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By use of data for surface tension, for the first time a method is presented for calculating true molar surface properties of liquids: free energy, entropy, and enthalpy. These new data allow full comparison with other molar quantities, such as enthalpy and entropy of vaporization. All data are at the normal boiling point. There are differences in behavior between various classes of nonpolar compounds. Rare gases and tetrahydrides of Group 14 form a separate category. The results agree with the experimental findings that water and alcohol molecules are aligned with the -OH groups attached to the surface. The data indicate that hydrogen peroxide and 1,2-ethanediol also have one -OH group directed toward the surface and one directed out toward the vapor phase. Small straight-chain amines have some structure at the surface, but the larger ones behave like the corresponding alkanes. Very polar compounds, such as nitriles, nitro compounds, and aldehydes, have little or no increased degree of order of molecules at the surface. Except for hydrogen-bonded compounds, molecules at the surface have surroundings similar to those in the bulk liquid.
In this paper the solid phase synthesis of various substituted purines is described starting from 4,6-dichloro-5-nitropyrimidine. The 4,6-dichloro-5-nitropyrimidine was coupled to Rink amide resin followed by displacement of the second chloride by an amino compound. Reduction of the nitro compound proved to be problematic but was achieved using lithium aluminum hydride/aluminum trichloride. The diamines (13) were then elaborated to purines by three different routes.
Nitroaromatic compounds for molecular electronic devices are prepared by the high-yielding oxidation of electron-deficient anilines using HOF generated in a fluorine-acetonitrile-water system.
Foodborne diseases caused by enterohemorrhagic Escherichia coli, Salmonella, and Campylobacter species are of public health and economic significance. Shedding of these pathogens during production and slaughter are risks for contamination of products for human consumption. Consequently, strategies are sought to prevent or reduce the carriage of these pathogens in food animals before slaughter. Experimental products containing chlorate salts have been proven efficacious in reducing concentrations of E. coli and Salmonella Typhimurium in the gut of cattle, sheep, swine, and poultry when administered as feed or water additives. Mechanistically, chlorate selectively targets bacteria expressing respiratory nitrate reductase activity, such as most members of the family Enterobacteriaceae, as this enzyme catalyzes the reduction of chlorate to lethal chlorite. Most beneficial gut bacteria lack respiratory nitrate reductase activity, and thus the technology appears compatible with many bacteria exhibiting competitive exclusion capabilities. More recently, select nitrocompounds have been investigated as potential feed additives, and although these nitrocompounds significantly reduce pathogens on their own, evidence indicates that they may most effectively be used to complement the bactericidal activity of chlorate. A particularly attractive aspect of the nitrocompound technology is that, as potent inhibitors of ruminal methanogenesis, they may allow producers the opportunity to recoup costs associated with their use. At present, neither chlorate nor the nitrocompounds have been approved as feed additives by the US Food and Drug Administration, and consequently they are not yet available for commercial use.
The electrochemical characteristics of nitrosochloramphenicol have been studied in aqueous buffer systems (pH 7.1) using direct current (d.c.) and differential pulse polarography, cyclic voltammetry and coulometric techniques. Up to 4 charge-transfer steps can be identified. The first reduction step is reversible both chemically and electrochemically, the charge-transfer product showing no tendency to undergo further reaction on the electrochemical time-scale. In contrast, the second reduction step is irreversible, with the product undergoing a fast following reaction to yield a redox-active species which was detected by cyclic voltammetry. From the data and by comparison with related systems, two reduction mechanisms are possible and are discussed.
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The gene encoding the 'classical nitroreductase' (CNR) of Salmonella typhimurium was disrupted. In this manner, cnr null mutant derivatives of strains TA1535 and TA1538 were constructed, and named YG7131 and YG7127, respectively. In both strain backgrounds, cnr gene disruption reduced nitrofurazone-reductase activity. This reduction almost completely eliminated the nitroreductase activity of strain TA1538. In contrast, the nitroreductase activity of strain TA1535 was much higher than that in TA1538. In this background, cnr gene disruption resulted in a reduction in nitroreductase activity by a similar absolute amount as in TA1538, but representing only about one-quarter of the original activity of TA1535. The results suggest that S. typhimurium has originally at least two distinct nitroreductases, one of which is already deficient in strain TA1538; the CNR is present in both TA1535 and TA1538. Also, these two strains (including their derivatives, TA98 and TA100) are not isogenic with regard to nitroreductase activity. After the introduction of plasmid pKM101, the sensitivities of the strains YG7132 and YG7128, the cnr-null mutants of TA98 and TA100, respectively, against several nitro compounds were compared with those of the conventional cnr-deficient strains TA98NR and TA100NR and the wild-type strains TA98 and TA100. The mutagenicities of 2-nitrofluorene and 1-nitropyrene in YG7132 or TA98NR were ten-fold lower than those of the compounds in TA98. Similarly, the mutagenicity of 2-(2-furyl)-3-(5-nitro-2-furyl) acrylamide in strain YG7128 or TA100NR was substantially lower than that of the compound in TA100. However, the mutagenicity of 2-nitronaphthalene in YG7128 was between those observed with TA100 and TA100NR, suggesting that a nitroreductase in S. typhimurium other than CNR is involved in the metabolic activation of this compound. The cnr gene of S. typhimurium positively hybridized with DNA at 13 min on the E. coli chromosome where the nfsB and nfnB genes of E. coli are mapped. These results suggest that the cnr gene of S. typhimurium is a counterpart of the nfsB and nfnB genes of E. coli, and that the newly constructed cnr-deletion strains are useful to assess the role of nitroreductases in the metabolic activation of mutagenic nitro compounds.
