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2-(2-Chloroethoxy)ethanol (CEE) belongs to the so-called cohort of concerns which were classified as highly potent mutagenic carcinogens by the World Health Organization. It is widely used in the synthesis of the essential anti-histamine drug hydroxyzine. In addition, it is used as a primary solvent in dyes, nitrocellulose, paints, inks and resins. Owing to its potential genotoxicity, an efficient liquid chromatography-tandem mass spectrometry method was developed for the quantitative estimation of CEE traces in an active pharmaceutical ingredients and in tablet dosage forms of hydroxyzine-free base. The chromatographic separation was achieved on a C

Anhydrous alkali sulfide (M2S, M = Li and Na) nanocrystals (NCs) are important materials central to the development of next generation cathodes and solid state electrolytes for advanced batteries, but not commercially available at present. This work reports an innovative method to directly synthesize M2S-NCs through alcohol-mediated reactions between alkali metals and hydrogen sulfide (H2S). In the first step, the alkali metal is complexed with alcohol in solution, forming metal alkoxide (ROM) and releasing hydrogen (H2). Next, H2S is bubbled through the ROM solution, where both chemicals are completely consumed to produce phase-pure M2S-NC precipitates and regenerate alcohol that can be recycled. The M2S-NC morphology may be tuned through choice of the alcohol and the solvent. Both synthetic steps are thermodynamically favorable (∆Gmo M2S + H2, makes good use of a hazardous chemical H2S and delivers two value-added products that naturally phase separate for easy recovery. This scalable approach provides an energy-efficient and environmentally-benign solution to the production of nanostructured materials required in emerging battery technologies.

In cancer bioassays, inhalation, but not drinking water exposure to ethyl tertiary‐butyl ether (ETBE), caused liver tumors in male rats, while tertiary‐butyl alcohol (TBA), an ETBE metabolite, caused kidney tumors in male rats following exposure via drinking water. To understand the contribution of ETBE and TBA kinetics under varying exposure scenarios to these tumor responses, a physiologically based pharmacokinetic model was developed based on a previously published model for methyl tertiary‐butyl ether, a structurally similar chemical, and verified against the literature and study report data. The model included ETBE and TBA binding to the male rat‐specific protein α2u–globulin, which plays a role in the ETBE and TBA kidney response observed in male rats. Metabolism of ETBE and TBA was described as a single, saturable pathway in the liver. The model predicted similar kidney AUC0–∞ for TBA for various exposure scenarios from ETBE and TBA cancer bioassays, supporting a male‐rat‐specific mode of action for TBA‐induced kidney tumors. The model also predicted nonlinear kinetics at ETBE inhalation exposure concentrations above ~2000 ppm, based on blood AUC0–∞ for ETBE and TBA. The shift from linear to nonlinear kinetics at exposure concentrations below the concentration associated with liver tumors in rats (5000 ppm) suggests the mode of action for liver tumors operates under nonlinear kinetics following chronic exposure and is not relevant for assessing human risk. Copyright © 2016 The Authors Journal of Applied Toxicology Published by John Wiley & Sons Ltd, Inhalation, but not drinking‐water exposure, to a high concentration of ethyl tertiary butyl ether was reported to cause liver tumors in male rats. Using a PBPK model for ethyl tertiary butyl ether and its metabolite tertiary butyl alcohol, under cancer bioassay exposure scenarios, showed a shift from linear to nonlinear kinetics at the exposure concentration associated with liver tumors. This suggests that a liver tumor mode of action that occurs under a high exposure concentration is not relevant for assessing human risk.

Several new energetic ethyl ethers of 1,2,4,5-tetrazine have been synthesized. These molecules display good thermal stability, good oxygen balance, and high densities. Included in these studies are a 2,2,2-trinitroethoxy 1,2,4,5-tetrazine and two fluorodinitroethoxy 1,2,4,5-tetrazines. One of these compounds was converted into the di-N-oxide derivative. The sensitivity of these materials towards destructive stimuli was determined, and overall the materials show promising energetic performance properties.

As one of the most important biomass platform molecules, ethanol needs to have its product chain chemically extended to meet future demands in renewable fuels and chemicals. Additionally, chemical conversion of ethanol under mild and green conditions is still a major challenge. In this work, ethanol is directly converted into 1,1-diethoxyethane (DEE) and H2 under mild photocatalytic conditions over platinum-loaded TiO2 nanotubes and nanorods. The reaction follows a tandem dehydrogenation-acetalization mechanism, in which ethanol is first dehydrogenated into acetaldehyde and H(+) ion by photogenerated holes, and then acetalization between acetaldehyde and ethanol proceeds through promotion by H(+) ions formed in real time. Excess H(+) ions are simultaneously reduced into H2 by photogenerated electrons. This photocatalytic process has a very high reaction rate over nanosized tubular and rod-like TiO2 photocatalysts, reaching 157.7 mmol g(-1) h(-1) in relatively low photocatalyst feeding. More importantly, the reaction is highly selective, with a nearly stoichiometric conversion of reacted ethanol into DEE. This photocatalytic dehydrogenation CO coupling of ethanol is a new green approach to the direct efficient conversion of ethanol into DEE and provides a promising channel for sustainable bioethanol applications.

