Über die katalysierte Flüssigphasenoxidation von cis- und trans-Oct-4-en

The Catalyzed Liquid-Phase Oxidation of cis- and trans-Oct-4-ene The influences of MoO₂(acac)₂

1 acac-Acetylacetonat.

, MoO ₃ and Co(acac) ₃ on the liquid-phase oxidation of cis- and trans-oct-4-ene at 110°C were studied. In the presence of molybdenum catalysts the yield of epoxides and the stereoselectivity of epoxide formation are increased. The results are in good agreement with the hypothesis that molybdenum compounds effect only the stereospecific reaction of the hydroperoxides formed with the starting olefin yielding the corresponding epoxide. The cobaltic complex increases the rate of autoxidation, but has no remarkable influence on the yield of epoxides. In the presence of Co(acac)₃ more trans-epoxide is formed from cis-oct-4-ene than in the uncatalyzed reaction. This can be explained by an increase of the lifetime of the intermediate peroxyalkyl radical, effected by complex formation of the radical with a cobalt species.     

Hydrolysis of glycerophosphocholine epoxides by human group IIA,V, and X secretory phospholipases A2

This study was prompted by recent reports that epoxyeicosatrienoic (EET) and epoxyeicosatetraenoic (EEQ) acids accelerate tumor growth and metastasis by stimulation of angiogenesis, while eicosapentaenoic (EPA) and epoxydocosapentaenoic (EDP) acids inhibit angiogenesis, tumor growth, and metastasis. Cytochrome P450 epoxygenases convert arachidonic to EET, eicosapentaenoic acid to EEQ, and docosahexaenoic acid to EDP, which are found both in free form and esterified to glycerophosphocholine (GPC). Both free and esterified epoxy (EP) acids are also formed during lipid autoxidation. For biological activity, the GPC-EP requires hydrolysis, which we presumed could occur by sPLA₂s located in proximity of lipoproteins carrying the lipid epoxides. The plasma lipoproteins were isolated by ultracentrifugation and analyzed by LC/ESI-MS. The GPC-EPs were identified by reference to standards and to retention times of phospholipid masses. The GPC-EP monoepoxides (corrected for isobaric ether overlaps) in stored human LDL, HDL, HDL₃, or APHDL ranged from 0 to 1 nmol/mg protein, but during 4-h incubation at 37°C increased to 1–5 nmol/mg protein. An incubation of autoxidized LDL, HDL, or HDL₃ with 1 μg/ml of group V or X sPLA₂ resulted in complete hydrolysis of diacyl GPC epoxide esters. Group IIA sPLA₂ at 1 μg/ml failed to produce significant hydrolysis in 4 h, but at 2.5 μg/ml in 8 h yielded almost 80% hydrolysis, which represented complete diacyl GPC-EP hydrolysis. The present study shows that group IIA, V, and X sPLA₂s are capable of extensive hydrolysis of PtdCho epoxides of autoxidized plasma lipoproteins. Therefore, all three human sPLA₂s were potentially capable of inducing epoxide biological activity in vivo.     

Über die katalysierte Flüssigphasenoxidation normalkettiger Alk-1-ene

The Catalyzed Liquid-Phase Oxidation of Normal Alk-1-enes The efficiencies of various homogeneous soluble transition metal compounds to increase epoxide yields in the autoxidation of alk-1-enes were studied. Combinations of typical autoxidation and typical epoxidation catalysts were also used. It was proved through balance experiments, that in no case yields of 50% or more of the corresponding epoxides were obtained. The simple mechanism (epoxidation via allylic hydroperoxides) assumed only insufficiently reflects the reaction course.     

