy discriminates nine diol-containing bioanalytes--catechol, dopamine, fructose, glucose, glucose-1-phosphate, glucose-6-phosphate, galactose, lactose, and sucrose--at low mM concentrations. Characteristic (19)F NMR fingerprints are interpreted as two-dimensional barcodes without the need of multivariate analysis techniques. PMID:26595191

  12. Sterols and triterpene diols in olive oil as indicators of variety and degree of ripening.

    PubMed

    Lukić, Marina; Lukić, Igor; Krapac, Marin; Sladonja, Barbara; Piližota, Vlasta

    2013-01-01

    Sterols and triterpene diols in olive oil as indicators of variety and degree of ripening derived from three olive varieties and produced at three different harvesting periods were studied. In order to test the stability of the proposed indicators, oils obtained were stored for 12 months at three different temperatures. Thirty-six samples in total were subjected to GC analysis and results were processed by multivariate chemometric methods (MANOVA, PCA, and SLDA). Campesterol, β-sitosterol, Δ(7)-campesterol/Δ(5,24)-stigmastadienol, clerosterol, uvaol, and campestanol/Δ(7)-avenasterol were established as the indicators of variety of fresh oils, while when stored oils were included in the model, the final three compounds were substituted by 24-methylene-cholesterol/stigmasterol. The most important variables for differentiating fresh oils according to degree of ripening were Δ(7)-campesterol/β-sitosterol, uvaol/stigmasterol, clerosterol/Δ(5)-avenasterol and sitostanol/uvaol, while stored oils were differentiated by campestanol/stigmasterol, erythrodiol, stigmasterol/Δ(7)-campesterol, Δ(5)-avenasterol, 24-methylene-cholesterol/β-sitosterol and 24-methylene-cholesterol. Results demonstrated that sterols and triterpene diols can be used as indicators of variety and degree of ripening among virgin olive oils. PMID:23017420

  13. Catalytic deoxydehydration of diols to olefins by using a bulky cyclopentadiene-based trioxorhenium catalyst.

    PubMed

    Raju, Suresh; Jastrzebski, Johann T B H; Lutz, Martin; Klein Gebbink, Robertus J M

    2013-09-01

    A bulky cyclopentadienyl (Cp)-based trioxorhenium compound was developed for the catalytic deoxydehydration of vicinal diols to olefins. The 1,2,4-tri(tert-butyl)cyclopentadienyl trioxorhenium (2) catalyst was synthesised in a two-step synthesis procedure. Dirhenium decacarbonyl was converted into 1,2,4-tri(tert-butyl)cyclopentadienyl tricarbonyl rhenium, followed by a biphasic oxidation with H2 O2 . These two new three-legged compounds with a 'piano-stool' configuration were fully characterised, including their single crystal X-ray structures. Deoxydehydration reaction conditions were optimised by using 2 mol % loading of 2 for the conversion of 1,2-octanediol into 1-octene. Different phosphine-based and other, more conventional, reductants were tested in combination with 2. Under optimised conditions, a variety of vicinal diols (aromatic and aliphatic, internal and terminal) were converted into olefins in good to excellent yields, and with minimal olefin isomerisation. A high turnover number of 1400 per Re was achieved for the deoxydehydration of 1,2-octanediol. Furthermore, the biomass-derived polyols (glycerol and erythritol) were converted into their corresponding olefinic products by 2 as the catalyst. PMID:23843348

  14. Carbamoyl Radical-Mediated Synthesis and Semipinacol Rearrangement of β-Lactam Diols

    PubMed Central

    Betou, Marie; Male, Louise; Steed, Jonathan W; Grainger, Richard S

    2014-01-01

    In an approach to the biologically important 6-azabicyclo[3.2.1]octane ring system, the scope of the tandem 4-exo-trig carbamoyl radical cyclization—dithiocarbamate group transfer reaction to ring-fused β-lactams is evaluated. β-Lactams fused to five-, six-, and seven-membered rings are prepared in good to excellent yield, and with moderate to complete control at the newly formed dithiocarbamate stereocentre. No cyclization is observed with an additional methyl substituent on the terminus of the double bond. Elimination of the dithiocarbamate group gives α,β- or β,γ-unsaturated lactams depending on both the methodology employed (base-mediated or thermal) and the nature of the carbocycle fused to the β-lactam. Fused β-lactam diols, obtained from catalytic OsO4-mediated dihydroxylation of α,β-unsaturated β-lactams, undergo semipinacol rearrangement via the corresponding cyclic sulfite or phosphorane to give keto-bridged bicyclic amides by exclusive N-acyl group migration. A monocyclic β-lactam diol undergoes Appel reaction at a primary alcohol in preference to semipinacol rearrangement. Preliminary investigations into the chemo- and stereoselective manipulation of the two carbonyl groups present in a representative 7,8-dioxo-6-azabicyclo[3.2.1]octane rearrangement product are also reported. PMID:24711140

  15. Natural and synthetic diastereoisomeric (−)-3′,4′,7-trihydroxyflavan-3,4-diols

    PubMed Central

    Drewes, S. E.; Roux, D. G.

    1965-01-01

    1. Rhodesian copalwood (Guibourtia coleosperma) contains three diastereo-isomeric leuco-fisetinidins. These consist of the (−)-2,3-cis–3,4-cis (2R,3R,4R) and (−)-2,3-cis–3,4-trans (2R,3R,4S) 3′,4′,7-trihydroxyflavan-3,4-diols, and the third was shown to be a 2,3-trans–3,4-cis isomer by means of paper ionophoresis. 2. There occurrence in similar proportions as tannin precursors also in the tropical hardwoods G. tessmannii and G. demeusii implies a close taxonomic relationship between these, and with G. coleosperma. 3. Epimerization of the natural (−)-3′,4′,7- trihydroxy-2,3-trans-flavan-3,4-trans-diol affords a mixture from which the (−)-2,3-cis–3,4-cis isomer was separated readily, but the (−)-2,3-trans–3,4-cis isomer was obtained with difficulty. These were formed by epimerization of the (−)-2,3-trans–3,4-trans isomer at C-2 and C-4, and at C-4, respectively. PMID:5862407

  16. Benzo(a)pyrene and 7,12-dimethylbenz(a)anthrecene differentially affect bone marrow cells of the lymphoid and myeloid lineages

    SciTech Connect

    Galvan, Noe; Page, Todd J.; Czuprynski, Charles J.; Jefcoate, Colin R. . E-mail: jefcoate@facstaff.wisc.edu

    2006-06-01

    Polycyclic aromatic hydrocarbons (PAHs) are common environmental contaminants that are carcinogenic and immunosuppressive. Benzo(a)pyrene (BP) and 7,12-dimethylbenz(a)anthracene (DMBA) are two prototypic PAHs known to impair the cell-mediated and humoral immune responses. We have previously shown that, in C57BL/6J mice, total bone marrow (BM) cellularity decreased two-fold following intraperitoneal DMBA treatment but not BP treatment. Here, we have used flow cytometry to demonstrate that BP and DMBA differentially alter the lymphoid and myeloid lineages. Following DMBA treatment, the pro/pre B-lymphocytes (B220{sup lo}/IgM{sup -}) and the immature B-lymphocytes (B220{sup lo}/IgM{sup +}) significantly decreased, while the mature B-lymphocytes (B220{sup hi}/IgM{sup +}) remained unaffected. In contrast, BP treatment decreased the pro/pre B-lymphocytes, and did not affect the immature B-lymphocytes or mature B-lymphocytes. The Gr-1{sup +} cells of the myeloid lineage were depleted 50% following DMBA treatment and only minimally depleted following BP treatment. Interestingly, the monocytes (7/4{sup +}1A8{sup lo}) and neutrophils (7/4{sup +}1A8{sup hi}) within this Gr-1{sup +} population were differentially affected by these PAHs. Monocytes and neutrophils were depleted following DMBA treatment whereas neutrophils decreased and monocytes increased following BP treatment. Although TNF{alpha} and CYP1B1 are implicated as essential mediators of hypocellularity, the similar induction of TNF{alpha} mRNA and CYP1B1 mRNA in the BM by BP and DMBA suggests that they are not limiting factors in mediating the different effects of these PAHs. Given that similar amounts of BP and DMBA reach the BM when administered intraperitoneally, their differential effects on the lymphoid and myeloid lineages probably stem from differences in reactive metabolites such as PAH quinones and PAH-dihydrodiol-epoxides.

  17. Different tumours induced by benzo(a)pyrene and its 7,8-dihydrodiol injected into adult mouse salivary gland.

    PubMed Central

    Wigley, C. B.; Amos, J.; Brookes, P.

    1978-01-01

    A comparison has been made between the carcinogenic activities of benzo(a)pyrene and the proposed proximate carcinogen, benzo(a)pyrene 7,8-dihydrodiol, in the adult C57BL mouse submandibular salivary gland. In preliminary studies using a range of doses, the dihydrodiol was slightly less active than the parent hydrocarbon in this system. There was a difference in the type of tumour induced by the 2 compounds. Benzo(a)pyrene induced tumours of the salivary glands at the site of injection, whereas the dihydrodiol induced malignant lymphosarcomas, particularly of the thymus, which were often metastatic to other orgnas. Possible reasons for the different sites of action of the 2 compounds are discussed. PMID:580763

  18. Biochemical responses of cnidarian larvae to mercury and benzo(a)pyrene exposure.

    PubMed

    Farina, Oriana; Ramos, Ruth; Bastidas, Carolina; García, Elia

    2008-12-01

    The biochemical responses of planulae from the coral Porites astreoides exposed to 10 microg/L of benzo(a)pyrene (B(a)P) and to 10 microg/L of mercury (Hg) was evaluated. The survivorship of larvae only dropped significantly after 48 h of B(a)P exposure, whereas it remained at 98% for Hg exposure and up to 96 h. Exposure to B(a)P significantly increased free thiols, and the activity of glutathione-S-transferase and catalase were unaltered under exposure of any of the contaminants. This study is the first contribution of the biochemical effects in cnidarian larvae exposed to contaminants. PMID:18820822

  19. Induction of hepatic cytochrome P450 isozymes, benzo(a)pyrene metabolism and DNA binding following exposure to polycyclic aromatic hydrocarbon residues generated during repeated fish fried oil in rats

    SciTech Connect

    Pandey, Manoj K.; Yadav, Sanjay; Parmar, Devendra; Das, Mukul . E-mail: mditrc@rediffmail.com

    2006-06-01

    In the present study the effect of repeated fish fried oil (RFFO) and its extract (RFFE) on hepatic cytochrome P450 (CYP) isozymes, benzo(a)pyrene (BP) metabolism and DNA adduct formation was undertaken. HPLC analysis of RFFO showed the presence of several polycyclic aromatic hydrocarbons. CYP in microsomes from control and RFFO-treated animals showed a peak at 450 nm; however, a shift of 2 nm in the SORET region along with significant induction was observed in microsomes prepared from 3-methylcholanthrene (MC)- and RFFE-treated animals. Activities of hepatic ethoxyresorufin-O-deethylase, methoxyresorufin-O-deethylase, aryl hydrocarbon hydroxylase and erythromycin-N-demethylase were found to be significantly (P < 0.05) induced following exposure of RFFE, whereas none of these enzymes were altered in RFFO-treated group. Immunoblot analysis revealed that RFFE and MC were potent inducers of CYP1A1, 1A1/2 and 3A1 isozymes, where as RFFO showed no change in these protein levels. RT-PCR analysis showed induction of cDNA of CYP1A1 and CYP3A1 by RFFE treatment. Hepatic microsomes prepared from RFFE exposed animals enhanced BP metabolism with a concomitant increase in the relative proportion of BP 7,8-diol. Hepatic microsomes prepared from animals pretreated with RFFE and MC significantly enhanced the binding of [{sup 3}H]-BP to calf thymus DNA. The overall results suggest that exposure to RFFE may induce hepatic CYP isozymes thereby producing enhanced reactive metabolites with a potential to bind with DNA that may result in cancer.

  20. Mutagenic characterization of cholesterol epoxides in Chinese hamster V79 cells.

    PubMed

    Peterson, A R; Peterson, H; Spears, C P; Trosko, J E; Sevanian, A

    1988-10-01

    The uptake, metabolism and alkylating properties of the diastereomeric cholesterol epoxides were studied using Chinese hamster lung fibroblasts (V79 cells). Specific emphasis is given to the comparative cyto- and geno-toxic effects of cholesterol 5 beta,6 beta-epoxide (beta CE) and cholesterol 5 alpha,6 alpha-epoxide (alpha CE) and data are provided for the first time indicating that beta CE can induce more 6-thioguanine-resistant cells than alpha CE. Cholesterol 5 beta,6 beta-epoxide induced colonies of cells resistant to 6-thioguanine at 2-3-fold the frequencies observed with the alpha-isomer, but neither compound produced ouabain-resistant colonies. The cytotoxicity (LD50) of alpha CE was estimated to be 45-50 microM whereas beta CE displayed an LD50 of 25-29 microM. Inhibition of DNA synthesis (IC50) was observed over the same dose ranges as the LD50 for each epoxide isomer. The epoxides were assimilated by cells to an equal extent, however, beta CE was metabolized to cholestane 3 beta,5 alpha-6 beta-triol twice as rapidly as the alpha-isomer. Both epoxides reacted with 4-(4'-nitrobenzyl)-pyridine to a similar extent, and with identical nucleophilic selectivity at pH 7.4, but their alkylating activity was estimated on this basis to be two orders of magnitude less than methyl methanesulfonate. Binding experiments with the DNA or cultured V79 cells or with calf-thymus DNA indicated that interactions were noncovalent and DNA binding did not correlate with the potency of the epoxides to induce the 6-thioguanine-resistant phenotype. Our results could be interpreted as indicating that both cholesterol epoxide isomers are weak mutagens or that they might induce some epigenetic event repressing the hypoxanthine guanine-phosphoribosyltransferase gene. The similarity of the epoxides' alkylating activity and their DNA-binding properties are inconsistent with their different potencies in inducing the 6-thioguanine-resistant phenotype, suggesting that the mechanism leading

  1. Epoxidation Activities of Human Cytochromes P450c17 and P450c21

    PubMed Central

    2015-01-01

    Some cytochrome P450 enzymes epoxidize unsaturated substrates, but this activity has not been described for the steroid hydroxylases. Physiologic steroid substrates, however, lack carbon–carbon double bonds in the parts of the pregnane molecules where steroidogenic hydroxylations occur. Limited data on the reactivity of steroidogenic P450s toward olefinic substrates exist, and the study of occult activities toward alternative substrates is a fundamental aspect of the growing field of combinatorial biosynthesis. We reasoned that human P450c17 (steroid 17-hydroxylase/17,20-lyase, CYP17A1), which 17- and 16α-hydroxylates progesterone, might catalyze the formation of the 16α,17-epoxide from 16,17-dehydroprogesterone (pregna-4,16-diene-3,20-dione). CYP17A1 catalyzed the novel 16α,17-epoxidation and the ordinarily minor 21-hydroxylation of 16,17-dehydroprogesterone in a 1:1 ratio. CYP17A1 mutation A105L, which has reduced progesterone 16α-hydroxylase activity, gave a 1:5 ratio of epoxide:21-hydroxylated products. In contrast, human P450c21 (steroid 21-hydroxylase, CYP21A2) converted 16,17-dehydroprogesterone to the 21-hydroxylated product and only a trace of epoxide. CYP21A2 mutation V359A, which has significant 16α-hydroxylase activity, likewise afforded the 21-hydroxylated product and slightly more epoxide. CYP17A1 wild-type and mutation A105L do not 21- or 16α-hydroxylate pregnenolone, but the enzymes 21-hydroxylated and 16α,17-epoxidized 16,17-dehydropregnenolone (pregna-5,16-diene-3β-ol-20-one) in 4:1 or 12:1 ratios, respectively. Catalase and superoxide dismutase did not prevent epoxide formation. The progesterone epoxide was not a time-dependent, irreversible CYP17A1 inhibitor. Our substrate modification studies have revealed occult epoxidase and 21-hydroxylase activities of CYP17A1, and the fraction of epoxide formed correlated with the 16α-hydroxylase activity of the enzymes. PMID:25386927

  2. Epoxide Opening of a 7,17-Seco-7,8-Epoxy-C19-Diterpenoid Alkaloid.

    PubMed

    Ji, Hong; Wang, Feng-Peng; Chen, Qiao-Hong

    2015-12-01

    A new and effective approach toward epoxide opening of a 7,17-seco-7,8-epoxy-C19-diterpenoid alkaloid is herein described. The starting epoxide was prepared from naturally occurring yunnaconitine via a nine-step transformation. Treatment of this epoxide with trifluoroacetic anhydride in dioxane at 110 degrees C followed by reduction with sodium boron hydride generated two epoxide opening compounds 7 and 8. Each of their structures is characteristic of a Δ8,15 bridgehead double bond and a 7β-oxygen-substituted group. PMID:26882668

  3. Impact of Stereochemistry on Ligand Binding: X-ray Crystallographic Analysis of an Epoxide-Based HIV Protease Inhibitor.

    PubMed

    Benedetti, Fabio; Berti, Federico; Campaner, Pietro; Fanfoni, Lidia; Demitri, Nicola; Olajuyigbe, Folasade M; De March, Matteo; Geremia, Silvano

    2014-09-11

    A new pseudopeptide epoxide inhibitor, designed for irreversible binding to HIV protease (HIV-PR), has been synthesized and characterized in solution and in the solid state. However, the crystal structure of the complex obtained by inhibitor-enzyme cocrystallization revealed that a minor isomer, with inverted configuration of the epoxide carbons, has been selected by HIV-PR during crystallization. The structural characterization of the well-ordered pseudopeptide, inserted in the catalytic channel with its epoxide group intact, provides deeper insights into inhibitor binding and HIV-PR stereoselectivity, which aids development of future epoxide-based HIV inhibitors. PMID:25221650

  4. Prostaglandin endoperoxide synthetase and the activation of benzo(a)pyrene to reactive metabolites in vivo in guinea pigs

    SciTech Connect

    Garattini, E.; Coccia, P.; Romano, M.; Jiritano, L.; Noseda, A.; Salmona, M.

    1984-11-01

    The role of prostaglandin endoperoxide synthetase in the in vivo activation of benzo(a)pyrene to reactive metabolites capable of interacting irreversibly with cellular macromolecules was studied in guinea pig liver, lung, kidney, spleen, small intestine, colon, and brain. DNA and protein covalent binding experiments were made after systemic administration of acetylsalicylic acid (200 mg/kg) followed by radiolabeled benzo(a)pyrene (4 microgram/kg). Results are compared with a control situation in which the prostaglandin endoperoxide synthetase inhibitor (acetylsalicylic acid) was not administered. No decrease in the level of DNA or protein benzo(a)pyrene-derived covalent binding was observed in any of the tissues studied.

  5. Synthesis of 5α-androstane-3α,17β-diol 17-O-glucuronide histaminyl conjugate for immunoassays.

    PubMed

    Vinš, Petr; Černý, Ivan; Mikšátková, Petra; Drašar, Pavel

    2016-05-01

    Simple method of preparation of 5α-androstane-3α,17β-diol 17-O-glucuronide N-histaminyl amide was developed for the construction of immunoanalytical kit. Improved method of glucuronide derivative synthesis was used, followed by hydroxybenzotriazole-dicyclohexylcarbodiimide coupling with histamine. PMID:26898541

  6. THE PHASE BEHAVIOR OF FLUORINATED DIOLS, DIVINYL ADIPATE, AND A FLUORINATED POLYESTER IN SUPERCRITICAL CARBON DIOXIDE. (R828131)

    EPA Science Inventory

    The use of supercritical carbon dioxide as a reaction medium for polyester synthesis is hindered by the low solubility of diols in CO2. However, it has been previously demonstrated that fluorinated compounds can exhibit greater miscibility with carbon dioxide than t...

  7. Boronate Affinity Fluorescent Nanoparticles for Förster Resonance Energy Transfer Inhibition Assay of cis-Diol Biomolecules.

    PubMed

    Wang, Shuangshou; Ye, Jin; Li, Xinglin; Liu, Zhen

    2016-05-17

    Förster resonance energy transfer (FRET) has been essential for many applications, in which an appropriate donor-acceptor pair is the key. Traditional dye-to-dye combinations remain the working horses but are rather nonspecifically susceptive to environmental factors (such as ionic strength, pH, oxygen, etc.). Besides, to obtain desired selectivity, functionalization of the donor or acceptor is essential but usually tedious. Herein, we present fluorescent poly(m-aminophenylboronic acid) nanoparticles (poly(mAPBA) NPs) synthesized via a simple procedure and demonstrate a FRET scheme with suppressed environmental effects for the selective sensing of cis-diol biomolecules. The NPs exhibited stable fluorescence properties, resistance to environmental factors, and a Förster distance comparable size, making them ideal donor for FRET applications. By using poly(mAPBA) NPs and adenosine 5'-monophosphate modified graphene oxide (AMP-GO) as a donor and an acceptor, respectively, an environmental effects-suppressed boronate affinity-mediated FRET system was established. The fluorescence of poly(mAPBA) NPs was quenched by AMP-GO while it was restored when a competing cis-diol compounds was present. The FRET system exhibited excellent selectivity and improved sensitivity toward cis-diol compounds. Quantitative inhibition assay of glucose in human serum was demonstrated. As many cis-diol compounds such as sugars and glycoproteins are biologically and clinically significant, the FRET scheme presented herein could find more promising applications. PMID:27089186

  8. Enantioselective Synthesis of Vicinal (R,R)-Diols by Saccharomyces cerevisiae Butanediol Dehydrogenase.

    PubMed

    Calam, Eduard; González-Roca, Eva; Fernández, M Rosario; Dequin, Sylvie; Parés, Xavier; Virgili, Albert; Biosca, Josep A

    2016-01-01

    Butanediol dehydrogenase (Bdh1p) from Saccharomyces cerevisiae belongs to the superfamily of the medium-chain dehydrogenases and reductases and converts reversibly R-acetoin and S-acetoin to (2R,3R)-2,3-butanediol and meso-2,3-butanediol, respectively. It is specific for NAD(H) as a coenzyme, and it is the main enzyme involved in the last metabolic step leading to (2R,3R)-2,3-butanediol in yeast. In this study, we have used the activity of Bdh1p in different forms-purified enzyme, yeast extracts, permeabilized yeast cells, and as a fusion protein (with yeast formate dehydrogenase, Fdh1p)-to transform several vicinal diketones to the corresponding diols. We have also developed a new variant of the delitto perfetto methodology to place BDH1 under the control of the GAL1 promoter, resulting in a yeast strain that overexpresses butanediol dehydrogenase and formate dehydrogenase activities in the presence of galactose and regenerates NADH in the presence of formate. While the use of purified Bdh1p allows the synthesis of enantiopure (2R,3R)-2,3-butanediol, (2R,3R)-2,3-pentanediol, (2R,3R)-2,3-hexanediol, and (3R,4R)-3,4-hexanediol, the use of the engineered strain (as an extract or as permeabilized cells) yields mixtures of the diols. The production of pure diol stereoisomers has also been achieved by means of a chimeric fusion protein combining Fdh1p and Bdh1p. Finally, we have determined the selectivity of Bdh1p toward the oxidation/reduction of the hydroxyl/ketone groups from (2R,3R)-2,3-pentanediol/2,3-pentanedione and (2R,3R)-2,3-hexanediol/2,3-hexanedione. In conclusion, Bdh1p is an enzyme with biotechnological interest that can be used to synthesize chiral building blocks. A scheme of the favored pathway with the corresponding intermediates is proposed for the Bdh1p reaction. PMID:26729717

  9. Enantioselective Synthesis of Vicinal (R,R)-Diols by Saccharomyces cerevisiae Butanediol Dehydrogenase

    PubMed Central

    Calam, Eduard; González-Roca, Eva; Fernández, M. Rosario; Dequin, Sylvie; Parés, Xavier; Virgili, Albert

    2016-01-01

    Butanediol dehydrogenase (Bdh1p) from Saccharomyces cerevisiae belongs to the superfamily of the medium-chain dehydrogenases and reductases and converts reversibly R-acetoin and S-acetoin to (2R,3R)-2,3-butanediol and meso-2,3-butanediol, respectively. It is specific for NAD(H) as a coenzyme, and it is the main enzyme involved in the last metabolic step leading to (2R,3R)-2,3-butanediol in yeast. In this study, we have used the activity of Bdh1p in different forms—purified enzyme, yeast extracts, permeabilized yeast cells, and as a fusion protein (with yeast formate dehydrogenase, Fdh1p)—to transform several vicinal diketones to the corresponding diols. We have also developed a new variant of the delitto perfetto methodology to place BDH1 under the control of the GAL1 promoter, resulting in a yeast strain that overexpresses butanediol dehydrogenase and formate dehydrogenase activities in the presence of galactose and regenerates NADH in the presence of formate. While the use of purified Bdh1p allows the synthesis of enantiopure (2R,3R)-2,3-butanediol, (2R,3R)-2,3-pentanediol, (2R,3R)-2,3-hexanediol, and (3R,4R)-3,4-hexanediol, the use of the engineered strain (as an extract or as permeabilized cells) yields mixtures of the diols. The production of pure diol stereoisomers has also been achieved by means of a chimeric fusion protein combining Fdh1p and Bdh1p. Finally, we have determined the selectivity of Bdh1p toward the oxidation/reduction of the hydroxyl/ketone groups from (2R,3R)-2,3-pentanediol/2,3-pentanedione and (2R,3R)-2,3-hexanediol/2,3-hexanedione. In conclusion, Bdh1p is an enzyme with biotechnological interest that can be used to synthesize chiral building blocks. A scheme of the favored pathway with the corresponding intermediates is proposed for the Bdh1p reaction. PMID:26729717

  10. NADH:Cytochrome b5 Reductase and Cytochrome b5 Can Act as Sole Electron Donors to Human Cytochrome P450 1A1-Mediated Oxidation and DNA Adduct Formation by Benzo[a]pyrene

    PubMed Central

    2016-01-01

    Benzo[a]pyrene (BaP) is a human carcinogen that covalently binds to DNA after activation by cytochrome P450 (P450). Here, we investigated whether NADH:cytochrome b5 reductase (CBR) in the presence of cytochrome b5 can act as sole electron donor to human P450 1A1 during BaP oxidation and replace the canonical NADPH:cytochrome P450 reductase (POR) system. We also studied the efficiencies of the coenzymes of these reductases, NADPH as a coenzyme of POR, and NADH as a coenzyme of CBR, to mediate BaP oxidation. Two systems containing human P450 1A1 were utilized: human recombinant P450 1A1 expressed with POR, CBR, epoxide hydrolase, and cytochrome b5 in Supersomes and human recombinant P450 1A1 reconstituted with POR and/or with CBR and cytochrome b5 in liposomes. BaP-9,10-dihydrodiol, BaP-7,8-dihydrodiol, BaP-1,6-dione, BaP-3,6-dione, BaP-9-ol, BaP-3-ol, a metabolite of unknown structure, and two BaP-DNA adducts were generated by the P450 1A1-Supersomes system, both in the presence of NADPH and in the presence of NADH. The major BaP-DNA adduct detected by 32P-postlabeling was characterized as 10-(deoxyguanosin-N2-yl)-7,8,9-trihydroxy-7,8,9,10-tetrahydro-BaP (assigned adduct 1), while the minor adduct is probably a guanine adduct derived from 9-hydroxy-BaP-4,5-epoxide (assigned adduct 2). BaP-3-ol as the major metabolite, BaP-9-ol, BaP-1,6-dione, BaP-3,6-dione, an unknown metabolite, and adduct 2 were observed in the system using P450 1A1 reconstituted with POR plus NADPH. When P450 1A1 was reconstituted with CBR and cytochrome b5 plus NADH, BaP-3-ol was the predominant metabolite too, and an adduct 2 was also generated. Our results demonstrate that the NADH/cytochrome b5/CBR system can act as the sole electron donor both for the first and second reduction of P450 1A1 during the oxidation of BaP in vitro. They suggest that NADH-dependent CBR can replace NADPH-dependent POR in the P450 1A1-catalyzed metabolism of BaP. PMID:27404282

  11. Epoxide-Mediated Differential Packaging of Cif and Other Virulence Factors into Outer Membrane Vesicles

    PubMed Central

    Ballok, Alicia E.; Filkins, Laura M.; Bomberger, Jennifer M.; Stanton, Bruce A.

