Nitro-substituted Compounds Research Articles

Correlation of the genotoxic activation and kinetic properties of Salmonella enterica serovar Typhimurium nitroreductases SnrA and cnr with the redox potentials of nitroaromatic compounds and quinones

Bacterial nitroreductases (NRs) catalyse the oxygen-insensitive reduction of several nitro-substituted compounds and quinones. SnrA and cnr NRs have been previously identified in Salmonella enterica serovar Typhimurium; they reduce several environmental nitro compounds that display mutagenic activity in the Ames test. Although some of their biochemical properties have been reported, the substrate specificity of each protein over mutagenic nitro compounds is unknown; even more, the possible relationship between their capacity to activate nitro compounds into mutagens and the redox properties of putative substrates has been poorly investigated. We have purified SnrA and cnr and investigated their capacity to activate several mutagens in the Ames test as well as their kinetic parameters K(m) and V(max). Our results show that SnrA and cnr are able to activate 2,7-dinitrofluorene with the same efficiency and a similar mutagenic potency in the YG7132 tester strain; 1-nitropyrene and 1,3-dinitropyrene were efficiently activated by cnr, whereas 1,8-dinitropyrene, 1,6-dinitropyrene and 2-nitrofluorene were scarcely activated by either NR. The mutagenic potency of nitro compounds obtained in the presence of either enzyme correlates with their redox potential reported in the literature. On the other hand, a good correlation was obtained between the catalytic efficiency (V(max)/K(m)) of the purified cnr with the redox potential of eight molecules including nitro-substituted compounds and quinones. No correlation between redox potential and catalytic efficiency by SnrA was observed, suggesting that factors other than redox potential such as the structure of the compounds are involved in the catalytic efficiency of SnrA.

The role of two putative nitroreductases, Frm2p and Hbn1p, in the oxidative stress response in Saccharomyces cerevisiae

The nitroreductase family is comprised of a group of FMN- or FAD-dependent enzymes that are able to metabolize nitrosubstituted compounds using the reducing power of NAD(P)H. These nitroreductases can be found in bacterial species and, to a lesser extent, in eukaryotes. There is little information on the biochemical functions of nitroreductases. Some studies suggest their possible involvement in the oxidative stress response. In the yeast Saccharomyces cerevisiae, two nitroreductase proteins, Frm2p and Hbn1p, have been described. While Frm2p appears to act in the lipid signalling pathway, the function of Hbn1p is completely unknown. In order to elucidate the functions of Frm2p and Hbn1p, we evaluated the sensitivity of yeast strains, proficient and deficient in both oxidative stress proteins, for respiratory competence, antioxidant-enzyme activities, intracellular reactive oxygen species (ROS) production and lipid peroxidation. We found reduced basal activity of superoxide dismutase (SOD), ROS production, lipid peroxidation and petite induction and higher sensitivity to 4-nitroquinoline-oxide (4-NQO) and N-nitrosodiethylamine (NDEA), as well as higher basal activity of catalase (CAT) and glutathione peroxidase (GPx) and reduced glutathione (GSH) content in the single and double mutant strains frm2Delta and frm2Delta hbn1Delta. These strains exhibited less ROS accumulation and lipid peroxidation when exposed to peroxides, H(2)O(2) and t-BOOH. In summary, the Frm1p and Hbn1p nitroreductases influence the response to oxidative stress in S. cerevisae yeast by modulating the GSH contents and antioxidant enzymatic activities, such as SOD, CAT and GPx.

