Nitro-substituted Compounds Research Articles

Novel 2-indolinone derivatives as promising agents against respiratory syncytial and yellow fever viruses.

Background: A vaccine or antiviral drug for respiratory syncytial virus (RSV) infections and a specific antiviral drug for yellow fever virus (YFV) infections has not yet been developed. Method: In this study, 2-indolinone-based N-(4-sulfamoylphenyl)hydrazinecarbothioamides were synthesized. Along with these new compounds, previously synthesized 2-indolinone-based N-(3-sulfamoylphenyl)hydrazinecarbothioamides were evaluated against various DNA and RNA viruses. Results: Some 2-indolinone compounds exhibited nontoxic and selective antiviral activities against RSV and YFV. Halogen substitution at the indole ring increased the anti-RSV activities. Moreover, 1-benzyl and 5-halogen or nitro-substituted compounds were the most effective compounds against YFV. Conclusion: Generally, the 3-sulfonamide-substituted compounds were determined to be more effective than 4-sulfonamide-substituted compounds against RSV and YFV.

Structural Diversity of Hydrogen-Bonded 4-Aryl-3,5-Dimethylpyrazoles for Supramolecular Materials.

The 1H-pyrazoles have high versatility and ability to form hydrogen-bonded supramolecular materials. In this study, the thermal stability, fluorescence, and H-bonding ability of the studied 3,5-dimethyl-4-(4-X-phenyl)-1H-pyrazoles showed large differences depending on the terminal substituent. Supramolecular structures were analyzed using X-ray diffraction and Hirshfeld surface calculations. Compounds were found to arrange in different hydrogen-bonded structures, depending on the substitution at the para position of the phenyl ring (X = OCH3, NO2, NH2). The methoxy-substituted compounds arranged in dimers through methanol bridges, the nitro-substituted compound formed supramolecular polymers or catemers, and the amino-substituted compound gave rise to a new structure based on a 2D hydrogen-bonded network.

Evolutionary aspects of the Viridiplantae nitroreductases

BackgroundNitroreductases are a family of evolutionarily related proteins catalyzing the reduction of nitro-substituted compounds. Nitroreductases are widespread enzymes, but nearly all modern research and practical application have been concentrated on the bacterial proteins, mainly nitroreductases of Escherichia coli. The main aim of this study is to describe the phylogenic distribution of the nitroreductases in the photosynthetic eukaryotes (Viridiplantae) to highlight their structural similarity and areas for future research and application. ResultsThis study suggests that homologs of nitroreductase proteins are widely presented also in Viridiplantae. Maximum likelihood phylogenetic tree reconstruction method and comparison of the structural models suggest close evolutional relation between cyanobacterial and Viridiplantae nitroreductases. ConclusionsThis study provides the first attempt to understand the evolution of nitroreductase protein family in Viridiplantae. Our phylogeny estimation and preservation of the chloroplasts/mitochondrial localization indicate the evolutional origin of the plant nitroreductases from the cyanobacterial endosymbiont. A defined high level of the similarity on the structural level suggests conservancy also for the functions. Directions for the future research and industrial application of the Viridiplantae nitroreductases are discussed.

Polar Diels-Alder Reactions Under Microwave Irradiation Employing Different Heterocyclic Compounds as Electrophiles

During the last twenty years, our research group has been working with aromatic nitrosubstituted compounds acting as electrophiles in Polar Diels-Alder (P-DA) reactions with different dienes of diverse nucleophilicity. In this type of reaction, after the cycloaddition reaction, the nitrated compounds obtained as the [4+2] cycloadducts suffer cis-extrusion with the loss of nitrous acid and a subsequent aromatization. In this form, the reaction results are irreversible. On the other hand, the microwave-assisted controlled heating become a powerful tool in organic synthesis as it makes the reaction mixture undergo heating by a combination of thermal effects, dipolar polarization and ionic conduction. As the Diels-Alder (D-A) reaction is one of the most important process in organic synthesis, the microwave (MW) irradiation was applied instead of conventional heating, and this resulted in better yields and shorter reaction times. Several substituted heterocyclic compounds were used as electrophiles and different dienes as nucleophiles. Two experimental situations are involved: one in the presence of Protic Ionic Liquids (PILs) as solvent and the other under solvent-free conditions. The analysis is based on experimental data and theoretical calculations.

Stability Study of Poly Nitro Substituted Compounds of cis-syn-cis-2,6-Dioxodecahydro-lH,5H-Diimidazo[4,5-b:4’,5’-e] Pyrazine

Due to their excellent performance both in density and high detonation velocity, poly nitro substituted cis-syn-cis-2,6- dioxodecahydro-lH,5H-diimidazo [4,5-b:4’,5’-e] pyrazine derivatives (2-5) attract our focus. The stabilities study showed that the sensitivity of these compounds is increasing with more nitro groups substituted. Although compound 5 with six nitro groups exhibits the most excellent detonation velocity, it is very sensitive to friction and impact. As isomer to each other, compound 2 and 3 showed not only low sensitivity but also good thermal stability with similar detonation performance to RDX and HMX. It suggests that they are potential energetic materials.