    2014-01-01

    Pseudomonas aeruginosa produces outer membrane vesicles (OMVs) that contain a number of secreted bacterial proteins, including phospholipases, alkaline phosphatase, and the CFTR inhibitory factor (Cif). Previously, Cif, an epoxide hydrolase, was shown to be regulated at the transcriptional level by epoxides, which serve as ligands of the repressor, CifR. Here, we tested whether epoxides have an effect on Cif levels in OMVs. We showed that growth of P. aeruginosa in the presence of specific epoxides but not a hydrolysis product increased Cif packaging into OMVs in a CifR-independent fashion. The outer membrane protein, OprF, was also increased under these conditions, but alkaline phosphatase activity was not significantly altered. Additionally, we demonstrated that OMV shape and density were affected by epoxide treatment, with two distinct vesicle fractions present when cells were treated with epibromohydrin (EBH), a model epoxide. Vesicles isolated from the two density fractions exhibited different protein profiles in Western blotting and silver staining. We have shown that a variety of clinically or host-relevant treatments, including antibiotics, also alter the proteins packaged in OMVs. Proteomic analysis of purified OMVs followed by an analysis of transposon mutant OMVs yielded mutants with altered vesicle packaging. Finally, epithelial cell cytotoxicity was reduced in the vesicles formed in the presence of EBH, suggesting that this epoxide alters the function of the OMVs. Our data support a model whereby clinically or host-relevant signals mediate differential packaging of virulence factors in OMVs, which results in functional consequences for host-pathogen interactions. PMID:25112474

  12. Final Report: Experimental and Theoretical Studies of Surface Oxametallacycles - Connections to Heterogeneous Olefin Epoxidation

    SciTech Connect

    Mark A. Barteau

    2009-09-15

    This project has aimed at the rational design of catalysts for direct epoxidation of olefins. This chemistry remains one of the most challenging problems in heterogeneous catalysis. Although the epoxidation of ethylene by silver catalysts to form ethylene oxide (EO) has been practiced for decades, little progress has been made in expanding this technology to other products and processes. We have made significant advances through the combination of surface science experiments, Density Functional Theory (DFT) calculations, and catalytic reactor experiments, toward understanding the mechanism of this reaction on silver catalysts, and to the rational improvement of selectivity. The key has been our demonstration of surface oxametallacycle intermediates as the species that control reaction selectivity. This discovery permits the influence of catalyst promoters on selectivity to be probed, and new catalyst formulations to be developed. It also guides the development of new chemistry with potential for direct epoxidation of more complex olefins. During the award period we have focused on 1. the formation and reaction selectivity of complex olefin epoxides on silver surfaces, and 2. the influence of co-adsorbed oxygen atoms on the reactions of surface oxametallacycles on silver, and 3. the computational prediction, synthesis, characterization and experimental evaluation of bimetallic catalysts for ethylene epoxidation. The significance of these research thrusts is as follows. Selective epoxidation of olefins more complex than ethylene requires suppression of not only side reactions available to the olefin such as C-H bond breaking, but it requires formation and selective ring closure of the corresponding oxametallacycle intermediates. The work carried out under this grant has significantly advanced the field of catalyst design from first principles. The combination of computational tools, surface science, and catalytic reactor experiments in a single laboratory has few

  13. Purification of a vitamin K epoxide reductase that catalyzes conversion of vitamin K 2,3-epoxide to 3-hydroxy-2-methyl-3-phytyl-2,3-dihydronaphthoquinone.

    PubMed Central

    Mukharji, I; Silverman, R B

    1985-01-01

    An enzyme from bovine liver microsomes that catalyzes the reduction of vitamin K 2,3-epoxide to 2- and 3-hydroxy-2-methyl-3-phytyl-2,3-dihydronaphthoquinone was purified 1152-fold to apparent homogeneity. Microsomes were solubilized with 3-[3-cholamidopropyl)dimethylammonio]-1-propanesulfonate (CHAPS), and the enzyme was purified by chromatography on PBE-94 ion exchanger, hydroxylapatite, and DEAE-cellulose, and then gel filtration on Sephacryl S-200. The homogeneity of the final preparation was established by polyacrylamide slab gel electrophoresis in the presence of sodium dodecyl sulfate. The molecular weight of the native enzyme is 25,000 and that of denatured enzyme is 12,400, which suggests that the enzyme is a dimer with identical subunits. No chromophoric cofactors are associated with the enzyme. Dithiothreitol and CHAPS are essential for activity, but high concentrations of glycerol reduces the activity. The enzyme is not inhibited by warfarin, a potent inhibitor of the vitamin K epoxide reductase, which catalyzes the conversion of vitamin K 2,3-epoxide to vitamin K. Evidence is presented indicating that the purified enzyme is not simply a fragment of the warfarin-sensitive vitamin K epoxide reductase. Images PMID:3857611

  14. Preliminary Feasibility Study of Benzo(a)Pyrene Oxidative Degradation by Fenton Treatment

    PubMed Central

    Homem, Vera; Dias, Zélia; Santos, Lúcia; Alves, Arminda

    2009-01-01

    Polycyclic aromatic hydrocarbons (PAHs) are considered priority compounds due to their toxic and carcinogenic nature. The concern about water contamination and the consequent human exposure has encouraged the development of new methods for PAHs removal. The purpose of this work was to study the feasibility of a degradation process of benzo(a)pyrene (BaP) in aqueous matrices by oxidation with Fenton reagent. A laboratory unit was designed to optimize the factors which may influence the process: pH (3.5 to 6.0), temperature (30 to 70°C), H2O2 (20 to 150 mg L−1), Fe2+ concentration (2.75 to 5.50 mg L−1), and the initial concentration of the pollutant (10 to 100 μg L−1). The pH did not influence significantly the results in the range studied. An increase in temperature from 30 to 70°C improved the removal efficiency from 90% to 100%. The same effect was observed for ferrous ion concentrations from 2.75 to 5.50 mg L−1 (increase from 78% to 100% removal). The H2O2 concentration played a double role during the process: from 20 to 50 mg L−1 an increase in the removal efficiency was achieved, but for higher concentrations (>50 mg L−1) the degradation is lower. This study proved that the degradation of benzo(a)pyrene by Fenton's reagent is a viable process. PMID:19936125

  15. The testosterone metabolite 3α-Diol enhances female rat sexual motivation when infused in the nucleus accumbens shell

    PubMed Central

    Hernández, Lizaida; Barreto Estrada, Jennifer L; Ortiz, José G; Carlos Jorge, Juan

    2010-01-01

    Aim The purpose of this study was to provide a quantitative assessment of female rat sexual behaviors after acute exposure to the A-ring reduced testosterone metabolite, androstanediol (3α-Diol), through the nucleus accumbens (NA) shell. Main outcome measures Quantitative analyses of female rat sexual behaviors and assessment of protein levels for the enzyme glutamic acid decarboxylase isoform 67 (GAD67) and gephyrin, a protein that participates in the clustering of GABA-A receptors in postsynaptic cells, were accomplished. Methods Female rats were ovariectomized and primed with estrogen and progesterone to induce sexual behaviors. Females received a 3α-Diol infusion via guided cannula that aimed to the NA shell five minutes prior to a sexual encounter with a stud male. The following parameters were videotaped and measured in a frame by frame analysis: lordosis quotient (LQ), Lordosis rating (LR), frequency and duration of proceptive behaviors (hopping/darting and ear wiggling). Levels of GAD67 and gephyrin were obtained by Western blot analysis two or twenty-four hours after the sexual encounter. Results Acute exposure to 3α-Diol in the NA shell enhanced LR, ear wiggling, and hopping/darting but not LQ. Some of these behavioral effects were counteracted by co-infusion of 3α-Diol plus the GABAA-receptor antagonist GABAzine. A transient reduction of GAD67 levels in the NA shell was detected. Conclusions The testosterone metabolite 3α-Diol enhances sexual proceptivity, but not receptivity, when infused into the NA shell directly. The GABAergic system may participate in the androgen-mediated enhancement of female rat sexual motivation. PMID:20646182

  16. "Old" metal oxide affinity chromatography as "novel" strategy for specific capture of cis-diol-containing compounds.

    PubMed

    Wang, Shao-Ting; Huang, Wei; Deng, Yi-Fan; Gao, Qiang; Yuan, Bi-Feng; Feng, Yu-Qi

    2014-09-26

    The metal oxide affinity chromatography (MOAC) materials have been extensively used for extraction of phosphate compounds in the past decade. Actually, some of these materials also possess adsorption affinity towards cis-diol-containing compounds, which was seldom explored in separation field so far. Here we present the proof-of-concept study to evaluate the feasibility of expanding MOAC for specific capture of cis-diol biomolecules. Benefitting from the high commercialisation of the metal oxide materials, such MOAC strategy possesses several advantages, like synthesis-free, low cost and high expandability. Firstly, the recognition of adenosine against 2'-deoxyadenosine was performed using zirconium oxide and cerium oxide, two typical commercial MOAC materials. The results showed that efficient adsorption and elution could be achieved easily by pH switching from basic to acidic. The isotherm curves demonstrated the adsorption process fitted well with Freundlich isotherm model and was spontaneous at room temperature (ΔG(0)<0) with an exothermic nature (ΔH(0)<0). Afterwards, the highly efficient and selective enrichment of various model cis-diol biomolecules, including ribonucleosides, glycopeptides and glycoproteins, was achieved using this MOAC strategy. Finally, the endogenous ribonucleosides and modified ribonucleosides were successfully purified from human urine sample, which demonstrated the potential application of MOAC materials in the enrichment of target compounds from complex biological samples. Besides the excellent performance of extraction for cis-diol-containing compounds, equally important is that these materials are commercially available with low cost, which makes the MOAC a promising strategy for the study of cis-diol biomolecules in metabolomics and proteomics. PMID:25138708

  17. Soluble Epoxide Hydrolase Dimerization Is Required for Hydrolase Activity*

    PubMed Central

    Nelson, Jonathan W.; Subrahmanyan, Rishi M.; Summers, Sol A.; Xiao, Xiangshu; Alkayed, Nabil J.

    2013-01-01

    Soluble epoxide hydrolase (sEH) plays a key role in the metabolic conversion of the protective eicosanoid 14,15-epoxyeicosatrienoic acid to 14,15-dihydroxyeicosatrienoic acid. Accordingly, inhibition of sEH hydrolase activity has been shown to be beneficial in multiple models of cardiovascular diseases, thus identifying sEH as a valuable therapeutic target. Recently, a common human polymorphism (R287Q) was identified that reduces sEH hydrolase activity and is localized to the dimerization interface of the protein, suggesting a relationship between sEH dimerization and activity. To directly test the hypothesis that dimerization is essential for the proper function of sEH, we generated mutations within the sEH protein that would either disrupt or stabilize dimerization. We quantified the dimerization state of each mutant using a split firefly luciferase protein fragment-assisted complementation system. The hydrolase activity of each mutant was determined using a fluorescence-based substrate conversion assay. We found that mutations that disrupted dimerization also eliminated hydrolase enzymatic activity. In contrast, a mutation that stabilized dimerization restored hydrolase activity. Finally, we investigated the kinetics of sEH dimerization and found that the human R287Q polymorphism was metastable and capable of swapping dimer partners faster than the WT enzyme. These results indicate that dimerization is required for sEH hydrolase activity. Disrupting sEH dimerization may therefore serve as a novel therapeutic strategy for reducing sEH hydrolase activity. PMID:23362272

  18. Soluble epoxide hydrolase dimerization is required for hydrolase activity.

    PubMed

    Nelson, Jonathan W; Subrahmanyan, Rishi M; Summers, Sol A; Xiao, Xiangshu; Alkayed, Nabil J

    2013-03-15

    Soluble epoxide hydrolase (sEH) plays a key role in the metabolic conversion of the protective eicosanoid 14,15-epoxyeicosatrienoic acid to 14,15-dihydroxyeicosatrienoic acid. Accordingly, inhibition of sEH hydrolase activity has been shown to be beneficial in multiple models of cardiovascular diseases, thus identifying sEH as a valuable therapeutic target. Recently, a common human polymorphism (R287Q) was identified that reduces sEH hydrolase activity and is localized to the dimerization interface of the protein, suggesting a relationship between sEH dimerization and activity. To directly test the hypothesis that dimerization is essential for the proper function of sEH, we generated mutations within the sEH protein that would either disrupt or stabilize dimerization. We quantified the dimerization state of each mutant using a split firefly luciferase protein fragment-assisted complementation system. The hydrolase activity of each mutant was determined using a fluorescence-based substrate conversion assay. We found that mutations that disrupted dimerization also eliminated hydrolase enzymatic activity. In contrast, a mutation that stabilized dimerization restored hydrolase activity. Finally, we investigated the kinetics of sEH dimerization and found that the human R287Q polymorphism was metastable and capable of swapping dimer partners faster than the WT enzyme. These results indicate that dimerization is required for sEH hydrolase activity. Disrupting sEH dimerization may therefore serve as a novel therapeutic strategy for reducing sEH hydrolase activity. PMID:23362272

  19. [Determination of epoxidized soybean oil in bottled foods].

    PubMed

    Kawamura, Yoko; Kanno, Shinji; Mutsuga, Motoh; Tanamoto, Kenichi

    2006-12-01

    A determination method for epoxidized soybean oil (ESBO) in bottled foods was developed and used to survey bottled foods on the Japanese market. The amount of sample required was decreased to 20 g and the standard addition method was adopted for the quantification, because lipid in foods interrupted the hydrolysis of ESBO. The recoveries were 87.1 and 98.9% and the determination limit was 5.0 microg/g for a 20 g sample, be cause lipid in foods interupted the hydrolysis of ESBO. The recoveries using the internal standard method varied widely, because hydrolysis of the internal standard, cis-11,14-eicosadienoic acid ethyl ester, was affected more than that of ESBO by coexisting lipid in the sample. ESBO was not detected in any of the bottled baby food samples examined (14 samples), though it had been frequently detected in previous European surveys. This difference may be related to the low fat content and low fluidity of the bottled baby foods retailed in Japan. On the other hand, ESBO was detected at levels of 25.7-494.0 microg/g in liver paste, pasta sauce, Sungan in spicy oil, and spicy oil. These foods had higher fat content and higher fluidity. However, ESBO intake from these foods appears unlikely to exceed the TDI in the EU (1 mg/kg bw/day). PMID:17228787

  20. Discovery of enantioselectivity of urea inhibitors of soluble epoxide hydrolase.

    PubMed

    Manickam, Manoj; Pillaiyar, Thanigaimalai; Boggu, PullaReddy; Venkateswararao, Eeda; Jalani, Hitesh B; Kim, Nam-Doo; Lee, Seul Ki; Jeon, Jang Su; Kim, Sang Kyum; Jung, Sang-Hun

    2016-07-19

    Soluble epoxide hydrolase (sEH) hydrolyzes epoxyeicosatrienoic acids (EETs) in the metabolic pathway of arachidonic acid and has been considered as an important therapeutic target for chronic diseases such as hypertension, diabetes and inflammation. Although many urea derivatives are known as sEH inhibitors, the enantioselectivity of the inhibitors is not highlighted in spite of the stereoselective hydrolysis of EETs by sEH. In an effort to explore the importance of enantioselectivity in the urea scaffold, a series of enantiomers with the stereocenter adjacent to the urea nitrogen atom were prepared. The selectivity of enantiomers of 1-(α-alkyl-α-phenylmethyl)-3-(3-phenylpropyl)ureas showed wide range differences up to 125 fold with the low IC50 value up to 13 nM. The S-configuration with planar phenyl and small alkyl groups at α-position is crucial for the activity and selectivity. However, restriction of the free rotation of two α-groups with indan-1-yl or 1,2,3,4-tetrahydronaphthalen-1-yl moiety abolishes the selectivity between the enantiomers, despite the increase in activity up to 13 nM. The hydrophilic group like sulfonamido group at para position of 3-phenylpropyl motif of 1-(α-alkyl-α-phenylmethyl-3-(3-phenylpropyl)urea improves the activity as well as enantiomeric selectivity. All these ureas are proved to be specific inhibitor of sEH without inhibition against mEH. PMID:27092411

  1. Soluble epoxide hydrolase deficiency ameliorates acute pancreatitis in mice.

    PubMed

    Bettaieb, Ahmed; Morisseau, Christophe; Hammock, Bruce; Haj, Fawaz

    2014-10-01

    Acute pancreatitis (AP) is a frequent gastrointestinal disorder that causes significant morbidity and its incidence has been progressively increasing. AP starts as a local inflammation in the pancreas that often leads to systemic inflammatory response and complications. Soluble epoxide hydrolase (sEH) is a cytosolic enzyme whose inhibition in murine models has beneficial effects in inflammatory diseases, but its significance in AP remains unexplored. To investigate whether sEH may have a causal role in AP we utilized sEH knockout (KO) mice to determine the effects of sEH deficiency on ceruelin- and arginine-induced AP. sEH expression increased at the protein and messenger RNA levels, as well as sEH activity in the early phase of cerulein- and arginine-induced AP in mice. In addition, amylase and lipase levels were lower in cerulein-treated sEH KO mice compared with non-treated controls. Moreover, pancreatic mRNA and serum concentrations of the inflammatory cytokines IL-1ß and IL-6 were lower in sEH KO mice compared with controls. Further, sEH KO mice exhibited decreased cerulein- and arginine-induced NF-?B inflammatory response, MAPKs activation and decreased cell death. These findings demonstrate a novel role for sEH in the progression of cerulein- and arginine-induced AP. PMID:26461340

  2. Disrupting Dimerization Translocates Soluble Epoxide Hydrolase to Peroxisomes

    PubMed Central

    Nelson, Jonathan W.; Das, Anjali J.; Barnes, Anthony P.; Alkayed, Nabil J.

    2016-01-01

    The epoxyeicosatrienoic acid (EET) neutralizing enzyme soluble epoxide hydrolase (sEH) is a neuronal enzyme, which has been localized in both the cytosol and peroxisomes. The molecular basis for its dual localization remains unclear as sEH contains a functional peroxisomal targeting sequence (PTS). Recently, a missense polymorphism was identified in human sEH (R287Q) that enhances its peroxisomal localization. This same polymorphism has also been shown to generate weaker sEH homo-dimers. Taken together, these observations suggest that dimerization may mask the sEH PTS and prevent peroxisome translocation. In the current study, we test the hypothesis that dimerization is a key regulator of sEH subcellular localization. Specifically, we altered the dimerization state of sEH by introducing substitutions in amino acids responsible for the dimer-stabilizing salt-bridge. Green Fluorescent Protein (GFP) fusions of each of mutants were co-transfected into mouse primary cultured cortical neurons together with a PTS-linked red fluorescent protein to constitutively label peroxisomes. Labeled neurons were analyzed using confocal microscopy and co-localization of sEH with peroxisomes was quantified using Pearson’s correlation coefficient. We find that dimer-competent sEH constructs preferentially localize to the cytosol, whereas constructs with weakened or disrupted dimerization were preferentially targeted to peroxisomes. We conclude that the sEH dimerization status is a key regulator of its peroxisomal localization. PMID:27203283

  3. COMPARISON OF THE GENOTOXIC ACTIVITIES OF THE K-REGION DIHYDRODIOL OF BENZO[A]PYRENE WITH BENZO[A]PYRENE IN MAMMALIAN CELLS: MORPHOLOGICAL CELL TRANSFORMATION; DNA DAMAGE; AND STABLE COVALENT DNA ADDUCTS

    EPA Science Inventory

    Benzo[a]pyrene (B[a]P) has been the most thoroughly studied polycyclic aromatic hydrocarbon (PAH) with regard to its occurrence, metabolism, toxicological and carcinogenic activities. Many mechanisms have been suggested to explain its carcinogenic activity, yet many questions sti...

  4. Dispersion of Vesicles Composed of Industrially Produced Alkyl (Oligo) Glucoside Using Diol-Boron Complexation.

    PubMed

    Aikawa, Tatsuo; Asano, Yuuka; Kondo, Takeshi; Yuasa, Makoto

    2016-07-01

    Alkyl (oligo)glucosides (AOG) are known to be environmentally compatible amphiphiles whose commercial applicability should be broadened. The present paper describes the preparation of molecular assemblies of industrially produced AOG, which is a mixture composed of different length of alkyl chains (C9-C12) with oligoglucoside moiety with a few (1-3) of glucose units. It was also described that regulation of the dispersibility of the molecular assemblies prepared by diol-boron complexation between the sugar moiety on AOG and boric acid in a dispersion medium. The molecular assembly of AOG was successfully formed by mixing AOG and cholesterols (CH). When using a suitable amount of CH (20-40 mol% with respect to AOG), the molecular assembly formed a vesicle structure. The dispersion ability of the resulting vesicle was dependent on both the boric acid concentration and pH of the dispersion medium. The light-scattering and ζ-potential measurements revealed that high concentrations (≥10 mM) of boric acid improved dispersibility the vesicles. In contrast, the vesicle agglomerated at low concentrations of boric acid (1-7.5 mM). In the absence of boric acid in dispersion medium, the vesicles were completely agglomerated. The optimum pH range for vesicle dispersion was found to be from neutral to basic (7.4-10.1). The (11)B NMR study revealed that borate ester formation occurred between boric acid and the diol of the sugar moiety on AOG vesicle. The present data suggest that borate ester formation that occurred on the surface of the vesicle provided negative charge to the vesicles, contributing to their dispersion via repulsive forces. PMID:27321117

  5. Polyethyleneimine-grafted boronate affinity materials for selective enrichment of cis-diol-containing compounds.

    PubMed

    Xue, Yun; Shi, Wenjun; Zhu, Bangjie; Gu, Xue; Wang, Yan; Yan, Chao

    2015-08-01

    Polyethyleneimine (PEI)-grafted and 3-acrylamidophenylboronic acid (AAPBA)-functionalized SiO2 boronate affinity materials were synthesized for the selective enrichment of cis-diol-containing compounds. Characterization results of scanning electron microscopy, Fourier transform infrared spectroscopy, elemental analysis, zeta potential, and X-ray photoelectron spectroscopy indicated the successful fabrication of SiO2@PEI-AAPBA materials. Chromatographic separation of test mixtures reveals that SiO2@PEI-AAPBA has high selective enrichment ability for cis-diol-containing compounds. The binding pH between SiO2@PEI-AAPBA and catechol was found to be as low as pH 4.5, while that between SiO2@PEI-AAPBA and adenosine was only ~7.5. This difference might be attributed to the strong electrostatic repulsion between the solid phase and analytes at a low pH. Furthermore, a diphasic separation column was fabricated based on boronate affinity chromatography, C18-reversed-phase chromatography and applied in pressurized capillary electrochromatography (pCEC). Results showed that four polar nucleosides could be well captured by the boronate affinity chromatography (BAC) section and separated by reversed phase pCEC. Finally, SiO2@PEI600-AAPBA-based solid-phase extraction technology was applied to the purification of ribonucleosides in real urine samples, and results of UHPLC-MS/MS revealed that the intensities of the extracted ions (a neutral mass loss of m/z 132.04 Da) of the ribonucleosides were significantly enhanced after the enrichment. PMID:26048816

  6. Heterologous expression, purification, and properties of diol dehydratase, an adenosylcobalamin-dependent enzyme of Klebsiella oxytoca.

    PubMed

    Tobimatsu, T; Sakai, T; Hashida, Y; Mizoguchi, N; Miyoshi, S; Toraya, T

    1997-11-01

    Recombinant adenosylcobalamin-dependent diol dehydratase of Klebsiella oxytoca overexpressed in Escherichia coli was purified to homogeneity. The enzyme has a low solubility and was extracted from the crude membrane fraction with 1% Brij 35 in a high recovery. Subsequent chromatography on DEAE-cellulose resulted in 4.9-fold purification of the enzyme in an overall yield of 65%. The enzyme thus obtained showed specific activity comparable to that of the wild-type enzyme of K. oxytoca. The apparent molecular weight determined by nondenaturing gel electrophoresis on a gradient gel was 220,000. The enzyme consists of equimolar amounts of the three subunits with apparent Mr of 60,000 (alpha), 30,000 (beta), and 19,000 (gamma). Therefore, the subunit structure of the enzyme is most likely alpha2beta2gamma2. The recombinant enzyme was also separated into components F and S upon DEAE-cellulose chromatography in the absence of substrate. Components F and S were identified as the beta subunit and alpha2gamma2 complex, respectively. Apparent Km for adenosylcobalamin, 1,2-propanediol, glycerol, and 1,2-ethanediol were 0.83 microM, 0.08 mM, 0.73 mM, and 0.56 mM, respectively. The three genes encoding the subunits of diol dehydratase were overexpressed individually or in various combinations in Escherichia coli. The alpha and gamma subunits mutually required each other for correct folding forming the soluble, active alpha2gamma2 complex (component S). Expression of the beta subunit in a soluble, active form (component F) was promoted by coexpression with both the alpha and gamma subunits, probably by coexistence with component S. These lines of evidence indicate that each subunit mutually affects the folding of the others in this heterooligomer enzyme. PMID:9344474

  7. GENETIC VARIATION IN SOLUBLE EPOXIDE HYDROLASE (EPHX2) AND RISK OF CORONARY HEART DISEASE: THE ATHEROSCLEROSIS RISK IN COMMUNITIES (ARIC) STUDY

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Endothelial dysfunction contributes to the development of coronary heart disease (CHD). Soluble epoxide hydrolase metabolizes epoxyeicosatrienoic acids in the vasculature and regulates endothelial function. We sought to determine whether genetic variation in soluble epoxide hydrolase (EPHX2) was ass...

  8. Genetic variation in soluble epoxide hydrolase (EPHX2) and risk of coronary heart disease: The Atherosclerosis Risk in Communities (ARIC) study

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Endothelial dysfunction contributes to the development of coronary heart disease (CHD). Soluble epoxide hydrolase metabolizes epoxyeicosatrienoic acids in the vasculature and regulates endothelial function. We sought to determine whether genetic variation in soluble epoxide hydrolase (EPHX2) was ass...

  9. Synthesis and physicochemical properties of epoxidized Tmp trioleate by in situ method

    NASA Astrophysics Data System (ADS)

    Samidin, Salma; Salimon, Jumat

    2014-09-01

    Tmp trioleate was initially synthesized via esterification of trimetilolprapane and oleic acid (90%) using 1.5% of H2SO4 as a catalyst. The production of Tmp trioleate was observed at 98% (w/w). The iodine value of Tmp trioleate was analyzed for further reaction of epoxidation. Epoxide was important reaction as an intermediate for preparation of chemical modified lubricants from vegetable oils. Finding the best way of epoxidation process will give high quality for further modification of oil instead of reduce the cost and time for the preparation process during reaction of epoxidation. In this study, the epoxidation of unsaturation Tmp trioleate with peroxyformic acid generated in-situ from hydrogen peroxide 30% in H2O2 with formic acid was studied. 95% conversion to oxygen oxirane content (OOC) ring was obtained. The derivatization showed an improvement of the compound's oxidative stability evidenced from pressurized differential scanning calorimetry (PDSC) data which are 177°C to 200°C. Physicochemical properties showed increasing of temperature of flash point from 280°C to 300°C and viscosity index (VI) from 146 to 154. However, the pour point showed increasing temperature which was -58.81°C to -17.32°C. From the data obtained, these derivatives have shown better performance of lubricity properties. Overall, the data indicates that these performances are compatible to the commercial lubricants.

