Reactions of singlet oxygen with pine pollen.

Exposure of pine pollen to single oxygen, generated in an aqueous environment, resulted in a decrease in the relative quantities of unsaturated fatty acids that could be recovered by solvent extraction of surface and near surface pollen lipids. The involvement of excited oxygen was confirmed by substitution of deuterium oxide for water, which led to a twofold greater decrease in the unsaturated acids. The potential environmental and biomedical implications of these observations are discussed in terms of this model system.

Structural identification of p-dioxane-2-one as the major urinary metabolite of p-dioxane.

Analysis by gas chromatography (GC) of the volatile compounds present in the urine from rats administered dioxane, a hepatic carcinogen to this species, revealed a major metabolite. The appearance of the metabolite was pH-dependent, undetectable at high pH; reacidification of the urine sample brought about the reappearance of the metabolite. The amount excreted was dose-dependent and time-dependent, reaching a maximum between 20 and 28 h after dioxane administration. Diethylene glycol administered to rats gave rise to the same metabolite. When isolated and purified from lyophilized urine by preparative GC, the metabolite exhibited an intense carbonyl band at 1750 cm-1 in the infrared spectrum. Nuclear magnetic resonance spectrum showed two triplets and one singlet with equal intensity at delta 3.85, 4.48 and 4.37, respectively. GC-mass spectrometric studies indicated a parent peak at m/e 102. The metabolite was identified as p-dioxane-2-one. Synthetic reference compound exhibited identical IR, NMR, and GC-mass spectra as the metabolite. The tentative pathway and the biological significance of dioxane metabolism are discussed.

Enhancement of toxicity and enzyme-repressing activity of p-dioxane by chlorination: stereoselective effects.

The acute toxicity of p-dioxane may be enhanced up to 1000-fold by chlorination of the compound. The effect was stereoselective. Of the stereoisomers tested, tetrachloro-p-dioxane, isomer I (2r, 3t, 5t, 6c) was over 80 times more toxic than isomer II (2r, 3c, 5t, 6t). The latter compound was also a potent repressor of hepatic dimethylnitrosamine-demethylase I (DMN-d) and aryl hydrocarbon hydroxylase (AHH).

Epoxide intermediates in the metabolism of naphthalene by the rat.

Twenty-one oxygenated metabolites of naphthalene have been isolated from rat urine and characterized by gas chromatography and gas chromatography and gas chromatography-mass spectrometry. Studied with naphthalene-1,4-d2 confirmed that the compounds characterized by GC/MS were derived from naphthalene. The structures of a number of metabolites were confirmed by synthesis. All but one of these metabolites were formed by processes involving epoxidation, and the structures of the metabolites support the hypothesis that multiple epoxides and a cyclic peroxide are involved in the in vivo metabolism of naphthalene by the rat. The evidence provided by this and our previous studied indicates that the anti-diepoxide of naphthalene is a mammalian metabolite. Ten methylthio metabolites were isolated in earlier studies. Excluding mercapturic acids, conjugates, and related compounds, the total number of isolated compounds is now 31, and several additional compounds must have been present as intermediates. The structures of epoxide intermediates are indicated by precursor-product relationships.

Identification and synthesis of the isomeric tetrahydroxytetrahydronaphthalene metabolites excreted in rat urine.

The structures of three isomeric 1,2,3,4-tetrahydroxytetrahydronaphthalene metabolites of naphthalene have been confirmed by synthesis. Six isometric 1,2,3,4-tetrahydroxy-1,2,3,4-tetrahydronaphthalene structures occurring in for dl-pairs and two mesoforms have been synthesized. Five were synthesized by the action of osmium tetroxide on the cis- and trans-1,2-dihydrodiols and cis- and trans-1,4-dihydrodiols. The sixth isomeric tetrahydrotetrol was synthesized by hydrolysis of trans-1,2-dihydroxy-syn-3,4-epoxy-1,2,3,4-tetrahydronaphthalene (the syn-dihydrodiolepoxide of naphthalene). By comparing the gas-chromatographic and mass-spectrometric properties of the synthetic and urinary tetrahydrotetrols, two of the urinary metabolites were identified as 1 beta, 2 alpha, 3 alpha, 4 beta- and structure of the third tetrahydrotetrol metabolite, 1 beta, 2 alpha, 3 beta, 4 alpha-tetrahydroxy-1,2,3,4-tetrahydronaphthalene, identified in earlier studies, was confirmed.

