RESUMO
Industrial analytical chemistry includes the measurement of the elemental composition and structure of molecules; the measurement of the concentration of specific molecules, atoms, and ions in contact with other molecules, atoms, and ions, the measurement of the energy and speed with which these reactions occur; and the separation of molecules, atoms, and ions specifically from other molecules, atoms and ions. It is also the measurement of the physical (interaction) and chemical (reaction) behavior of collections of molecules and how this behavior is controlled by the presence of other molecules and ions. Many excellent devices for separation and measurement have been developed to accomplish these tasks. Each of these attains a level of sensitivity and selectivity beyond which further improvement would be difficult. However, by coupling these techniques in various configurations, improved data can be generated in a short time span. Such techniques are often referred to as hyphenated, tandem, combined, or coupled. A more inclusive term is multidimensional techniques. In this paper, we briefly describe some of the most significant developments our laboratory has made in these and related techniques.
RESUMO
The stereochemistry of the metabolism of vic-dihaloalkanes to alkenes has been studied. This glutathione-dependent biotransformation may occur by two mechanism. The first mechanism involves the nucleophilic attack of glutathione on the substrate resulting in S-(beta-haloalkyl)glutathione formation; subsequent attack of a second thiol on the sulfur atom of the conjugate yields glutathione disulfide, ethylene, and halide ion. Alternatively, glutathione may abstract a halide ion from the substrate and form ethylene, halide ion, and glutathione sulfenyl halide. These pathways were distinguished by determining the stereoisomeric alkenes formed in the metabolism of meso- and racemic 2,3-dibromobutane, erythro- and threo-2-bromo-3-chlorobutane, and meso-1,2-dideutero-1,2-dichloroethane. The stereochemical configurations of the 2-butenes and 1,2-dideuteroethylene were determined by gas chromatography and by Fourier-transform infrared spectroscopy, respectively. When incubated with glutathione and rat liver cytosol, meso- and racemic 2,3-dibromogutane were converted exclusively to (E)- and (Z)-2-butene, respectively. On the other hand, erytho- and threo-2-bromo-3-chlorobutane were converted to a mixture of (E)- and (Z)-2-butene. meso-1,2-Dideutero-1,2-dichloroethane was converted exclusively to (Z)-1,2-dideuteroethylene. These results suggest that the 2,3-dibromobutanes are metabolized to 2-butenes by a direct E2 elimination, whereas 2-bromo-3-chlorobutanes undergo metabolism to 2-butenes by both an E2 elimination and a substitution-elimination sequence. However, 1,2-dihaloethane metabolism to ethylene proceeds only by the substitution-elimination mechanism; this result is consisent with the formation of ethylene-S-glutathionylepisulfonium ion, a possible reactive species involved in 1,2-dihaloethane mutagenicity.
Assuntos
Alcenos/metabolismo , Glutationa/metabolismo , Hidrocarbonetos Halogenados/metabolismo , Fígado/metabolismo , Animais , Biotransformação , Citosol/metabolismo , Técnicas In Vitro , Masculino , Ratos , EstereoisomerismoRESUMO
The metabolism of acrylonitrile (AN) in rats was studied in conjunction with toxicological and pharmacokinetic studies to help assess the potential hazard of exposure to AN in the workplace. Rats were administered 30 mg/kg [1-14C] AN or [2,3-14C] AN orally. Radiolabeled metabolites excreted in the urine during the first 16 h were separated by ion-exclusion liquid chromatography and identified (after derivatization) by gas chromatography-infrared spectroscopy and/or gas chromatography-mass spectrometry. Two major urinary metabolites were identified as thiocyanate and N-acetyl-S-(2-cyanoethyl)cysteine. A third was tentatively identified as 4-acetyl-3-carboxy-5-cyanotetrahydro-1,4-2H-thiazine. AN was not detected in the urine. One possible scheme for the AN metabolic pathways is proposed.