Electron-impact mass spectrometry for location of epoxide position in long chainvic-dialkyl and trialkyl epoxides

Plots of percent abundance vs m/e for selected series of ions (differing by 14 mass units) obtained by low resolution mass spectrometry allowed the epoxide position to be located in 30 C₁₇−C₂₁vic-dialkyl and trialkyl epoxides. Major diagnostic fragmentations are as follows. In thevic-dialkyl epoxides of the study, fragments useful for determining epoxide position result from α-cleavage, and epoxide position may be recognized by the maxima obtained in a plot of percent abundance vs m/e values in the C_nH_2n−1O series (113, 127, 141 ….); a similar plot of percent abundances vs m/e values in the C_nH_2n−2 series (110, 124, 138 ….) also shows maxima for ions corresponding to those obtained by transannular cleavage plus water elimination. In the trialkyl epoxides, fragments most useful for locating epoxide position are those obtained from ions corresponding to α-cleavage plus H-transfer; epoxide position may, thus, be recognized by the maxima obtained in a plot of percent abundance vs m/e values in the C_nH_2nO series (72, 86, 100 ….). Transannular cleavage with H-transfer produces C_nH_2n+1O products (m/e 115, 129, 143….), with the fragment containing the methyl substituent being much more abundant.     

Metabolism of epoxidized phosphatidylcholine by phospholipase A2 and epoxide hydrolase

The isolation and measurement of phospholipid epoxides as major peroxidation products in biomembrane preparations prompted an investigation of enzymatic mechanisms which may be responsible for their elimination. Analysis of microsomal epoxide hydrolase and phospholipase A₂ activity against a phospholipid epoxide commonly encountered in tissues indicated it to be a poor substrate for epoxide hydrolase, but rapidly hydrolyzed by phospholipase A₂. Microsomal and purified phospholipase A₂ preparations hydrolyzed the phospholipid epoxide at rates 2-fold greater than were observed with a monoenoic phospholipid from which the epoxide would be derived. The product fatty acid epoxide,cis-9,10-epoxystearic acid, was rapidly hydrated by microsomal and cytosolic epoxide hydrolase. On the basis of earlier reports demonstrating increased phospholipase activity against oxidized phospholipids, and on the results of the present study, a model for the metabolism of oxidized membrane phospholipids is proposed.     

Acute Hypercapnia/Ischemia Alters the Esterification of Arachidonic Acid and Docosahexaenoic Acid Epoxide Metabolites in Rat Brain Neutral Lipids

In the brain, approximately 90% of oxylipins are esterified to lipids. However, the significance of this esterification process is not known. In the present study, we (1) validated an aminopropyl solid phase extraction (SPE) method for separating esterified lipids using 100 and 500 mg columns and (2) applied the method to quantify the distribution of esterified oxylipins within phospholipids (PL) and neutral lipids (NL) (i.e. triacylglycerol and cholesteryl ester) in rats subjected to head-focused microwave fixation (controls) or CO₂-induced hypercapnia/ischemia. We hypothesized that oxylipin esterification into these lipid pools will be altered following CO₂-induced hypercapnia/ischemia. Lipids were extracted from control (n = 8) and CO₂-asphyxiated (n = 8) rat brains and separated on aminopropyl cartridges to yield PL and NL. The separated lipid fractions were hydrolyzed, purified with hydrophobic–lipophilic–balanced SPE columns, and analyzed with ultra-high-pressure liquid chromatography coupled to tandem mass spectrometry. Method validation showed that the 500 mg (vs 100 mg) aminopropyl columns yielded acceptable separation and recovery of esterified fatty acid epoxides but not other oxylipins. Two epoxides of arachidonic acid (ARA) were significantly increased, and three epoxides of docosahexaenoic acid (DHA) were significantly decreased in brain NL of CO₂-asphyxiated rats compared to controls subjected to head-focused microwave fixation. PL-bound fatty acid epoxides were highly variable and did not differ significantly between the groups. This study demonstrates that hypercapnia/ischemia alters the concentration of ARA and DHA epoxides within NL, reflecting an active turnover process regulating brain fatty acid epoxide concentrations.     