The development of new protecting groups that undergo neighbouring group participation (NGP) via six-membered ring intermediates to promote the formation of α-1,2-cis glycosidic linkages complements the established use of 5-ring NGP in terms of stereochemical outcome. A selection of glycosyl donors was synthesised that possessed novel 2-iodo- and 2-(phenylseleno)ethyl ether protecting groups in an attempt to promote highly α-selective glycosylation by 6-ring NGP. Although the fully armed donors produced α-glucosides as the predominant reaction products, low-temperature NMR studies did not show NGP by the observation of cyclised reaction intermediates. The corresponding disarmed glycosyl donors were unexpectedly less stereoselective. NMR spectroscopy revealed that the 2-iodoethyl ether did not participate in any of the glycosylation processes; however, the 2-(phenylseleno)ethyl ether did participate, and β-configured cyclic intermediates were observed. The fact that considerable amounts of β-glycoside product were formed in these latter cases indicated that the predominant reaction pathway to product did not occur through the observed cyclic species. Clearly, a fine balance exists during glycosylation reactions, and the reaction pathway to product depends on a variety of factors. Notably, the formation of cyclised intermediates by 6-ring NGP is not on its own sufficient to ensure high levels of α-stereoselectivity.

Many dose–response studies collect data on correlated outcomes. For example, in developmental toxicity studies, uterine weight and presence of malformed pups are measured on the same dam. Joint modeling can result in more efficient inferences than independent models for each outcome. Most methods for joint modeling assume standard parametric response distributions. However, in toxicity studies, it is possible that response distributions vary in location and shape with dose, which may not be easily captured by standard models. To address this issue, we propose a semiparametric Bayesian joint model for a binary and continuous response. In our model, a kernel stick-breaking process prior is assigned to the distribution of a random effect shared across outcomes, which allows flexible changes in distribution shape with dose shared across outcomes. The model also includes outcome-specific fixed effects to allow different location effects. In simulation studies, we found that the proposed model provides accurate estimates of toxicological risk when the data do not satisfy assumptions of standard parametric models. We apply our method to data from a developmental toxicity study of ethylene glycol diethyl ether. Copyright © 2013 John Wiley & Sons, Ltd.

The carbon-oxygen stretching vibration in a series of substituted benzhydrols and their 2-(dimethylamino)ethyl ethers was found to be affected by the inductive and mesomeric effects of the substituents.

Following our previous reports on the spectroscopy and photochemistry of methyl and ethyl ethers of simple acyclic and non-strained cyclic α-oxo oximes, we have now studied 4-(methoxyimino)-2,2,3,3-tetramethylcyclobutanone (1), of which the ring is severely strained, 3,5,5-trimethyl-4(5H)-isoxazolone (8), of which the (Z)-oxime function is constrained in a five-membered ring, and 6-(benzyloxyimino)-2,2,5,5-tetramethylcyclohexanone (10), which is a benzyl ether. Upon irradiation of (E)-1 with λ 254 nm, the main process is photodissociation, leading to the same type of products as obtained with the six-membered ring homologue 3, but in addition to 2,2,3,3-tetramethyl-4-oxobutanenitrile (13) and 2,2,3,3-tetramethylcyclopropanone O-methyloxime (21). The triplet-sensitized irradiation of (E)-l, in contrast to that of the higher homologues, leads, in addition to E-Z isomerization, to photodissociation, yielding the same photoproducts as obtained after direct irradiation with 254 nm. The 4-isoxazolone 8 is photostable against radiation of 350 and 300 nm. Irradiation of 8 with λ. 254 nm leads to population of the excited singlet ππ* state and subsequent photodecomposition as a result of inital N-O homolysis, the observed products being carbon monoxide, acetonitrile, acetone and small amounts of ethanol. The occurrence of the photodecomposition is in agreement with the theoretical prediction' that the excited singlet ππ* (Z)-α-oxo oxime ethers would give N-O homolysis, provided that the other route of deactivation via Z-E isomerization, which has a much lower energy barrier on the potential energy surface, cannot take place. The photochemistry of the benzyl ether (Z)-10, of which the intercarbonyl-iminyl dihedral angle is approx. 45° and the π systems of the phenyl and the C = N-O moieties are perpendicular to one another, with λ 350, 300 and 254 nm is different from that of the corresponding methyl ether 36 in two ways. Firstly, on using λ 350 and 300 nm decomposition was observed which is, however, slow relative to the Z-E isomerization and, secondly, the photodecomposition products are of a different nature, since the assigned primary and secondary product from 10 are benzaldehyde and 6-(benzoylamino)-2,2,5,5-tetramethylcyclohexanone (32), respectively. Mechanisms have been presented to explain the formation of the photoproducts obtained from 1, 8 and 10.