Zerovalent Iron에 의해 유도되는 제초제 Dicamba의 산화적 분해

Dicamba(3,6-dichloro-2-methoxybenzoic acid) is used to control for pre and post-emergence of annual and perennial broad-leaf weeds. It is very soluble in water and highly mobile, acidic herbicide. So it is easily moved and detected in groundwater. Zerovalent iron(ZVI) has been used for the reductive degradation of certain compounds through amination of nitro-substituted compounds and dechlorination of chloro-substituted compounds. In this study, we investigated the potential of ZVI for the oxidative degradation of dicamba in water. The degradation rate of dicamba by ZVI was more rapidly increased in pH 3.0 than pH 5.0 solution. The degradation percentage of dicamba was increased with increasing amount of ZVI from 0.05% to 1.0%(w/v) and reached above 90% within 3 hours of reaction. As a result of identification by GC-MS after derivatization with diazomethane, we obtained three degradation products of dicamba by ZVI. They were identified 4-hydroxy dicamba or 5-hydroxy dicamba, 4,5-dihydroxy dicamba and 3,6-dichloro-2-methoxyphenol. 4-Hydroxy dicamba or 5-hydroxy dicamba and 4,5-dihydroxy dicamba are hydroxylation products of dicamba. 3,6-dichloro-2-methoxyphenol is hydroxyl group substituted compound instead of carboxyl group in dicamba. We also confirmed the same degradation products of dicamba in the Fenton reaction which is one of oxidation processes using ferric sulfate and hydrogen peroxide. But we could not find out the dechlorinated degradation products of dicamba by ZVI.

Synthesis and properties of fluorescent conjugated oligomers for chemosensing application

Two conjugated polymers comprised of fluorene and benzene and linked by vinylene bonds have been synthesized via Heck reaction. The obtained polymers were characterized by NMR, UV, fluorescent spectroscopy, GPC and thermal analysis. Both of the polymers are fluorescent and show fluorescence quenching sensitivity towards nitro-substituted compound, indicating that they have the potential to be used as sensing materials for chemical vapour.

Synthesis and Conformational Analysis of Macrocyclic Dihydroxystilbenes Linked between thepara–paraPositions

A new family of diphenylethanes has been synthesized as conformationally restricted analogues of antimitotic combretastatins. The two phenyl rings are linked between the para-phenolic positions through a 3-oxapentamethylene or hexamethylene chain. The key macrocyclization step was achieved in moderate yields by using an intramolecular McMurry pinacol coupling of linked aromatic dialdehydes, except for the nitro-substituted compounds. The relative stereochemistry of the isomeric pinacols was determined by a combination of spectroscopic, chemical derivatization, and molecular-modeling approaches. The NMR spectra of these compounds (with a polyoxygenated crownophane skeleton) indicate severe conformational restrictions relative to their parent combretastatins; the rotation of the phenyl rings is hampered by interactions of their substituents and the linker and the conformational restrictions imposed by the substituted bridge.

QSAR studies and pharmacophore identification for arylsubstituted cycloalkenecarboxylic acid methyl esters with affinity for the human dopamine transporter

Data from a series of 29 monoamine transport inhibitors were used to generate 2D and 3D QSAR models for their binding affinity to the human dopamine transporter (hDAT). Among the inhibitors were many non-nitrogen containing compounds. The 2D QSAR analysis resulted in the equation −log K i = 4.00 − 3.93 E LUMO − 0.67 E HOMO − 3.24 σ p, which predicted the importance of electron withdrawing groups in the aromatic moiety. However, the model failed to predict the observed poor binding of nitro-substituted compounds. In contrast, a derived 3D QSAR model was capable of predicting these more correctly.

In silico identification of a new group of specific bacterial and fungal nitroreductases-like proteins

The nitroreductase family comprises a group of FMN- or FAD-dependent and NAD(P)H-dependent enzymes able to metabolize nitrosubstituted compounds. The nitroreductases are found within bacterial and some eukaryotic species. In eukaryotes, there is little information concerning the phylogenetic position and biochemical functions of nitroreductases. The yeast Saccharomyces cerevisiae has two nitroreductase proteins: Frm2p and Hbn1p. While Frm2p acts in lipid signaling pathway, the function of Hbn1p is unknown. In order to elucidate the function of Frm2p/Hbn1p and the presence of homologous sequences in other prokaryotic and eukaryotic species, we performed an in-depth phylogenetic analysis of these proteins. The results showed that bacterial cells have Frm2p/Hbn1p-like sequences (termed NrlAp) forming a distinct clade within the fungal Frm2p/Hbn1p family. Hydrophobic cluster analysis and three-dimensional protein modeling allowed us to compare conserved regions among NrlAp and Frm2/Hbn1p proteins. In addition, the possible functions of bacterial NrlAp and fungal Frm2p/Hbn1p are discussed.