The Consequences of Soluble Epoxide Hydrolase Deletion on Tumorigenesis and Metastasis in a Mouse Model of Breast Cancer

Epoxides and diols of polyunsaturated fatty acids (PUFAs) are bioactive and can influence processes such as tumor cell proliferation and angiogenesis. Studies with inhibitors of the soluble epoxide hydrolase (sEH) in animals overexpressing cytochrome P450 enzymes or following the systemic administration of specific epoxides revealed a markedly increased incidence of tumor metastases. To determine whether PUFA epoxides increased metastases in a model of spontaneous breast cancer, sEH^-/- mice were crossed onto the polyoma middle T oncogene (PyMT) background. We found that the deletion of the sEH accelerated the growth of primary tumors and increased both the tumor macrophage count and angiogenesis. There were small differences in the epoxide/diol content of tumors, particularly in epoxyoctadecamonoenic acid versus dihydroxyoctadecenoic acid, and marked changes in the expression of proteins linked with cell proliferation and metabolism. However, there was no consequence of sEH inhibition on the formation of metastases in the lymph node or lung. Taken together, our results confirm previous reports of increased tumor growth in animals lacking sEH but fail to substantiate reports of enhanced lymph node or pulmonary metastases.     

Alkoxysilane oligomer modified epoxide primers

Telechelic resins with reactive end groups (epoxy phosphate and epoxy ester) were synthesized using bisphenol-A (BPA) epoxide. The bisphenol-A based epoxide, the epoxy phosphate, and the epoxy ester were all modified with tetraethylorthosilicate (TEOS) oligomers, which were prepared through the hydrolysis and condensation of TEOS monomer with water under acidic condition. The epoxide/polysilicate (organic/inorganic) hybrid systems were characterized systematically, using FTIR, ¹H, ¹³C, ³¹P, and ²⁹Si NMR, and MALDI-TOF. The modified epoxides were thermally cured with a melamine-formaldehyde resin, cast on steel substrates. The coating performance of the modified epoxides was evaluated by pencil hardness, crosshatch adhesion, reverse and direct impact resistance, mandrel bending, and pull-off adhesion. Viscoelastic properties of the hybrid systems were also evaluated as a function of polysilicate content. Corrosion performance was evaluated via salt spray (fog) test for 264 h. Salt spray analysis revealed that inorganically modified epoxides provided improvement over the unmodified epoxide resins with respect to both corrosion resistance and adhesion to steel substrates.     

Repeatability of Pheromone Blend Composition in Individual Males of the Southern Green Stink Bug, Nezara viridula

The males of Nezara viridula (Heteroptera, Pentatomidae) produce a blend of four terpenoid compounds. The proportion of these four compounds varies among different populations. The terpenoid content of the volatile emission from individual males of a French population was monitored for several days with headspace solid-phase microextraction. The total amount of terpenoid compounds collected on an SPME fiber from one virgin male bug emitting over the course of 1 hr was very variable between samples. More than 50% of males released pheromone, at least during one part of the observation period. The relative percentages of bisabolene, nerolidol, trans-bisabolene epoxide, and cis-bisabolene epoxide were calculated and compared. The proportion of nerolidol in the blend showed a large dispersion between samples and a high coefficient of variation. The percentage values for bisabolene and its trans and cis epoxides were less dispersed, and the coefficients of variation for both epoxides were low. The proportion of trans epoxide relative to the two epoxides, which has been considered characteristic of pheromone strains of N. viridula, showed the smallest coefficient of variation. The repeatability index (RI) varied between 0.57 and 0.85 for the four compounds. Repeatability was particularly high for the two epoxide isomers. Stability in epoxide production was confirmed by statistical analysis (ANOVA), which revealed significant differences in the percentages of cis and trans epoxides between individuals. Correspondingly, the RI of the ratio of trans to cis + trans epoxides was over 0.8. Our study confirms the existence of an interindividual variation of the trans to cis epoxide ratio within populations of Nezara viridula but indicates that each individual reproducibly emits both isomers in the same proportion day after day.     