The A antigen in Marek's Disease Virus infected cell cultures was found to be stable at 37° C or lower for long periods, to be rapidly inactivated at temperatures at 75° C to 100° C, unaffected by ether or chloroform, tolerate pH 1.7 for 4 1/2 hours, but is inactivated by pH 12.1 in 4 1/2 hours. Trypsin inactivates the antigen activity in 40–60 minutes at 37° C and it remains in the supernatant after centrifugation at 100,000 × G for 120 minutes. A antigen preparations were found inhibitory to the replication of MDV in cell cultures and to VSV plaque formation in CK cultures, but not in L cells. The possibility that the A antigen is an interferon -associated protein is discussed.

The response of lymph nodes and skin to repeated topical application of oxazolone was investigated histologically in mice. The initial paracortical response in the nodes was followed by a prolonged germinal centre reaction and the development of numerous plasma cells. The epidermis which initially showed an acute inflammatory reaction with erosion, healed despite repeated painting.

Hepatocytes were isolated from livers of fasted rats by a two–step Ca++–free/collagenase perfusion method. Suspensions of parenchymal liver cells were incubated in the absence and presence of three different anaesthetics, diethyl ether, pentobarbital and fentanyl at various concentrations. Their influence on the hepatocytes was monitored by measuring protein synthesis as the incorporation of L–(U–14C) valine (50 mCi/ mol, 4.2 mM) into liver proteins. Diethyl ether representing anaesthetics mainly affecting cellular membranes unspecifically, inhibited protein synthesis markedly, concentrations of approximately 10, 20 and 30 mM caused 27, 50 and 74 per cent inhibition respectively, of cellular protein synthesis. The rate of synthesis of medium proteins was somewhat more reduced indicating a greater susceptibility of the synthetic process of these proteins or that ether also inhibited protein secretion from cells to media. The effect of diethyl ether was completely reversible when the anaesthetic was removed by changing the medium. Pentobarbital representing barbiturate anaesthetics, reduced the synthesis of cell and medium proteins very little, while the opiate anaesthetic fentanyl had no inhibitory effect. These results demonstrate a potential hepatotoxic mechanism for membrane active drugs like diethyl ether. They also indicate that special precautions should be taken when this type of anaesthesia is used during the study of hepatic protein synthesis

An inhalation exposure of male rats to 300 p.p.m. of a commercial turpentine 6 hrs daily 5 days a week for 8 weeks enhanced the activities of drug biotransformation enzymes of liver microsomes considerably. The activities of NADPH cytochrome c reductase and 7-ethoxycoumarin deethylase, and microsomal content of cytochrome P-450 were increased 35-60% during the first weeks of the experiment, but had a tendency to return towards the control values later on. A similar enhancement of activities was also found in liver microsomal epoxide hydratase and UDP glucuronosyltransferase, but these enzyme activities tended to adapt less during the experiment. The turpentine treatment increased the affinity of liver microsomal cytochrome P-450 to alpha-pinene (the main component of the turpentine). The present data suggests that exposure to turpentine is able to modify considerably the biotransformation of drugs.

Pathways for formation of previously observed autoxidation products of ethoxylated surfactants have been studied by DFT (B3LYP). In addition to the established radical-chain reaction, several mechanistic possibilities for intramolecular fragmentation of the intermediate radicals have been characterized concerning reaction barriers and energies of transition states. The results can rationalize the formation of previously observed autoxidation products, including several, which have been implicated as strongly allergenic.

Ethylene glycol, its dimethyl ether, and some related compounds have been studied using the MM4 molecular mechanics force field. The MM4 calculated structural and energetic results have been brought into satisfactory agreement with a considerable number of experimental data and MP2/6-311++G(2d,2p) ab initio calculations. The heats of formation of these compounds are also well calculated. The MM4 ethylene glycol conformations in particular are in good agreement, both geometrically and in terms of energy, with those from the ab initio calculations. The corresponding dimethyl ether is of special interest, because it has been suggested that the trans-gauche conformation is unusually stable due to the hydrogen bonding of a hydrogen on a methyl group with the more distant oxygen. It is shown in the present work that while this conformation is more stable than might have been expected, the energy is adequately calculated by MM4 without using any hydrogen bonding between the CH bond and the oxygen. If such hydrogen bonding occurs, it amounts to no more than about 0.5 kcal/mol in energy, and is too small to detect with certainty. Additionally, energetic relationships in trans-1,2-dimethoxycyclohexane, 1,3,5,7-tetraoxadecalin, and 3-methoxytetrahydropyran have been studied, and the calculated results are compared with experimental information, which is adequately reproduced. © 2003 Wiley Periodicals, Inc. J Comput Chem 24: 1490–1503, 2003

A series of ethers of 7,8-cyclopenta-fused analogs of the orvinols related to buprenorphine were prepared and evaluated in opioid-binding and functional assays. Comparison of the ethyl ethers 4b and 5b with the parent alcohols 4a and 5a, respectively, in both the (5′R) (=5′β) and (5′S) (=5′α) series, shows that the 20-OH group in the orvinols (corresponding to 5′-OH of 4 and 5) is not crucial for opioid activity, although in the [35S]GTPγS assay, the 5′β-ethyl ether 4b had 80-fold greater κ-agonist potency than its epimer 5b. Increasing the size of the 5′β-OR group has a major effect on μ-agonist efficacy and potency, a more modest effect on δ-efficacy, and no effect on κ-activity. These data show that μ- and δ-agonist efficacy is favoured by lipophilic binding in the area occupied by the tBu in the lowest-energy conformation of buprenorphine, and that κ-agonist binding may involve interaction with an H-bond-donor group in that region.