  10. Synthesis and physicochemical properties of epoxidized Tmp trioleate by in situ method

    SciTech Connect

    Samidin, Salma; Salimon, Jumat

    2014-09-03

    Tmp trioleate was initially synthesized via esterification of trimetilolprapane and oleic acid (90%) using 1.5% of H{sub 2}SO{sub 4} as a catalyst. The production of Tmp trioleate was observed at 98% (w/w). The iodine value of Tmp trioleate was analyzed for further reaction of epoxidation. Epoxide was important reaction as an intermediate for preparation of chemical modified lubricants from vegetable oils. Finding the best way of epoxidation process will give high quality for further modification of oil instead of reduce the cost and time for the preparation process during reaction of epoxidation. In this study, the epoxidation of unsaturation Tmp trioleate with peroxyformic acid generated in-situ from hydrogen peroxide 30% in H{sub 2}O{sub 2} with formic acid was studied. 95% conversion to oxygen oxirane content (OOC) ring was obtained. The derivatization showed an improvement of the compound's oxidative stability evidenced from pressurized differential scanning calorimetry (PDSC) data which are 177°C to 200°C. Physicochemical properties showed increasing of temperature of flash point from 280°C to 300°C and viscosity index (VI) from 146 to 154. However, the pour point showed increasing temperature which was −58.81°C to −17.32°C. From the data obtained, these derivatives have shown better performance of lubricity properties. Overall, the data indicates that these performances are compatible to the commercial lubricants.

  11. Zirconium phenylphosphonate-anchored methyltrioxorhenium as novel heterogeneous catalyst for epoxidation of cyclohexene.

    PubMed

    He, Sha; Liu, Xin; Zhao, Hongyue; Zhu, Yue; Zhang, Fazhi

    2015-01-01

    Epoxidation of olefins to epoxides is widely recognized as an important unit process in the manufacture of fine chemicals and intermediates. Developing an environmentally benign heterogeneous catalytic system for olefin epoxidation with high activity and selectivity is still a challenge in this research field. Herein, we report our attempts to synthesize novel zirconium phenylphosphonate-anchored methyltrioxorhenium (MTO/ZrPP) heterogeneous catalysts by a conventional impregnation method and evaluate their catalytic performance for epoxidation of cyclohexene using urea-hydrogen peroxide adduct (UHP) as oxidant without the addition of base ligands. The MTO/ZrPP catalyst samples are characterized by powder X-ray diffraction (XRD), Fourier transform infrared (FT-IR), inductively coupled plasma emission spectrometry (ICP-ES), high resolution transmission electron microscopy (HRTEM), X-ray photoelectron spectroscopy (XPS), and solid-state (1)H magic-angle spinning nuclear magnetic resonance ((1)H MAS NMR) techniques. Meanwhile, the density functional theory (DFT) calculation is carried out to further understand the structure feature and interactions of the MTO/ZrPP catalyst. It is revealed that MTO is anchored on support surface by the favored hydrogen-bonding interaction between two oxo ligands of MTO and two H atoms from the adjacent phenyls of ZrPP. MTO/ZrPP catalyst displays excellent catalytic activity for cyclohexene epoxidation. Moreover, only cyclohexene oxide production can be obtained under the employed reaction conditions. PMID:25313467

  12. USE OF ULTRASONICS IN THE RAPID EXTRACTION OF HI-VOL FILTERS FOR BENZO-A-PYRENE (BAP) ANALYSIS

    EPA Science Inventory

    A rapid simple procedure was developed to extract residual Benzo-a-pyrene from a single hi-vol filter strip. It involves quantitative dispensing of cyclohexane, 10 minutes of ultrasonication at 78C and a quiescent period of 1 hour. At that time the solvent is ready for chromatogr...

  13. Effects on specific promoter DNA methylation in zebrafish embryos and larvae following benzo[a]pyrene exposure

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Benzo[a]pyrene (BaP) is an established reproductive and developmental toxicant. BaP exposure in humans and animals has been linked to infertility and multigenerational health consequences. DNA methylation is the most studied epigenetic mechanism that regulates gene expression, and mapping of methyla...

  14. Species-specific testicular and hepatic microsomal metabolism of benzo(a)pyrene, an ubiquitous toxicant and endocrine disruptor

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Information on the metabolism of the environmental toxicant, benzo(a)pyrene (BaP) in the male reproductive system is crucial for understanding BaP-induced infertility. Microsomes were isolated from the liver and testes of rat, mouse, hamster, ram, boar, bull, and monkey and incubated with BaP. Post-...

  15. DDT, PCB AND BENZO(A)PYRENE LEVELS IN WHITE CROAKER 'GENYONEMUS LINEATUS' FROM SOUTHERN CALIFORNIA (JOURNAL VERSION)

    EPA Science Inventory

    This paper presents the results of PCB, DDT and benzo(a)pyrene (BaP) determination in white croaker (Genyonemus lineatus) sampled from the coastal waters of metropolitan Los Angeles. The purpose of this research was to assess the potential health hazard caused by the consumption ...

  16. ADDITIVITY OF IN VIVO MUTATION INDUCTION BY CUMULATIVE EXPOSURES TO BENZO[A]PYRENE OR DIBENZO[A,L]PYRENE

    EPA Science Inventory

    Dibenzo[a,l]pyrene (DB[a,l]P) and benzo[a]pyrene (B[a]P) are polycyclic aromatic hydrocarbons (PAH) found in cigarette smoke condensate, coal combustion processes and in some environmental pollutants. In this study, we investigated the effect of dosing regimen on the mutagenicity...

  17. USE OF MULTIPHOTON LASER SCANNING MICROSCOPY TO IMAGE BENZO[A]PYRENE AND METABOLITES IN FISH EGGS

    EPA Science Inventory

    Multiphoton laser scanning microscopy (MPLSM) is a promising tool to study the tissue distribution of environmental chemical contaminants during fish early life stages. One such chemical for which this is possible is benzo[a]pyrene (BaP), a polycyclic aromatic hydrocarbon that a...

  18. MUTAGENICITY OF BENZO(A)PYRENE METABOLITES GENERATED ON THE ISOLATED PERFUSED LUNG FOLLOWING PARTICULATE EXPOSURE (JOURNAL VERSION)

    EPA Science Inventory

    The isolated perfused rabbit lung (IPL) is being used to study the effects of particulate exposure on the pulmonary metabolism of benzo(a)pyrene (BaP). Pasturealla-free New Zealand white rabbits were treated intraperitoneally with BaP prior to kill. The isolated lungs were then a...

  19. USE OF MULTIPHOTON LASER SCANNING MICROSCOPY TO IMAGE BENZO[A]PYRENE AND METABOLITES IN FISH EARLY LIFE STAGES

    EPA Science Inventory

    Multiphoton laser scanning micrsocopy holds promise as a tool to study the tissue distribution of environmental chemical contaminants during fish early life stage development. One such chemical for which this is possible is benzo[a]pyrene (BaP), a polyaromatic hydrocarbon that a...

  20. 40 CFR 63.1427 - Process vent requirements for processes using extended cookout as an epoxide emission reduction...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ..., liters. Dliq, i = Density of reactor liquid, kg/liter. Cvap, i = Concentration of epoxide in the reactor... end of the ECO, liters. Dliq, f = Density of reactor liquid, kg/liter. Cvap, f = Concentration of... liquid at the point in time when all epoxide has been added to the reactor and prior to any venting....

  1. 40 CFR 63.1427 - Process vent requirements for processes using extended cookout as an epoxide emission reduction...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ..., weight percent. Vliq, i = Volume of reactor liquid at the onset of the ECO, liters. Dliq, i = Density of.... Dliq, f = Density of reactor liquid, kg/liter. Cvap, f = Concentration of epoxide in the reactor vapor... operator shall determine the concentration of epoxide in the reactor liquid at the point in time when...

  2. 40 CFR 63.1427 - Process vent requirements for processes using extended cookout as an epoxide emission reduction...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ..., weight percent. Vliq, i = Volume of reactor liquid at the onset of the ECO, liters. Dliq, i = Density of.... Dliq, f = Density of reactor liquid, kg/liter. Cvap, f = Concentration of epoxide in the reactor vapor... operator shall determine the concentration of epoxide in the reactor liquid at the point in time when...

  3. A biotechnological approach to the synthesis of epoxides: bioconversion of hydrocarbons by Pseudomonas oleovorans during growth in a multiphase system

    SciTech Connect

    De Smet, M.J.

    1983-04-01

    This communication examines the oxidation of alkanes and alkenes by Pseudomonas oleovorans. A variety of substrates were tested in order to extend the practical use of P. oleovorans for the synthesis of chiral epoxides. Concludes that hydrocarbon fermentations of P. oleovorans might be an important tool not only in the production of epoxides but also in the production of aliphatic polyesters and biosurfactants.

  4. Epoxidation of alkenes through oxygen activation over a bifunctional CuO/Al2O3 catalyst.

    PubMed

    Scotti, Nicola; Ravasio, Nicoletta; Zaccheria, Federica; Psaro, Rinaldo; Evangelisti, Claudio

    2013-03-01

    The epoxidation of alkenes was carried out over a CuO/Al(2)O(3) catalyst using cumene as an oxygen carrier, through a one-pot reaction, giving high conversion and selectivity with different substrates. Trans-β-methylstyrene gave the corresponding epoxide in 95% yield after 3 h. PMID:23358661

  5. Increased Silver Activity for Direct Propylene Epoxidation via Subnanometer Size Effects

    SciTech Connect

    Lei, Y.; Mehmood, Faisal; Lee, Sang Soo; Greeley, Jeffrey P.; Lee, Byeongdu; Seifert, Soenke; Winans, R. E.; Elam, J. W.; Meyer, R. J.; Redfern, Paul C.; Teschner, D.; Schlogl, Robert; Pellin, M. J.; Curtiss, Larry A.; Vajda, S.

    2010-04-09

    Production of the industrial chemical propylene oxide is energy-intensive and environmentally unfriendly. Catalysts based on bulk silver surfaces with direct propylene epoxidation by molecular oxygen have not resolved these problems because of substantial formation of carbon dioxide. We found that unpromoted, size-selected Ag3 clusters and ~3.5-nanometer Ag nanoparticles on alumina supports can catalyze this reaction with only a negligible amount of carbon dioxide formation and with high activity at low temperatures. Density functional calculations show that, relative to extended silver surfaces, oxidized silver trimers are more active and selective for epoxidation because of the open-shell nature of their electronic structure. The results suggest that new architectures based on ultrasmall silver particles may provide highly efficient catalysts for propylene epoxidation.

  6. A broadly applicable and practical oligomeric (salen) Co catalyst for enantioselective epoxide ring-opening reactions

    PubMed Central

    White, David E.; Tadross, Pamela M.; Lu, Zhe

    2014-01-01

    The (salen) Co catalyst (4a) can be prepared as a mixture of cyclic oligomers in a short, chromatography-free synthesis from inexpensive, commercially available precursors. This catalyst displays remarkable enhancements in reactivity and enantioselectivity relative to monomeric and other multimeric (salen) Co catalysts in a wide variety of enantioselective epoxide ring-opening reactions. The application of catalyst 4a is illustrated in the kinetic resolution of terminal epoxides by nucleophilic ring-opening with water, phenols, and primary alcohols; the desymmetrization of meso epoxides by addition of water and carbamates; and the desymmetrization of oxetanes by intramolecular ring opening with alcohols and phenols. The favorable solubility properties of complex 4a under the catalytic conditions facilitated mechanistic studies, allowing elucidation of the basis for the beneficial effect of oligomerization. Finally, a catalyst selection guide is provided to delineate the specific advantages of oligomeric catalyst 4a relative to (salen) Co monomer 1 for each reaction class. PMID:25045188

  7. Copper nanocrystal plane effect on stereoselectivity of catalytic deoxygenation of aromatic epoxides.

    PubMed

    Xiao, Bin; Niu, Zhiqiang; Wang, Yang-Gang; Jia, Wei; Shang, Jian; Zhang, Lan; Wang, Dingsheng; Fu, Yao; Zeng, Jie; He, Wei; Wu, Kai; Li, Jun; Yang, Jinlong; Liu, Lei; Li, Yadong

    2015-03-25

    Previous studies have shown that crystal planes of heterogeneous catalysts could display enhanced activity, such that higher turnover or chemoselectivity could be achieved. Here we report an example where the reaction stereoselectivity was significantly affected by the catalyst crystal planes. In copper-catalyzed deoxygenation reaction of aromatic epoxides, copper cubes, wires, and plates gave the olefin products with different cis/trans selectivities, whereas homogeneous copper catalysts showed poor selectivity. Scanning tunneling microscope and density functional theory studies revealed that the different adsorption mode and higher adsorption strength of epoxide oxygen on Cu{100} plane were responsible for the observed variation of selectivity. The copper-catalyzed deoxygenation reaction provided new practical access to cis-olefins from readily available aromatic epoxides. Our work also indicated that nanocrystal catalysts may provide useful stereochemical control in organic reactions. PMID:25778784

  8. Inhibiting an Epoxide Hydrolase Virulence Factor from Pseudomonas aeruginosa Protects CFTR.

    PubMed

    Bahl, Christopher D; Hvorecny, Kelli L; Bomberger, Jennifer M; Stanton, Bruce A; Hammock, Bruce D; Morisseau, Christophe; Madden, Dean R

    2015-08-17

    Opportunistic pathogens exploit diverse strategies to sabotage host defenses. Pseudomonas aeruginosa secretes the CFTR inhibitory factor Cif and thus triggers loss of CFTR, an ion channel required for airway mucociliary defense. However, the mechanism of action of Cif has remained unclear. It catalyzes epoxide hydrolysis, but there is no known role for natural epoxides in CFTR regulation. It was demonstrated that the hydrolase activity of Cif is strictly required for its effects on CFTR. A small-molecule inhibitor that protects this key component of the mucociliary defense system was also uncovered. These results provide a basis for targeting the distinctive virulence chemistry of Cif and suggest an unanticipated role of physiological epoxides in intracellular protein trafficking. PMID:26136396

  9. Epoxidized natural rubber toughened aqueous resole type liquefied EFB resin: Physical and chemical characterization

    NASA Astrophysics Data System (ADS)

    Amran, Umar Adli; Zakaria, Sarani; Chia, Chin Hua

    2013-11-01

    A preliminary study on the reaction between aqueous resole type resinified liquefied palm oil empty fruit bunches fibres (RLEFB) with epoxidized natural rubber (ENR). Liquefaction of empty fruit bunches (EFB) is carried out at different ratio of phenol to EFB (P:EFB). Resole type phenolic resin is prepared using sodium hydroxide (NaOH) as the catalyst with the ratio of liquefied EFB (LEFB) to formaldehyde (LEFB:F) of 1:1.8. 50% epoxidation of epoxidized natural rubber (ENR-50) is used to react with resole resin by mixing with ENR with aqueous resole resin. The cured resin is characterized with FT-IR and SEM. Aqueous system have been found to be unsuitable medium in the reaction between resin and ENR. This system produced a highly porous product when RLEFB/ENR resin is cured.

  10. Prenatal Exposure to Benzo(a)pyrene Impairs Later-Life Cortical Neuronal Function

    PubMed Central

    McCallister, Monique M.; Maguire, Mark; Ramesh, Aramandla; Aimin, Qiao; Liu, Sheng; Khoshbouei, Habibeh; Aschner, Michael; Ebner, Ford F.; Hood, Darryl B.

    2009-01-01

    Prenatal exposure to environmental contaminants, such as Benzo(a)pyrene [B(a)P] has been shown to impair brain development. The overarching hypothesis of our work is that glutamate receptor subunit expression is crucial for cortical evoked responses and that prenatal B(a)P exposure modulates the temporal developmental expression of glutamatergic receptor subunits in the somatosensory cortex. To characterize prenatal B(a)P exposure on the development of cortical function, pregnant Long Evans rats were exposed to low-level B(a)P (300μg/kg BW) by oral gavage on gestational days 14 to 17. At this exposure dose, there was no significant effect of B(a)P on 1) the number of pups born per litter, 2) the pre-weaning growth curves and 3) initial and final brain to body weight ratios. Control and B(a)P-exposed offspring were profiled for B(a)P metabolites in plasma and whole brain during the pre-weaning period. No detectable levels of metabolites were found in the control offspring. However, a time-dependent decrease in total metabolite concentration was observed in B(a)P-exposed offspring. On PND100-120, cerebrocortical mRNA expression was determined for the glutamatergic NMDA receptor subunit (NR2B) in control and B(a)P-exposed offspring. Neural activity was also recorded from neurons in primary somatic sensory (barrel) cortex. Semiquantitative PCR from B(a)P-exposed offspring revealed a significant 50% reduction in NR2B mRNA expression in B(a)P-exposed offspring relative to controls. Recordings from B(a)P-exposed offspring revealed that N-methyl-D-aspartate (NMDA) receptor -dependent neuronal activity in barrel cortex evoked by whisker stimulation was also significantly reduced (70%) as compared to controls. Analysis showed that the greatest deficit in cortical neuronal responses occurred in the shorter latency epochs from 5-20ms post-stimulus. The results suggest that in utero exposure to benzo(a)pyrene results in diminished mRNA expression of the NMDA NR2B receptor

  11. Soluble epoxide hydrolase limits mechanical hyperalgesia during inflammation

    PubMed Central

    2011-01-01

    Background Cytochrome-P450 (CYP450) epoxygenases metabolise arachidonic acid (AA) into four different biologically active epoxyeicosatrienoic acid (EET) regioisomers. Three of the EETs (i.e., 8,9-, 11,12- and 14,15-EET) are rapidly hydrolysed by the enzyme soluble epoxide hydrolase (sEH). Here, we investigated the role of sEH in nociceptive processing during peripheral inflammation. Results In dorsal root ganglia (DRG), we found that sEH is expressed in medium and large diameter neurofilament 200-positive neurons. Isolated DRG-neurons from sEH-/- mice showed higher EET and lower DHET levels. Upon AA stimulation, the largest changes in EET levels occurred in culture media, indicating both that cell associated EET concentrations quickly reach saturation and EET-hydrolyzing activity mostly effects extracellular EET signaling. In vivo, DRGs from sEH-deficient mice exhibited elevated 8,9-, 11,12- and 14,15-EET-levels. Interestingly, EET levels did not increase at the site of zymosan-induced inflammation. Cellular imaging experiments revealed direct calcium flux responses to 8,9-EET in a subpopulation of nociceptors. In addition, 8,9-EET sensitized AITC-induced calcium increases in DRG neurons and AITC-induced calcitonin gene related peptide (CGRP) release from sciatic nerve axons, indicating that 8,9-EET sensitizes TRPA1-expressing neurons, which are known to contribute to mechanical hyperalgesia. Supporting this, sEH-/- mice showed increased nociceptive responses to mechanical stimulation during zymosan-induced inflammation and 8,9-EET injection reduced mechanical thresholds in naive mice. Conclusion Our results show that the sEH can regulate mechanical hyperalgesia during inflammation by inactivating 8,9-EET, which sensitizes TRPA1-expressing nociceptors. Therefore we suggest that influencing the CYP450 pathway, which is actually highly considered to treat cardiovascular diseases, may cause pain side effects. PMID:21970373

  12. Evaluation of fish models of soluble epoxide hydrolase inhibition.

    PubMed Central

    Newman, J W; Denton, D L; Morisseau, C; Koger, C S; Wheelock, C E; Hinton, D E; Hammock, B D

    2001-01-01

    Substituted ureas and carbamates are mechanistic inhibitors of the soluble epoxide hydrolase (sEH). We screened a set of chemicals containing these functionalities in larval fathead minnow (Pimphales promelas) and embryo/larval golden medaka (Oryzias latipes) models to evaluate the utility of these systems for investigating sEH inhibition in vivo. Both fathead minnow and medaka sEHs were functionally similar to the tested mammalian orthologs (murine and human) with respect to substrate hydrolysis and inhibitor susceptibility. Low lethality was observed in either larval or embryonic fish exposed to diuron [N-(3,4-dichlorophenyl), N'-dimethyl urea], desmethyl diuron [N-(3,4-dichlorophenyl), N'-methyl urea], or siduron [N-(1-methylcyclohexyl), N'-phenyl urea]. Dose-dependent inhibition of sEH was a sublethal effect of substituted urea exposure with the potency of siduron < desmethyl diuron = diuron, differing from the observed in vitro sEH inhibition potency of siduron > desmethyl diuron > diuron. Further, siduron exposure synergized the toxicity of trans-stilbene oxide in fathead minnows. Medaka embryos exposed to diuron, desmethyl diuron, or siduron displayed dose-dependent delays in hatch, and elevated concentrations of diuron and desmethyl diuron produced developmental toxicity. The dose-dependent toxicity and in vivo sEH inhibition correlated, suggesting a potential, albeit undefined, relationship between these factors. Additionally, the observed inversion of in vitro to in vivo potency suggests that these fish models may provide tools for investigating the in vivo stability of in vitro inhibitors while screening for untoward effects. PMID:11171526

  13. METABOLISM OF BENZO[A]PYRENE AND PERSISTENCE OF DNA ADDUCTS IN THE BROWN BULLHEAD (ICTALURUS NEBULOSUS)

    EPA Science Inventory

    The in vitro metabolism of [3H]benzo[a]pyrene (BP) and [14C]benzo[a]pyrene-7,8-dihydrodiol (BP-7,8-diol) by liver of brown bullhead (Ictalurus Nebulosus) was characterized, as was the formation and persistence of BP-DNA adducts in vivo. ompared to rat liver microsomes, bullhead l...

  14. Long chain diol index (LDI) as an organic-based sea surface temperature proxy in the Korean East Sea (NW Pacific)

    NASA Astrophysics Data System (ADS)

    Gal, Jong-Ku; Kim, Jung-Hyun; Kang, Su-Jin; Lee, Dong-Hun; Shin, Kyung-Hoon

    2016-04-01

    Long chain diol index (LDI) was introduced as an organic-based sea surface temperature (SST) proxy. LDI is expressed as the C30 1,15-diol abundance relative to those of C28 1,13-, C30 1,13- and C30 1,15-diols. There were a few studies which accessed the potential of LDI based on the culture, core top sediments, suspended particulate organic matters, and down-core sediments. However it is still unknown about the source of the diols and robustness as the SST proxy in the various marine environments. In the current study, we examined the applicability of the LDI in the East Sea of Korea where productivity and thus sedimentation rates are high. We will compare the LDI data with those of alkenone-based UK'37 by analyzing two multicores covering the last 100 year.

  15. The separation and synthesis of lipidic 1,2- and 1,3-diols from natural phenolic lipids for the complexation and recovery of boron.

    PubMed

    Tyman, John H P; Mehet, Satinderjit K

    2003-12-01

    A study has been made of the semi-synthesis of 1,3-diols (anacardic alcohols) from natural phenolic lipid resources from Anacardium occidentale and Anacardium giganteum which have given C15 and C11 derivatives, respectively. An isomeric 1,3-diol (isoanacardic alcohol) has been obtained from cardanol separated from technical cashew nut-shell liquid. Homologous 1,3-diols have been synthesised from a range of synthetic 2-alkyl-, 3-alkyl- and 4-alkylphenols and from 6-alkylsalicylic acids. The natural 1,2-diol, urushiol, from Rhus vernicifera has been purified. All these lipidic compounds have been studied for their complexation and the potential recovery of boron as boric acid. PMID:14623453

  16. Asymmetric epoxidation of allylic alcohols catalyzed by vanadium-binaphthylbishydroxamic Acid complex.

    PubMed

    Noji, Masahiro; Kobayashi, Toshihiro; Uechi, Yuria; Kikuchi, Asami; Kondo, Hisako; Sugiyama, Shigeo; Ishii, Keitaro

    2015-03-20

    A vanadium-binaphthylbishydroxamic acid (BBHA) complex-catalyzed asymmetric epoxidation of allylic alcohols is described. The optically active binaphthyl-based ligands BBHA 2a and 2b were synthesized from (S)-1,1'-binaphthyl-2,2'-dicarboxylic acid and N-substituted-O-trimethylsilyl (TMS)-protected hydroxylamines via a one-pot, three-step procedure. The epoxidations of 2,3,3-trisubstituted allylic alcohols using the vanadium complex of 2a were easily performed in toluene with a TBHP water solution to afford (2R)-epoxy alcohols in good to excellent enantioselectivities. PMID:25714329

  17. The selection reaction of homogeneous catalyst in soy-epoxide hydroxylation

    NASA Astrophysics Data System (ADS)

    Elvistia Firdaus, Flora

    2014-04-01

    Hydroxylation reaction of soy-epoxide has resulted soy-polyol; a prepolymeric material for polyurethane. The conversion and selectivity of soy-epoxide butanol based to hydroxylation was found higher than soy-ethylene glycol (EG) based. These reactions were performed by sulfur acid which commonly known as homogeneous catalyst. Conversion and selectivity of homogeneous catalyst compared to bentonite; a heteregeneous catalyst was lower as in fact the mixtures were more viscous. The catalysis were significantly effected to cell morphology. Foams were conducted by heterogeneous catalyst resulted an irregular form of windows while homogeneous catalyst are more ordered.

  18. Synthesis of phytuberin. 4-endo-tet acid-catalyzed cyclization of alpha-hydroxy epoxides.

    PubMed

    Prangé, Thierry; Rodríguez, María S; Suárez, Ernesto

    2003-05-30

    The total synthesis of phytuberin, a phytoalexin of the Solanum genus, from (-)-alpha-santonin is reported. The key steps include (a) reductive cleavage of the C-O bond of the gamma-lactone with concomitant protection of the C1 double bond, (b) Sharpless stereocontrolled hydroxy-assisted epoxidation of allylic alcohol 6 and simultaneous deprotection of the C1 double bond, (c) a rare 4-endo-tet acid-catalyzed cyclization of an alpha-hydroxy epoxide, and (d) an unprecedented 4-exo selenocyclization of a homoallylic alcohol. PMID:12762747

  19. Ni(II) salts and 2-propanol effect catalytic reductive coupling of epoxides and alkynes.

    PubMed

    Beaver, Matthew G; Jamison, Timothy F

    2011-08-01

    A Ni-catalyzed reductive coupling of alkynes and epoxides using Ni(II) salts and simple alcohol reducing agents is described. Whereas previously reported conditions relied on Ni(cod)(2) and Et(3)B, this system has several advantages including the use of air-stable and inexpensive Ni(II) precatalysts (e.g., NiBr(2)·3H(2)O) as the source of Ni(0) and simple alcohols (e.g., 2-propanol) as the reducing agent. Deuterium-labeling experiments are consistent with oxidative addition of an epoxide C-O bond that occurs with inversion of configuration. PMID:21718038

  20. Liquid chromatographic determination of benzo(a)pyrene in total particulate matter of cigarette smoke

    SciTech Connect

    Tomkins, B.A.; Jenkins, R.A.; Griest, W.H.; Reagan, R.R.; Holladay, S.K.

    1985-09-01

    The benzo(a)pyrene (BaP) delivery of reference and commercially available tobacco cigarettes, as well as reference and placebo marijuana cigarettes, is determined using a sequential liquid chromatographic/liquid chromatographic procedure. The total particulate matter of sample cigarette smoke is collected using a Cambridge filter pad, which is ultrasonically extracted with acetone. The resulting extract is filtered, then fractionated using semipreparative-scale normal phase liquid chromatography (LC). Quantitative determination is achieved using analytical-scale reverse phase LC equipped with a fluorescence detector. The method is precise (+/- 10-15% relative standard deviation) and yields 85% or better BaP recovery at the ng/cig. level. A single pad may be analyzed in 8 person-hours, while a more typical lot of 12 pads (6 pads each for 2 cigarette brands) may be analyzed in 10 person-days.

