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2-(Fluoromethyl)-3-phytyl-1,4-naphthoquinone and its 2,3-epoxide. Inhibition of vitamin K epoxide reductase.

2-(Fluoromethyl)-3-phytyl-1,4-naphthoquinone (7) was synthesized from the known compound 2-bromo-3-methyl-1,4-dimethoxynaphthalene by N-bromosuccinimide bromination of the 3-methyl group, conversion to the corresponding 3-fluoromethyl compound with silver fluoride, attachment of the 3-phytyl substitutent via the lithium diaryl cuprate and phytyl bromide, and then silver oxide oxidation to 7. Epoxidation with basic hydrogen peroxide gave the corresponding 2,3-oxide (1) in a very low yield. Compound 1 was not a time-dependent inhibitor of beef liver microsomal vitamin K epoxide reductase, but it was a competitive, reversible inhibitor. It was not possible to determine if 1 was a substrate for the enzyme because the expected product of reduction, namely 7, rapidly decomposed under the assay conditions.

Animals↗

Gold nanoparticle formation during bromoaurate reduction by amino acids.

The synthesis and characterization of water-soluble dispersions of gold nanoparticles by the reduction of a potassium tetrabromoaurate precursor solution using the amino acids L-tyrosine, glycyl-L-tyrosine, and L-arginine using alkaline synthesis conditions are reported. The particle sizes determined by small-angle X-ray scattering (SAXS) and high-resolution transmission electron microscopy (HRTEM) measurements are found to be inversely proportional to the rate of particle formation, which was determined by time-resolved UV-visible spectrophotometry measurements, and vary very slowly at intermediate gold concentrations and rapidly at the extremes. Dispersions produced with a mixture of the two amino acids glycyl-L-tyrosine and L-tyrosine showed particle sizes and particle size distributions which were directly proportional to the ratio of the two L-amino acids, thus offering the possibility for control over the properties of the gold nanoparticle dispersions.

Amino Acids↗

Cross-coupling reactions of arylsilanols with substituted aryl halides.

[reaction: see text] The palladium-catalyzed cross-coupling of arylsilanols with aryl iodides and aryl bromides (in the presence of cesium carbonate) furnished various biaryl products in high yield. An extensive series of optimizations led to the identification of key variables, including activator, solvent, catalyst, and hydration level, that influence the rate and selectivity of the process. Manipulation of these features provided an effective coupling method of wide scope and generality.

Biphenyl Compounds↗

Asymmetric aza-Mannich reactions of sulfinimines: scope and application to the total synthesis of a bromopyrrole alkaloid.

[reaction: see text] An asymmetric intermolecular aza variant of the Mannich reaction is reported utilizing chiral sulfinimine anions as the nucleophile and N-sulfonyl aldimines as the electrophilic component. A wide range of nucleophiles and electrophiles are tolerated by the reaction conditions, delivering the condensation products in good to excellent yield with a high degree of stereocontrol. Application of this methodology to the total synthesis of a natural product is reported.

Alkaloids↗

Fumigant-related illnesses: Washington State's five-year experience.

OBJECTIVE: Exposure to fumigants may have severe or persistent health effects. Washington State's fumigant-related illnesses were reviewed to better understand the circumstances surrounding exposure and resultant health effects. METHODS: Fumigant-related illnesses reported to and investigated by the Washington State Department of Health were reviewed. Illnesses considered by Department of Health to be definitely, probably, or possibly related to pesticide exposure were then analyzed. RESULTS: From 1992-1996, 39 (3.3%) of 1192 definite, probable, or possible cases of pesticide-related illnesses involved exposures to fumigants. Fumigant exposures during this period were to aluminum phosphide (15), methyl bromide (12), metam-sodium (9), and zinc phosphide (3). Symptoms included respiratory problems and eye and/or skin irritation for the majority of exposures, and no deaths were reported. The nature of exposure for these cases included exposure to applicators (17), reentry into a fumigated structure (9), improper storage or disposal (6), reentry into treated agricultural fields (4), drift from treated fields (2), and other (1). CONCLUSIONS: Review of fumigant exposures should be used to prevent future events through continued enforcement of established regulations and training of applicators.

Adult↗

Reductive dehalogenation of bromoform in aqueous solution.

The hybrid semiconducter-macrocycle catalyst TiO2-cobalt phthalocyanine promotes the solar photolysis of aqueous bromoform under anaerobic conditions. The major decomposition products are dibromoethane and HBr. Bromomethane and methane were produced only after prolonged photolysis (30 hr). Acetone, derived from added 2-propanol, was the only observed oxidation product. Preliminary experiments showed that electrolytic reduction of aqueous carbon tetrachloride at a vitamin B12-modified silver electrode produced the expected lower homologues but with surprisingly high yields of methane.

Chemical Phenomena↗

Toxicities of microencapsulated tribromomethane, dibromochloromethane and bromodichloromethane administered in the diet to Wistar rats for one month.

The gelatin-starch syrup microencapsulation method was applied to subacute toxicity studies of tribromomethane (TBM), dibromochloromethane (DBCM) and bromodichloromethane (BDCM). Groups of Wistar rats (7 males and 7 females) both sexes were given diet containing microcapsules of each of these trihalomethanes (THMs) at the following concentrations: TBM, 0.068, 0.204 and 0.612% in males, and 0.072, 0.217 and 0.651% in females; DBCM, 0.020, 0.062 and 0.185% in males, and 0.038, 0.113 and 0.338% in females; BDCM, 0.024, 0.072 and 0.215% in males, and 0.024, 0.076 and 0.227% in females. Suppression of body weight gain was seen in each high-dose males fed TBM or BDCM and females fed DBCM or BDCM. Histopathologically, hepatic lesions such as vacuolization and swelling of liver cells were significantly noted in both sexes of all groups fed TBM, in both sexes of the middle- and high-dose groups fed DBCM, and in males of the high-dose group and in females of the middle- and high-dose groups fed BDCM. In addition, single cell necroses were observed in males and females fed DBCM and in males fed BDCM. Hepatic cord abnormalities were also noted in males of the high-dose group fed BDCM. Although no increases in serum transaminase activities (ASAT, ALAT) were evident in either sex fed any of the THMs, decreases in triglyceride content, cholinesterase and lactate dehydrogenase activity were observed. Renal lesions reported to occur in gavage studies were not found in the present feeding study. Lowest-observed-adverse-effect-level (LOAEL) of TBM and no-observed-adverse-effect-level (NOAEL) of DBCM and BDCM were determined to be 56.4 mg/kg, 18.3 mg/kg and 20.6 mg/kg, respectively, under the present experimental conditions.

Administration, Oral↗

Determination of iron limiting values according to PH. EUR. using 1,3-dibromo-5,5-dimethylhydantoin (DBH) instead of elemental bromine. Analytical methods of pharmacopoeias with DBH in respect to environmental and economical concern. Part 8.

PH. EUR. 2002 uses elemental bromine performing iron limit tests for maleic acid (iron 5 ppm) and titanium dioxide (iron 200 ppm). 1,3-Dibromo-5,5-dimethylhydantoin (DBH) can replace bromine water. For the iron limit test of maleic acid bivalent iron is oxidized to trivalent iron by bromine resp. DBH, because the unsaturated, in high concentration existing acid reacts substantially slower. On the other hand maleic acid removes the excess of bromine. The bromine oxidation for the iron limiting values of titanium dioxide according to the pharmacopoeia is not required. Metallic iron as well as ferrous salts are converted to trivalent iron, when the titanium test solution is prepared by boiling with concentrated sulphuric acid in the presence of anhydrous sodium sulphate.

Bromine↗