Novel types of mitochondrial respiration inhibitors at complex I, with emphasis on acaricidal activity, have been designed and prepared. The synthetic approach to these 4-pyrimidinylphenyl ethyl ethers and amines with a specific ketal or oxime function in the phenyl side chain is outlined. Bioassays demonstrate their high potential against important spider mites, like Tetranychus urticae and Panonychus ulmi. Structure-activity relationship studies and several biological parameters are discussed.

In an extension of previous work, tricyclo[4.1.0.02,7]heptan-3-ol (5) was synthesised in four steps from benzvalene. Methanesulfonates 12 and 6b, c, prepared from 5 and 4-halotricyclo[4.1.0.02,7]hept-4-en-3-ols 4b, c, were too unstable to be isolated, but were unambiguously characterised by their NMR spectra. On treatment of the unsubstituted tricycloheptenol 4a with methanesulfonyl chloride, the expected mesylate 6a could not be observed. Even at −40°C, only its consecutive products 3-chlorotricyclo[4.1.0.02,7]hept-4-en (7a) and 7-chloronorbornadiene (8a) were discernible. The analogous reaction of 6b occurred only at room temperature, with formation of the dichlorotricycloheptene 7b and the dichloronorbornadiene 8b. Rearrangement products of 6b and 12 were the chloronorbornadiene mesylate 10b and anti-7-norbornenyl mesylate (13), respectively. – The solvolysis of 6b, c in aqueous ethanol and of 6b in 2,2,2-trifluoroethanol (TFE) gave nonrearranged products exclusively, i.e. the alcohols 4b, c, the ethyl ethers 17b, c, and the trifluoroethyl ether 18b. In contrast, from 12 only rearranged products arose, namely anti-7-norbornenol (30) and its ethyl ether 31. The solvolysis of the unsubstituted tricycloheptenyl p-nitrobenzoate 11a in 80% aqueous ethanol proceeded about equally fast in parallel reactions with cycloalkyl-oxygen and acyl-oxygen cleavage. In addition to the tricycloheptenol 4a, the tricycloheptenyl ethyl ether 17a, ethyl 7-norbornadienyl ether (19), 7-norbornadienyl p-nitrobenzoate (20), and ethyl p-nitrobenzoate were formed. No acyl-oxygen cleavage took place in TFE as solvent, where the tricycloheptenyl trifluoroethyl ether 18a, 20, 7-norbornadienyl trifluoroethyl ether (21), and the cyclopentadienylvinyl trifluoroethyl ethers 22/23 were produced. A new mechanism is proposed for the route to the major products 22/23 via the intermediate 7-norbornadienyl cation (9a), which was attacked by TFE at the two-membered bridge stabilising the positive charge. Thus formed, tricyclo-[3.2.0.02,7]hept-3-en-endo-6-yl trifluoroethyl ether (24) underwent a Diels-Alder cycloreversion generating the cyclopentadienylvinyl trifluoroethyl ether 25, the immediate precursor of 22/23. – From kinetic data for these processes and thermochemical data for appropriate hydrocarbons, the enthalpy difference between the C7H7 cations, tricyclo-[4.1.0.02,7]hept-4-en-3-yl (3a) and 7-norbornadienyl (9a), was calculated to be only 8 kcal mol−1.

An oxovanadium compound obtained from VO(OEt)Cl2 and AgOTf or MesSiOTf efficiently induced dehydrogenative aromatization of α,β-unsaturated cyclohexenones to give aryl ethyl ethers in good yields.

Tetraetboxysilane was treated with alkyl- and aryllithium reagents for the preparation of organosilyl ethyl ethers of the type R 3 SiOEt, R 2 R′SiOEt, and R 2 Si(OEt) 2 , that can be reduced to the organosilanes R 3 SiH, R 2 R′SiH, and R 2 SiH 2 , respectively. Compounds of the type RR′R′SiOEt cannot be cleanly formed. The reduction procedure involves treatment of the silyl alkoxy ethers with diisobutylaluminium hydride (DIBALH) and hydrolysis of the remaining alkylaluminium compounds with Na 2 SO 4 ·10H 2 O. This hydrolysis provides a convenient method for the isolation of R 3 SiH, R 2 R′SiH, and R 2 SiH 2 compounds without hydrolysis of the SiH moiety that often occurs in standard aqueous work-up procedures of unhindered silanes.