Influence of the core structure on the development of polar order and superstructural chirality in liquid crystalline phases formed by silylated bent-core molecules: lateral substituents

The influence of lateral substituents was studied for a new series of bent-core liquid crystals with heptamethyltrisiloxane units at both ends of the aliphatic side chains. These materials were investigated by polarized light microscopy, differential scanning calorimetry, X-ray scattering and electro-optical methods. An antiferroelectric switching columnar phase was found for the non-substituted compound. Different types of non-switching columnar phases were obtained for molecules having substituents (CH, NO) in the bay position, whereas a temperature-dependent transition from polar to non-polar smectic phases was found for molecules having substituents (Cl, CN) adjacent to one of the ester linking units. For the CN-substituted compound a new phase sequence SmCP-SmC-Cub-Iso was observed. The occurrence of the cubic phase is associated with a steric frustration due to the bulky silyl groups. The special rectangular columnar mesophase of the nitro-substituted compound is discussed with respect to its relation to B7-type mesophases.

Direct LD-FTMS detection of mineral-associated PAHs and their influence on the detection of co-existing amino acids

Polycyclic aromatic hydrocarbon (PAH) compounds and amino acids (AAs) are both ubiquitous throughout the universe and can be co-located in mineral matrices (e.g., meteorites); therefore, co-detection of PAHs and AAs associated with terrestrial and extra-terrestrial minerals is of interest. Nine PAH compounds representing four chemical classes of PAH (unsubstituted, acetyl-, amino-, and nitro-substituted) were applied onto the surface of quartz, plagioclase, olivine, and ilmenite mineral standards and analyzed using laser desorption/ionization Fourier transform mass spectrometry (LD-FTMS). Mass-to-charge peaks derived from PAH compounds were detected from the surfaces of all minerals evaluated. All PAH compounds were detected in the positive ion mode, whereas only nitro-substituted PAH compounds were detected in negative ion mode. In this and earlier studies, the ability to directly detect mineral-associated AAs by LD-FTMS was dependent on the mineral geomatrix. On iron-bearing minerals AAs appeared as highly fragmented ions in the spectra or were not detectable; however, the addition of the PAH chrysene enabled the ionization and detection of AAs threonine and histidine by LD-FTMS. Thus, for mineral systems such as meteorites, interstellar dust particles, soils, and sediments, the co-detection of AAs associated with PAHs by LD-FTMS is feasible.

TNT transformation products are affected by the growth conditions of Raoultella terrigena

High concentrations of 2,4,6-trinitrotoluene (TNT) and related nitroaromatic compounds are commonly found in soil and groundwater at former explosive plants. The bacterium, Raoultella terrigena strain HB, isolated from a contaminated site, converts TNT into the corresponding amino products. Radio-HPLC analysis with [(14)C]TNT identified aminodinitrotoluene, diaminonitrotoluene and azoxy-dimers as the main metabolites. Transformation rate and the type of metabolites that predominated in the culture medium and within the cells were significantly influenced by the culture conditions. The NAD(P)H-dependent enzymatic reduction of nitro-substituted compounds by cell-free extracts of R. terrigena was evaluated in vitro.