  1. Digestive determinants of benzo[a]pyrene and phenanthrene bioaccumulation by a deposit-feeding polychaete

    SciTech Connect

    Penry, D.L.; Weston, D.P.

    1998-11-01

    The uptake of hydrophobic contaminants from ingested sediment can contribute significantly to body burdens of deposit feeders, and feeding behavior and digestive physiology can play important roles in bioaccumulation. The authors examined the uptake of polycyclic aromatic hydrocarbons (PAHs) by the deposit-feeding polychaete Abarenicola pacifica in experiments in which worms were first acclimated to low or high organic carbon sediments with 0.08 or 0.45% total organic carbon, respectively and then transferred to low or high organic carbon test sediments contaminated with radiolabeled phenanthrene or benzo[a]pyrene. Ingestion rate was measurements are essential in many types of bioaccumulation studies because differences in ingestion rates between sediment types may confound some traditional measures of bioavailability. Physiological acclimation to the low or high organic carbon sediments did not appear to affect PAH uptake from the test sediments, but acclimation did affect biotransformation capabilities, particularly for phenanthrene.

  2. Octanol-water partition coefficient of benzo(a)pyrene: measurement, calculation, and environmental implications

    SciTech Connect

    Mallon, B.J.; Harrison, F.L.

    1984-03-01

    Benzo(a)pyrene (BaP) is a potent carcinogen produced in significant quantities during pyrolysis of such substances as coal, wood, and cigarettes. Several researchers have shown that the lipophilic storage and soil sediment accumulation of many organic solutes is proportional to the partitioning between octanol-1 and water. The octanol-water partition coefficient (P) is defined as P = C/sub o//C/sub w/, where C/sub o/ and C/sub w/ are the concentration of the solute in n-octanol and water. Considerable data are available demonstrating that P values measured in the laboratory can be used to predict the environmental behavior of organic pollutants. Literature searches reveal that calculated, but not measured, log P values are reported for BaP. This laboratory study was initiated to define better the log P of BaP.

  3. Movements of benzo(a)pyrene across the hemochorial placenta of the guinea pig

    SciTech Connect

    Kelman, B.J.; Springer, D.L.

    1982-01-01

    In an effort to determine fetal exposure resulting from maternally administered benzo(a)pyrene (BaP), the clearance of radiolabeled BaP from mother to fetus was measured across the hemochorial placenta of the guinea pig at 60 days of gestation. Using techniques previously reported for other toxic materials, the fetal circulation of the placenta was isolated. BaP injected into the maternal circulation, and the concentration of BaP determined in the perfusate. The clearance of BaP from mother to fetus was high following intravenous injection. Clearances appeared to be a function of umbilical blood flow, and ranged from 0.59 to 2.40 ml/min at an umbilical flow of 2.5 ml/min. Since clearances of BaP approximated those obtained for tritiated water, it is apparent that circulating BaP gains easy access to the fetus.

  4. Live cell imaging of the intracellular compartmentalization of the contaminate benzo[a]pyrene.

    PubMed

    Ali, Rizwan; Trump, Saskia; Lehmann, Irina; Hanke, Thomas

    2015-05-01

    This study investigates the cellular response of murine hepatoma cells to the polycyclic aromatic hydrocarbon benzo[a]pyrene (B[a]P) using two-photon and confocal laser scanning microscopy. The intracellular distribution of B[a]P and the B[a]P/AhR complex was visualized time- and concentration-dependent for up to 48 h of exposure. B[a]P was predominantly found in lipid droplets, endoplasmic reticulum and lysosomes, where B[a]P is collected and forms large aggregates. Changes in mitochondrial membrane potential and bleb formation due to high B[a]P concentrations were observed. The imaging data presented in this study provide new insights into the systemic cellular regulation following B[a]P exposure. PMID:24700684

  5. Evaluating enzymes that generate genotoxic benzo[a]pyrene metabolites using sensor arrays.

    PubMed

    Wang, Bingquan; Jansson, Ingela; Schenkman, John B; Rusling, James F

    2005-03-01

    Arrays with individually addressable, demountable electrodes coated with ultrathin DNA/enzyme films were evaluated to estimate relative rates of genotoxic bioactivation of benzo[a]pyrene (BP) for several different enzymes simultaneously. Specifically, cytochrome (cyt) P450cam, cyt P40 1A2, and myoglobin in the array were activated with H2O2 to metabolize BP to genotoxic metabolites. DNA damage by the metabolites was detected by increases in square wave voltammetric oxidation peaks using Ru(bpy)3(2+) as catalyst. Cyt P450cam and cyt P450 1A2 showed 3-fold higher activity for genotoxic bioactivation of BP than myoglobin. The ability of the arrays to generate and detect metabolite-based DNA damage simultaneously for several enzymes is a rapid and promising approach to identify and characterize enzymes involved in genotoxicity of drugs and pollutants. PMID:15732919

  6. Chlorophyll catalyse the photo-transformation of carcinogenic benzo[a]pyrene in water

    NASA Astrophysics Data System (ADS)

    Luo, Lijuan; Lai, Xueying; Chen, Baowei; Lin, Li; Fang, Ling; Tam, Nora F. Y.; Luan, Tiangang

    2015-08-01

    Algal blooms cause great damage to water quality and aquaculture. However, this study showed that dead algal cells and chlorophyll could accelerate the photo-transformation of benzo[a]pyrene (BaP), a ubiquitous and persistent pollutant with potently mutagenic and carcinogenic toxicities, under visible light irradiation. Chlorophyll was found to be the major active substance in dead algal cells, and generated a high level of singlet oxygen to catalyse the photo-transformation of BaP. According to various BaP metabolites formed, the degradation mechanism was proposed as that chlorophyll in dead algal cells photo-oxidized BaP to quinones via photocatalytic generation of singlet oxygen. The results provided a good insight into the role of chlorophyll in the photo-transformation of organic contaminants and could be a possible remediation strategy of organic pollutants in natural environment.

  7. Chlorophyll catalyse the photo-transformation of carcinogenic benzo[a]pyrene in water

    PubMed Central

    Luo, Lijuan; Lai, Xueying; Chen, Baowei; Lin, Li; Fang, Ling; Tam, Nora F. Y.; Luan, Tiangang

    2015-01-01

    Algal blooms cause great damage to water quality and aquaculture. However, this study showed that dead algal cells and chlorophyll could accelerate the photo-transformation of benzo[a]pyrene (BaP), a ubiquitous and persistent pollutant with potently mutagenic and carcinogenic toxicities, under visible light irradiation. Chlorophyll was found to be the major active substance in dead algal cells, and generated a high level of singlet oxygen to catalyse the photo-transformation of BaP. According to various BaP metabolites formed, the degradation mechanism was proposed as that chlorophyll in dead algal cells photo-oxidized BaP to quinones via photocatalytic generation of singlet oxygen. The results provided a good insight into the role of chlorophyll in the photo-transformation of organic contaminants and could be a possible remediation strategy of organic pollutants in natural environment. PMID:26239357

  8. Base substitution mutations induced by metabolically activated aflatoxin B1.

    PubMed

    Foster, P L; Eisenstadt, E; Miller, J H

    1983-05-01

    We have determined the base substitutions generated by metabolically activated aflatoxin B1 in the lacI gene of a uvrB- strain of Escherichia coli. By monitoring over 70 different nonsense mutation sites, we show that activated aflatoxin B1 specifically induced GxC leads to TxA transversions. One possible pathway leading to this base change involves depurination at guanine residues. We consider this mechanism of mutagenesis in the light of our other findings that the carcinogens benzo[a]pyrene diol epoxide and N-acetoxyacetylaminofluorene also specifically induce GxC leads to TxA transversions. PMID:6405385

  9. Ring Expansion of Cyclic 1,2-Diols to form Medium Sized Rings via Ruthenium Catalyzed Transfer Hydrogenative [4+2] Cycloaddition

    PubMed Central

    Kasun, Zachary A.; Geary, Laina M.

    2014-01-01

    A new method for the ring expansion of cyclic diols is described. Using improved conditions for the ruthenium(0) catalyzed cycloaddition of cyclic 1,2-diols with 1,3-dienes, fused [n.4.0] bicycles 3a–3r (n = 3–6) are formed, which upon exposure to iodosobenzene diacetate engage in oxidative cleavage to form the 9–12 membered rings 4a–4r. PMID:24890278

  10. Predicting lung dosimetry of inhaled particleborne benzo[a]pyrene using physiologically based pharmacokinetic modeling.

    PubMed

    Campbell, Jerry; Franzen, Allison; Van Landingham, Cynthia; Lumpkin, Michael; Crowell, Susan; Meredith, Clive; Loccisano, Anne; Gentry, Robinan; Clewell, Harvey

    2016-09-01

    Benzo[a]pyrene (BaP) is a by-product of incomplete combustion of fossil fuels and plant/wood products, including tobacco. A physiologically based pharmacokinetic (PBPK) model for BaP for the rat was extended to simulate inhalation exposures to BaP in rats and humans including particle deposition and dissolution of absorbed BaP and renal elimination of 3-hydroxy benzo[a]pyrene (3-OH BaP) in humans. The clearance of particle-associated BaP from lung based on existing data in rats and dogs suggest that the process is bi-phasic. An initial rapid clearance was represented by BaP released from particles followed by a slower first-order clearance that follows particle kinetics. Parameter values for BaP-particle dissociation were estimated using inhalation data from isolated/ventilated/perfused rat lungs and optimized in the extended inhalation model using available rat data. Simulations of acute inhalation exposures in rats identified specific data needs including systemic elimination of BaP metabolites, diffusion-limited transfer rates of BaP from lung tissue to blood and the quantitative role of macrophage-mediated and ciliated clearance mechanisms. The updated BaP model provides very good prediction of the urinary 3-OH BaP concentrations and the relative difference between measured 3-OH BaP in nonsmokers versus smokers. This PBPK model for inhaled BaP is a preliminary tool for quantifying lung BaP dosimetry in rat and humans and was used to prioritize data needs that would provide significant model refinement and robust internal dosimetry capabilities. PMID:27569524

  11. Sustainable Pathways to Pyrroles through Iron-Catalyzed N-Heterocyclization from Unsaturated Diols and Primary Amines.

    PubMed

    Yan, Tao; Barta, Katalin

    2016-09-01

    Pyrroles are prominent scaffolds in pharmaceutically active compounds and play an important role in medicinal chemistry. Therefore, the development of new, atom-economic, and sustainable catalytic strategies to obtain these moieties is highly desired. Direct catalytic pathways that utilize readily available alcohol substrates have been recently established; however, these approaches rely on the use of noble metals such as ruthenium or iridium. Here, we report on the direct synthesis of pyrroles using a catalyst based on the earth-abundant and inexpensive iron. The method uses 2-butyne-1,4-diol or 2-butene-1,4-diol that can be directly coupled with anilines, benzyl amines, and aliphatic amines to obtain a variety of N-substituted pyrroles in moderate-to-excellent isolated yields. PMID:27493031

  12. Synthesis of meta-Terphenyl-2,2''-diols by Anodic C-C Cross-Coupling Reactions.

    PubMed

    Lips, Sebastian; Wiebe, Anton; Elsler, Bernd; Schollmeyer, Dieter; Dyballa, Katrin M; Franke, Robert; Waldvogel, Siegfried R

    2016-08-26

    The anodic C-C cross-coupling reaction is a versatile synthetic approach to symmetric and non-symmetric biphenols and arylated phenols. We herein present a metal-free electrosynthetic method that provides access to symmetric and non-symmetric meta-terphenyl-2,2''-diols in good yields and high selectivity. Symmetric derivatives can be obtained by direct electrolysis in an undivided cell. The synthesis of non-symmetric meta-terphenyl-2,2''-diols required two electrochemical steps. The reactions are easy to conduct and scalable. The method also features a broad substrate scope, and a large variety of functional groups are tolerated. The target molecules may serve as [OCO](3-) pincer ligands. PMID:27490451

  13. [Diol column as stationary phase for high performance liquid chromatographic analysis of carbohydrates in drinks with evaporative light scattering detection].

    PubMed

    Wei, Y; Guo, L; Ding, M Y

    2001-11-01

    A high performance liquid chromatographic method with a diol column and evaporative light scattering detector (ELSD) was established for the direct analysis of fructose, glucose, sucrose, maltose and raffinose in mixture. A separation column (Lichrospher 100 Diol, 250 mm x 4.0 mm i.d., 5 microns, Hewlett-Packard, USA) and a guard column (Zorbax Rx-SIL, 12.5 mm x 4.6 mm i.d., 5 microns) were used. The mobile phase was a mixture of dichloromethane-methanol (3.2:1, volume ratio). Regression equations revealed linear relationship (correlation coefficients: 0.995-0.999) between the mass of carbohydrates injected and the peak area of carbohydrates detected by ELSD. The detection limits of ELSD (S/N = 3) were about 0.20 microgram for all carbohydrates. This system could be used for the routine analysis of simple carbohydrates in some common drinks on market. PMID:12545463

  14. Transport of a carcinogen, benzo[a]pyrene, from particulates to lipid bilayers: a model for the fate of particle-adsorbed polynuclear aromatic hydrocarbons which are retained in the lungs.

    PubMed

    Lakowicz, J R; Bevan, D R; Riemer, S C

    1980-05-01

    Fluorescence spectroscopic methods were used to investigate the effects of adsorption of benzo[a]pyrene to particulate matter on its rate of uptake into model membranes composed of dipalmitoyl L-alpha-phosphatidylcholine. From these experiments we conclude the following: 1. Adsorption of benzo[a]pyrene to four types of asbestos (anthophyllite, crocidolite, chrysotile, and amosite) and a variety of non-fibrous particles (hematite, silica, titanium dioxide, porous glass and talc) results in increased rates of membrane uptake when compared with aqueous suspensions of benzo[a]pyrene microcrystals. Benzo[a]pyrene was not released from carbon black. 2. Asbestos-adsorbed benzo[a]pyrene was transferred to the membranes most rapidly. 3. Adsorption of benzo[a]pyrene to the surface of the particles is necessary for its enhanced transport into membranes. That is, simple mixtures of benzo[a]pyrene microcrystals and particulates do not show enhanced transport. 4. Particle-enhanced transport of benzo[a]pyrene is not correlated with the effects of the particles on vesicle integrity, binding of vesicles to the particles, or the concentrations of either particles or vesicles. The rate limiting step for transport of benzo[a]pyrene into vesicles appears to be its rate of desorption from the surface of the particle. Following desorption, membrane uptake of benzo[a]pyrene is rapid. PMID:6892996

  15. Lipase-catalyzed synthesis of aliphatic polyesters via copolymerization of lactone, dialkyl diester, and diol.

    PubMed

    Jiang, Zhaozhong

    2008-11-01

    Candida antarctica lipase (CALB) has been successfully used as catalyst for copolymerization of dialkyl diester with diol and lactone to form aliphatic polyesters. The polymerization reactions were performed using a two stage process: first stage oligomerization under low vacuum followed by second stage polymerization under high vacuum. Use of the two-stage process is required to obtain products with high molecular weights at high yields for the following reasons: (i) the first stage reaction ensures that the monomer loss via evaporation is minimized to maintain 1:1 diester to diol stoichiometric ratio, and the monomers are converted to nonvolatile oligomers; (ii) use of high vacuum during the second stage accelerates equilibrium transesterification reactions to transform the oligomers to high molecular weight polymers. Thus, terpolymers of omega-pentadecalactone (PDL), diethyl succinate (DES), and 1,4-butanediol (BD) with a M w of whole product (nonfractionated) up to 77000 and M w/ M n between 1.7 and 4.0 were synthesized in high yields (e.g., 95% isolated yield). A desirable reaction temperature for the copolymerizations was found to be around 95 degrees C. At 1:1:1 PDL/DES/BD monomer molar ratio, the resultant terpolymers contained equal moles of PDL, succinate, and butylene repeat units in the polymer chains. (1)H and (13)C NMR analyses were used to determine the polyester microstructures. The synthesized PDL-DES-BD terpolymers possessed near random structures with all possible combinations of PDL, succinate, and butylene units via ester linkages in the polymer backbone. Furthermore, thermal stability and crystallinity of a pure PDL-DES-BD terpolymer with 1:1:1 PDL to succinate to butylene unit ratio and M w of 85400 were studied by thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC). The copolyester was found to be a semicrystalline material with a T g of -34 degrees C and a T m of 64 degrees C, which degrades in a single weight loss

  16. Transformation of a series of saturated isomeric steroidal diols by Aspergillus tamarii KITA reveals a precise stereochemical requirement for entrance into the lactonization pathway.

    PubMed

    Hunter, A Christy; Collins, Catherine; Dodd, Howard T; Dedi, Cinzia; Koussoroplis, Salomé-Juliette

    2010-11-01

    Four isomers of 5α-androstan-3,17-diol have been transformed by the filamentous fungus Aspergillus tamarii, an organism which has the ability to convert progesterone to testololactone in high yield through an endogenous four step enzymatic pathway. The only diol handled within the lactonization pathway was 5α-androstan-3α,17β-diol which, uniquely underwent oxidation of the 17β-alcohol to the 17-ketone prior to its Baeyer-Villiger oxidation and the subsequent production of 3α-hydroxy-17a-oxa-D-homo-5α-androstan-17-one. This demonstrated highly specific stereochemical requirements of the 17β-hydroxysteroid dehydrogenase for oxidation of this specific steroidal diol to occur. In contrast, the other three diols were transformed within the hydroxylation pathway resulting in functionalization at C-11β. Only 5α-androstan-3β,17α-diol could bind to the hydroxylase in multiple binding modes undergoing monohydroxylation in 6β and 7β positions. Evidence from this study has indicated that hydroxylation of saturated steroidal lactones may occur following binding of ring-D in its open form in which an α-alcohol is generated with close spatial parity to the C-17α hydroxyl position. All metabolites were isolated by column chromatography and were identified by (1)H, (13)C NMR and DEPT analysis and further characterized using infra-red, elemental analysis and accurate mass measurement. PMID:20832471

  17. Theoretical investigations of the reaction between 1,4-dithiane-2,5-diol and azomethine imines: mechanisms and diastereoselectivity.

    PubMed

    Zheng, Linjie; Qiao, Yan; Lu, Mengxue; Chang, Junbiao

    2015-07-21

    In the present study, mechanistic insights into the domino reaction between 1,4-dithiane-2,5-diol and azomethine imines were derived from the computational study with B3LYP and M06-2X functionals. On the whole, the domino process comprises two consecutive reactions: cleavage of 1,4-dithiane-2,5-diol leading to mercaptoacetaldehyde and [3 + 3] cycloaddition of mercaptoacetaldehyde with azomethine imines. The cleavage of 1,4-dithiane-2,5-diol can take place via multiple possible pathways (1A-1E), and pathway 1E in which double-methanol molecules mediate the proton transfer process is the most energetically favorable, with an energy barrier of 19.9 kcal mol(-1). For the [3 + 3] cycloaddition, three possible pathways (2F-2H) were explored. The calculated energy profiles reveal that pathway 2H with activation energies ranging from 6.9 to 10.2 kcal mol(-1) is more energetically favorable than pathways 2F and 2G. Specifically, pathway 2H comprises three reaction steps: deprotonation of mercaptoacetaldehyde by DABCO allows for the formation of the thiol anion, which subsequently launches a nucleophilic attack on azomethine imines followed by intramolecular cyclization resulting in the final products. The calculated results are in agreement with the experimental observations that the reaction can proceed most efficiently in the presence of both DABCO and methanol. Furthermore, the hydrogen bonding interaction is identified to be the main factor determining the observed diastereoselectivity The current systematic theoretical study gives a full scenario of the reaction between 1,4-dithiane-2,5-diol and azomethine imines catalyzed by DABCO, and thus provides some valuable clues for further investigation and development of this kind of important reaction. PMID:26079432

  18. Sequential O-Nitrosoaldol and Grignard Addition Process: A New Enantio- and Diastereoselective Entry to Chiral 1,2-Diols**

    PubMed Central

    Jiao, Peng; Kawasaki, Masanori

    2012-01-01

    Chiral 1,2-diols are prepared from chiral α-aminoxylated aldehydes or cyclohexanone and Grignard reagents in high diastereoselectivities (>87:13 dr) and high enantioselectivities (>93% ee). The presence of the ate complex of CeCl3·2LiCl is essential for the high overall yields and high stereoselectivities. The N-O bond of α-aminoxylated carbonyl compound is cleaved by organometallic reagent. PMID:19343748

  19. Simple Preparation of Rhodococcus erythropolis DSM 44534 as Biocatalyst to Oxidize Diols into the Optically Active Lactones.

    PubMed

    Martinez-Rojas, Enriqueta; Olejniczak, Teresa; Neumann, Konrad; Garbe, Leif-Alexander; Boratyñski, Filip

    2016-09-01

    In the current study, we present a green toolbox to produce ecological compounds like lactone moiety. Rhodococcus erythropolis DSM 44534 cells have been used to oxidize both decane-1,4-diol () and decane-1,5-diol () into the corresponding γ- () and δ-decalactones () with yield of 80% and enantiomeric excess (ee) = 75% and ee = 90%, respectively. Among oxidation of meso diols, (-)-(1S,5R)-cis-3-oxabicyclo[4.3.0]non-7-en-2-one (5a) with 56% yield and ee = 76% as well as (-)-(2R,3S)-cis-endo-3-oxabicyclo[2.2.1]dec-7-en-2-one (6a) with 100% yield and ee = 90% were formed. It is worth mentioning that R. erythropolis DSM 44534 grew in a mineral medium containing ethanol as the sole source of energy and carbon Chirality 28:623-627, 2016. © 2016 Wiley Periodicals, Inc. PMID:27496202

  20. Juvenile hormone diol kinase, a calcium-binding protein with kinase activity, from the silkworm, Bombyx mori.

    PubMed

    Li, Sheng; Zhang, Qi-Rui; Xu, Wei-Hua; Schooley, David A

    2005-11-01

    Juvenile hormone (JH) diol kinase (JHDK) is an important enzyme involved in the JH degradation pathway. Bombyx mori (Bommo)-JHDK cDNA (637bp) contains an open reading frame encoding a 183-amino acid protein, which reveals a high degree of identity to the two previously reported JHDKs. JHDK is similar to GTP-binding proteins with three conserved sequence elements involved in purine nucleotide binding, contains eight alpha-helices and three EF-hand motifs, and resembles the three-dimensional model of 2SCP and some other calcium-binding proteins. The Bommo-JHDK gene has only a single copy in the silkworm haploid genome, contains only one exon, and its 5'-upstream sequence does not have a JH response element. Although Bommo-JHDK is highly expressed in the gut of the silkworm, its mRNA expression remains at a constant level during larval development suggesting this enzyme is constitutive and not regulated by JH, at least at the transcriptional level. Recombinant Bommo-JHDK catalyzed the conversion of 10S-JH diol into JH diol phosphate, confirming its enzymatic function. Recombinant enzyme formed a dimer and had biochemical characteristics similar to other JHDKs. Bommo-JHDK, a calcium-binding protein with kinase activity, provides unique insights on how JH levels are regulated in the silkworm. PMID:16203205

  1. Antioxidants Inhibit Formation of 3-Monochloropropane-1,2-diol Esters in Model Reactions.

    PubMed

    Li, Chang; Jia, Hanbing; Shen, Mingyue; Wang, Yuting; Nie, Shaoping; Chen, Yi; Zhou, Yongqiang; Wang, Yuanxing; Xie, Mingyong

    2015-11-11

    The capacities of six antioxidants to inhibit the formation of 3-monochloropropane-1,2 diol (3-MCPD) esters were examined in this study. Inhibitory capacities of the antioxidants were investigated both in chemical models containing the precursors (tripalmitoyl glycerol, 1,2-dipalmitoyl-sn-glycerol, monopalmitoyl glycerol, and sodium chloride) of 3-MCPD esters and in oil models (rapeseed oil and sodium chloride). Six antioxidants, butylated hydroxytoluene (BHT), butylated hydroxy anisole (BHA), tert-butyl hydroquinone (TBHQ), propyl gallate (PG), L-ascorbyl palmitate (AP), and α-tocopherol (VE), were found to exhibit inhibiting capacities on 3-MCPD ester formation both in chemical models and in oil models. TBHQ provided the highest inhibitory capacity both in chemical models and in oil models; 44% of 3-MCPD ester formation was inhibited in the presence of TBHQ (66 mg/kg of oil) after heating of rapeseed oil at 230 °C for 30 min, followed by PG and AP. BHT, BHA, and VE appeared to have weaker inhibitory abilities in both models. VE exhibited the lowest inhibition rate; 22% of 3-MCPD esters were inhibited in the presence of VE (172 mg/kg of oil) after heating of rapeseed oil at 230 °C for 30 min. In addition, the inhibition rates of PG and VE decreased dramatically with an increase in temperature or heating time. The results suggested that some antioxidants, such as TBHQ, PG, and AP, could be the potential inhibitors of 3-MCPD esters in practice. PMID:26478126

  2. Cloning, expression, and characterization of coenzyme-B12-dependent diol dehydratase from Lactobacillus diolivorans.

    PubMed

    Wei, Xuqin; Meng, Xiaolei; Chen, Yunlai; Wei, Yutuo; Du, Liqin; Huang, Ribo

    2014-01-01

    The three gldCDE genes from Lactobacillus diolivorans, that encode the three subunits of the glycerol dehydratase, were cloned and the proteins were co-expressed in soluble form in Escherichia coli with added sorbitol and betaine hydrochloride. The purified enzyme exists as a heterohexamer (α2β2γ2) structure with a native molecular mass of 210 kDa. It requires coenzyme B12 for catalytic activity and is subject to suicide inactivation by glycerol during catalysis. The enzyme had maximum activity at pH 8.6 and 37 °C. The apparent K m values for coenzyme B12, 1,2-ethanediol, 1,2-propanediol, and glycerol were 1.5 μM, 10.5 mM, 1.3 mM, and 5.8 mM, respectively. Together, these results indicated that the three genes gldCDE encoding the proteins make up a coenzyme B12-dependent diol dehydratase and not a glycerol dehydratase. PMID:24078133

  3. Mechanism of action of adenosylcobalamin: hydrogen transfer in the inactivation of diol dehydratase by glycerol.

    PubMed

    Bachovchin, W W; Moore, K W; Richards, J H

    1978-05-30

    We have investigated the kinetic characteristics of the inactivation of the adenosylcobalamin-dependent enzyme propanediol dehydratase by glycerol, (RS)-1,1-dideuterioglycerol, (R)-1,1-dideuterioglycerol, and perdeuterioglycerol in the presence of 1,2-propanediol and 1,1-dideuterio-1,2-propanediol. The results imply that hydrogen (or deuterium) attached to C-1 of 1,2-propanediol participates in the inactivation process and contributes to the expression of a kinetic isotope effect on the rate of inactivation. The mechanism for this inactivation must involve the cofactor as an intermediate hydrogen carrier, presumably in the form of 5'-deoxyadenosine. Moreover, a mechanism involving a rate-determining transfer of hydrogen from an intermediate containing three equivalent hydrogens quantitatively accounts for all of the results. When diol dehydratase holoenzyme is inactivated by [1-3H]glycerol, 5'-deoxyadenosine which is enriched in tritium by a factor of 2.1 over that in glycerol can be isolated from the reaction mixture. PMID:667021

  4. Identification of Novel Regulatory Cholesterol Metabolite, 5-Cholesten, 3β,25-Diol, Disulfate

    PubMed Central

    Ren, Shunlin; Kim, Jin Koung; Kakiyama, Genta; Rodriguez-Agudo, Daniel; Pandak, William M.; Min, Hae-Ki; Ning, Yanxia