An excellent candidate as a proton substitute in man-made organic reactions is certainly a Lewis acid. Our goal is to engineer an artificial proton substitute of a special shape, which could be utilized as an effective artificial enzyme for chemical reactions, by harnessing the high reactivity of the aluminum atom toward oxygen. Such a concept was initially researched by examining the recognition ability of a specially designed organoaluminum receptors for various oxygen-containing substrates. Our initial finding on the successful discrimination between structurally very similar methyl and ethyl ethers with exceptionally bulky methylaluminum bis (2, 6-di-tert-butyl-4-methylphenoxide) (MAD) as a highly efficient Lewis acidic receptor induced us to study the more intricate question of diastereoface differentiation for the chiral ether and carbonyl oxygens. Thus, based on our conceptually new diastereoselective activation of ether and carbonyl moieties, exceptionally bulky organoaluminum reagents, MABR and MAPH have been devised in addition to MAD. These organoaluminum receptors can be successfully utilized for various regio- and stereocontrolled organic transformations. Furthermore, electronical stabilization of aldehyde functionalities has been accomplished with MAPH by the two parallel phenyl groups of aluminum ligands.

Deprotonated 1-(benzotriazol-1-yl)propargyl ethyl ethers react with propargyl, allyl and alkyl bromides to give the expected substituted derivatives 2, 4 and 9, respectively. Subsequent eliminations of the benzotriazolyl group upon treatment with NaH or ZnBr2, and elaboration of the acetylene group, generate ethoxy substituted enediynes 3, 6, 8, dienynes 7 and enynes 12. Grignard reagents or LiAlH4 convert 9 into α-ethoxy substituted alkynes 10 and 11.

Enediynyl ethyl ethers 14/17 were synthesized by using the Pd(PPh3)4-catalyzed cross-coupling reactions between enynyl iodides 13/16 and (2-ethoxyethynyl)zinc chloride. Thermolysis of these enediynyl ethyl ethers in refluxing chlorobenzene (132 °C) promoted a retro-ene reaction to produce enyne−ketenes, which underwent the Moore cyclization reactions to form the biradicals having a phenyl radical center and a phenoxy radical center. The presence of two radical centers in the same molecule simultaneously provided many opportunities for intramolecular decay through disproportionation, radical−radical combination, and the formation of o-quinone methide.

A new general route to conjugated enynyl ketones was developed based on a two-step procedure. First, palladium-catalyzed cross-coupling reactions of 1-(benzotriazol-1-yl)propargyl ethyl ether (3) and vinyl triflates or vinyl bromides afforded the key intermediates [1-(benzotriazol-1-yl)-1-enynyl]methyl ethyl ethers 5a-d in good yields. Then reactions of compounds 5 with primary halides gave intermediates 8, which were hydrolyzed by dilute acid to enynyl ketones 9a-g. Similar palladium-catalyzed coupling reactions of 3 with various aryl iodides followed by an analogous sequence afforded aryl-substituted propargyl ethers 12a-d and thence alkynyl ketones 13a,b.

Rats were injected with the pyrrolizidine alkaloids heliotrine, indicine, or anacrotine, and killed after 20 hr. Alkaloid metabolites conjugated to haemoglobin thiol groups were recovered in the form of pyrrolic monoethyl ethers, by treating blood samples with ethanolic silver nitrate under "buffered" conditions. Chemically prepared putative toxic metabolites of the alkaloids--dehydroheliotrine, dehydroindicine, and dehydroanacrotine--were also allowed to react in vitro with blood and with an immobilized thiol, thiol-Sepharose, and subsequently the S-conjugated pyrroles were again recovered as ethyl ethers. The recovered pyrrolic ethers were identified by comparing them with reference compounds prepared from ethanol and the dehydro-alkaloids, and the structures of the S-bound pyrroles were deduced. Blood from rats given the 9-monoester alkaloids heliotrine or indicine contained pyrrolic residues, S-bound at their 9-position. Anacrotine-treated rats yielded two diastereomeric 7-ethers, showing that dehydrocrotanecine 7-conjugates had been present in the blood. The products from alkaloid-treated rats were identical with those from blood or thiol-Sepharose treated with the corresponding dehydro-alkaloids in vitro. This supported the view that proximal metabolites leading to S-binding in vivo were the dehydro-derivatives of the alkaloids. In each case the thiols were attacked by the most reactive centre of the dehydro-alkaloid: the 9-ester in dehydroheliotrine and dehydroindicine, and the 7-ester in dehydroanacrotine. Accordingly, simple chemical reactions could account for the products formed in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)

Salicylic acid derivatives were prepared by Me3SiOTf-catalyzed [3 + 3] cyclization of 1,3-bis(silyl enol ethers) with 1,1,3,3-tetramethoxypropane.

Nine bacterial strains isolated from two hydrocarbon-contaminated soils were selected because of their capacity for growth in culture media amended with 200 mg/L of one of the following gasoline oxygenates: Methyl-tert-butyl ether (MTBE), ethyl-tert-butyl ether (ETBE), and tert-amyl methyl ether (TAME). These strains were identified by amplification of their 16S rRNA gene, using fDl and rD1 primers, and were tested for their capacity to grow and biotransform these oxygenates in both mineral and cometabolic media. The isolates were classified as Bacillus simplex, Bacillus drentensis, Arthrobacter sp., Acinetobacter calcoaceticus, Acinetobacter sp., Gordonia amicalis (two strains), Nocardioides sp., and Rhodococcus ruber. Arthrobacter sp. (strain MG) and A. calcoaceticus (strain M10) consumed 100 (cometabolic medium) and 82 mg/L (mineral medium) of oxygenate TAME in 21 d, respectively, under aerobic conditions. Rhodococcus ruber (strain E10) was observed to use MTBE and ETBE as the sole carbon and energy source, whereas G. amicalis (strain T3) used TAME as the sole carbon and energy source for growth. All the bacterial strains transformed oxygenates better in the presence of an alternative carbon source (ethanol) with the exception of A. calcoaceticus (strain M10). The capacity of the selected strains to remove MTBE, ETBE, and TAME looks promising for application in bioremediation technologies.