Novel Five-Ring Bent-Core Compounds Exhibiting a Transition from the Electro-optically Nonswitchable to a Switchable B7 Phase

Two homologous series of achiral five-ring bent-core compounds derived from 2-cyano- or 2-nitro-resorcinol having terminal n-alkyl carboxylate groups have been synthesized and characterized. All the compounds investigated show enantiotropic mesophases. Interestingly, the compounds derived from 2-cyanoresorcinol display two mesophases and the higher temperature mesophase shows unusual electro-optical characteristics. In contrast, the nitro-substituted compounds exhibit only one mesophase, which switches electro-optically. This mesophase and the higher temperature phase exhibited by the cyano-substituted compounds show similar characteristics and have been shown to be the same. These observations are unusual but very interesting and represent the first example of a transition from the electro-optically nonswitchable B7X phase to a switchable B7FE phase.

Synthesis and Biological Evaluation of (E)-3-(Nitrophenyl)-1-(pyrazin-2-yl)prop-2-en-1-ones

The title (E)-(3-nitrophenyl)-1-(pyrazin-2-yl)prop-2-en-1-ones were prepared by the Claisen- Schmidt condensation of acetylpyrazines and 2-nitro-, 3-nitro- and 4-nitrobenzaldehyde in pyridine using diethylamine as the catalyst. The compounds were bioassayed for in vitro antifungal, antimycobacterial and photosynthesis-inhibiting activity. The high potency of (E)-1-(5-tert-butylpyrazin-2-yl)-3-(4-nitrophenyl)prop-2-en-1-one againstMycobacterium tuberculosis(MIC 0.78 μg/ml) and moderate activities of several compounds againstTrichophyton mentagrophytesandCandidaspp. do not support the assumption that phenolic groups are essential for antimycobacterial and antifungal activity of chalcones and their analogues. In fact, the nitro-substituted compounds were superior to the previously described hydroxylated congeners with antimycobacterial activity (MIC ≥ 12.5 μg/ml). The compounds also reduced chlorophyll content in green algaChlorella vulgaris, and some of them inhibited photosynthetic electron transport in spinach chloroplasts as well. The photosynthesis-inhibiting activity of nitro derivatives was lower than that of the corresponding hydroxylated analogues.

Synthesis and Antitumor Activity of Sulfur-Containing 9-Anilinoacridines

A series of sulfur-containing 9-anilinoacridines related to amsacrine were synthesized and evaluated for their anticancer potential. Among the compounds, both diol-containing compounds, 2a and 3, were the most cytotoxic of the sulfide series against V-79 cells in vitro (IC(90) = 2.1 microM and 1.9 microM, respectively). Among the non-alkyl-substituted compounds (7-9), compounds with electron-donating substitution para to the sulfide (7 and 9) were more cytotoxic than the electron-withdrawing nitro-substituted compound 8. The limited SAR suggested the importance of hydroxyl functionality along with its location for the cytotoxicity in the series. A preliminary anticancer screening against P388 leukemia showed that 2a is highly active in vivo as well. Topoisomerase II inhibitory activity appeared to be involved in the cytotoxicity of compound 2a. Sulfoxide compound 2b, which is 6-7-fold less cytotoxic than its sulfide 2a, appears to be a potential bioreductive anticancer prodrug on the basis of its bioreductive metabolism findings.

Synthesis and optical properties of push–pull type tetrapyrazinoporphyrazines

The optical properties of push–pull type tetrapyrazinoporphyrazines based on 2,3-dicyanopyrazines were demonstrated. They have alkoxyphenyl substituent as an electron donor group at 5-position, and nitro- or sulfonyl-phenyl substituents as an electron acceptor group at 6-position of 2,3-dicyanopyrazine. The absorption and fluorescence maxima of nitro-substituted compounds were observed at 427–444 and 453–494 nm, respectively. In the case of sulfonyl-substituted compounds, the hypsochromic shift of absorption and fluorescence maxima were 59–104 and 13–79 nm, respectively.