    2014-01-01

    Oxysterol sulfation plays an important role in regulation of lipid metabolism and inflammatory responses. In the present study, we report the discovery of a novel regulatory sulfated oxysterol in nuclei of primary rat hepatocytes after overexpression of the gene encoding mitochondrial cholesterol delivery protein (StarD1). Forty-eight hours after infection of the hepatocytes with recombinant StarD1 adenovirus, a water-soluble oxysterol product was isolated and purified by chemical extraction and reverse-phase HPLC. Tandem mass spectrometry analysis identified the oxysterol as 5-cholesten-3β, 25-diol, disulfate (25HCDS), and confirmed the structure by comparing with a chemically synthesized compound. Administration of 25HCDS to human THP-1-derived macrophages or HepG2 cells significantly inhibited cholesterol synthesis and markedly decreased lipid levels in vivo in NAFLD mouse models. RT-PCR showed that 25HCDS significantly decreased SREBP-1/2 activities by suppressing expression of their responding genes, including ACC, FAS, and HMG-CoA reductase. Analysis of lipid profiles in the liver tissues showed that administration of 25HCDS significantly decreased cholesterol, free fatty acids, and triglycerides by 30, 25, and 20%, respectively. The results suggest that 25HCDS inhibits lipid biosynthesis via blocking SREBP signaling. We conclude that 25HCDS is a potent regulator of lipid metabolism and propose its biosynthetic pathway. PMID:25072708

  5. Acute toxicity of 2-butyne-1,4-diol in laboratory animals.

    PubMed

    Jedrychowski, R A; Czajkowska, T; Stetkiewicz, J; Stetkiewicz, I

    1992-04-01

    Acute toxicity of 2-butyne-1,4-diol (BYD) was evaluated in laboratory animals. The evaluation involved acute oral and dermal toxicity in rats, dermal and ocular irritation in rabbits and skin sensitization in guinea pigs. The oral LD50 values for BYD were 132 mg kg-1 in male rats and 176 mg kg-1 in female rats. Post-mortem histology showed severe damage in lungs, liver and kidneys. In surviving rats, moderate to severe degenerative changes were observed in the liver but only mild lesions in the kidneys. In acute dermal toxicity studies the test chemical was applied either as a solid substance or as 40% aqueous solution at a dose of 5 g kg-1 for 24 h. Within 48 h of application of the diluted test material, half of the rats died. Liver and kidneys were the primary targets and different stages of degeneration, including necrosis, were observed. No deaths occurred after application of the solid substance. In rabbits, BYD was slightly irritant to skin and eyes. No allergic contact dermatitis was observed in guinea pigs. PMID:1556377

  6. Exposure assessment of 3-monochloropropane-1, 2-diol esters from edible oils and fats in China.

    PubMed

    Li, Chang; Nie, Shao-Ping; Zhou, Yong-Qiang; Xie, Ming-Yong

    2015-01-01

    3-monochoropropane-1, 2-diol (3-MCPD) esters from edible oils are considered to be a possible risk factor for adverse effects in human. In the present study, the exposure assessment of 3-MCPD esters to Chinese population was performed. A total of 143 edible oil and fat samples collected from Chinese markets were determined for the concentrations of 3-MCPD esters. The concentration data together with the data of fats consumed were analyzed by the point evaluation and probabilistic assessment for the exposure assessment. The point evaluation showed that the mean daily intake (DI) of 3-MCPD esters were lower than the value of provisional maximum tolerable daily intake (PMTDI) of 3-MCPD (2 µg/kg BW/d). The mean DI values in different age groups obtained from probabilistic assessment were similar to the results of the point evaluation. However, in high percentiles (95th, 97.5th, 99th), the DI values in all age groups were undesirably higher than the value of PMTDI. Overall, the children and adolescents exposed more to 3-MCPD esters than the adults. Uncertainty was also analyzed for the exposure assessment. Decreasing the level of 3-MCPD esters in edible oils and consuming less oil were top priority to minimize the risk of 3-MCPD esters. PMID:25447762

  7. Novel approaches to analysis of 3-chloropropane-1,2-diol esters in vegetable oils.

    PubMed

    Moravcova, Eliska; Vaclavik, Lukas; Lacina, Ondrej; Hrbek, Vojtech; Riddellova, Katerina; Hajslova, Jana

    2012-03-01

    A sensitive and accurate method utilizing ultrahigh performance liquid chromatography (U-HPLC) coupled to high resolution mass spectrometry based on orbitrap technology (orbitrapMS) for the analysis of nine 3-chloropropane-1,2-diol (3-MCPD) diesters in vegetable oils was developed. To remove the interfering triacylglycerols that induce strong matrix effects, a clean-up step on silica gel column was used. The quantitative analysis was performed with the use of deuterium-labeled internal standards. The lowest calibration levels estimated for the respective analytes ranged from 2 to 5 μg kg(-1). Good recovery values (89-120%) and repeatability (RSD 5-9%) was obtained at spiking levels of 2 and 10 mg kg(-1). As an alternative, a novel ambient desorption ionization technique, direct analysis in real time (DART), hyphenated with orbitrapMS, was employed for no separation, high-throughput, semi-quantitative screening of 3-MCPD diesters in samples obtained by chromatographic fractionation. Additionally, the levels of 3-MCPD diesters measured in reallife vegetable oil samples (palm oil, sunflower oil, rapeseed oil) using both methods are reported. Relatively good agreement of the data generated by U-HPLC-orbitrapMS and DART-orbitrapMS were observed. With regard to a low ionization yield achieved for 3-MCPD monoesters, the methods presented in this paper were not yet applicable for the analysis of these contaminants at the naturally occurring levels. PMID:22287050

  8. Mussel-inspired soft-tissue adhesive based on poly(diol citrate) with catechol functionality.

    PubMed

    Ji, Yali; Ji, Ting; Liang, Kai; Zhu, Lei

    2016-02-01

    Marine mussels tightly adhering to various underwater surfaces inspires human to design adhesives for wet tissue adhesion in surgeries. Characterization of mussel adhesive plaques describes a matrix of proteins containing 3,4-dihydroxyphenylalanine (DOPA), which provides strong adhesion in aquatic conditions. Several synthetic polymer systems have been developed based on this DOPA chemistry. Herein, a citrate-based tissue adhesives (POEC-d) was prepared by a facile one-pot melt polycondensation of two diols including 1,8-octanediol and poly(ethylene oxide) (PEO), citric acid (CA) and dopamine, and the effects of hydrophilic and soft PEO on the properties of adhesives were studied. It was found that the obtained adhesives exhibited water-soluble when the mole ratio of PEO to 1,8-octanediol was 70%, and the equilibrium swelling percentage of cured adhesive was about 144%, and degradation rate was in the range of 1-2 weeks. The cured adhesives demonstrated soft rubber-like behavior. The lap shear adhesion strength measured by bonding wet pig skin was in the range of 21.7-33.7 kPa, which was higher than that of commercial fibrin glue (9-15 kPa). The cytotoxicity tests showed the POEC-d adhesives had a low cytotoxicity. Our results supports that POEC-d adhesives, which combined strong wet adhesion with good biodegradability, acceptable swelling ratio, good elasticity and low cytotoxicity, have potentials in surgeries where surgical tissue adhesives, sealants, and hemostatic agents are used. PMID:26704547

  9. Influence of dough ingredients on 3-chloropropane-1,2-diol (3-MCPD) formation in toast.

    PubMed

    Breitling-Utzmann, C M; Hrenn, H; Haase, N U; Unbehend, G M

    2005-02-01

    The influence of different dough ingredients such as fat, salt, sourdough, emulsifiers, and sugar on the formation of 3-chloropropane-1,2-diol (3-MCPD) during toast preparation under domestic conditions was investigated. In comparison with a fat-free recipe, addition of 1% peanut fat considerably increased 3-MCPD formation, but varying the fat (2-5%) or salt (1.6-2.4%) contents within technological acceptable limits did not show any significant differences. A baking agent, which is usually commercially applied by many toast bakers or industrial toast manufacturers, increased 3-MCPD formation in toasted bread slices. Considerable evidence was found that the baking agent's main component sucrose had the major part in increasing 3-MCPD levels. Emulsifiers containing monoacylglycerols moderately increased 3-MCPD levels, but the addition of lecithin did not have any significant influence. 3-MCPD levels showed a good correlation with the lightness (L* value) of the bread slices; their 3-MCPD content increased exponentially towards dark coloured toasts. The relation between 3-MCPD and 2-MCPD was an average of 3:1 in all samples. Dichloropropanols such as, for example, 1,3-dichloropropanol could not be detected. PMID:15823998

  10. Identification of novel regulatory cholesterol metabolite, 5-cholesten, 3β,25-diol, disulfate.

    PubMed

    Ren, Shunlin; Kim, Jin Koung; Kakiyama, Genta; Rodriguez-Agudo, Daniel; Pandak, William M; Min, Hae-Ki; Ning, Yanxia

    2014-01-01

    Oxysterol sulfation plays an important role in regulation of lipid metabolism and inflammatory responses. In the present study, we report the discovery of a novel regulatory sulfated oxysterol in nuclei of primary rat hepatocytes after overexpression of the gene encoding mitochondrial cholesterol delivery protein (StarD1). Forty-eight hours after infection of the hepatocytes with recombinant StarD1 adenovirus, a water-soluble oxysterol product was isolated and purified by chemical extraction and reverse-phase HPLC. Tandem mass spectrometry analysis identified the oxysterol as 5-cholesten-3β, 25-diol, disulfate (25HCDS), and confirmed the structure by comparing with a chemically synthesized compound. Administration of 25HCDS to human THP-1-derived macrophages or HepG2 cells significantly inhibited cholesterol synthesis and markedly decreased lipid levels in vivo in NAFLD mouse models. RT-PCR showed that 25HCDS significantly decreased SREBP-1/2 activities by suppressing expression of their responding genes, including ACC, FAS, and HMG-CoA reductase. Analysis of lipid profiles in the liver tissues showed that administration of 25HCDS significantly decreased cholesterol, free fatty acids, and triglycerides by 30, 25, and 20%, respectively. The results suggest that 25HCDS inhibits lipid biosynthesis via blocking SREBP signaling. We conclude that 25HCDS is a potent regulator of lipid metabolism and propose its biosynthetic pathway. PMID:25072708

  11. Diastereoselective synthesis of CF3-substituted, epoxide-fused heterocycles with β-(trifluoromethyl)vinylsulfonium salts.

    PubMed

    Fritz, Sven P; West, Thomas H; McGarrigle, Eoghan M; Aggarwal, Varinder K

    2012-12-21

    CF(3)-substituted vinyl diphenylsulfonium triflate is an effective annulation reagent for the formation of α-CF(3) substituted, epoxide-fused heterocycles (pyrrolidines, piperidines, and tetrahydrofurans). This simple method affords a variety of valuable heterocyclic building blocks in a highly diastereoselective manner (dr >20:1). PMID:23231752

  12. Synthesis of an Epoxide Carbonylation Catalyst: Exploration of Contemporary Chemistry for Advanced Undergraduates

    ERIC Educational Resources Information Center

    Getzler, Yutan D. Y. L.; Schmidt, Joseph A. R.; Coates, Geoffrey W.

    2005-01-01

    A class of highly active, well-defined compounds for the catalytic carbonylation of epoxides and aziridines to beta-lactones and beta-lactams are introduced. The synthesis of one of the catalysts involves a simple imine condensation to form the ligand followed by air-sensitive metalation and salt metathesis steps.

  13. EPOXIDATION OF SMALL ORGANIC MOLECULES USING A SPINNING TUBE-IN-TUBE REACTOR

    EPA Science Inventory

    The commodity-scale epoxidation of several organic molecules has been carried out using a Spinning Tube-in-Tube (STTr) reactor (manufactured by Kreido Laboratories). This reactor, which embodies and facilitates the use of Green Chemistry principles and Process Intensification, a...

  14. Hydroxylation and Epoxidation of Fatty Acids by Bacillus megaterium ALA2

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bacillus megaterium ALA2 produces many new oxygenated fatty acids from linoleic acid. Strain ALA2 hydroxylated palmitic acid to omega-1, omega-2, and omega-3 hydroxy palmitate. Now we found that strain ALA2 also epoxidized linoleic acid to 12,13-epoxy-9(Z)-octadecenoic acid and 9,10-epoxy-12(Z)-oc...

  15. Thermal behavior of epoxidized cardanol diethyl phosphate as novel renewable plasticizer for poly(vinyl chloride)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A novel plasticizer, epoxidized cardanol diethyl phosphate (ECEP), based on cardanol was synthesized. Chemical structure of ECEP was characterized by fourier transform infrared (FTIR), 1H-nuclear magnetic resonance(1H NMR) and 13C-nuclear magnetic resonance(13C NMR) spectroscopy. Effects of ECEP sub...

  16. Catalyzed ring-opening polymerization of epoxidized soybean oil by hydrated and anhydrous fluoroantimonic acids

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Ring-opening polymerization of epoxidized soybean oil (ESO) catalyzed by the super acid, fluroantimonic acid hexahydrate (HSbF6-6H2O), and the anhydrous form (HSbF6) in ethyl acetate was conducted in an effort to develop useful biodegradable polymers. The resulting polymerized ESO (SA-RPESO and SAA-...

  17. Lewis Acid Catalyzed Ring-opening Polymerization of Epoxidized Soybean Oil in Liquid Carbon Dioxide

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Ring-opening polymerization of epoxidized soybean oil (ESO) catalyzed by boron trifluoride diethyl etherate (BF3•OEt2), in liquid carbon dioxide, was conducted in an effort to develop useful biobased biodegradable polymers. The resulting polymers (RPESO) were characterized by FTIR spectroscopy, diff...

  18. Boron Trifluoride Catalized Ring-Opening Polymerization of Epoxidized Soybean Oil in Liquid Carbon Dioxide

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Boron trifluoride diethyl etherate (BF3.OEt2) catalyzed ring-opening polymerization of epoxidized soybean oil (ESO), in liquid carbon dioxide, was conducted in an effort to develop useful biobased biodegradable polymers. The resulting polymers (RPESO) were characterized by FTIR spectroscopy, differ...

  19. Formation of furan fatty alkyl esters from their bis-epoxide fatty esters

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Reactions of epoxidized alkyl soyate with four different alcohols: ethanol, isopropyl alcohol, 2-ethylhexanol, benzyl alcohol, in the presence of Bronsted acid catalyst, were investigated. Products that were not reported in prior studies of similar reactions were found. These were furan fatty acid a...

  20. EXPRESSION AND CHARACTERIZATION OF THE RECOMBINANT JUVENILE HORMONE EPOXIDE HYDROLASE (JHEH) FROM MANDUCA SEXTA. (R825433)

    EPA Science Inventory

    The cDNA of the microsomal Juvenile Hormone Epoxide Hydrolase (JHEH) from Manduca sexta was expressed in vitro in the baculovirus system. In insect cell culture, the recombinant enzyme (Ms-JHEH) was produced at a high level (100 fold over background EH catalytic activit...

  1. Ultrathin CuO nanorods: controllable synthesis and superior catalytic properties in styrene epoxidation.

    PubMed

    Jia, Wei; Liu, Yuxi; Hu, Pengfei; Yu, Rong; Wang, Yu; Ma, Lei; Wang, Dingsheng; Li, Yadong

    2015-05-25

    Ultrathin copper oxide (CuO) nanorods with diameters of ∼3.6 nm were obtained in one step using oleylamine (OAm) as both the solvent and the surface controller. The oriented attachment is responsible for the formation of the ultrathin CuO nanorods. Furthermore, this ultrathin nanostructure catalyst exhibited excellent activity and high styrene oxide yields in styrene epoxidation. PMID:25920405

  2. (Salen)Mn(III) Catalyzed Asymmetric Epoxidation Reactions by Hydrogen Peroxide in Water: A Green Protocol

    PubMed Central

    Ballistreri, Francesco Paolo; Gangemi, Chiara M. A.; Pappalardo, Andrea; Tomaselli, Gaetano A.; Toscano, Rosa Maria; Trusso Sfrazzetto, Giuseppe

    2016-01-01

    Enantioselective epoxidation reactions of some chosen reactive alkenes by a chiral Mn(III) salen catalyst were performed in H2O employing H2O2 as oxidant and diethyltetradecylamine N-oxide (AOE-14) as surfactant. This procedure represents an environmentally benign protocol which leads to e.e. values ranging from good to excellent (up to 95%). PMID:27420047

  3. Sultones and Sultines via a Julia–Kocienski Reaction of Epoxides

    PubMed Central

    Smith, Geoffrey M T; Burton, Paul M; Bray, Christopher D

    2015-01-01

    The development of the homologous Julia–Kocienski reaction has led to the discovery of two new reaction modes of epoxides with sulfones. These pathways allow rapid and direct access to a range of γ-sultones and γ-sultines. PMID:26503062

  4. FORMATION OF HEMOGLOBIN ADDUCTS OF ACRYLAMIDE AND ITS EPOXIDE METABOLITE GLYCIDAMIDE IN THE RAT

    EPA Science Inventory

    A method was developed for the determination of hemoglobin (Hb) adducts form by the neurotoxic agent acrylamide and its mutagenic epoxide metabolite glycidamide. he method was based on simultaneous measurements of the cysteine adducts formed by these two agents by means of gas ch...

  5. Differences in Catalytic Sites for CO Oxidation and Propylene Epoxidation on Au Nanoparticles

    SciTech Connect

    Lee, W.S.; Stach, E.; Zhang, R.; Akatay, M.C.; Baertsch, C.D.; Ribeiro, F.H.; Delgass, W.N.

    2011-08-29

    Sintering and increased Au loading of Au/TS-1 causes the rate of CO oxidation per mole of Au to increase, whereas that for epoxidation of propylene in O{sub 2} and H{sub 2} decreases. This opposite trend in rate behavior shows that the catalytic sites for the two reactions must be different.

  6. Graphene oxide as an acid catalyst for the room temperature ring opening of epoxides.

    PubMed

    Dhakshinamoorthy, Amarajothi; Alvaro, Mercedes; Concepción, Patricia; Fornés, Vicente; Garcia, Hermenegildo

    2012-06-01

    The minute amount of hydrogen sulfate groups introduced into the graphene oxide (GO) obtained by Hummers oxidation of graphite renders this material as a highly efficient, recyclable acid catalyst for the ring opening of epoxides with methanol and other primary alcohols as nucleophile and solvent. PMID:22534622

  7. Synthesis of epoxidized cardanol and its antioxidative properties for vegetable oils and biodiesel

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A novel antioxidant epoxidized cardanol (ECD), derived from cardanol, was synthesized and characterized by FT-IR, 1H-NMR and 13C-NMR. Oxidative stability of ECD used in vegetable oils and biodiesel was evaluated by pressurized differential scanning calorimetry (PDSC) and the Rancimat method, respect...

  8. Indirubin 3'-Epoxide Induces Caspase-Independent Cell Death in Human Neuroblastoma.

    PubMed

    Kurita, Masahiro; Hanada, Satoshi; Ichimaru, Yoshimi; Saito, Hiroaki; Tabata, Keiichi; Asami, Satoru; Miyairi, Shinichi; Suzuki, Takashi

    2016-01-01

    Indirubin inhibits cyclin-dependent kinases by binding to their ATP-binding site, thereby exerting potent cytotoxicity on some tumor cells. We examined the anti-tumor effect of indirubin 3'-epoxide on human neuroblastoma cell lines (IMR-32, SK-N-SH, and NB-39). The results revealed potent cytotoxicity of indirubin 3'-epoxide against the IMR-32 (IC50: 0.16 µM) and SK-N-SH (IC50: 0.07 µM) cells. Furthermore, it also induced an increase of the sub-G1 population in the IMR-32 cells. Examination by Hoechst 33342 staining revealed apoptosis characterized by cell shrinkage, nuclear condensation and nuclear fragmentation in a concentration-dependent manner. Furthermore, annexin V-propidium iodide (PI) double-staining revealed an increase in the percentage of early apoptotic cells following treatment of the cells with indirubin 3'-epoxide without activation of caspases. In addition, significant decreases in the protein level of survivin and poly(ADP-ribose)polymerase (PARP), and increase in that of apoptosis-inducing factor (AIF) were found in the nuclei of the cells. These results suggest that indirubin 3'-epoxide induced caspase-independent apoptosis through mechanisms involving DNA fragmentation and inhibition of DNA repair. PMID:27251501

  9. 40 CFR 63.1431 - Process vent annual epoxides emission factor plan requirements.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... factor plan requirements. 63.1431 Section 63.1431 Protection of Environment ENVIRONMENTAL PROTECTION... group determination procedures in the NESHAP for Group I Polymers and Resins (40 CFR part 63, subpart U... Production § 63.1431 Process vent annual epoxides emission factor plan requirements. (a) Applicability...

  10. Surface Tension Studies of Alkyl Esters and Epoxidized Alkyl Esters Relevant to Oleochemically Based Fuel Additives

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We report the surface tension of several epoxidized oleochemicals and their comparable fatty esters at temperatures between 25 and 60 deg C. Surface tensions of the olefins measured at 40 deg C range from 25.9 mN m-1, for isobutyl oleate, to 28.4 mN m-1 for methyl linoleate. The epoxy versions of ...

  11. Engineering of an epoxide hydrolase for efficient bioresolution of bulky pharmaco substrates

    PubMed Central

    Kong, Xu-Dong; Yuan, Shuguang; Li, Lin; Chen, She; Xu, Jian-He; Zhou, Jiahai

    2014-01-01

    Optically pure epoxides are essential chiral precursors for the production of (S)-propranolol, (S)-alprenolol, and other β-adrenergic receptor blocking drugs. Although the enzymatic production of these bulky epoxides has proven difficult, here we report a method to effectively improve the activity of BmEH, an epoxide hydrolase from Bacillus megaterium ECU1001 toward α-naphthyl glycidyl ether, the precursor of (S)-propranolol, by eliminating the steric hindrance near the potential product-release site. Using X-ray crystallography, mass spectrum, and molecular dynamics calculations, we have identified an active tunnel for substrate access and product release of this enzyme. The crystal structures revealed that there is an independent product-release site in BmEH that was not included in other reported epoxide hydrolase structures. By alanine scanning, two mutants, F128A and M145A, targeted to expand the potential product-release site displayed 42 and 25 times higher activities toward α-naphthyl glycidyl ether than the wild-type enzyme, respectively. These results show great promise for structure-based rational design in improving the catalytic efficiency of industrial enzymes for bulky substrates. PMID:25331869

  12. Epoxide hydrolase activities and epoxy fatty acids in the mosquito Culex quinquefasciatus

    PubMed Central

    Xu, Jiawen; Morisseau, Christophe; Yang, Jun; Mamatha, Dadala M.

    2015-01-01

    Culex mosquitoes have emerged as important model organisms for mosquito biology, and are disease vectors for multiple mosquito-borne pathogens, including West Nile virus. We characterized epoxide hydrolase activities in the mosquito Culex quinquefasciatus, which suggested multiple forms of epoxide hydrolases were present. We found EH activities on epoxy eicosatrienoic acids (EETs). EETs and other eicosanoids are well-established lipid signaling molecules in vertebrates. We showed EETs can be synthesized in vitro from arachidonic acids by mosquito lysate, and EETs were also detected in vivo both in larvae and adult mosquitoes by LC-MS/MS. The EH activities on EETs can be induced by blood feeding, and the highest activity was observed in the midgut of female mosquitoes. The enzyme activities on EETs can be inhibited by urea-based inhibitors designed for mammalian soluble epoxide hydrolases (sEH). The sEH inhibitors have been shown to play diverse biological roles in mammalian systems, and they can be useful tools to study the function of EETs in mosquitoes. Besides juvenile hormone metabolism and detoxification, insect epoxide hydrolases may also play a role in regulating lipid signaling molecules, such as EETs and other epoxy fatty acids, synthesized in vivo or obtained from blood feeding by female mosquitoes. PMID:25686802

  13. Formation of furan fatty alkyl esters from their bis-epoxide fatty esters

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Reactions of epoxidized alkyl soyate with four different alcohols: ethanol, isopropyl alcohol, 2-ethylhexanol, and benzyl alcohol were investigated in the presence of Bronsted acid catalyst. Products not reported in prior studies of similar reactions were found. These were furan fatty acid alkyl est...

  14. Predicting efficient C(60) epoxidation and viable multiple oxide formation by theoretical study

    PubMed

    Manoharan

    2000-02-25

    The epoxidation of C(60) by various oxidizing agents such as dimethyldioxirane (DMD), methyl(trifluoromethyl)dioxirane (MTMD), and bis(trifluoromethyl)dioxirane (BTMD) has been probed computationally by the AM1 method. The computations have revealed that for the reaction forming C(60)O through a concerted "spiro" transition state, the currently used DMD involves its HOMO lone-pair and the LUMO (pi) of fullerene in an inverse electron demand fashion. This is distinct from the DMD reaction with ethylene. On the other hand, the addition of CF(3) groups lowers the LUMO (peroxide sigma) of MTMD and BTMD by virtue of negative hyperconjugation; the oxidants can then attack the fullerene nucleophilically at an increased rate to the maximum extent. These estimations have thus established that the strong electrophilic oxidizing agents remarkably enhance the fullerene epoxidation. DMD further produces C(60)O(2) and C(60)O(3) via multiple epoxidations, as C(60)O might best be produced quantitatively by MTMD and BTMD. The regiochemistry of the multiple oxidation products in which the subsequent oxidations take place at the adjacent sites is consistent with the increased nucleophilicity of the nearest double bonds attached to the prevailing epoxide function. PMID:10814058

  15. Mononuclear Nonheme High-Spin Iron(III)-Acylperoxo Complexes in Olefin Epoxidation and Alkane Hydroxylation Reactions.