Impaired pulmonary gas exchange resulting in arterial hypoxemia is frequently observed in patients during general anesthesia. Recent animal investigations have revealed that pulmonary hypoxia-induced vasoconstriction (a local mechanism which redistributes pulmonary blood flow from poorly to more amply ventilated regions) is abolished by commonly used inhalation anesthetics. Injectable anesthetics do not have this effect. The present work was undertaken to study whether pulmonary vasoconstriction in response to ventilation hypoxia could be elicted in man during intravenous anesthesia, and to find out whether any response thus obtained is reduced by diethyl ether and halothane. Under intravenous anesthesia, unilateral hypoxia (UH) was induced in two groups of young men by ventilating one lung, the test lung, with N2 and the other with O2. In both groups the time period of UH was subdivided into two sequences, one sequence with and one without inhalation anesthesia. In 10 subjects (group A), inhalation anesthesia was administered during the second sequence, and in 7 subjects (group B), inhalation anesthesia was given during the first sequence. The blood flow distribution (BFD) to the test lung during air breathing and following each of the two sequences of UH was determined by lung scintigraphy. The median test lung BFD in group A decreased from 49% (range 40–45%) of total pulmonary blood flow to 24.5% (range 19–32%) during UH. By superimposing ipsilateral inhalation anesthesia, it increased to 34% (range 27–48%). The increase was significant both for the diethyl ether and halothane subgroups. BFD to the test lung during the first period of UH was significantly higher during diethyl ether or halothane administration (group B) than during administration of intravenous anesthesia only (group A). The damping effect of inhalation anesthetics on the response to hypoxia was demonstrated at blood concentrations comparable to those used in clinical anesthesia. It is therefore likely that inhibition of hypoxia-induced pulmonary vasoconstriction contributes to the development of arterial hypoxemia during diethyl ether and halothane anesthesia in man.

The end results of therapy of 1,358 breast cancer patients were studied. Anaesthesia was performed by ether-nitrogen-oxygen (554 cases) or halothane-nitrogen-oxygen (804 cases) mixture with addition of oxygen. The method of Holstead was employed in all cases. A comparison of groups of patients on the basis of such parameters as the anaesthetic used, age and degree of tumour progression (according to the TNM classification and results of post-operative histological assays) showed them to be identical. The study showed that the type of anaesthesia influenced the end results of therapy of cancer patients: the survival rates of patients receiving halothane anaesthesia were much higher than those of the ether-anaesthetized patients. The differences were most pronounced among patients who received pre-operative radiation therapy and post-operative chemotherapy as well as in cases of metastasis spread into regional lymph nodes. The mechanism of the effect of the anaesthetic on the survival rates of cancer patients may be explained on the basis of the data available on the varying influences of anaesthetics on the pituitary-adrenal cortec system and carcinemia development during operation as well as the role of immunity in tumour cell implantation and growth of metastases.

The performances of an Oxford miniature vaporizer (OMV) and a Fluotec Mark III vaporizer filled with an azeotropic mixture of halothane and diethyl ether were studied. Gas concentrations were estimated using an EMMA gas analyser and a MIRAN spectrophotometer. Calibration tables for both vaporizers were derived. In a small clinical series with air as the carrier gas, to which a small amount of oxygen was added, the azeotrope was found to be a satisfactory anaesthetic agent, giving a short awakening time and an almost pain-free postoperative course.

1 The effect of the ether anaesthesia on the plasma half-life of N-(2 hydroxy ethyl) 2-phenyl ethyl carbamate has been studied in rats. 2 The plasma half-life of the carbamate was considerably shorter in animals anaesthetized with ether prior to drug administration than in control rats. 3 The longer plasma half-life of the carbamate in control animals was shown to be due to enterohepatic circulation. 4 Inhibition of this phenomenon by ether was responsible for the shorter plasma half-life of the carbamate in animals anaesthetized with this agent before drug administration. 5 The possible mechanisms by which the ether-induced effect is brought about are discussed.