Mechanism for the differential toxicity of neonicotinoid insecticides in the honey bee, Apis mellifera

Laboratory bioassays were conducted to determine the contact honey bee toxicity of commercial and candidate neonicotinoid insecticides. The nitro-substituted compounds were the most toxic to the honey bee in our laboratory studies with LD50 values of 18 ng/bee for imidacloprid, 22 ng for clothianidin, 30 ng for thiamethoxam, 75 ng for dinotefuran and 138 ng for nitenpyram. The cyano-substituted neonicotinoids exhibited a much lower toxicity with LD50 values for acetamiprid and thiacloprid of 7.1 and 14.6 μg/bee, respectively. Piperonyl butoxide, triflumizole and propiconazole increased honey bee toxicity of acetamiprid 6.0-, 244- and 105-fold and thiacloprid 154-, 1,141- and 559-fold, respectively, but had a minimal effect on imidacloprid (1.70, 1.85 and 1.52-fold, respectively). The acetamiprid metabolites, N-demethyl acetamiprid, 6-chloro-3-pyridylmethanol and 6-chloro-nicotinic acid when applied topically, produced no mortality at 50 μg/bee. These results suggest that P450s are an important mechanism for acetamiprid and thiacloprid detoxification and their low toxicity to honey bees. When honey bees were placed in cages in forced contact with alfalfa treated with acetamiprid and the synergist, triflumizole, in combination at their maximum recommended application rates, no mortality was detected above that of the control.

A polar biaxial smectic A phase in new unsymmetrical compounds composed of bent-core molecules

The synthesis and liquid crystalline properties of several new compounds unsymmetrically substituted about two different central phenyl rings are reported. All the compounds contain a strongly polar terminal cyano/nitro substituent. Some of the nitro-substituted compounds derived from 3-hydroxybenzoic acid show a transition from the partial bilayer uniaxial smectic A (SmAd) phase to a polar partial bilayer biaxial smectic A (SmAdPA) phase. The analogous cyano-substituted derivatives exhibit only a SmAd phase. However, compounds containing a 4-cyanobiphenyl moiety in the terminal position and derived from 1,3-dihydroxybenzene show the SmAd – SmAdPA transition. The mesophases were characterized using polarizing optical microscopy, differential scanning calorimetry, X-ray diffraction studies, conoscopic examination and miscibility studies.

Mechanism for the differential toxicity of neonicotinoid insecticides in the honey bee, Apis mellifera

Laboratory bioassays were conducted to determine the contact honey bee toxicity of commercial and candidate neonicotinoid insecticides. The nitro-substituted compounds were the most toxic to the honey bee in our laboratory studies with LD 50 values of 18 ng/bee for imidacloprid, 22 ng for clothianidin, 30 ng for thiamethoxam, 75 ng for dinotefuran and 138 ng for nitenpyram. The cyano-substituted neonicotinoids exhibited a much lower toxicity with LD 50 values for acetamiprid and thiacloprid of 7.1 and 14.6 μg/bee, respectively. Piperonyl butoxide, triflumizole and propiconazole increased honey bee toxicity of acetamiprid 6.0-, 244- and 105-fold and thiacloprid 154-, 1,141- and 559-fold, respectively, but had a minimal effect on imidacloprid (1.70, 1.85 and 1.52-fold, respectively). The acetamiprid metabolites, N-demethyl acetamiprid, 6-chloro-3-pyridylmethanol and 6-chloro-nicotinic acid when applied topically, produced no mortality at 50 μg/bee. These results suggest that P450s are an important mechanism for acetamiprid and thiacloprid detoxification and their low toxicity to honey bees. When honey bees were placed in cages in forced contact with alfalfa treated with acetamiprid and the synergist, triflumizole, in combination at their maximum recommended application rates, no mortality was detected above that of the control.