The analysis of 1,2-epoxyalkanes by gas liquid chromatography

Terminal epoxides react quantitatively with methanol in the presence of boron trifluoride to give both primary and secondary hydroxy methyl ethers. These derivatives are useful in the analysis of terminal epoxide mixtures by gas liquid chromatography. This procedure is compared with the conventional method and with a procedure in which the 1,2-epoxyalkanes are reduced to the corresponding secondary alcohols with LiAlH₄. A statistical analysis of experimental data obtained from known mixtures of long chain epoxides is described. Results of this analysis demonstrate the improved accuracy and precision of the method as compared to the other methods investigated. LiAlH₄ reduction is the preferred method of analysis for the more reactive epoxides as well as for the cyclic epoxides. This procedure is particularly useful in the analysis of epoxides containing a tertiary carbon atom. The application of this technique to other epoxides is expected to improve their analysis, but further work is necessary. Presented at the AOCS Meeting, Minneapolis, October 1969.     

Thermodynamic Properties of the Arene Epoxides and the Relative Carcinogenicities of Benzo[a]pyrene and Benzo[e]pyrene

Abstract

The thermodynamic stabilities of all possible arene oxides of benzo[a]pyrene and benzo[e]pyrene, and of the two parent compounds, have been obtained using semiempirical AM1 and molecular mechanics calculations. The calculations predict that all K-region epoxides are highly stabilized compared to other epoxides for both PAHs. The terminal ring epoxides include proximal and distal types, either close to or remote from the bay-region, respectively. The distal epoxides correspond to the necessary first intermediates in the enzymatic activation process leading to the ultimate bay-region dihydrodiol epoxide carcinogens. There are marked differences in the calculated heats of formation of the distal benzo[a]pyrene-7,8-epoxide and benzo[e]pyrene-9,10-epoxide (compared to either the respective parent PAHs or the K-region epoxides) favoring the epoxide from benzo[a]pyrene. One can propose that these thermodynamic differences may be a principal factor responsible for facile initiation of the activating metabolic pathway mediating the carcinogenicity of benzo[a]pyrene, and the blocking of the corresponding mechanism in benzo[e]pyrene.     

Detection of Polynuclear Aromatic Hydrocarbon Diol Epoxide-Derived DNA and Globin Adducts in Humans by Gas Chromatography-Mass Spectrometry

Gas chromatography-negative ion chemical ionization-mass spectrometry-selected ion monitoring (GC-NICI-MS-SIM) was employed to detect tetramethyl ether derivatives of tetraols released upon hydrolysis of DNA and globin adducts derived from diol epoxides of polynuclear aromatic hydrocarbons (PAH). The methodology involves the following steps: 1) isolation of DNA or globin; 2) mild acid hydrolysis under vacuum; 3) isolation of the resulting tetraols and derivatization to the corresponding tetramethyl ethers using CH₃I; 4) HPLC purification followed by GC-NICI-MS-SIM analysis. Analysis of human globin samples by this method indicates the presence of adducts which release chrysene-1,2,3,4-tetraol and benzo[a]pyrene-7,8,9,10-tetraol in smokers and nonsmokers. The level of BP-diol epoxide globin adducts in smokers was significantly higher than that in nonsmokers (2.75 vs 0.96 fmol/mg globin). The concentration of chrysene diol-epoxide globin adducts in the same subjects was about two orders of magnitude greater than that of BP-diol epoxide adducts. BP-diol epoxide DNA adducts have also been identified in surgical specimens of human lung tissue.     

Biocatalytic Potential of the Epoxide Hydrolase from Agrobacterium radiobacter AD1 and a Mutant with Enhanced Enantioselectivity

Optically pure epoxides are useful synthons for a variety of biologically active compounds. The epoxide hydrolase obtained from Agrobacterium radiobacter AD1 hydrolyses racemic aryl epoxides with moderate and aliphatic epoxides with low enantioselectivity. The three‐dimensional structure of this enzyme indicates that two tyrosine residues interact with the epoxide oxygen. Mutating one of these, tyrosine 215, to a phenylalanine (Y215F) resulted in an enzyme with increased enantioselectivity towards aryl epoxides. The relatively strong decrease in activity towards the remaining enantiomers makes this enzyme a much better biocatalyst than the wild‐type enzyme for the preparation of optically pure (S)‐styrene oxide derivatives.     