Experimental carbon–proton coupling constants are reported for 36 monosubstituted allenes, 20 ethenes and 5 butatrienes. The data for the allenes cover a range of substituents in which either the first atom of the substituent (all Group IV–VII elements of the second and third row are covered) and/or the substitution of that atom is varied. The electronegativity (σI) of the substituent directly attached to the coupled carbon atom is correlated with the 1J(CH) coupling. This is also borne out by the good correlations between 1J(CH) values in the allenes and 1J(CH) values in various other classes of chemical compounds. Theoretically calculated 1J(CH) values correctly reflect the substituent effects on the experimental values in the allenes, ethenes and butatrienes spearately, but fail to give a satisfactory description of the differences in 1J(CH) for these types of compounds. In disubstituted allens and ethenes the substituent effects on 1J(CH) values are additive. The experimental and calculated values differ by less than 1 Hz. Two- and three-bond carbon–proton couplings are also discussed in terms of electronegativity, substituent and hybridization effects and mutual relationships. Large values, up to 6 Hz, are found for 4J(CH) and 5J(CH) in the allenes and butatrienes. These large values are ascribed to σ-π interactions. For geometrically equivalent couplings a constant ratio of nJ(CH)/nJ(HH) is found in the ethenes (0.65; n = 3) and in the allenes and butatrienes (0.55; n = 4 and 5, respectively). 1J(CH) and 3J(CH) coupling constants are used for the conformational analyses of vinyl, allenyl and butatrienyl ethers and thioethers. At room temperature the methyl and ethyl ethers are predominantly in an s-cis conformation, whereas the iso-propyl allenyl ether is a mixture of s-cis and s-trans; the tert-butyl allenyl ether exists mainly in the s-trans conformation. The thioethers are all in the s-cis conformation.

Fish meals and fish flour with low oil content were artificially infected with Salmonella oranienburg. In nine trials the effect of moisture content, temperature, atmospheric oxygen content, addition of an antioxidant, ethoxyquin (EQ) and of some short chain unsaturated organic acids, crude fish oil, a highly unsaturated fraction of fish oil, the free fatty acids derived from this fraction and of different extracts of fish meals on the death rate of Salmonella, was studied. Elevated temperature (30 oC), an oxygen atmosphere and material containing highly unsaturated oils or fatty acids accelerated Salmonella death rate. EQ was shown not to have a bactericidal action and when added in conjunction with highly unsaturated oil or fatty acids counteracted the bactericidal effect of these materials. A high death rate seemed to accompany active oxidation in the test media.

The effect of diethyl ether anesthesia on phosphatidylcholine biosynthesis in hamster organs was investigated. Ether administration did not affect the incorporation of radioactive choline into phosphatidylcholine in the liver, heart, lung, brain and spleen. A significant (29%) decrease in the labeling of phosphatidylcholine was detected in the kidney of ether-treated hamsters. Reduction in phosphatidylcholine labeling was not due to a diminished radioactive choline uptake but a decrease in the conversion of phosphocholine to CDP-choline. The accumulation of labeled phosphocholine was caused by the translocation of CTP:phosphocholine cytidylyltransferase from microsomal (more-active) form to cytosolic (less-active) form. Ether administration appears to modulate the cytidylyltransferase in hamster kidney differently than that in other hamster organs.

Titrated stocks of hepatitis B virus and Hutchinson strain non-A, non-B hepatitis virus were diluted in normal serum to contain, respectively, greater than or equal to 10(6) and greater than or equal to 10(4) chimpanzee infectious doses (CID50) per milliliter and exposed to 1% Tween 80 and 20% ether at 4 degrees C for 18 h. After evaporation of the ether, the treated sera were each inoculated into two chimpanzees. The animals remained free of serologic and biochemical evidence of hepatitis during a 6-month follow-up period, and were then shown to be susceptible to infection by challenge with the original untreated inocula. To assess the effect of exposure to Tween 80/ether on coagulation factors, four lots of antihemophilic factor (AHF) concentrate and 2 lots of commercial factor IX concentrate were treated as above. For the AHF concentrate there was an average of 70% recovery of factor VIII procoagulant activity, 93% recovery of factor VIII-related antigen, and 73% recovery of fibronectin opsonin activity and no detectable change in ristocetin cofactor activity or in fibronectin antigen. Crossed immunoelectrophoresis revealed no change in migration rate of fibrinogen, fibronectin, and von Willebrand factor (vWF), although the quantity of fibrinogen was reduced. Factor VIII procoagulant activity and vWF activity remained associated during chromatography on BioGel A15.

1. The effects of ether stress on noradrenaline (NA) and dopamine levels in different regions of the rat brain were studied. 2. Exposure to ether vapour (90 s) caused a significant decrease in the concentration of hypothalamic NA but had no effect on catecholamine (CA) concentrations in the other regions studied. 3. Treatment with betamethasone alone (20 microgram/ml) given in the drinking water for 24 h, had no effect on CA levels in the cerebral cortex, midbrain or hypothalamus. However, pretreatment with this dose of steroid prevented the decreases in hypothalamic NA which were normally seen after ether stress and also induced significant increases in the concentration of midbrain NA. 4. The data provide further support for the involvement of NA in the regulation stress-induced corticotrophin (ACTH) release and indicate that centres other than the hypothalamus may be involved in mediating the inhibitory action of betamethasone on the response to ether stress.

Six orbiviruses, Corriparta, Wallal, Eubenangee, D'Aguilar, Warrego and Mitchell River, were inactivated within 30 min in solutions of pH less than 6. All but Wallal virus resisted treatment with ether at 1 degrees for 22 h but only Corriparta virus resisted treatment with chloroform at 1 degrees for 22 h. The genomes of the orbiviruses, including Corriparta virus, after electrophoresis in acrylamide gels separated into basically similar patterns which were distinct from the pattern of reovirus RNA.