Urinary bivalent sulfur metabolites of phenanthrene excreted by the rat and guinea pig.

After the administration of phenanthrene (50 mg/kg, ip) to young adult male rats and guinea pigs, a series of bivalent sulfur urinary metabolites were isolated and characterized by gas chromatography and gas chromatography-mass spectrometry. Seven methylthio metabolites were isolated from the neutral fraction of hydrolyzed rat urine, whereas only two were detected in guinea pig urine. The major methylthio metabolite excreted by each species was 9-hydroxy-10-methylthio-9, 10-dihydrophenanthrene. This was observed as a second-day metabolite in the rat, and its appearance was accompanied by 9-phenanthrol. In addition to the methylthio compounds, which were excreted predominantly as glucuronides, six acidic bivalent sulfur metabolites were isolated from hydrolyzed rat urine and identified by GC/MS; five were present in hydrolyzed guinea pig urine. The major acidic metabolite in hydrolyzed rat urine was the hydroxydihydromercapturic acid N-acetyl-S-(9-hydroxy-9, 10-dihydro-10-phenanthryl)-L-cysteine. The major acidic metabolite in guinea pig urine was the mercaptoacetic acid S-(9-hydroxy-9, 10-dihydro-10-phenanthryl)mercaptoacetic acid, but the hydroxydihydromercapturic acid was also present.

Identification of new sulfur-containing metabolites of naphthalene in mouse urine.

Seven acidic sulfur-containing metabolites were isolated from mouse urine following administration of naphthalene. The metabolites have been identified as (1-hydroxy-1,2-dihydro-2-naphthalenylthio)acetic acid (I), 2-hydroxy-3-(1-hydroxy-1,2-dihydro-2-naphthalenylthio)propanoic acid (II), (1,2,3-trihydroxy-1,2,3,4-tetrahydro-4-naphthalenylthio)acetic acid (III), and N-acetyl-S-(1-hydroxy-1,2-dihydro-2-naphthalenyl)-L-cysteine (IV). The dehydration products of I, II, and IV, namely 1-(naphthalenylthio)acetic acid (V), 2-hydroxy-3-(1-naphthalenylthio)propanoic acid (VI), and N-acetyl-S-(1-naphthalenyl)-L-cysteine (VII), respectively, were also present in several urinary extracts. Nine methylthio derivatives were identified in the neutral extract of urine. These metabolites were the following: 1-methylthionaphthalene, trans-1-hydroxy-2-methylthio-1,2-dihydronaphthalene, two stereoisomeric 1,2,3-trihydroxy-4-methylthio-1,2,3,4-tetrahydronaphthalenes, 1,3-di(methylthio)-2,4-dihydroxy-1,2,3,4-tetrahydronaphthalene, 1,4-di(methylthio)-2,3-dihydroxy-1,2,3,4-tetrahydronaphthalene, two methylthiohydroxy-naphthalenes, and a methylthiodihydroxydihydronaphthalene. Following intraperitoneal administration of N-acetyl-S-(1-hydroxy-1,2-dihydro-2-naphthalenyl)-L-cysteine to mice, the acidic metabolites I, II, and unchanged IV were found. The gas-chromatographic and gas chromatographic-mass spectral properties of the methyl ester-trimethylsilyl derivatives of the acidic sulfur metabolites of naphthalene are presented.

Mass spectra of the oxygenated products generated from phenanthrene under simulated environmental conditions.