    PubMed

    Wang, Bin; Lee, Yong-Min; Clémancey, Martin; Seo, Mi Sook; Sarangi, Ritimukta; Latour, Jean-Marc; Nam, Wonwoo

    2016-02-24

    Mononuclear nonheme high-spin iron(III)-acylperoxo complexes bearing an N-methylated cyclam ligand were synthesized, spectroscopically characterized, and investigated in olefin epoxidation and alkane hydroxylation reactions. In the epoxidation of olefins, epoxides were yielded as the major products with high stereo-, chemo-, and enantioselectivities; cis- and trans-stilbenes were oxidized to cis- and trans-stilbene oxides, respectively. In the epoxidation of cyclohexene, cyclohexene oxide was formed as the major product with a kinetic isotope effect (KIE) value of 1.0, indicating that nonheme iron(III)-acylperoxo complexes prefer C═C epoxidation to allylic C-H bond activation. Olefin epoxidation by chiral iron(III)-acylperoxo complexes afforded epoxides with high enantioselectivity, suggesting that iron(III)-acylperoxo species, not high-valent iron-oxo species, are the epoxidizing agent. In alkane hydroxylation reactions, iron(III)-acylperoxo complexes hydroxylated C-H bonds as strong as those in cyclohexane at -40 °C, wherein (a) alcohols were yielded as the major products with high regio- and stereoselectivities, (b) activation of C-H bonds by the iron(III)-acylperoxo species was the rate-determining step with a large KIE value and good correlation between reaction rates and bond dissociation energies of alkanes, and (c) the oxygen atom in the alcohol product was from the iron(III)-acylperoxo species, not from molecular oxygen. In isotopically labeled water (H2(18)O) experiments, incorporation of (18)O from H2(18)O into oxygenated products was not observed in the epoxidation and hydroxylation reactions. On the basis of mechanistic studies, we conclude that mononuclear nonheme high-spin iron(III)-acylperoxo complexes are strong oxidants capable of oxygenating hydrocarbons prior to their conversion into iron-oxo species via O-O bond cleavage. PMID:26816269

  16. Biomimetic iron-catalyzed asymmetric epoxidation of aromatic alkenes by using hydrogen peroxide.

    PubMed

    Gelalcha, Feyissa Gadissa; Anilkumar, Gopinathan; Tse, Man Kin; Brückner, Angelika; Beller, Matthias

    2008-01-01

    A novel and general biomimetic non-heme Fe-catalyzed asymmetric epoxidation of aromatic alkenes by using hydrogen peroxide is reported herein. The catalyst consists of ferric chloride hexahydrate (FeCl(3)6 H(2)O), pyridine-2,6-dicarboxylic acid (H(2)(pydic)), and readily accessible chiral N-arenesulfonyl-N'-benzyl-substituted ethylenediamine ligands. The asymmetric epoxidation of styrenes with this system gave high conversions but poor enantiomeric excesses (ee), whereas larger alkenes gave high conversions and ee values. For the epoxidation of trans-stilbene (1 a), the ligands (S,S)-N-(4-toluenesulfonyl)-1,2-diphenylethylenediamine ((S,S)-4 a) and its N'-benzylated derivative ((S,S)-5 a) gave opposite enantiomers of trans-stilbene oxide, that is, (S,S)-2 a and (R,R)-2 a, respectively. The enantioselectivity of alkene epoxidation is controlled by steric and electronic factors, although steric effects are more dominant. Preliminary mechanistic studies suggest the in situ formation of several chiral Fe-complexes, such as [FeCl(L*)(2)(pydic)]HCl (L*=(S,S)-4 a or (S,S)-5 a in the catalyst mixture), which were identified by ESIMS. A UV/Vis study of the catalyst mixture, which consisted of FeCl(3)6 H(2)O, H(2)(pydic), and (S,S)-4 a, suggested the formation of a new species with an absorbance peak at lambda=465 nm upon treatment with hydrogen peroxide. With the aid of two independent spin traps, we could confirm by EPR spectroscopy that the reaction proceeds via radical intermediates. Kinetic studies with deuterated styrenes showed inverse secondary kinetic isotope effects, with values of k(H)/k(D)=0.93 for the beta carbon and k(H)/k(D)=0.97 for the alpha carbon, which suggested an unsymmetrical transition state with stepwise O transfer. Competitive epoxidation of para-substituted styrenes revealed a linear dual-parameter Hammett plot with a slope of 1.00. Under standard conditions, epoxidation of 1 a in the presence of ten equivalents of H(2) (18)O resulted in an absence

  17. Hasse diagram as a green analytical metrics tool: ranking of methods for benzo[a]pyrene determination in sediments.

    PubMed

    Bigus, Paulina; Tsakovski, Stefan; Simeonov, Vasil; Namieśnik, Jacek; Tobiszewski, Marek

    2016-05-01

    This study presents an application of the Hasse diagram technique (HDT) as the assessment tool to select the most appropriate analytical procedures according to their greenness or the best analytical performance. The dataset consists of analytical procedures for benzo[a]pyrene determination in sediment samples, which were described by 11 variables concerning their greenness and analytical performance. Two analyses with the HDT were performed-the first one with metrological variables and the second one with "green" variables as input data. Both HDT analyses ranked different analytical procedures as the most valuable, suggesting that green analytical chemistry is not in accordance with metrology when benzo[a]pyrene in sediment samples is determined. The HDT can be used as a good decision support tool to choose the proper analytical procedure concerning green analytical chemistry principles and analytical performance merits. PMID:27038058

  18. Regioselective Isomerization of 2,3-Disubstituted Epoxides to Ketones: An Alternative to the Wacker Oxidation of Internal Alkenes.

    PubMed

    Lamb, Jessica R; Mulzer, Michael; LaPointe, Anne M; Coates, Geoffrey W

    2015-12-01

    We report an alternative pathway to the Wacker oxidation of internal olefins involving epoxidation of trans-alkenes followed by a mild and highly regioselective isomerization to give the major ketone isomers in 66-98% yield. Preliminary kinetics and isotope labeling studies suggest epoxide ring opening as the turnover limiting step in our proposed mechanism. A similar catalytic system was applied to the kinetic resolution of select trans-epoxides to give synthetically useful selectivity factors of 17-23 for benzyl-substituted substrates. PMID:26522052

  19. Discovery of a Novel Microsomal Epoxide Hydrolase-Catalyzed Hydration of a Spiro Oxetane.

    PubMed

    Li, Xue-Qing; Hayes, Martin A; Grönberg, Gunnar; Berggren, Kristina; Castagnoli, Neal; Weidolf, Lars

    2016-08-01

    Oxetane moieties are increasingly being used by the pharmaceutical industry as building blocks in drug candidates because of their pronounced ability to improve physicochemical parameters and metabolic stability of drug candidates. The enzymes that catalyze the biotransformation of the oxetane moiety are, however, not well studied. The in vitro metabolism of a spiro oxetane-containing compound AZD1979 [(3-(4-(2-oxa-6-azaspiro[3.3]heptan-6-ylmethyl)phenoxy)azetidin-1-yl)(5-(4-ethoxyphenyl)-1,3,4-oxadiazol-2-yl)methanone] was studied and one of its metabolites, M1, attracted our interest because its formation was NAD(P)H independent. The focus of this work was to elucidate the structure of M1 and to understand the mechanism(s) of its formation. We established that M1 was formed via hydration and ring opening of the oxetanyl moiety of AZD1979. Incubations of AZD1979 using various human liver subcellular fractions revealed that the hydration reaction leading to M1 occurred mainly in the microsomal fraction. The underlying mechanism as a hydration, rather than an oxidation reaction, was supported by the incorporation of (18)O from H2 (18)O into M1. Enzyme kinetics were performed probing the formation of M1 in human liver microsomes. The formation of M1 was substantially inhibited by progabide, a microsomal epoxide hydrolase inhibitor, but not by trans-4-[4-(1-adamantylcarbamoylamino)cyclohexyloxy]benzoic acid, a soluble epoxide hydrolase inhibitor. On the basis of these results, we propose that microsomal epoxide hydrolase catalyzes the formation of M1. The substrate specificity of microsomal epoxide hydrolase should therefore be expanded to include not only epoxides but also the oxetanyl ring system present in AZD1979. PMID:27256986

  20. Reusable manganese compounds containing pyrazole-based ligands for olefin epoxidation reactions.

    PubMed

    Manrique, Ester; Poater, Albert; Fontrodona, Xavier; Solà, Miquel; Rodríguez, Montserrat; Romero, Isabel

    2015-10-28

    We describe the synthesis of new manganese(ii) and manganese(iii) complexes containing the bidentate ligands 2-(3-pyrazolyl)pyridine, pypz-H, and 3(5)-(2-hydroxyphenyl)pyrazole, HOphpz-H, with formula [MnX2(pypz-H)2] (X = Cl(-), 1, CF3SO3(-), 2, OAc(-), 3 or NO3(-) (4)), [MnCl2(pypz-H)(H2O)2], 5, or [MnCl(Ophpz-H)2], 6. All the complexes have been characterized through analytical, spectroscopic and electrochemical techniques. Single X-ray structure analysis revealed a six-coordinated Mn(ii) ion in complexes 1-5, and a five-coordinated Mn(iii) ion in complex 6. Compound 5 is the first co-crystal of Mn(ii) containing Cl and H2O ligands together with bidentate nitrogen ligands. The catalytic activity of complexes 1-6 has been tested with regard to the epoxidation of styrene and, in the case of 1, 5 and 6, other alkenes have been epoxidized using peracetic acid as oxidant in different media, among which glycerol, a green solvent never used in epoxidation reactions using peracetic acid as oxidant. The catalysts show moderate to high conversions and selectivities towards the corresponding epoxides. For complexes 1, 5 and 6, a certain degree of cis→trans isomerization is observed in the case of cis-β-methylstyrene. These observations have been explained through computational calculations. The reutilization of catalysts 1 and 6 for the epoxidation of alkenes has been evaluated in [bmim] : acetonitrile mixture (bmim = 1-butyl-3-methylimidazolium), allowing the effective recyclability of the catalytic system and keeping high conversion and selectivity values up to 12 successive runs, in all cases. PMID:26389716

  1. Titania-silica mixed oxides. II. Catalytic behaviour in olefin epoxidation

    SciTech Connect

    Hutter, R.; Mallat, T.; Baiker, A.

    1995-04-15

    Various titania-silica aerogels prepared by an alkoxide-sol-gel route have been tested in the epoxidation of bulky olefins using cumene hydroperoxide as oxidant. The drying method, the titanium content between 2 and 20 wt%, and the calcination temperature between 473 and 1073 K were the most important preparation parameters, influencing the catalytic behaviour of the aerogels. The aerogels dried by semicontinuous extraction with supercritical CO{sub 2} at low temperature (LT aerogel) were found to be much more efficient epoxidation catalysts than aerogels prepared by high-temperature supercritical drying and conventionally dried xerogels. The reaction rate of cyclohexene epoxidation over LT aerogels increased monotonically with increasing Ti content. In the range of 333-363 K the catalysts containing 20 wt% TiO{sub 2} (20LT) showed high activity and selectivity (79-93% to peroxide and 87-100% to epoxide) in the oxidation of various cyclic olefins, including cyclododecene, norbornene, cyclohexene, and limonene. Catalytic experiments, FTIR, and UV-vis spectroscopy indicated that the LT aerogels consist of two different types of active species: titanium well-dispersed in the silica matrix and titania nanodomains. The key factors determining the activity and selectivity of sol-gel titania-silica catalysts are the morphology (surface area and pore size) and the relative proportions of Ti-O-Si and Ti-O-Ti structural parts. A comparative study of the epoxidation of cyclohexene, cyclododecene, and norbornene over structurally different titania-silica catalysts, indicates that 20LT shows better catalytic behaviour in these reactions than Ti zeolites and silica-supported titania. 46 refs., 12 figs., 3 tabs.

  2. In Silico Prediction of Cytochrome P450-Mediated Biotransformations of Xenobiotics: A Case Study of Epoxidation.

    PubMed

    Zhang, Jing; Ji, Li; Liu, Weiping

    2015-08-17

    Predicting the biotransformation of xenobiotics is important in toxicology; however, as more compounds are synthesized than can be investigated experimentally, powerful computational methods are urgently needed to prescreen potentially useful candidates. Cytochrome P450 enzymes (P450s) are the major enzymes involved in xenobiotic metabolism, and many substances are bioactivated by P450s to form active compounds. An example is the conversion of olefinic substrates to epoxides, which are intermediates in the metabolic activation of many known or suspected carcinogens. We have calculated the activation energies for epoxidation by the active species of P450 enzymes (an iron-oxo porphyrin cation radical oxidant, compound I) for a diverse set of 36 olefinic substrates with state-of-the-art density functional theory (DFT) methods. Activation energies can be estimated by the computationally less demanding method of calculating the ionization potentials of the substrates, which provides a useful and simple predictive model based on the reaction mechanism; however, the preclassification of these diverse substrates into weakly polar and strongly polar groups is a prerequisite for the construction of specific predictive models with good predictability for P450 epoxidation. This approach has been supported by both internal and external validations. Furthermore, the relation between the activation energies for the regioselective epoxidation and hydroxylation reactions of P450s and experimental data has been investigated. The results show that the computational method used in this work, single-point energy calculations with the B3LYP functional including zero-point energy and solvation and dispersion corrections based on B3LYP-optimized geometries, performs well in reproducing the experimental trends of the epoxidation and hydroxylation reactions. PMID:26200167

  3. Pilot scale production, characterization, and optimization of epoxidized vegetable oil-based resins

    NASA Astrophysics Data System (ADS)

    Monono, Ewumbua Menyoli

    Novel epoxidized sucrose soyate (ESS) resins perform much better than other vegetable oil-based resins; thus, they are of current interest for commercial scale production and for a wide range of applications in coatings and polymeric materials. However, no work has been published that successfully scaled-up the reaction above a 1 kg batch size. To achieve this goal, canola oil was first epoxidized at a 300 g scale to study the epoxidation rate and thermal profile at different hydrogen peroxide (H2O2) addition rates, bath temperatures, and reaction times. At least 83% conversion of double bonds to oxirane was achieved by 2.5 h, and the reaction temperature was 8-15 °C higher than the water bath temperature within the first 30-40 min of epoxidation. A 38 L stainless steel kettle was modified as a reactor to produce 10 kg of ESS. Twenty 7-10 kg batches of ESS were produced with an overall 87.5% resin yield and > 98% conversion after batch three. The conversion and resin quality were consistent across the batches due to the modifications on the reaction that improved mixing and reaction temperature control within 55-65 oC. The total production time was reduced from 8 to 4 days due to the fabrication of a 40 L separatory funnel for both washing and filtration. A math model was developed to optimize the epoxidation process. This was done by using the Box-Behnken design to model the conversion at various acetic acid, H2O2, and Amberlite ratios and at various reaction temperatures and times. The model had an adjusted R2 of 97.6% and predicted R2 of 96.8%. The model showed that reagent amounts and time can be reduced by 18% without compromising the desired conversion value and quality.

  4. Intercalation of 1,n-diols into strontium phenylphosphonate: how the shape of the host layers influences arrangement of the guest molecules.

    PubMed

    Melánová, Klára; Kovář, Petr; Beneš, Ludvík; Svoboda, Jan; Veteška, Marek; Pospíšil, Miroslav; Zima, Vítězslav

    2015-12-15

    Strontium phenylphosphonate intercalates with 1,n diols (n=2-4, 6-8) having general formula SrC6H5PO3⋅x(HO(CH2)nOH)⋅yH2O were prepared by precipitation from strontium phenylphosphonate solution and the corresponding diols. Prepared compounds exhibit a very good stability at ambient conditions. The intercalates were characterized by X-ray diffraction, thermogravimetry and elemental analysis. Thanks to the existence of free spaces among the benzene rings the diols exhibit a peculiar intercalation behavior. This behavior is explained on the basis of molecular simulation, which facilitated to elucidate the arrangement of the diol (guest) molecules in the specifically shaped space between the layers of the host material. From the structural point of view the intercalates can be divided into two subgroups: (i) intercalates with 1,2- to 1,4-diols and (ii) intercalates with 1,6- to 1,8-diols. The alkanediols of the first group are immersed in the free spaces among the benzene groups, their molecules adopt a horseshoe shape meaning cis conformation and are bonded by both of their OH groups to one host layer. The longer alkanediol chains of the second group allow anchoring to both neighboring layers of the host forming a kind of pillared structure in the interlayer space. The diol molecules are in this case bonded to the host layers by their OH groups to the oxygen atoms of the host layers and to water molecules present in the interlayer space through hydrogen bonds. The values of the basal spacing obtained from the experimental powder X-ray patterns are in a very good agreement with the basal spacing values calculated from the models. The molecular simulation of a 1,5-pentanediol intercalate, which we were not be able to synthesize, explained why this intercalate cannot be stable. PMID:26319335

  5. Determination of benzo[a]pyrene and dibenzopyrenes in a Chinese coal fly ash certified reference material.

    PubMed

    Masala, Silvia; Bergvall, Christoffer; Westerholm, Roger

    2012-08-15

    Air pollution from coal combustion is of great concern in China because coal is the country's principal source of energy and it has been estimated that coal combustion is one of the main sources of polycyclic aromatic hydrocarbon (PAH) emissions in the nation. This study reports the concentrations of 15 PAHs including benzo[a]pyrene, dibenzo[a,l]pyrene, dibenzo[a,e]pyrene, dibenzo[a,i]pyrene and dibenzo[a,h]pyrene in a coal fly ash certified reference material (CRM) from China. To the best of our knowledge, dibenzo[a,l]pyrene, dibenzo[a,i]pyrene and dibenzo[a,h]pyrene concentrations in coal fly ash particles have not previously been reported. Benzo[a]pyrene is the only one of the studied hydrocarbons whose concentration in the coal fly ash CRM had previously been certified. The concentration of this species measured in this present work was twice the certified value. This is probably because of the exhaustive accelerated solvent extraction method employed. Consecutive extractions indicated an extraction recovery in excess of 95% for benzo[a]pyrene. For the other determined PAHs, repeat extractions indicated recoveries above 90%. PMID:22728296

  6. Cholesterol metabolite, 5-cholesten-3beta, 25-diol 3-sulfate, promotes hepatic proliferation in mice

    PubMed Central

    Zhang, Xin; Bai, Qianming; Kakiyama, Genta; Xu, Leyuan; Kim, Jin Kyung; Pandak, William M.; Ren, Shunlin

    2012-01-01

    Oxysterols are well known as physiological ligands of Liver X receptors (LXRs). Oxysterols, 25-Hydroxycholesterol (25HC) and 27-hydroxycholesterol as endogenous ligands of LXRs, suppress cell proliferation via LXRs signaling pathway. Recent reports have shown that sulfated oxysterol, 5-cholesten-3β, 25-diol 3-sulfate (25HC3S) as LXRs antagonist, plays an opposite direction to oxysterols in lipid biosynthesis. The present report was to explore the effect and mechanism of 25HC3S on hepatic proliferation in vivo. Following administration, 25HC3S had a 48 h half life in the circulation and widely distributed in mouse tissues. Profiler™ PCR array and RTqPCR analysis showed that either exogenous or endogenous 25HC3S generated by overexpression of oxysterol sulfotransferase (SULT2B1b) plus administration of 25HC significantly up-regulated the proliferation gene expression of Wt1, Pcna, cMyc, cyclin A, FoxM1b, and CDC25b in a dose-dependent manner in liver while substantially down-regulating the expression of cell cycle arrest gene Chek2 and apoptotic gene Apaf1. Either exogenous or endogenous administration of 25HC3S significantly induced hepatic DNA replication as measured by immunostaining of the PCNA labeling index and was associated with reduction in expression of LXR response genes, such as ABCA1 and SREBP-1c. Synthetic LXR agonist T0901317 effectively blocked 25HC3S-induced hepatic proliferation. Conclusions: 25HC3S may be a potent regulator of hepatocyte proliferation and oxysterol sulfation may represent a novel regulatory pathway in liver proliferation via inactivating LXR signaling. PMID:22732306

  7. Epoxide pathways improve model predictions of isoprene markers and reveal key role of acidity in aerosol formation

    EPA Science Inventory

    Isoprene significantly contributes to organic aerosol in the southeastern United States where biogenic hydrocarbons mix with anthropogenic emissions. In this work, the Community Multiscale Air Quality model is updated to predict isoprene aerosol from epoxides produced under both ...

  8. Isolation of β-Cryptoxanthin-epoxides, Precursors of Cryptocapsin and 3'-Deoxycapsanthin, from Red Mamey (Pouteria sapota).

    PubMed

    Turcsi, Erika; Murillo, Enrique; Kurtán, Tibor; Szappanos, Ádám; Illyés, Tünde-Zita; Gulyás-Fekete, Gergely; Agócs, Attila; Avar, Péter; Deli, József

    2015-07-01

    From an extract of red mamey (Pouteria sapota) β-cryptoxanthin-5,6-epoxide, β-cryptoxanthin-5',6'-epoxide, 3'-deoxycapsanthin, and cryptocapsin were isolated and characterized by UV-vis spectroscopy, electronic circular dichroism (ECD), nuclear magnetic resonance (NMR) spectroscopy, and mass spectrometry (MS). Epoxidation of β-cryptoxanthin delivered the β-(5'R,6'S)- and (5'S,6'R)-cryptoxanthin-5',6'-epoxides, which were identified by HPLC-ECD analysis. These carotenoids among others are quite common in the fruits of Central America, and as they are natural provitamins A, they should play an important role in the diet of the mostly vitamin A deficient population of this region. PMID:26057604

  9. Fingerprinting of traditional Chinese medicines on the C18-Diol mixed-mode column in online or offline two-dimensional liquid chromatography on the single column modes.

    PubMed

    Wang, Qing; Tong, Ling; Yao, Lin; Zhang, Peng; Xu, Li

    2016-06-01

    In the present study, a mixed-mode stationary phase, C18-Diol, was applied for fingerprint analysis of traditional Chinese medicines. Hydrophobic, hydrogen bonding and electrostatic interactions were demonstrated to contribute the retention separately or jointly, which endowed the C18-Diol stationary phase with distinct selectivity compared to the bare C18 one. The separation of total alkaloids extracted from Fritillaria hupehensis was compared on the C18-Diol and conventional C18 column with the greater resolving power and better symmetry responses on the former one. Besides, a novel two-dimensional liquid chromatography on the single column (2D-LC-1C) was realized on C18-Diol with the offline mode for the alcohol extract of Fritillaria hupehensis and online mode for Ligusticum chuanxiong Hort. The early co-eluted extracted components with great polarity on the first dimension were reinjected on the same column and well separated on the second dimension. The results exhibited that the two complementary RPLC and HILIC modes on C18-Diol stationary phase enhanced the separation capacity and revealed more abundant chemical information of the sample, which was a powerful tool in analyzing complex herbal medicines. PMID:27031576

  10. Synthesis of beta-lactones by the regioselective, cobalt and Lewis acid catalyzed carbonylation of simple and functionalized epoxides.

    PubMed

    Lee, J T; Thomas, P J; Alper, H

    2001-08-10

    The PPNCo(CO)(4) and BF(3) x Et(2)O catalyzed carbonylation of simple and functionalized epoxides in DME gives the corresponding beta-lactones regioselectively in good to high yields. The carbonylation occurred selectively at the unsubstituted C-O bond of the epoxide ring, and this reaction tolerates various functional groups such as alkenyl, halide, hydroxy, and alkyl ether. PMID:11485465

  11. Nazarov cyclization of divinyl and arylvinyl epoxides: application in the synthesis of resveratrol-based natural products.

    PubMed

    Sudhakar, Gangarajula; Satish, Kovela

    2015-04-20

    New variation in the Nazarov cyclization has been developed by preparing divinyl and arylvinyl epoxides as pentadienyl cation precursors for the first time. Highly substituted cyclopentadienes, hydrindienes, and indenes were synthesized to demonstrate the compatibility of this reaction with substrates bearing a variety of substitutions and having different types of epoxides. Application of this method in the synthesis of resveratrol-based natural products was also demonstrated. PMID:25760544

  12. A New Biocatalyst for Production of Optically Pure Aryl Epoxides by Styrene Monooxygenase from Pseudomonas fluorescens ST

    PubMed Central

    Di Gennaro, Patrizia; Colmegna, Andrea; Galli, Enrica; Sello, Guido; Pelizzoni, Francesca; Bestetti, Giuseppina

    1999-01-01

    We developed a biocatalyst by cloning the styrene monooxygenase genes (styA and styB) from Pseudomonas fluorescens ST responsible for the oxidation of styrene to its corresponding epoxide. Recombinant Escherichia coli was able to oxidize different aryl vinyl and aryl ethenyl compounds to their corresponding optically pure epoxides. The results of bioconversions indicate the broad substrate preference of styrene monooxygenase and its potential for the production of several fine chemicals. PMID:10347083

  13. Involvement of DNA polymerase beta overexpression in the malignant transformation induced by benzo[a]pyrene

    PubMed Central

    Zhao, Wei; Wu, Mei; Lai, Yanhao; Deng, Wenwen; Liu, Yuan; Zhang, Zunzhen

    2014-01-01

    Objective To explore the relationship between DNA polymerase β (pol β) overexpression and benzo[a]pyrene (BaP) carcinogenesis. Methods Firstly, mouse embryonic fibroblasts that express wild-type level of DNA polymerase β (pol β cell) and high level of pol β (pol β oe cell) were treated by various concentrations of BaP to determine genetic instability induced by BaP under differential expression levels of pol β. Secondly, malignant transformation of pol β cells by low concentration of BaP (20 μM) was determined by soft agar colony formation assay and transformation focus assay. Thirdly, the mRNA and protein levels of BaP-transformed pol β cells (named pol β-T cells) was measured by reverse transcriptase-polymerase chain reaction (RT-PCR) and western blot, and the genetic instability of these cells were examined by HPRT gene mutation assay and random amplified polymorphic DNA (RAPD) assay. Results Pol β cells were successfully transformed into malignant pol β-T cells by an exposure to low concentration of BaP for 6 months. Pol β-T cells exhibited increased levels of pol β gene expression, HPRT gene mutation frequency and polymorphisms of RAPD products that were comparable to those of pol β oe cells. Conclusion Pol β overexpression and its-associated genetic instability may play a key role in BaP carcinogenesis. PMID:23652152

  14. Poly(ADP-Ribose) Glycohydrolase (PARG) Silencing Suppresses Benzo(a)pyrene Induced Cell Transformation

    PubMed Central

    Huang, Peiwu; Zhuang, Zhixiong; Liu, Jianjun; Gao, Wei; Liu, Yinpin; Huang, Haiyan

    2016-01-01

    Benzo(a)pyrene (BaP) is a ubiquitously distributed environmental pollutant and known carcinogen, which can induce malignant transformation in rodent and human cells. Poly(ADP-ribose) glycohydrolase (PARG), the primary enzyme that catalyzes the degradation of poly(ADP-ribose) (PAR), has been known to play an important role in regulating DNA damage repair and maintaining genomic stability. Although PARG has been shown to be a downstream effector of BaP, the role of PARG in BaP induced carcinogenesis remains unclear. In this study, we used the PARG-deficient human bronchial epithelial cell line (shPARG) as a model to examine how PARG contributed to the carcinogenesis induced by chronic BaP exposure under various concentrations (0, 10, 20 and 40 μM). Our results showed that PARG silencing dramatically reduced DNA damages, chromosome abnormalities, and micronuclei formations in the PARG-deficient human bronchial epithelial cells compared to the control cells (16HBE cells). Meanwhile, the wound healing assay showed that PARG silencing significantly inhibited BaP-induced cell migration. Furthermore, silencing of PARG significantly reduced the volume and weight of tumors in Balb/c nude mice injected with BaP induced transformed human bronchial epithelial cells. This was the first study that reported evidences to support an oncogenic role of PARG in BaP induced carcinogenesis, which provided a new perspective for our understanding in BaP exposure induced cancer. PMID:27003318

  15. Reproductive toxicity assessment of benzo[a]pyrene in the marine polychaete Perinereis nuntia

    NASA Astrophysics Data System (ADS)

    Wu, Qingyang; Wang, Shuqi; Chen, Xiaopeng; Li, Ping

    2016-07-01

    Benzo[a]pyrene (B[a]P) is an increasingly present marine environmental pollutant, yet our understanding of the long-term consequences of reproductive toxicity in marine benthic polychaetes remains limited. To test the reproductive toxicity of B[a]P on polychaetes, Perinereis nuntia was exposed to B[a]P-contaminated artificial seawater and sexual maturation, the sex ratio, number of eggs spawned, fertilization and hatching rated, as well as vitellogenin (VTG) mRNA expression levels were analyzed. A low concentration of B[a]P (2.5 μg/L) had no Effects on the rate of sexual maturation, spawning, or fertilization but significantly increased the sex ratio (female: male) from 1.6±0.15:1 to 2.3±0.18:1, inhibited hatching rate by 27%, and significantly increased VTG mRNA expression level by 3.7-fold following a 60-day exposure, compared with those in the solvent controls. A higher concentration of B[a]P (25 μg/L) caused more serious Effects; sexual maturation, fertilization success, and hatching decreased by 31%, 17% and 46%, respectively, and the sex ratio (female: male) and VTG mRNA gene expression level increased by 54% and 7.1-fold, respectively. These results demonstrate that sublethal concentrations of B[a]P negatively aff ect reproductive performance of the sandworm P. nuntia.

  16. Influence of the carcinogenic pollutant benzo(a)pyrene on plant development

    SciTech Connect

    Forrest, V.J.

    1987-01-01

    To investigate the growth altering abilities of PAHs in plants, polypodiaceous fern gametophytes were grown under sterile conditions on media containing the PAH, benzo(a)pyrene (BP) at doses ranging from 0.1 to 10.0 ug/ml. The growth pattern characteristic of these plants enables alterations in growth and morphogenesis to be observed at the cellular level in a whole plant system. Doses of BP in the range 0.1-3.2 ug/ml enhanced the onset of morphogenesis. The low (0.1 and 0.32 ug) and high (1.0 and 3.2 ug) doses of BP were found to accelerate and inhibit growth, respectively. The 10.0 ug dose was toxic to the ferns and resulted in decreased germination of spores and reduced survival of plants. A slight but significant decrease in survival was also observed with ferns treated with 3.2 ug. Metabolism experiments were conducted utilizing radiolabeled BP, high performance liquid chromatography, and liquid scintillation spectrometry.