Ethoxyformic acid anhydride, amino-1 H-tetrazole, and photooxidation in the presence of rose bengal, which are reagents known to react with histidine residues of proteins, were shown to in-activate monoamine oxidase. Ethoxyformic acid anhydride reacted with about 6 histidine residues per 100000 g of protein under the experimental conditions adopted and completely inactivated the enzyme. However, NH2OH reactivated the ethoxyformic acid derivative to 100% of the value of the enzyme treated with 0.2 M NH2OH only. Since NH2OH specifically deacylates N-ethoxyformylimidazole, it was shown that at least some of the histidine residues are essential for activity. In addition, photooxidation experiments in the presence of 0.01% rose bengal confirmed that only histidine residues of bovine hepatic monoamine oxidase are destroyed under the designated experimental conditions. About 9 histidine residues per 100000 g of protein were destroyed during the photo-oxidation experiments. In the presence of substrate, kynuramine or benzylamine, only 7 histidine residues were destroyed, which indicates that 2 histidine residues per 100000 g of protein are essential for activity.

Sphingomyelin synthesis was studied in cultured Novikoff rat hepatoma cells by following transfer of [14C]choline label into sphingomyelin (SPH). The study was facilitated by the fact that prelabeling of the cells with [Methyl-14C]choline resulted in rapid accumulation of essentially all the label (≈95%) in phosphatidylcholine (PC). The redistribution of PC label during a 15-hr chase was dependent upon the extracellular choline concentration. Under conditions of free choline diffusion (500 μM choline), loss of lable from PC was most pronounced, and the percentage of total radioactivity that became trapped in the extracellular water-soluble choline pool was an order of magnitude greater than in low choline medium (27 μM choline). Despite the significant loss of water-soluble label from the cells in high choline medium, SPH labeling proceeded at essentially the same rate at either choline concentration. During the label chase in 500 μM choline, the specific radioactivity of PC decreased, but the specific radioactivity of SPH continued to increase for 9–12 hr until it reached the specific radioactivity of PC. In the presence of 300 μM neophenoxine (NPO), transfer of label from PC into SPH was stimulated. NPO also decreased the specific radioactivity of PC to about the same extent as that of SPH was increased. Because transfer of choline label from PC to SPH was not affected by loss or dilution of water-soluble precursors, and because the specific radioactivity of PC and SPH, in the absence or presence of NPO, responded in a characteristic precursor product fashion, we conclude that sphingomyelin synthesis in Novikoff cells circumvents the water-soluble choline pool and that phosphatidylcholine serves as the immediate choline source. All our data support the phosphatidylcholine:ceramide cholinephosphotransferase pathway of sphingomyelin synthesis.

The mechanisms of formation of m/z 73 ions in the mass spectrum of the ionized title compound were investigated by deuterium substitution and by examining the decompositions of metastable ions. Two routes to the [C4H9O]+ ions were found in the normal spectrum. The ethyl lost by the major pathway contains the α- and β-hydrogens and a γ-hydrogen from the butyl group. The minor route involves the loss of ethylene from the [MH]+ ion. There were metastable peaks for losses of ethyl, ethanol and methyl from the molecular ion. The ethyl contains the α- and β-methylenes and a γ-hydrogen, while the methyl is the δ-methyl of the butyl group. The labeling data rule out a previous mechanistic proposal for the loss of ethyl and support a mechanism involving stepwise isomerization to the sec-butyl ethyl ether molecular ion. However, the metastable ion chemistries of the molecular ions from the n- and sec-butyl ethyl ethers are highly dissimilar, perhaps due to decompositions from different electronic states. The n-pentyl methyl ether ions loses both ethyl and propyl, apparently following rearrangements to the 3-pentyl and 2-pentyl ether ions. Di n-butyl and n-butyl methyl ethers also give metastable peaks for loss of methyl, ethyl and the shorter chain alcohol.

SUMMARY A method of inhalation anaesthesia using diethyl ether, following induction with thiopentone, is described in ponies. The high concentrations of ether needed to maintain anaesthesia were obtained by using a Marrett head in circle vaporizer. This method should only be used in ponies, since the diameter of the tubing is too small for use on larger horses. RESUME On utilise l'inhalation de diethyl ether apres induction au thiopentone pour anasthesier des poneys. Les concentrations elevees d'ether necessaires au maintien de l'anesthesie sont obtenues en employant un dispositif de MARETT dans le vaporisateur. Cette methode doit etre reservee au poneys car le diametre des canalisations utilisees est insuffisant pour l'emploi sur des chevaux de taille normale. ZUSAMMENFASSUNG Es wird eine Methode zur Inhalationsnarkose bei Ponies beschrieben, bei der nach Thiopental-Einleitung Diaethyl-Aether verwendet wird. Die hohen Aetherkonzentrationen, die zur Erhaltung der Narkosetiefe benotigt werden, konnten erreicht werden mit Hilfe eines Marrett-Kopfs in einem Kreisverdampfer. Diese Methode sollte nur bei Ponies angewendet werden, weil der Rohrendurchmesser fur erwachsene Pferde nicht ausreicht.