The photooxidation of phenanthrene under stimulated environmental conditions to 9,10-epoxy-9,10-dihydrophenanthrene, among other oxygenated products, serves as a model for the conversion of polycyclic aromatic hydrocarbons to potentially mutagenic and/or carcinogenic products. The separation and identification were achieved by glass capillary gas chromatography mass spectrometry, and by comparison of gas chromatographic retention times and mass spectral fragmentation patterns with data observed for authentic samples obtained independently through synthesis or from commercial sources. The structural rearrangements of 2,2'-di-substituted biphenyls such as 2-formyl biphenyl-2'-carboxylic acid, 2,2' diformyl biphenyl and diphenic acid anhydride, induced upon electron impact are investigated and discussed in detail. The mass spectral comparison of 9,10-epoxy-9,10-dihydrophenanthrene, a primary mammalian metabolite of phenanthrene, and certain other structural isomers was conducted and the results of this study suggest a mass spectral technique capable of differentiating arene oxides from oxepin, phenol and carbonyl isomers. A discussion of the potential impact of the sensitized photooxidation of more condensed environmental polycyclic aromatic hydrocarbon pollutants is presented and the role of bioactive arene oxides produced under such photooxidation conditions is also discussed. Related oxides of polycyclic aromatic hydrocarbons are known to be proximate carcinogens and/or mutagens generated by metabolic activation. The role and significance of solar induced oxidation in the weathering of petroleum hydrocarbons at air-sea interfaces and the incorporation of potentially bioactive organic residues in the food chain are also addressed.

Differences in the risk of homicide and other fatal injuries between postpartum women and other women of childbearing age: implications for prevention.

OBJECTIVES: This study compared injury deaths between postpartum women and other women aged 15 to 44. METHODS: Risk ratios and 95% confidence intervals (CIs) were computed for injury fatality rates. RESULTS: Fifty percent (29/58) of postpartum injury deaths were homicides, compared with 26% (427/1648) of injury deaths among nonpregnant, nonpostpartum women. For females aged 15 to 19, the homicide rate was 2.6 times higher (95% CI = 1.17, 5.95) for postpartum females than for other females. The motor-vehicle fatality rate was lower for postpartum females than for nonpregnant, nonpostpartum females (risk ratio = 0.30, CI = 0.18, 0.48). CONCLUSIONS: Postpartum females aged 15 to 19 years were at higher risk of homicide. Postpartum women were at reduced risk of motor-vehicle fatalities.

"High-load" polyethylene glycol-polystyrene (PEG-PS) graft supports for solid-phase synthesis.

The choice of a polymeric support is a key factor for the success of solid-phase methods for syntheses of organic compounds and biomolecules such as peptides and oligonucleotides. Classical Merrifield solid-phase peptide synthesis (SPPS), performed on low cross-linked hydrophobic polystyrene (PS) beads, sometimes suffers from sequence-dependent coupling difficulties. The concept of incorporating polyethylene glycol (PEG) into supports for solid-phase synthesis represents a successful approach to alleviating such problems. Previous reports from our laboratories have shown the advantages of "low-load" PEG-PS (0.15-0.25 mmol/g) for SPPS. Herein, we demonstrate that the beneficial aspects of the PEG-PS concept can be extended with resins that have higher loadings (0.3-0.5 mmol/g).

Methylthio metabolites of naphthalen excreted by the rat.

Eight methylthio metabolites have been found as urinary products of the metabolism of naphthalene in the rat. One was 1-methylthionaphthalene. A second was a methylthio analog and the dihydrodiol, and a third was naphthalene substituted with one hydroxyl and one methylthio group. Two compounds with common structural elements were found; one of these was prepared by synthesis from anti-1,2:3,4-naphthalene dioxide and one from 1 beta, 2 alpha-dithyroxy-3 alpha, 4 alpha-epoxy-1,2,3,4-tetrahydronaphthalene by reaction with 2-keto-4-methylthiobutyric acid or with methionine. Each of these compounds contained one methythio group and three hydroxyl groups substituted on a tetrahydronaphthalene structure. Two metabolites with two methylthio groups and two hydroxyl substituents on a tetrahydronaphthalene ring were also detected; one of these was prepared by synthesis from the dioxide. The most likely metabolic origin of these methylthio metabolites is through the reaction of epoxides (including the diepoxide) with a nucleophile which may be methyl mercaptan, 2-keto-4-methylthiobutyric acid, or methionine.