A surfactant-like ionic liquid with permanganate dissolved as a highly selective epoxidation system

A ligand-free catalytic epoxidation system using permanganate in a surfactant-like ionic liquid (IL) medium was developed. The results indicate that the IL takes crucial effects in the epoxide selectivity. The loading of permanganate is also found critical in preventing over-oxidation of epoxides. The system with 0.3 mol% permanganate and 3.5-equivalent CH₃CO₃H is able to achieve excellent yields and selectivity of epoxides. The study of epoxidation with KMnO₄ in IL medium reveals an unusual oxidation behavior of permanganate not found in traditional solvents.     

Chemical structure and dynamic mechanical behavior of silk fibers modified with different kinds of epoxides

The chemical reactivity of epoxide molecules toward silk fibroin was investigated by determining the rate of conversion of reactive amino acid residues. Significant differences were found between two different bifunctional epoxides, diglycidyl ethers of ethylene glycol (E) and resorcinol (R), the former reacting at a higher extent with arginine and tyrosine. The moisture regain decreased by reaction with epoxides, at a variable rate and extent, according to the hydrophobic/hydrophilic properties of epoxides. A two-step behavior was observed when moisture regain values relating to the silk content in modified silk, fibers were plotted as a function of the weight gain. Dynamic mechanical data showed that the major loss peak became broader and its temperature shifted to lower values following the increase of weight gain. The loss peak temperatures showed a linear relationship with the amount of weight gain. The fine structural changes induced by reaction with eposides will be discussed in terms of chemical and steric factors of the epoxides, as well as of epoxide location within the different structural domains of silk fibers. © 1994 John Wiley & Sons, Inc.     

Influence of vitamin E and nitrogen dioxide on lipid peroxidation in rat lung and liver microsomes

Rat lung and liver microsomes were used to examine the effects of dietary vitamin E deficiency on membrane lipid peroxidation. Microsomes from vitamin-E-deficient rats displayed increased lipid peroxidation in comparison to microsomes from vitamin-E-supplemented controls. The extent of lipid peroxidation, as determined by measurement of thiobarbituric acid reacting materials, was enhanced by addition of reduced iron and ascorbate (or NADPH). Rats fed a vitamin-E-supplemented diet and exposed to 3 ppm NO₂ for 7 days did not exhibit increases in microsomal lipid peroxidation compared to air-breathing controls. However, increases were found in microsomes prepared from rats fed a vitamin-E-deficient diet and exposed to NO₂. Lung microsomes from vitamin-E-fed rats contained almost 10 times as much vitamin E as liver microsomes when expressed in terms of polyunsaturated fatty acid content. The extent of lipid peroxidation was, in turn, considerably less in lung than in liver microsomes. Lipid peroxidation in lung microsomes from vitamin-E-deficient rats was comparable to liver microsomes from vitamin-E-supplemented rats as was the content of vitamin E in these respective microsomal samples. A combination of vitamin E deficiency and NO₂ exposure resulted in the greatest increases in lung and liver microsomal lipid peroxidation with the largest relative increases occurring in lung microsomes. An inverse relationship was found between the extent of lipid peroxidation and vitamin E content. Most of the peroxidation in lung microsomes appeared to proceed nonenzymatically whereas peroxidation in liver was largely enzymatic. Vitamin E appears to be assimilated by the lung during oxidant inhalation, but with dietary vitamin E deprivation, the margin for protection in lung may be less than in liver.     