Observation of a transition from non-switchable B7 mesophase to an antiferroelectric sub-phase in strongly polar bent-core compoundsElectronic supplementary information (ESI) available: data for compounds 7, 8 and 9 as well as the general synthetic procedure for the preparation of the compounds of series II. See http://www.rsc.org/suppdata/jm/b3/b309138d/

The synthesis and characterization of two new homologous series of five-ring Schiff's base esters exhibiting the non-switchable B7 mesophase are reported. These compounds have been derived from either 2-nitro- or 2-cyanoresorcinol. Interestingly, three higher homologues of the nitro-substituted compounds undergo a transition from the non-switchable B7 mesophase to an antiferroelectric sub-phase (B7AF1), which is the first example of such a transition. In addition to comparing the mesomorphic behaviour of the two series of compounds, the effect of reversing the azomethine linkage group in these series of compounds has also been examined. The mesophases have been characterized by conventional techniques.

Identification and characterization of SnrA, an inducible oxygen-insensitive nitroreductase in Salmonella enterica serovar Typhimurium TA1535

The biological activity of many nitrosubstituted compounds, many of which are produced commercially or have been identified as environmental contaminants, is dependent on metabolic activation catalyzed by nitroreductases. In the current study, we have cloned a nitroreductase gene, Salmonella typhimurium nitroreductase A ( snrA), from S. enterica serovar Typhimurium strain TA1535, and characterized the purified gene product. SnrA is 240 amino acids in length and shares 87% sequence identity to the Escherichia coli homolog, E. coli nitroreductase A (NfsA). SnrA is the major nitroreductase in S. enterica serovar Typhimurium strain TA1535 and catalyzes nitroreduction through a ping-pong bi-bi mechanism in a NADPH and flavine mononucleotide (FMN) dependent manner. SnrA exhibits extremely low levels of FMN reductase activity but the nitroreductase activity of SnrA is competitively inhibited by exogenously added FMN. Treatment of TA1535 with paraquat resulted in induction of nitroreductase activity, suggesting that SnrA is a member of the S. enterica serovar Typhimurium SoxRS regulon associated with cellular defense against oxidative damage. Examination of the microbial genomes databases shows that SnrA homologs are widely distributed in the microbial world, being present in isolates of both Archea and Eubacteria. Southern hybridization and PCR failed to detect the snrA gene in the closely related S. enterica serovar Typhimurium strain TA1538. S. enterica serovar Typhimurium strains TA1535 and TA1538 and their derivatives are commonly used in mutagenicity testing. Differences in metabolic capacity between these two strains may have implications for the interpretation of mutagenicity data.

Benzyl alcohols as accelerators in the photoinitiated cationic polymerization of epoxide monomers

AbstractBenzyl alcohols display marked accelerating effects on the onium salt photoinitiated cationic ring‐opening polymerizations of epoxide monomers. The participation of radicals in these polymerizations was demonstrated, and a pronounced accelerating effect on the polymerization rate was observed depending on the character of the substituent on the benzene ring of the alcohol. 4‐Methoxybenzyl alcohol was considerably more reactive than benzyl alcohol, whereas the analogous chloro‐ and nitrosubstituted compounds were less reactive. Piperonyl alcohol was even more reactive as an accelerator in these polymerizations. The UV irradiation of an onium salt cationic photoinitiator generates Brönsted acids that initiate the cationic ring‐opening polymerization of the epoxide monomer. In the presence of benzyl alcohol, the usual polymerization mechanism is diverted and proceeds by a more‐rapid activated monomer mechanism. As a result, benzyl ether groups are incorporated at the termini of the polymer chains. Aryl radicals that are also generated by photolysis of the onium salt abstract labile benzyl ether protons, and the benzyl ether radicals that are produced are subsequently oxidized by the onium salt to afford the corresponding benzyl carbocations. This takes place by a chain process. The polymer bound benzyl cations serve as additional sites for the initiation of cationic polymerization. It is proposed that these two mechanisms acting in synergy with one another account for the observed accelerating effect on the polymerization rate. © 2002 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 40: 2298–2309, 2002