  17. Newsagents' daily personal exposures to benzo(a)pyrene in Genoa, Italy

    NASA Astrophysics Data System (ADS)

    Piccardo, Maria Teresa; Stella, Anna; Redaelli, Anna; Minoia, Claudio; Valerio, Federico

    Daily personal exposures to benzo(a)pyrene (BaP) of 31 newsagents working in Genoa, Italy, were evaluated throughout 1998 during two different seasonal periods (February-April and May-June). Exposures of smoker and non-smoker subjects were compared. The highest BaP exposures were those of smokers during the cold period (2.20±0.84 ng/m 3). During this same period, the BaP exposure for non-smoker subjects was 1.00±0.32 ng/m 3. Both smoker and non-smoker exposures showed a seasonal dependence, with the lowest values occurring in the warm period (smokers: 1.46±0.72 ng/m 3, non-smokers: 0.65±0.25 ng/m 3). Compared to the cold period, the warm period produced a nearly 35% reduction in BaP exposures in both smoker and non-smoker subjects. A linear correlation was observed between personal exposures and number of cigarettes smoked daily. An increase in average daily BaP exposure of 0.071±0.009 ng/m 3 for every cigarette, due to passive smoke, was calculated. Mean BaP concentrations calculated from fixed monitoring stations were nearly 40% higher than mean personal exposures of non-smoker newsagents.

  18. Synthesis of modified potato starches for aqueous solubilization of benzo[a]pyrene.

    PubMed

    Delsarte, Isabelle; Danjou, Pierre-Edouard; Veignie, Etienne; Rafin, Catherine

    2016-06-25

    For soil rehabilitation, the surfactant-enhanced remediation has emerged as a promising technology. For this purpose, starch derivatives were difunctionalized by 1,4-butane sultone (BS) and 2-octen-1-ylsuccinic anhydride (OSA). Eight distinct products were obtained under different synthesis conditions. The chemical structural characteristics were investigated by (1)H NMR spectroscopy. The compounds were evaluated for their apparent aqueous solubility and their ability to increase the solubility of a hydrophobic pollutant such as benzo[a]pyrene (BaP), used as a polycyclic aromatic hydrocarbon model. In comparison with native starch, the best obtained compound increased starch apparent aqueous solubility by a factor of 10 (up to 3.50g/L) and also stimulated 77-fold BaP aqueous solubilization (up to 232.97μg/L) underlining its very high surfactant property. In this study, the right balance between hydrophobic character (octenyl succinate group (OS) grafted) of starch derivatives and starch apparent aqueous solubility (BS grafted) was highlighted. PMID:27083796

  19. Benzo[a]pyrene and Benzo[k]fluoranthene in Some Processed Fish and Fish Products

    PubMed Central

    Olatunji, Olatunde S.; Fatoki, Olalekan S.; Opeolu, Beatrice O.; Ximba, Bhekumusa J.

    2015-01-01

    In this study, the concentration levels of the probable carcinogenic PAH fractions, benzo[a]pyrene (BaP) and benzo[k]fluoranthrene (BkF) in fillets of some processed fish species were investigated. Fish species comprising Merluccius poli (hake), Tyrsites atun (snoek), Seriola lalandi (yellow-tail) and Brama brama (angel fish) were bought in fish shops at Gordon’s Bay, Western Cape, South Africa. The fish were gutted, filleted and prepared for edibility by frying, grilling and boiling. Polycyclic aromatic hydrocarbons were extracted from each homogenized fish sample, cleaned-up using solid phase extraction (SPE), and analysed for the PAH fractions, BaP and BkF using a Gas Chromatograph coupled with a Flame Ionization Detector (GC-FID). The sum of the two PAHs (∑2PAH) i.e., BaP and BkF ranged between 0.56 and 1.46 µg/kg, in all boiled, grilled and fried fish species. The fried fish extracts showed significantly higher (p < 0.05) abundance of ∑2PAH, than grilled and boiled fish. Dietary safety and PAHs toxicity was also discussed. PMID:25607603

  20. Detection of the carcinogenic water pollutant benzo[a]pyrene with an electro-switchable biosurface.

    PubMed

    Lux, Gregor; Langer, Andreas; Pschenitza, Michael; Karsunke, Xaver; Strasser, Ralf; Niessner, Reinhard; Knopp, Dietmar; Rant, Ulrich

    2015-04-21

    The toxic nature of polycyclic aromatic hydrocarbons (PAHs), in particular benzo[a]pyrene (B[a]P), neccessitates the monitoring of PAH contamination levels in food and the environment. Here we introduce an indirect immunoassay format using electro-switchable biosurfaces (ESB) for the detection of B[a]P in water. The association of anti-B[a]P antibodies to microelectrodes is analyzed in real-time by measuring changes in the oscillation dynamics of DNA nanolever probes, which are driven to switch their orientations by high-frequency electrical actuation. From the association kinetics, the active concentration of anti-B[a]P, and hence the B[a]P contamination of the sample, can be determined with picomolar sensitivity. The detection limit of the assay improves with measurement time because increasingly accurate analyses of the binding kinetics become possible. It is demonstrated that an exceedance of the permissible 10 ng/L (40 pM) limit for B[a]P is detectable in an unprecedented short assay time (<1 h), using a simple three-step workflow involving minimal sample preparation. The reproducibility was satisfying with standard deviations below 5%. Further, the utility of the assay for practical applications is exemplified by analyzing a river water sample. PMID:25822755

  1. Induction of benzo(a)pyrene metabolism in human mammary epithelial cells by manufactured gas residues

    SciTech Connect

    Goth-Goldstein, R.; Levine, G.; Leadon, S.A.; Chaloupka, K.; Safe, S.

    1994-12-31

    This study was undertaken to evaluate the non-genotoxic effects of manufactured gas plant residues which present complex mixtures of polycyclic aromatic hydrocarbons. The effect of these residues on benzo(a)pyrene (BaP) metabolism in human mammary epithelial cells was studied. Cells were preincubated with hexane-extractable coal tar material for 16 hr, then incubated with {sup 3}H-BaP for 2 hr and the amount of BaP metabolites in cell extracts was determined by HPLC. An up to 5-fold increase over control in BaP metabolites was seen after preincubation with 0.2 {mu}g/ml coal tar material (a oncytotoxic dose). Coal tar extracts were equally effective as pure BaP in inducing BaP metabolism. As BaP constitutes less than 1% of the coal tar, other components in the coal tar mixtures appear to be even more potent than BaP in inducing the enzyme system responsible for BaP metabolism. The increase in BaP metabolites was accompanied by a proportional increase in P4501A1 mRNA as measured by Northern blotting, and resulted in an increase of BaP adducts to DNA. These results show that coal tars and other P450-inducting compounds can act as cocarcinogens by enhancing the genotoxic effects of compounds metabolized by the P4501A1 enzyme.

  2. Bioavailability of atrazine, pyrene and benzo[a]pyrene in European river waters

    USGS Publications Warehouse

    Akkanen, J.; Penttinen, S.; Haitzer, M.; Kukkonen, J.V.K.

    2001-01-01

    Thirteen river waters and one humic lake water were characterized. The effects of dissolved organic matter (DOM) on the bioavailability of atrazine, pyrene and benzo[a]pyrene (B[a]P) was evaluated. Binding of the chemicals by DOM was analyzed with the equilibrium dialysis technique. For each of the water samples, 24 h bioconcentration factors (BCFs) of the chemicals were measured in Daphnia magna. The relationship between DOM and other water characteristics (including conductivity, water hardness and pH), and bioavailability of the chemicals was studied by performing several statistical analyses, including multiple regression analyses, to determine how much of the variation of BCF values could be explained by the quantity and quality of DOM. The bioavailability of atrazine was not affected by DOM or any other water characteristics. Although equilibrium dialysis showed binding of pyrene to DOM, the bioavailability of pyrene was not significantly affected by DOM. The bioavailability of B[a]P was significantly affected by both the quality and quantity of DOM. Multiple regression analyses, using the quality (ABS270 and HbA%) and quantity of DOM as variables, explainedup to 70% of the variation in BCF of B[a]P in the waters studied. ?? 2001 Elsevier Science Ltd. All rights reserved.

  3. Benzo(a)pyrene induced lung cancer: Role of dietary phytochemicals in chemoprevention.

    PubMed

    Kasala, Eshvendar Reddy; Bodduluru, Lakshmi Narendra; Barua, Chandana C; Sriram, Chandra Shekhar; Gogoi, Ranadeep

    2015-10-01

    Lung cancer is the major cause of overall cancer deaths, and chemoprevention is a promising strategy to control this disease. Benzo(a)pyrene [B(a)P], a polycyclic aromatic hydrocarbon, is one among the principal constituents of tobacco smoke that plays a key role in lung carcinogenesis. The B(a)P induced lung cancer in mice offers a relevant model to study the effect of natural products and has been widely used by many researchers and found considerable success in ameliorating the pathophysiological changes of lung cancer. Currently available synthetic drugs that constitute the pharmacological armamentarium are themselves effective in managing the condition but not without setbacks. These hunches have accelerated the requisite for natural products, which may be used as dietary supplement to prevent the progress of lung cancer. Besides, these agents also supplement the conventional treatment and offer better management of the condition with less side effects. In the context of soaring interest toward dietary phytochemicals as newer pharmacological interventions for lung cancer, in the present review, we are attempting to give a silhouette of mechanisms of B(a)P induced lung carcinogenesis and the role of dietary phytochemicals in chemoprevention. PMID:26398396

  4. Benzene, benzo(a)pyrene, and lead in smoke from tobacco products other than cigarettes.

    PubMed Central

    Appel, B R; Guirguis, G; Kim, I S; Garbin, O; Fracchia, M; Flessel, C P; Kizer, K W; Book, S A; Warriner, T E

    1990-01-01

    Benzene, benzo(a)pyrene (BaP), and lead in mainstream smoke from cigars, roll-your-own (RYO) cigarette and pipe tobaccos were sampled to evaluate their potential health significance. Results with reference cigarettes were consistent with published values, providing support for the methodology employed. The emissions of benzene and BaP, expressed as mass emitted per gram of tobacco consumed, were similar for all products evaluated; for benzene, the mean values for cigars, RYO cigarette and pipe tobaccos were 156 +/- 52, 68 +/- 11, and 242 +/- 126 micrograms/g, respectively. Mean values for BaP were 42 +/- 7 and 48 +/- 4 ng/g for cigars and RYO cigarette tobacco, respectively. Lead values were below the limit of reliable quantitation in all cases. The mean benzene concentrations in a puff ranged from 1 to 2 x 10(5) micrograms/m3 for cigars, RYO cigarette and pipe tobaccos. For BaP, the puff concentration averaged about 60 micrograms/m3 for cigars and RYO cigarette tobacco. The results suggest that smoking cigars, pipes or RYO cigarettes leads to potential exposures which exceed the No Significant Risk levels of benzene and BaP set pursuant to California's Proposition 65. These tobacco products are now required to bear a health hazard warning when sold in California. We recommend that this be adopted as national policy. PMID:2327532

  5. Poly(ADP-Ribose) Glycohydrolase (PARG) Silencing Suppresses Benzo(a)pyrene Induced Cell Transformation.

    PubMed

    Li, Xuan; Li, Xiyi; Zhu, Zhiliang; Huang, Peiwu; Zhuang, Zhixiong; Liu, Jianjun; Gao, Wei; Liu, Yinpin; Huang, Haiyan

    2016-01-01

    Benzo(a)pyrene (BaP) is a ubiquitously distributed environmental pollutant and known carcinogen, which can induce malignant transformation in rodent and human cells. Poly(ADP-ribose) glycohydrolase (PARG), the primary enzyme that catalyzes the degradation of poly(ADP-ribose) (PAR), has been known to play an important role in regulating DNA damage repair and maintaining genomic stability. Although PARG has been shown to be a downstream effector of BaP, the role of PARG in BaP induced carcinogenesis remains unclear. In this study, we used the PARG-deficient human bronchial epithelial cell line (shPARG) as a model to examine how PARG contributed to the carcinogenesis induced by chronic BaP exposure under various concentrations (0, 10, 20 and 40 μM). Our results showed that PARG silencing dramatically reduced DNA damages, chromosome abnormalities, and micronuclei formations in the PARG-deficient human bronchial epithelial cells compared to the control cells (16HBE cells). Meanwhile, the wound healing assay showed that PARG silencing significantly inhibited BaP-induced cell migration. Furthermore, silencing of PARG significantly reduced the volume and weight of tumors in Balb/c nude mice injected with BaP induced transformed human bronchial epithelial cells. This was the first study that reported evidences to support an oncogenic role of PARG in BaP induced carcinogenesis, which provided a new perspective for our understanding in BaP exposure induced cancer. PMID:27003318

  6. Differential gene expression analysis of benzo(a)pyrene toxicity in the clam, Ruditapes philippinarum.

    PubMed

    Liu, Tong; Pan, Luqing; Jin, Qian; Cai, Yuefeng

    2015-05-01

    Polycyclic aromatic hydrocarbons (PAHs) are known for their carcinogenic, teratogenic and mutagenic properties. Benzo(a)pyrene (BaP) possesses the greatest carcinogenic potential among the various PAHs. In this study, digital gene expression (DGE) was performed to investigate the digestive gland transcriptome profile of the clam Ruditapes philippinarum exposed to BaP. A total of 10,508,312 and 11,414,297 clean reads were generated respectively, from control and BaP exposure DGE libraries. One hundred and forty-five differentially expressed genes were detected after comparing two libraries with 58 up-regulated and 87 down-regulated genes. GO annotation and KEGG pathway analyses were performed on all genes to understand their biological functions and processes. The results showed that numerous enriched differentially expressed genes are related to growth and development, antioxidant metabolism, apoptosis and detoxification metabolism. Quantitative real-time PCR was performed to verify the expressed genes of DGE. Our results provide evidences that RNA-seq is a powerful tool for toxicology and capable of generating novel and valuable information at the transcriptome level for characterizing deleterious effects caused by BaP. PMID:25686690

  7. Coinhibition of viral interferon induction by benzo(a)pyrene and chrysotile asbestos

    SciTech Connect

    Hahon, N.; Booth, J.A.

    1986-06-01

    Benzo(a)pyrene (B(a)P) and its noncarcinogenic analog, benzo(e)pyrene (B(e)P), each in combination with chrysotile, were studied for their inhibitory effects on interferon (IFN) induction by influenza virus in rhesus monkey kidney (LLC-MK/sub 2/) cell monolayers. B(a)P alone had no adverse effect on IFN induction; however, from 60 to 70% inhibition of IFN production occurred when B(a)P was enzymatically activated by rat liver S9. Chrysotile's inhibitory effect on the IFN process was similar in magnitude to that of activated B(a)P. The combination of activated B(a)P with chrysotile resulted in coinhibition of IFN induction which significantly exceeded the inhibitory activity of the reagents tested alone or in other combinations. B(e)P alone or with S9 neither affected IFN induction nor was it capable of further enhancing chrysotile's inhibition of IFN synthesis. These findings provide further evidence of enhanced deleterious action by the combination of asbestos and activated B(a)P on a biological defense mechanism and further support the discriminatory power and credibility of the inhibition IFN induction assay for evaluating potential carcinogens.

  8. The oxidation of benzo[a]pyrene mediated by lipid peroxidation in irradiated synthetic diets.

    PubMed

    Gower, J D; Wills, E D

    1986-03-01

    The effect of gamma-irradiation (1000-4000 Gy) on the formation of lipid peroxides and on the oxidation of the environmental carcinogen benzo[a]pyrene (BP) has been studied in mixtures of starch/fat and BP which were used as models for natural foods. When mixtures containing polyunsaturated fats (mackerel oil and cod-liver oil which contain relatively large proportions of C20:5 and C22:6) were exposed to gamma-irradiation, large concentrations of lipid peroxide were formed and a concomitant oxidation of BP to mutagenic and toxic BP quinones took place. The rate of BP oxidation was closely related to the extent of peroxidation of the lipids in the starch mixtures and was dependent on the dose of gamma-irradiation and the presence of air. Mackerel oil also underwent peroxidation during the storage of both irradiated and unirradiated starch/mackerel oil/BP mixtures and this resulted in a significant oxidation of the BP present in these samples. Antioxidants such as vitamin E and BHA inhibited both lipid peroxidation and BP oxidation resulting from gamma-irradiation. These results demonstrate that the species generated during the peroxidation of unsaturated fats in foodstuffs can react with polycyclic aromatic hydrocarbons such as BP and convert them into active mutagenic and toxic products. This has important toxicological implications, particularly as the consumption of polyunsaturated fat in the Western world is increasing and gamma-irradiation may soon be widely used for food sterilization. PMID:3485594

  9. Benzo[a]pyrene and Benzo[k]fluoranthene in some processed fish and fish products.

    PubMed

    Olatunji, Olatunde S; Fatoki, Olalekan S; Opeolu, Beatrice O; Ximba, Bhekumusa J

    2015-01-01

    In this study, the concentration levels of the probable carcinogenic PAH fractions, benzo[a]pyrene (BaP) and benzo[k]fluoranthrene (BkF) in fillets of some processed fish species were investigated. Fish species comprising Merluccius poli (hake), Tyrsites atun (snoek), Seriola lalandi (yellow-tail) and Brama brama (angel fish) were bought in fish shops at Gordon's Bay, Western Cape, South Africa. The fish were gutted, filleted and prepared for edibility by frying, grilling and boiling. Polycyclic aromatic hydrocarbons were extracted from each homogenized fish sample, cleaned-up using solid phase extraction (SPE), and analysed for the PAH fractions, BaP and BkF using a Gas Chromatograph coupled with a Flame Ionization Detector (GC-FID). The sum of the two PAHs (∑2PAH) i.e., BaP and BkF ranged between 0.56 and 1.46 µg/kg, in all boiled, grilled and fried fish species. The fried fish extracts showed significantly higher (p < 0.05) abundance of ∑2PAH, than grilled and boiled fish. Dietary safety and PAHs toxicity was also discussed. PMID:25607603

  10. Effect of ageing on benzo[a]pyrene extractability in contrasting soils.

    PubMed

    Duan, Luchun; Naidu, Ravi; Liu, Yanju; Palanisami, Thavamani; Dong, Zhaomin; Mallavarapu, Megharaj; Semple, Kirk T

    2015-10-15

    Changes in benzo[a]pyrene (B[a]P) extractability over 160 days ageing in four contrasting soils varying in organic matter content and clay mineralogy were investigated using dichloromethane: acetone 1:1 (DCM/Ace), 60 mM hydroxypropyl-β-cyclodextrin (HPCD) solution, 1-butanol (BuOH) and Milli-Q water. The B[a]P extractability by the four methods decreased with ageing and a first-order exponential model could be used to describe the kinetics of release. Correlation of the kinetic rate constant with major soil properties showed a significant effect of clay and sand contents and pore volume fraction (<6 nm) on sequestration of the desorbable fraction (by HPCD) and the water-extractable fraction. Analysis of (14)C-B[a]P in soils after ageing showed a limited loss of B[a]P via degradation. Fractionation of B[a]P pools associated with the soil matrix was analysed according to extractability of B[a]P by the different extraction methods. A summary of the different fractions is proposed for the illustration of the effect of ageing on different B[a]P-bound fractions in soils. This study provides a better understanding of the B[a]P ageing process associated with different fractions and also emphasises the extraction capacity of the different methods employed. PMID:25917695

  11. Cell metabolic changes of porphyrins and superoxide anions by anthracene and benzo(a)pyrene.

    PubMed

    Uribe-Hernández, Raúl; Pérez-Zapata, Aura J; Vega-Barrita, María L; Ramón-Gallegos, Eva; Amezcua-Allieri, Myriam A

    2008-09-01

    The aim of this work was to evaluate the induction of protoporphyrins IX (PpIX) activity and superoxide anions (SO) in human leukocytes exposed to anthracene (ANT) and benzo(a)pyrene (B(a)P). The leukocyte LC(50)s for both hydrocarbons and the PpIX accumulation and SO overproduction were measured. The LC(50)s were 0.35 and 3.23μM for ANT and B(a)P, respectively. A linear relationship (r=0.97, p<0.01) between PpIX and ANT concentration was obtained. The induced accumulation of PpIX was proportional (r=0.63, p<0.01) to B(a)P concentration. SO overproduction showed a linear relationship (r=0.83, p<0.05) with ANT concentrations. The linear regression analysis of the effect of B(a)P on the superoxide anion overproduction showed a good coefficient (r=0.97, p<0.01), showed that ANT and B(a)P exposure induces PpIX accumulation, probably by disruption of the haem biosynthesis. ANT and B(a)P induce SO overproduction, perhaps through a process of redox cycling. PMID:21791370

  12. Use of intestinal Pseudomonas aeruginosa in fish to detect the environmental pollutant benzo[a]pyrene.

    PubMed

    Karami, Ali; Christianus, Annie; Ishak, Zamri; Shamsuddin, Zulkifli Hj; Masoumian, Majid; Courtenay, Simon C

    2012-05-15

    This study examined the potential of Pseudomonas aeruginosa abundance in the intestines of fish as an indicator of exposure to benzo[a]pyrene (BaP). P. aeruginosa populations were enumerated in juvenile African catfish (Clarias gariepinus) injected intramuscularly three days previous with 0, 10, 30, 40, 50 or 70mg/kg of BaP. Hepatic EROD and GST activities and biliary fluorescent aromatic compounds (FACs) 1-OH BaP, 3-OH BaP, 7,8-D BaP and BaP were quantified to investigate agreements between the new indicator and established fish biomarkers. The shape of bacterial population (logarithm of colony-forming unit) dose-response curve generally matched those of biliary FACs concentrations. Conversely, the EROD and GST dose-response curves were generally the mirror images of the bacterial population curve. Changes in intestinal P. aeruginosa population appear to be an indirect effect of BaP exposure because exposure to 0-100μg/ml BaP had no effect on P. aeruginosa populations grown on agar plates containing BaP. Using intestinal P. aeruginosa population of fish as a universal indicator of BaP pollution in aquatic environments is discussed.Conversely, the EROD and GST dose-response curves were generally the mirror images of the bacterial population curve. PMID:22417397

  13. Can biomonitors effectively detect airborne benzo[a]pyrene? An evaluation approach using modelling

    NASA Astrophysics Data System (ADS)

    Ratola, Nuno; Jiménez-Guerrero, Pedro

    2016-04-01

    Biomonitoring data available on levels of atmospheric polycyclic aromatic hydrocarbons (PAHs) in pine needles from the Iberian Peninsula were used to estimate air concentrations of benzo[a]pyrene (BaP) and, at the same time, fuelled the comparison with chemistry transport model representations. Simulations with the modelling system WRF+EMEP+CHIMERE were validated against data from the European Monitoring and Evaluation Programme (EMEP) air sampling network. Modelled atmospheric concentrations were used as a consistent reference in order to compare the performance of vegetation-to-air estimating methods. A spatial and temporal resolution of 9 km and 1 h was implemented. The field-based database relied on a pine needles sampling scheme comprising 33 sites in Portugal and 37 sites in Spain complemented with the BaP measurements available from the EMEP sites. The ability of pine needles to act as biomonitoring markers for the atmospheric concentrations of BaP was estimated by converting the levels obtained in pine needles into air concentrations by six different approaches, one of them presenting realistic concentrations when compared to the modelled atmospheric values. The justification for this study is that the gaps still exist in the knowledge of the life cycles of semi-volatile organic compounds (SVOCs), particularly the partition processes between air and vegetation. The strategy followed in this work allows for the effective estimation by the model of concentrations in air and vegetation and of the best approaches to estimate atmospheric levels from values found in vegetation.

  14. Site-specific imaging of elemental steps in dehydration of diols on TiO(2)(110).

    PubMed

    Acharya, Danda P; Yoon, Yeohoon; Li, Zhenjun; Zhang, Zhenrong; Lin, Xiao; Mu, Rentao; Chen, Long; Kay, Bruce D; Rousseau, Roger; Dohnálek, Zdenek

    2013-11-26

    Scanning tunneling microscopy is employed to follow elemental steps in conversion of ethylene glycol and 1,3-propylene glycol on partially reduced TiO2(110) as a function of temperature. Mechanistic details about the observed processes are corroborated by density functional theory calculations. The use of these two diol reactants allows us to compare and contrast the chemistries of two functionally similar molecules with different steric constraints, thereby allowing us to understand how molecular geometry may influence the observed chemical reactivity. We find that both glycols initially adsorb on Ti sites, where a dynamic equilibrium between molecularly bound and deprotonated species is observed. As the diols start to diffuse along the Ti rows above 230 K, they irreversibly dissociate upon encountering bridging oxygen vacancies. Surprisingly, two dissociation pathways, one via O-H and the other via C-O bond scission, are observed. Theoretical calculations suggest that the differences in the C-O/O-H bond breaking processes are the result of steric factors enforced upon the diols by the second Ti-bound OH group. Above ∼400 K, a new stable intermediate centered on the bridging oxygen (Ob) row is observed. Combined experimental and theoretical evidence shows that this intermediate is most likely a new dioxo species. Further annealing leads to sequential C-Ob bond cleavage and alkene desorption above ∼500 K. Simulations demonstrate that the sequential C-Ob bond breaking process follows a homolytic diradical pathway, with the first C-Ob bond breaking event accompanied with a nonadiabatic electron transfer within the TiO2(110) substrate. PMID:24134162

  15. In Vivo Anti-Tumor Activity and Toxicological Evaluations of Perillaldehyde 8,9-Epoxide, a Derivative of Perillyl Alcohol

    PubMed Central

    Andrade, Luciana Nalone; Amaral, Ricardo Guimarães; Dória, Grace Anne Azevedo; Fonseca, Cecília Santos; da Silva, Tayane Kayane Mariano; Albuquerque Júnior, Ricardo Luiz Cavalcante; Thomazzi, Sara Maria; do Nascimento, Lázaro Gomes; Carvalho, Adriana Andrade; de Sousa, Damião Pergentino

    2016-01-01

    Recent studies have revealed the high cytotoxicity of p-menthane derivatives against human tumor cells. In this study, the substance perillaldehyde 8,9-epoxide, a p-menthane class derivative obtained from (S)-(−)-perillyl alcohol, was selected in order to assess antitumor activity against experimental sarcoma 180 tumors. Toxicological effects related to the liver, spleen, kidneys and hematology were evaluated in mice submitted to treatment. The tumor growth inhibition rate was 38.4%, 58.7%, 35.3%, 45.4% and 68.1% at doses of 100 and 200 mg/kg/day for perillaldehyde 8,9-epoxide, perillyl alcohol and 25 mg/kg/day for 5-FU intraperitoneal treatments, respectively. No toxicologically significant effect was found in liver and kidney parameters analyzed in Sarcoma 180-inoculated mice treated with perillaldehyde 8,9-epoxide. Histopathological analyses of the liver, spleen, and kidneys were free from any morphological changes in the organs of the animals treated with perillaldehyde 8,9-epoxide. In conclusion, the data suggest that perillaldehyde 8,9-epoxide possesses significant antitumor activity without systemic toxicity for the tested parameters. By comparison, there was no statistical difference for the antitumor activity between perillaldehyde 8,9-epoxide and perillyl alcohol. PMID:26742032

  16. Synthetic reactions with rare taccalonolides reveal the value of C-22,23 epoxidation for microtubule stabilizing potency.