A previous study of substituent effects on the photo-cleavage of 1-acyl-7-nitroindolines has been extended to examine the effects of electron-donating and electron-withdrawing substituents. 1-Acetyl-4,5-methylenedioxy-7-nitroindoline was inert to 350 nm irradiation, reinforcing an earlier finding that excessive electron-donation by substituents can divert the excited state into non-productive pathways. By contrast, the 1-acetyl-5,7-dinitro- and 1-acetyl-4-methoxy-5,7-dinitroindolines and respectively both showed improved photolysis efficiency in aqueous solution compared to the 1-acyl-4-methoxy-7-nitro compound . Unlike , both and gave mixed photoproducts, the corresponding dinitroindolines and the 5-nitro-7-nitrosoindoles. These results are interpreted in terms of a previous mechanistic study. Investigation of the 4-methoxy-5,7-dinitroindoline conjugate of L-glutamate showed that the stoichiometry of glutamate release upon photolysis was only 65-77% of the theoretical value, suggesting that photolysis of these dinitro compounds may involve pathways other than the clean photolysis previously observed for mono-nitro compounds such as .
Basing on the results of EPR investigations and an analysis of literature data an assumption was made of the new factors in the mechanism of the radiosensitizing action of nitro compounds. It was assumed that irradiation-induced accumulation of toxic products of incomplete reduction of the nitro group of these compounds--nitroso- and hydroxyl amino-derivates--in tumor hypoxic zones played the main role in the radiosensitizing action of nitro compounds.
Arthrobacter sp. isolated from sewage oxidized ammonium to hydroxylamine, a bound hydroxylamine compound, a hydroxamic acid, a substance presumed to be a primary nitro compound, nitrite, and nitrate. The concentration of free hydroxylamine-nitrogen reached 15 mug/ml. The identification of hydroxylamine was verified by mass spectrometric analysis of its benzophenone oxime derivative. The bound hydroxylamine was tentatively identified as 1-nitrosoethanol on the basis of its mass spectrum, chemical reactions, and infrared and ultraviolet spectra. Hydroxylamine formation by growing cells was relatively independent of pH, but the accumulation of nitrite was strongly favored in alkaline solutions. The formation of hydroxylamine but not nitrite was regulated by the carbon to nitrogen ratio of the medium. The hydroxamic acid was the dominant product of nitrification in iron-deficient media, but hydroxylamine, nitrite, and 1-nitrosoethanol formation was favored in iron-rich solutions. Heterotrophic nitrification by Arthrobacter sp. was not inhibited by several compounds at concentrations which totally inhibited autotrophic nitrification.
Nitro benzenoid musk compounds (Musk tibetene [CAS no. 145-39-1], Musk ambrette [83-66-9], Musk moskene [116-66-5], Musk ketone [81-14-1] and Musk xylene [81-15-2]) and non-nitro benzenoid musks (Celestolide [13171-00-1], Galaxolide [1222-05-5]) and Fixolide [1506-02-1] [21445-77-7] were analysed in 15 human adipose tissue samples from Switzerland by gas chromatography/high resolution mass spectrometry. The levels of Musk xylene and Galaxolide ranged up to 288 ng/g lipids and 171 ng/g lipids, respectively. The concentrations of non-nitro benzenoid musks found in human adipose tissue raise concern since very few toxicological data are available.
Most of the main categories of bactericidal agents, namely, aliphatic and heterocyclic nitro compounds, metal derivatives and chelators, quinones, azo dyes, and iminium-type ions, are proposed to exert their action by a unified mechanism. The toxic effect is believed to result generally from the catalytic production of reactive oxygen radicals that usually arise via electron transfer. Cyclic voltammetry was performed on a number of these agents. Reductions were for the most part reversible, with potentials in the favorable range of -0.20 to -0.58 V.
