Dimethyl ether chemical ionization mass spectrometry of alpha-amino acids.

Dimethyl ether (DME) is a useful reagent gas for the characterization of a variety of diverse biologically important or environmentally significant classes of compounds. In this work the gas-phase ion-molecule reactions of DME with 23 alpha-amino acids were investigated and the collision-induced dissociation (CID) fragmentations of the protonated molecules and their most prominent adduct ions were studied. The identities and relative abundances of the adduct ions varied widely and, not unexpectedly, were dependent on the nature of the R substituent in H2NCH(R)CO2H. With a few exceptions, notably serine and threonine, protonated molecules and [M + 13]+ adduct ions were highly abundant, and in most cases methoxymethylene cations [M + 45]+ were also prominent. The solvated methoxymethylene cation [M + 91]+ was seen in very modest abundance or not at all, except for serine and threonine, when it was the most abundant. CID fragmentations of the protonated molecules generated in the DME plasma showed similar characteristics to those generated by fast atom bombardment in that sequential elimination of H2O and CO to the iminium ion was the predominant process in the majority of cases, and was also accompanied by the loss of NH3 in the cases of cysteine, glutamine, ornithine and lysine. Loss of NH3 alone was the predominant process for tryptophan, and for arginine and methionine the fragmentations were dominated by the guanidino and methylthio substituents, respectively.

Nitroreduction of 2,4-dinitrotoluene in vitro by cytochrome P-450 induced H4IIE cells.

Conditions have been established for H4IIE rat hepatoma cell cultures in which effects of cytochrome P-450 induction on the metabolism of a munitions wastestream pollutant can be studied. Under these conditions, the polychlorinated hydrocarbon 2,3,4,7,8-pentachlorodibenzfuran (PCDBF) induced cytochrome P-450 (1A1) aryl hydrocarbon hydroxylase (AHH) activity over a wide range of concentrations without significant cytotoxic effects. The munition pollutant 2,4-dinitrotoluene (2,4-DNT) did not induce AHH activity itself, but its metabolism was considerably altered when applied to PCDBF induced cultures. Production of amino nitrotoluene isomers was greatly enhanced in induced cultures as compared to uninduced controls, as was the conversion of radiolabeled 2,4-DNT to relatively more polar metabolites. To some extent, the results with H4IIE cells parallel those reported for animals exposed to 2,4-DNT after induction of cytochrome P-450 AHH activity. The preliminary findings suggest that with further development and validation, H4IIE cultures could be of use in characterizing metabolites that result from exposure to chemical mixtures involving a P-450 (1A1) inducer.

Hypochlorite-promoted transformations of trichothecenes, 3. Deoxynivalenol.

Treatment of deoxynivalenol [3] in MeOH with hypochlorite bleach containing added NaOH gave rise to a single major product, the 9 alpha, 10 alpha, 12 beta, 13 beta-diepoxy-8,15-hemiketal 4. Thus, the reaction followed a very different course from that observed for verrucarol [2], where rearrangement involving opening of the starting 12,13-epoxide and a haloform-like oxidation took place.

Fate and distribution of 3H-labeled T-2 mycotoxin in guinea pigs.

T-2 toxin is a potent cytotoxic metabolite produced by the Fusarium species. The fate and distribution of 3H-labeled T-2 toxin were examined in male guinea pigs. Radioactivity was detected in all body tissues within 30 min after an im injection of an LD50 dose (1.04 mg/kg) of T-2 toxin. The plasma concentration of trichothecene molar equivalents versus time was multiphasic, with an initial absorption half-life equal to or less than 30 min. Bile contained a large amount of radioactivity which was identified as HT-2, 4-deacetylneosolaniol, 3'-hydroxy HT-2, 3'-hydroxy T-2 triol, and several more-polar unknowns. These T-2 metabolites are excreted from liver via bile into the intestine. Within 5 days, 75% of the total radioactivity was excreted in urine and feces at a ratio of 4 to 1. The appearance of radioactivity in the excreta was biphasic. Metabolic derivatives of T-2 excreted in urine were T-2 tetraol, 4-deacetylneosolaniol, 3'-hydroxy HT-2, and several unknowns. These studies showed a rapid appearance in and subsequent loss of radioactivity from tissues and body fluids. Only 0.01% of the total administered radioactivity was still detectable in tissues at 28 days. The distribution patterns and excretion rates suggest that liver and kidney are the principal organs of detoxication and excretion of T-2 toxin and its metabolites.

Agonist effects of beta-phenethylamines on the noradrenergic cyclic adenosine 3',5'-monophosphate generating system in rat limbic forebrain. Stereoisomers of p-hydroxynorephedrine.

Significant agonist activity for the specific noradrenergic cyclic adenosine 3',5'-monophosphate (cAMP) generating system in rat limbic forebrain requires a beta-3,4-dihydroxyphenethylamine with a beta-hydroxyl group in the R configuration. Thus, neither of the enantiomers of p-hydroxynorephedrine nor of p-hydroxynorpseudoephedrine mimics the agonist activity of (R)-norepinephrine. It has yet to be established whether or not one of the p-hydroxynorephedrines exhibits antagonist activity in this same system.