    PubMed

    Peng, Jiangnan; Risinger, April L; Li, Jing; Mooberry, Susan L

    2014-07-24

    The taccalonolides are microtubule stabilizers isolated from plants of the genus Tacca. Taccalonolide AF is 231 times more potent than the major metabolite taccalonolide A and differs only by the oxidation of the C-22,23 double bond in A to an epoxy group in AF. In the current study, 10 other rare natural taccalonolides were epoxidized and in each case epoxidation improved potency. The epoxidation products of taccalonolide T and AI were the most potent, with IC50 values of 0.43 and 0.88 nM, respectively. These potent taccalonolides retained microtubule stabilizing effects, and T-epoxide demonstrated antitumor effects in a xenograft model of breast cancer. Additional reactions demonstrated that reduction of the C-6 ketone resulted in an inactive taccalonolide and that C-22,23 epoxidation restored its activity. These studies confirm the value of C-22,23 epoxidation as an effective strategy for increasing the potency of a wide range of structurally diverse taccalonolide microtubule stabilizers. PMID:24959756

  17. Repellent activities of stereoisomers of p-menthane-3,8-diols against Anopheles gambiae (Diptera: Culicidae).

    PubMed

    Barasa, Stephen S; Ndiege, Isaiah O; Lwande, Wilber; Hassanali, Ahmed

    2002-09-01

    Four stereoisomers of p-menthane-3,8-diol, which make up the natural product obtained from Eucalyptus citriodora, were synthesized through stereoselective procedures. Repellency assays showed that all the four were equally active against Anopheles gambiae s.s. Racemic blends and the diastereoisomeric mixture of all the four isomers were also equally repellent. 1-alpha-terpeneol, with a single hydroxyl function at C-8 and unsaturation at C-8, and menthol, with a single hydroxyl function at C-3, were not repellent. The practical implication of these results is discussed. PMID:12349856

  18. (Enantio)selective Hydrogen Autotransfer: Ruthenium-Catalyzed Synthesis of Oxazolidin-2-ones from Urea and Diols.

    PubMed

    Peña-López, Miguel; Neumann, Helfried; Beller, Matthias

    2016-06-27

    A novel strategy for the synthesis of oxazolidin-2-ones from vicinal diols and urea is described. In this heterocycle synthesis, two different C-O and C-N bonds are sequentially formed in a domino process consisting of nucleophilic substitution and alcohol amination. The use of readily available starting materials and the good atom economy render this process environmentally benign. While this transformation is already highly chemo- and regioselective, we also developed the first asymmetric version of this method using (R)-(+)-MeO-BIPHEP as the chiral ligand. PMID:27072612

  19. New example of spontaneous resolution among aryl glycerol ethers: 3-(2,6-dichlorophenoxy)propane-1,2-diol

    NASA Astrophysics Data System (ADS)

    Bredikhina, Zemfira A.; Kurenkov, Alexey V.; Zakharychev, Dmitry V.; Krivolapov, Dmitry B.; Bredikhin, Alexander A.

    2016-08-01

    Using a set of simple tests, based on the properties of ideal conglomerate phase diagrams, it has been suggested to the conglomerate-formative nature of 3-(2,6-dichlorophenoxy)-propane-1,2-diol 1. Additional arguments have been drawn during the study of a single crystal X-ray diffraction study of the compound. The crystal packing details have been evaluated and discussed. Racemic 1 have been resolved into individual (S)- and (R)-components by a preferential crystallization procedure.

  20. The six-membered ring chair conformation of butane-1,3-diol in the gas phase

    NASA Astrophysics Data System (ADS)

    Caminati, Walther; Corbelli, Giorgio

    1982-02-01

    Only one conformer of butane-1,3-diol is detectable by conventional microwave spectroscopy. Analysis of the CH 2OHCH 2CHOHMe and CH 2ODCH 2CHODMe isotopic species has allowed the determination of this conformation as a hydrogen-chelated six-membered ring in a distorted chair configuration. The hydrogen atom in position 1 is the proton donor; the methyl group is trans to the C 1-C 2 bond and the hydroxyl hydrogen in position 3 is trans to the C 2-C 3 bond.

  1. Asymmetric Iridium-Catalyzed C-C Coupling of Chiral Diols via Site-Selective Redox-Triggered Carbonyl Addition.

    PubMed

    Shin, Inji; Krische, Michael J

    2016-01-01

    Cyclometalated π-allyliridium C,O-benzoate complexes modified by axially chiral chelating phosphine ligands display a pronounced kinetic preference for primary alcohol dehydrogenation, enabling highly site-selective redox-triggered carbonyl additions of chiral primary-secondary 1,3-diols with exceptional levels of catalyst-directed diastereoselectivity. Unlike conventional methods for carbonyl allylation, the present redox-triggered alcohol C-H functionalizations bypass the use of protecting groups, premetalated reagents, and discrete alcohol-to-aldehyde redox reactions. PMID:26187028

  2. Photoinduced electron transfer and fluorescence mechanisms in covalently linked polynuclear aromatic-nucleotide complexes

    SciTech Connect

    Geacintov, N.E.; Mao, Bing; Zhao, Rushen; Chen, Junxin; Liu, Tong Ming; Ya, Nai-Qi; France, L.L.; Sutherland, J.D.

    1992-04-01

    The fluorescence of polycyclic aromatic hydrocarbon-nucleic acid complexes is quenched by photoinduced electron transfer mechanisms in aqueous solutions at ambient temperatures. These effects are illustrated with the biologically important compound benzo[a]pyrene-7,8-diol-9,10-epoxide (BPDE), a mutagenic and carcinogenic metabolite of the environmental pollutant benzo[a]pyrene, which forms covalent mutagenic lesions with 2{prime}-deoxyguanosine (dG) residues in DNA. The dependence of the fluroescence yeild and fluorescence decay times of the covalent model adduct (+)-trans-BPDE-N{sup 2}-dG as a function of temperature and methanol/water composition are described. Because of the sensitivity of the fluorescence of the pyrenyl residue to the polarity of the microenvironment, the magnitude of the fluorescence yield can be used to distinguish between highly hydrophobic (e.g. intercalation) and other more solvent-exposed BPDE-nucleic acid binding sites.

  3. Photoinduced electron transfer and fluorescence mechanisms in covalently linked polynuclear aromatic-nucleotide complexes

    SciTech Connect

    Geacintov, N.E.; Mao, Bing; Zhao, Rushen; Chen, Junxin; Liu, Tong Ming; Ya, Nai-Qi . Dept. of Chemistry); France, L.L.; Sutherland, J.D. )

    1992-01-01

    The fluorescence of polycyclic aromatic hydrocarbon-nucleic acid complexes is quenched by photoinduced electron transfer mechanisms in aqueous solutions at ambient temperatures. These effects are illustrated with the biologically important compound benzo(a)pyrene-7,8-diol-9,10-epoxide (BPDE), a mutagenic and carcinogenic metabolite of the environmental pollutant benzo(a)pyrene, which forms covalent mutagenic lesions with 2{prime}-deoxyguanosine (dG) residues in DNA. The dependence of the fluroescence yeild and fluorescence decay times of the covalent model adduct (+)-trans-BPDE-N{sup 2}-dG as a function of temperature and methanol/water composition are described. Because of the sensitivity of the fluorescence of the pyrenyl residue to the polarity of the microenvironment, the magnitude of the fluorescence yield can be used to distinguish between highly hydrophobic (e.g. intercalation) and other more solvent-exposed BPDE-nucleic acid binding sites.

  4. From epoxidized linseed oil to bioresin: an overall approach of epoxy/anhydride cross-linking.

    PubMed

    Pin, Jean-Mathieu; Sbirrazzuoli, Nicolas; Mija, Alice

    2015-04-13

    Biorenewable resources can be used as green monomers to design tailored structures for formulations that can play an important role as functional materials. The choice of optimal structures depends on the targeted properties and applications. This work focuses on the elaboration of biobased materials with toughened mechanical properties based on epoxidized linseed oil. This result was obtained by an overall approach of cross-linking process, that is, starting with the optimal choice of hardeners and finally favoring the side reactions of polymerization. Therefore, the anionic alternating copolymerization of epoxide with mono- and dianhydrides was investigated to tailor the parameters that led to maximal conversions and properties. The obtained highly cross-linked networks perform well, as demonstrated by good impact strengths, high glass transition temperatures, and excellent thermal stability, which opens up the possibility of using these emergent materials for industrial applications. PMID:25754910

  5. Controlling Catalytic Selectivity via Adsorbate Orientation on the Surface: From Furfural Deoxygenation to Reactions of Epoxides.

    PubMed

    Pang, Simon H; Medlin, J Will

    2015-04-16

    Specificity to desired reaction products is the key challenge in designing solid catalysts for reactions involving addition or removal of oxygen to/from organic reactants. This challenge is especially acute for reactions involving multifunctional compounds such as biomass-derived aromatic molecules (e.g., furfural) and functional epoxides (e.g., 1-epoxy-3-butene). Recent surface-level studies have shown that there is a relationship between adsorbate surface orientation and reaction selectivity in the hydrogenation pathways of aromatic oxygenates and the ring-opening or ring-closing pathways of epoxides. Control of the orientation of reaction intermediates on catalytic surfaces by modifying the surface or near-surface environment has been shown to be a promising method of affecting catalytic selectivity for reactions of multifunctional molecules. In this Perspective, we review recent model studies aimed at understanding the surface chemistry for these reactions and studies that utilize this insight to rationally design supported catalysts. PMID:26263134

  6. Synthesis, characterization and catalytic activities towards epoxidation of olefins of dinuclear copper(II) complexes

    NASA Astrophysics Data System (ADS)

    Halder, Shibashis; Mukherjee, Aparajita; Ghosh, Koushik; Dey, Sudipto; Nandi, Mahasweta; Roy, Partha

    2015-12-01

    Two copper(II) complexes, [Cu2(L1)Cl3].2H2O (1) and [Cu2(L2)(N3)Cl2] (2) where HL1 = 4-methyl-2,6-bis((2-morpholinoethylimino)methyl)phenol and HL2 = 4-methyl-2,6-bis((3-morpholinopropylimino)methyl)phenol have been synthesized and characterized by elemental analysis, various spectroscopic methods, TGA and single crystal X-ray diffraction analysis. Single crystal X-ray diffraction analysis reveals that in both the complexes, two copper atoms are linked by phenoxo oxygen atom and a bridging ligand, namely chloride and azide, respectively. These complexes have been used as catalyst for the epoxidation of cyclohexene, styrene, α-methyl styrene, trans-stilbene and norbornene using tert-butyl hydroperoxide as the oxidant in acetonitrile under mild conditions. All of the substrates undergo conversion to produce respective epoxide as the major product.

  7. Block Copolymerization of Lactide and an Epoxide Facilitated by a Redox Switchable Iron-Based Catalyst.

    PubMed

    Biernesser, Ashley B; Delle Chiaie, Kayla R; Curley, Julia B; Byers, Jeffery A

    2016-04-18

    A cationic iron(III) complex was active for the polymerization of various epoxides, whereas the analogous neutral iron(II) complex was inactive. Cyclohexene oxide polymerization could be "switched off" upon in situ reduction of the iron(III) catalyst and "switched on" upon in situ oxidation, which is orthogonal to what was observed previously for lactide polymerization. Conducting copolymerization reactions in the presence of both monomers resulted in block copolymers whose identity can be controlled by the oxidation state of the catalyst: selective lactide polymerization was observed in the iron(II) oxidation state and selective epoxide polymerization was observed in the iron(III) oxidation state. Evidence for the formation of block copolymers was obtained from solubility differences, GPC, and DOSY-NMR studies. PMID:26991820

  8. Conglomerate formative precursor of chiral drug timolol: 3-(4-Morpholino-1,2,5-thiadiazol-3-yloxy)-propane-1,2-diol

    NASA Astrophysics Data System (ADS)

    Bredikhin, Alexander A.; Zakharychev, Dmitry V.; Fayzullin, Robert R.; Bredikhina, Zemfira A.; Gubaidullin, Aidar T.

    2015-05-01

    Solid state properties of 3-(4-N-morpholino-1,2,5-thiadiazol-3-yloxy)-propane-1,2-diol 3, the synthetic precursor of popular drug timolol, have been investigated. The original solubility test, the data of X-ray diffraction and DSC methods indicate that the compound is prone to spontaneous resolution. Diol 3 crystallizing from both enantiopure or racemic feed material forms "guaifenesin-like" crystal packing in which the classic H-bonded bilayers, framed in both sides by hydrophobic molecular fragments, act as the basic supramolecular motif. The main chain conformation of the molecules in the crystals of diol 3 differs from that in the guaifenesin crystals, and this fact changes the absolute configuration of spiral columns formed by intermolecular hydrogen bonds in crystals of 3 as compared with guaifenesin crystals.

  9. Direct Epoxidation of Propylene over Stabilized Cu+ Surface Sites on Ti Modified Cu2O

    SciTech Connect

    Yang, X.; Kattel, S.; Xiong, K.; Mudiyanselage, K.; Rykov, S.; Senanayake, S. D.; Rodriguez, J. A.; Liu, P.; Stacchiola, D. J.; Chen, J. G.

    2015-07-17

    Direct propylene epoxidation by O2 is a challenging reaction because of the strong tendency for complete combustion. Results from the current study demonstrate the feasibility to tune the epoxidation selectivity by generating highly dispersed and stabilized Cu+ active sites in a TiCuOx mixed oxide. The TiCuOx surface anchors the key surface intermediate, oxametallacycle, leading to higher selectivity for epoxidation of propylene.

  10. Potent antimalarial 1,2,4-trioxanes through perhydrolysis of epoxides.

    PubMed

    Hao, Hong-Dong; Wittlin, Sergio; Wu, Yikang

    2013-06-01

    Perhydrolysis of a sterically congested multifunctional epoxide was achieved in ethereal H2O2 with the aid of a recently developed Mo catalyst. The resulting hydroperoxide cyclized to give a 1,2,4-trioxane, which could be readily elaborated into qinghaosu and a range of novel analogues. Some of the compounds with two such trioxane moieties showed in vitro antimalarial activity comparable to or even better than that of artesunate or chloroquine. PMID:23576327

  11. Monolithic Nickel (II) Oxide Aerogels Using an Organic Epoxide: The Importance of the Counter Ion

    SciTech Connect

    Gash, A E; Satcher, J H; Simpson, R L

    2004-01-13

    The synthesis and characterization of nickel (II) oxide aerogel materials prepared using the epoxide addition method is described. The addition of the organic epoxide propylene oxide to an ethanolic solution of NiCl{sub 2} 6H{sub 2}O resulted in the formation of an opaque light green monolithic gel and subsequent drying with supercritical CO{sub 2} gave a monolithic aerogel material of the same color. This material has been characterized using powder X-ray diffraction, electron microscopy, elemental analysis, and nitrogen adsorption/desorption analysis. The results indicate that the nickel (II) oxide aerogel has very low bulk density (98 kg/m{sup 3} ({approx}98 %porous)), high surface area (413 m{sup 2}/g), and has a particulate-type aerogel microstructure made up of very fine spherical particles with an open porous network. By comparison, a precipitate of Ni{sub 3}(NO{sub 3}){sub 2}(OH){sub 4} is obtained when the same preparation is attempted with the common Ni(NO{sub 3}){sub 2} 6H{sub 2}O salt as the precursor. The implications of the difference of reactivity of the two different precursors are discussed in the context of the mechanism of gel formation via the epoxide addition method. The synthesis of nickel (II) oxide aerogel, using the epoxide addition method, is especially unique in our experience. It is our first example of the successful preparation of a metal oxide aerogel using a metal divalent metal ion and may have implications for the application of this method to the preparation of aerogels or nanoparticles of other divalent metal oxides. To our knowledge this is the first report of a monolithic pure nickel (II) oxide aerogel materials.

  12. A stable epoxide as a potential endogenous estrogen metabolite: Possible significance in breast cancer?

    PubMed

    Raeside, James I

    2016-06-01

    Epoxides as reactive intermediates of estrogen metabolism have been considered to be potential precursors of the 2- and 4-hydroxy, catechol estrogens and even to be mutagenic/carcinogenic agents themselves. The labile nature of the intermediates has made proof of their existence difficult in natural biological conditions. In our studies on estrogen metabolism in vitro, in various tissues from several laboratory and domestic species, there was chromatographic evidence of formation of a stable estrogen metabolite that could be seen after incubation with radiolabeled estrone, but not with unlabeled substrate. Investigation with acid treatment of the metabolite yielded material detected as 6-hydroxy-estrone-suggesting the presence of an additional oxygen atom in the molecule. An identification of the "unknown compound" has not yet been made but, with this evidence, the properties revealed so far can best be met by assuming the presence of 5,6-epoxy-estrone. The recent favorable reports on the role of 5α,6α-epoxy-cholesterol in breast cancer has led to the hypothesis that the formation of a similar, stable epoxide of an estrogen could potentially be a compound of interest. If a metabolic pathway from estrone to 6-hydroxy-estrone through a stable epoxide has indeed been observed, it would suggest that identifying and screening for the enzymes responsible for its production, as opposed to those generating the catecholestrogens, could provide valuable information in relation to breast cancer. The balance in production of estrogen epoxides could be a key factor in determining normal health or risk of tumor development. PMID:27142140

  13. A non-canonical caleosin from Arabidopsis efficiently epoxidizes physiological unsaturated fatty acids with complete stereoselectivity.

    PubMed

    Blée, Elizabeth; Flenet, Martine; Boachon, Benoît; Fauconnier, Marie-Laure

    2012-10-01

    In plants, epoxygenated fatty acids (EFAs) are constituents of oil seeds as well as defence molecules and components of biopolymers (cutin, suberin). While the pleiotropic biological activities of mammalian EFAs have been well documented, there is a paucity of information on the physiological relevance of plant EFAs and their biosynthesis. Potential candidates for EFA formation are caleosin-type peroxygenases which catalyze the epoxidation of unsaturated fatty acids in the presence of hydroperoxides as co-oxidants. However, the caleosins characterized so far, which are mostly localized in seeds, are poor epoxidases. In sharp contrast, quantitative RT-PCR analysis revealed that PXG4, a class II caleosin gene, is expressed in roots, stems, leaves and flowers of Arabidopsis. Expressed in yeast, PXG4 encodes a calcium-dependent membrane-associated hemoprotein able to catalyze typical peroxygenase reactions. Moreover, we show here that purified recombinant PXG4 is an efficient fatty acid epoxygenase, catalyzing the oxidation of cis double bonds of unsaturated fatty acids. Physiological linoleic and linolenic acids proved to be the preferred substrates for PXG4; they are oxidized into the different positional isomers of the monoepoxides and into diepoxides. An important regioselectivity was observed; the C-12,13 double bond of these unsaturated fatty acids being the least favored unsaturation epoxidized by PXG4, linolenic acid preferentially yielded the 9,10-15,16-diepoxide. Remarkably, PXG4 catalyzes exclusively the formation of (R),(S)-epoxide enantiomers, which is the absolute stereochemistry of the epoxides found in planta. These findings pave the way for the study of the functional role of EFAs and caleosins in plants. PMID:22913587

  14. The stability of the three transmembrane and the four transmembrane human vitamin K epoxide reductase models

    NASA Astrophysics Data System (ADS)

    Wu, Sangwook

    2016-04-01

    The three transmembrane and the four transmembrane helix models are suggested for human vitamin K epoxide reductase (VKOR). In this study, we investigate the stability of the human three transmembrane/four transmembrane VKOR models by employing a coarse-grained normal mode analysis and molecular dynamics simulation. Based on the analysis of the mobility of each transmembrane domain, we suggest that the three transmembrane human VKOR model is more stable than the four transmembrane human VKOR model.

  15. Imidazolinium salts as catalysts for the ring-opening alkylation of meso epoxides by alkylaluminum complexes.

    PubMed

    Zhou, H; Campbell, E J; Nguyen, S T

    2001-07-12

    [reaction: see text] Imidazolinium salts and their N-heterocyclic carbene (NHC) derivatives catalyze the alkylation of a variety of meso epoxides in the presence of triethylaluminum (yield = 70-90%), under mild conditions. Imidazolinium salts are better catalysts than their NHC derivatives but can lead to dimerization side reactions under extended reaction time. Preformed NHC.AlEt(3) complexes and Wanzlick-type olefins, which are dimers of free NHCs, are also catalysts for this reaction. PMID:11440586

  16. Mechanistic study of secondary organic aerosol components formed from nucleophilic addition reactions of methacrylic acid epoxide

    NASA Astrophysics Data System (ADS)

    Birdsall, A. W.; Miner, C. R.; Mael, L. E.; Elrod, M. J.

    2014-08-01

    Recently, methacrylic acid epoxide (MAE) has been proposed as a precursor to an important class of isoprene-derived compounds found in secondary organic aerosol (SOA): 2-methylglyceric acid (2-MG) and a set of oligomers, nitric acid esters and sulfuric acid esters related to 2-MG. However, the specific chemical mechanisms by which MAE could form these compounds have not been previously studied. In order to determine the relevance of these processes to atmospheric aerosol, MAE and 2-MG have been synthesized and a series of bulk solution-phase experiments aimed at studying the reactivity of MAE using nuclear magnetic resonance (NMR) spectroscopy have been performed. The present results indicate that the acid-catalyzed MAE reaction is more than 600 times slower than a similar reaction of an important isoprene-derived epoxide, but is still expected to be kinetically feasible in the atmosphere on more acidic SOA. The specific mechanism by which MAE leads to oligomers was identified, and the reactions of MAE with a number of atmospherically relevant nucleophiles were also investigated. Because the nucleophilic strengths of water, sulfate, alcohols (including 2-MG), and acids (including MAE and 2-MG) in their reactions with MAE were found to be of a similar magnitude, it is expected that a diverse variety of MAE + nucleophile product species may be formed on ambient SOA. Thus, the results indicate that epoxide chain reaction oligomerization will be limited by the presence of high concentrations of non-epoxide nucleophiles (such as water); this finding is consistent with previous environmental chamber investigations of the relative humidity-dependence of 2-MG-derived oligomerization processes and suggests that extensive oligomerization may not be likely on ambient SOA because of other competitive MAE reaction mechanisms.

  17. Mechanistic study of secondary organic aerosol components formed from nucleophilic addition reactions of methacrylic acid epoxide

    NASA Astrophysics Data System (ADS)

    Birdsall, A. W.; Miner, C. R.; Mael, L. E.; Elrod, M. J.

    2014-12-01

    Recently, methacrylic acid epoxide (MAE) has been proposed as a precursor to an important class of isoprene-derived compounds found in secondary organic aerosol (SOA): 2-methylglyceric acid (2-MG) and a set of oligomers, nitric acid esters, and sulfuric acid esters related to 2-MG. However, the specific chemical mechanisms by which MAE could form these compounds have not been previously studied with experimental methods. In order to determine the relevance of these processes to atmospheric aerosol, MAE and 2-MG have been synthesized and a series of bulk solution-phase experiments aimed at studying the reactivity of MAE using nuclear magnetic resonance (NMR) spectroscopy have been performed. The present results indicate that the acid-catalyzed MAE reaction is more than 600 times slower than a similar reaction of an important isoprene-derived epoxide, but is still expected to be kinetically feasible in the atmosphere on more acidic SOA. The specific mechanism by which MAE leads to oligomers was identified, and the reactions of MAE with a number of atmospherically relevant nucleophiles were also investigated. Because the nucleophilic strengths of water, sulfate, alcohols (including 2-MG), and acids (including MAE and 2-MG) in their reactions with MAE were found to be of similar magnitudes, it is expected that a diverse variety of MAE + nucleophile product species may be formed on ambient SOA. Thus, the results indicate that epoxide chain reaction oligomerization will be limited by the presence of high concentrations of non-epoxide nucleophiles (such as water); this finding is consistent with previous environmental chamber investigations of the relative humidity dependence of 2-MG-derived oligomerization processes and suggests that extensive oligomerization may not be likely on ambient SOA because of other competitive MAE reaction mechanisms.

  18. Lysophosphatidic acids are new substrates for the phosphatase domain of soluble epoxide hydrolase[S

    PubMed Central

    Oguro, Ami; Imaoka, Susumu

    2012-01-01

    Soluble epoxide hydrolase (sEH) is a bifunctional enzyme that has a C-terminus epoxide hydrolase domain and an N-terminus phosphatase domain. The endogenous substrates of epoxide hydrolase are known to be epoxyeicosatrienoic acids, but the endogenous substrates of the phosphatase activity are not well understood. In this study, to explore the substrates of sEH, we investigated the inhibition of the phosphatase activity of sEH toward 4-methylumbelliferyl phosphate by using lecithin and its hydrolyzed products. Although lecithin itself did not inhibit the phosphatase activity, the hydrolyzed lecithin significantly inhibited it, suggesting that lysophospholipid or fatty acid can inhibit it. Next, we investigated the inhibition of phosphatase activity by lysophosphatidyl choline, palmitoyl lysophosphatidic acid, monopalmitoyl glycerol, and palmitic acid. Palmitoyl lysophosphatidic acid and fatty acid efficiently inhibited phosphatase activity, suggesting that lysophosphatidic acids (LPAs) are substrates for the phosphatase activity of sEH. As expected, palmitoyl, stearoyl, oleoyl, and arachidonoyl LPAs were efficiently dephosphorylated by sEH (Km, 3–7 μM; Vmax, 150–193 nmol/min/mg). These results suggest that LPAs are substrates of sEH, which may regulate physiological functions of cells via their metabolism. PMID:22217705

  19. Persistence and changes in bioavailability of dieldrin, DDE and heptachlor epoxide in earthworms over 45 years

    USGS Publications Warehouse

    Beyer, W. Nelson; Gale, Robert W.

    2013-01-01

    The finding of dieldrin (88 ng/g), DDE (52 ng/g), and heptachlor epoxide (19 ng/g) in earthworms from experimental plots after a single moderate application (9 kg/ha) 45 years earlier attests to the remarkable persistence of these compounds in soil and their continued uptake by soil organisms. Half-lives (with 95 % confidence intervals) in earthworms, estimated from exponential decay equations, were as follows: dieldrin 4.9 (4.3-5.7) years, DDE 5.3 (4.7-6.1) years, and heptachlor epoxide 4.3 (3.8-4.9) years. These half-lives were not significantly different from those estimated after 20 years. Concentration factors (dry weight earthworm tissue/dry weight soil) were initially high and decreased mainly during the first 11 years after application. By the end of the study, average concentration factors were 1.5 (dieldrin), 4.0 (DDE), and 1.8 (heptachlor epoxide), respectively.

  20. Novel bio-based thermoset resins based on epoxidized vegetable oils for structural adhesives

    NASA Astrophysics Data System (ADS)

    Sivasubramanian, Shivshankar

    Conventional engineered wood composites are bonded for the most part through formaldehyde-based structural adhesives such as urea formaldehyde (UF), melamine formaldehyde (MF), phenol formaldehyde (PF) and resorcinol formaldehyde (RF). Formaldehyde is a known human carcinogen; the occupational exposure and emission after manufacturing of these binders is raising more and more concern. With increasing emphasis on environmental issues, there is clear incentive to replace these hazardous conventional formaldehyde-based binders with cco-friendly resins having similar properties but derived from renewable sources, bearing in mind the economics of the structural wood composite industry. In this thesis, the curing reaction of bio-derived epoxy thermosets with inexpensive, low-toxicity precursors, including polyimines and amino acids was investigated. Epoxidized linseed oil (ELO) and epoxidized soybean oil (ESO) were successfully crosslinked with both branched polyethyleneimine (PEI) and triethylenetetramine (fETA). Epoxidized castor oil (ECO) was crosslinked with polyethyleneimine (PEI), having different molecular weights. Curing conditions were optimized through solvent uptake and soluble fraction analysis. Finally, the mechanical properties of the optimized compositions of rigid bioepoxies were evaluated using dynamic mechanical rheological testing (DMRT). While not as stiff as conventional materials, optimized materials have sufficient room temperature moduli to show promise for coatings and as binders in engineered wood products.