Various endogenous and exogenous compounds exert cytotoxic effects via oxygen reduction. In general, these are reduced by intracellular enzymes (reductases of various kinds) in one-electron transfer reactions, before they in turn reduce O2 to O2, the superoxide anion radical. Thus, a cycle is formed of O2 uptake at the expense of cellular reducing equivalents, notably NADPH, generating further active oxygen species (figs 1,2). Structures capable of 'redox cycling' include catechols and other quinone compounds, iron chelates, and aromatic nitro compounds. Several anticancer agents, and also some mutagens, operate on this principle, and their toxic effects may be explained by redox cycling. The particular importance of hypoxic conditions for deleterious O2 effects is given by the concomitant flux through reductive as well as oxidative pathways. Toxic effects include membrane damage resulting from peroxidative reactions of polyunsaturated fatty acids (lipid peroxidation), as well as the attack of reactive oxygen species on proteins (enzymes) and nucleic acids; thus O2 metabolism is linked to carcinogenicity and mutagenicity. Lipid peroxidation is also induced by various halogenated compounds such as carbon tetrachloride. Again, hypoxic conditions are particularly critical because, on the one hand, metabolic activation leading to the free radical is enhanced and, on the other hand, oxygen required for the maintenance of lipid peroxidation is still available. - Powerful antioxidant systems of the cell maintain low steady state concentrations of oxygen metabolites, and toxic effects may, in part, also be explained by the constant drain of reducing equivalents resulting from redox cycling.
We use the topological sub-structural molecular design (TOPS-MODE) approach to formulate structural alert rules for chromosome aberration (CA) of organic compounds. First, a classification model was developed to group chemicals as active/inactive respect to CA. A procedure for extracting structural information from orthogonalized TOPS-MODE descriptors was then implemented. The contributions of bonds to CA in all the molecules studied were then generated using the orthogonalized classification model. Using this information we propose 22 structural alert rules which are ready to be implemented in expert systems for the automatic prediction of CA. They include, among others, structural alerts for N-nitroso compounds (ureas, urethanes, guanidines, triazines), nitro compounds (aromatic and heteroaromatic), alkyl esters or phosphoric acids, alkyl methanesulfonates, sulphonic acids and sulphonamides, epoxides, aromatic amines, azaphenanthrene hydrocarbons, etc. The chemico-biological analysis of some of the structural alerts found is also carried out showing the potential of TOPS-MODE as a knowledge generator.
Cellular metabolism and, in particular, oxidation-reduction systems are linked to responses to drugs and toxic agents in several ways. Major connections are given by the NADPH/NADP+ system and the GSH/GSSG system. Intracellular reductive pathways generally use NADPH as the electron donor. From a toxicological point of view, NADPH can be considered both as a "detoxicant" and as a "toxicant". In the former case, NADPH supports the glutathione redox cycle by maintaining a negative redox potential of GSH to permit its detoxication functions to occur. NADPH is also the main donor for reducing equivalents in drug oxidations by the cytochrome P-450-dependent monooxygenase system which, with some notable exceptions, serves important purposes in detoxication. The sources of NADPH reducing equivalents depend on the nutritional state: major sources in the fed state are represented by the cytosolic pentose phosphate shunt dehydrogenases, whereas mitochondrial sources linked to isocitrate dehydrogenase provide the bulk of NADPH reducing equivalents in the fasted state. As a "toxicant", NADPH supports redox cycling reactions involving various drugs and other compounds of quinoid structure, aromatic nitro compounds and iron chelates with formation of superoxide anion radicals and subsequent formation of other oxygen derived radical species. This presentation focuses on recent work carried out with isolated hepatocytes and perfused rat liver with respect to "oxidative stress". The noninvasive techniques of measurement of low-level chemiluminescence and of volatile hydrocarbons (ethane, pentane) as well as glutathione release and calcium release have been employed.
Genotoxicity and cytotoxic effects of eight new nitrothiophenic compounds with trypanocidal activity were determined by means of the SOS Chromotest assay. Our results indicate that all nitro compounds with one aromatic ring in the R group were genotoxic without and with metabolic activation. The compounds with two aromatic rings in the R group, except for indazol-1-yl, were strongly cytotoxic but they were unable to induce SOS functions without metabolic activation. However, after metabolic activation no cytotoxic effect was observed for these compounds. The role of the nitroreductases to explain the different genotoxic responses of these nitrothiophenic derivatives is discussed.
An identification reaction for tolbutamide given in several pharmacopoeias involves the reaction of n-butylamine, formed by acid hydrolysis of tolbutamide, with diazotised p-nitroaniline to yield a characteristic red colour of unknown structure(s). It is demonstrated that, by using TLC methods, this red colour can be separated into 8 red or yellow coloured components. The structures of these isolated compounds were determined by spectroscopical methods and, in six cases, confirmed by unequivocal synthesis. These coloured components include one pentazdiene, five triazenes and two nitro compounds.