1H-NMR Characterization of Epoxides Derived from Polyunsaturated Fatty Acids

In recent years, ¹H NMR has been used to study epoxides in lipid oxidation and industrial processes, but the peak assignments reported for monoepoxides and diepoxides have been inconsistent. Lack of clear assignments for chemical shifts of epoxides derived from polyunsaturated fatty acids (PUFA) has also limited the use of ¹H NMR in detecting and quantifying these products during both oxidative degradation and industrial epoxidation. In this study, ¹H NMR was used to characterize the epoxides synthesized from trilinolein, trilinolenin, canola oil, and fish oils by reaction with formic acid and hydrogen peroxide. Assignments for epoxides derived from PUFA in canola oil and fish oil were between 2.90–3.23 ppm and 2.90–3.28 ppm, distinct from other chemical groups in these oils. Chemical shifts of epoxy groups moved downfield with an increasing number of epoxy groups in the fatty acid chain. Hence, peaks for diepoxides appeared at 3.00, 3.09, and 3.14 ppm and for triepoxides at 3.00, 3.16, and 3.21 ppm. Results also suggested that stereoisomers of diepoxides and triepoxides were formed during the epoxidation process under the conditions of this study. These new assignments for di‐ and tri‐epoxide stereoisomers were supported by GC–MS analysis of their methyl esters, H–H COSY experiments, and a re‐evaluation of several previous epoxide‐related studies.     

Adaptive relationships of epoxide hydrolase in herbivorous arthropods

Epoxide hydrolase catalyzes a simple hydrolysis of reactive cyclic ethers that may otherwise alkylate and impair critical proteins and nucleic acids required for life. Although much less studied than the cytochrome P-450 monooxygenases that produce epoxides, differences in subcellular, tissue, pH, substrate, and inhibitor specificities argue for at least three forms of insect epoxide hydrolase. Increasing numbers of epoxides are being identified as plant allelochemicals, antifeedants, and essential hormones or precursors for herbivorous arthropods, and in many cases an associated alkene to diol pathway of metabolism is found. A role for epoxide hydrolase in arthropod-plant interactions is strongly supported by species comparisons and by age-activity and induction studies. Two major limitations for study in biochemical ecology of epoxide hydrolase are the lack of an effective in vivo inhibitor and a range of commercially available radiolabeled substrates for the enzymes.     

Autoxidation of fatty acid monolayers adsorbed on silica gel: II. Rates and products

Unsaturated fatty acid monolayers on silica gel have been autoxidized, and the rate of fatty acid disappearance and products obtained from those membrane-like assemblies have been studied Fatty acid monolayers consisting of pure linoleic acid, linolelaidic acid, and oleic acid were autoxidized at 60 C. The rates of autoxidation of linoleic acid and linolelaidic acid monolayers followed by the disappearance of substrates are considerably faster than that in bulk phase, and the rates conform to apparent first order kinetics. Autoxidation of linoleic and linolelaidic acid monolayers, unlike bulk phase, produced only a small amount of diene conjugation, and the major products formed were identified as 9,10-epoxy and 12,13-epoxyoctadecenoic acid in roughly equal quantities. The epoxidation is stereospecific, withcis andtrans olefins givingcis andtrans epoxides, respectively. Oleic acid was autoxidized to only a small extent during 27 hr and produced no detectable amount of epoxide.     

Preparation and cured properties of novel cycloaliphatic epoxy resins

Preparation and characterization of novel cycloaliphatic epoxy resins, which are derived from octadienyl compounds, were studied. From a model peracetic acid epoxidation reaction using 2,7-octadienyl acetate-1, the structure of the liquid resins is estimated to be mainly terminal epoxides and some amount of inner epoxide depending on the epoxide content. The epoxy resins offer lower toxicity and lower vapor pressure. The reactivity of the resin with acid anhydrides is moderate but faster than that of traditional cyclohexane epoxide-type resins and slower than that of the glycidyl ester-type resins. This reactivity was also examined using model compounds. The heat deflection temperature of the hexahydro-phthalic anhydride-cured resins is shown to be directly proportional to the number of epoxy groups in the molecules. The flexural strength of the cured resins is nearly equivalent to that of the commercial resins, although the flexural elongation of the resins is larger than that of the rigid cyclohexane epoxide-type resins. The thermal stability of the cured resins is comparable to typical rigid cycloaliphatic resins; furthermore, high water resistance of the cured resins is suggested to be attributed to the hydrophobic character of the C₈ chain by cross-linking. © 1993 John Wiley & Sons, Inc.