Synthetic Approaches to Nitro-Substituted Isoxazoles

Nitro-substituted isoxazoles are of utmost interest both as versatile intermediates for targeted organic synthesis and as perspective bioactive compounds for drug development. Nevertheless, the existing approaches to them usually lack generality and strongly depend on the position of the nitro group and on the presence of other substituents in the isoxazole ring. This review provides the first systematization of all available data concerning synthetic approaches to 3-, 4-, and 5-nitroisoxazoles. There are a number of preparative approaches to 4-nitroisoxazoles based on classical heterocyclization reactions of nitro-substituted compounds and the nitration of isoxazoles. 3-Nitro- and, especially, 5-nitroisoxazoles are much less readily available. A few methods affording 3-nitroisoxazoles have been reported, often employing the heterocyclization of unsaturated compounds by treatment with sodium nitrite. The sole general preparative method for 5-nitroisoxazoles, containing a variety of functional groups, employs the heterocyclization of electrophilic alkenes by treatment with tetranitromethane activated with triethylamine.1 Introduction2 Synthesis of 4-Nitroisoxazoles2.1 Nitration of Isoxazoles2.2 Condensations of α-Nitro Ketones or Their Oximes2.3 1,3-Dipolar Cycloaddition of Nitrile Oxides to Acetylenes and Their Synthetic Equivalents2.4 Heterocyclization of Acetylene Derivatives by Treatment with Sodium Nitrite2.5 Heterocyclization of Nitro Derivatives of 1,3-Diketones and Their Synthetic Equivalents2.6 Miscellaneous Methods3 Synthesis of 3-Nitroisoxazoles3.1 Heterocyclization of Acetylene Derivatives or 1,3-Dihalogenoalkenes by Treatment with Sodium Nitrite3.2 Heterocyclization of Morita–Baylis–Hillman Acetates by Treatment with Sodium Nitrite3.3 1,3-Dipolar Cycloadditions4 Synthesis of 5-Nitroisoxazoles4.1 1,3-Dipolar Cycloadditions4.2 Synthesis Using Polynitro Compounds5 Conclusion

Synthesis, Antibacterial and Antioxidant Activities of Some Tridentate Substituted Salicylaldimines

Five substituted tridentate salicylaldimines, (E)-2-((2-hydroxybenzylidene)amino)phenol, (E)-2-(((2-hydroxyphenyl)imino)methyl)-4-nitrophenol, (E)-4-chloro-2-(((2-hydroxyphenyl)imino)methyl) phenol, (E)-2-(((2-hydroxyphenyl)imino)methyl)-4-methoxyphenol, (E)-4-bromo-2-(((2-hydroxy-phenyl)imino)methyl)-6-methoxyphenol were synthesised and characterised by elemental analysis, IR, UV and NMR (1H and 13C). They were screened against some multi-drug resistance Gram-positive (Streptococcus agalactiae and Staphylococcus aureus), and Gram-negative (Escherichia coli, Klebsiella pneumonia, Proteus mirabilis, Pseudomonas aeruginosa and Salmonella typhimurium) organisms by the agar-well diffusion method. The total antioxidant capacities of the salicylaldimines were determined by the phosphomolybdenum assay. Their antibacterial and antioxidant activities were screened to understand the substituents effects. The result showed that the methoxy-substituted compound exhibited the highest antibacterial and antioxidant activities while the nitro-substituted compound exhibited the least activities. This implies that the electron-donating group of the compound increases its antibacterial and antioxidant activities. The one-way analysis of variance was performed with MINITAB 17 at 95% confidence level.

A Novel Mechanism of Inactivating Antibacterial Nitro Compounds in the Human Pathogen Staphylococcus aureus by Overexpression of a NADH-Dependent Flavin Nitroreductase.

Recently, the nitro-substituted bisquaternary bisnaphthalimides were reported to have substantial anti-infective activity against Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA). Here, we selected resistant S. aureus clones by cultivation in increasing concentrations of the most active compound, MT02. Interestingly, MT02-resistant variants induced a diffusible red color of the broth. Chromatographic and spectroscopic investigations revealed a stepwise reduction of the bisquaternary bisnaphthalimides' nitro groups to amino groups. The corresponding derivatives were completely inactive against staphylococci. RNA sequencing experiments revealed a strong overexpression of a novel oxidoreductase in MT02-resistant strains. Deletion mutants of this enzyme did not produce the red color and were not able to develop resistance against bisquaternary bisnaphthalimides. Biochemical reactions confirmed an NADH-dependent deactivation of the nitro-substituted compounds. Thus, this is the first report of a nitroreductase-based antibiotic resistance mechanism in the human pathogen S. aureus.

A novel nitroreductase-enhanced MRI contrast agent and its potential application in bacterial imaging

Nitroreductases (NTRs) are known to be able to metabolize nitro-substituted compounds in the presence of reduced nicotinamide adenine dinucleotide (NADH) as an electron donor. NTRs are present in a wide range of bacterial genera and, to a lesser extent, in eukaryotes hypoxic tumour cells and tumorous tissues, which makes it an appropriate biomarker for an imaging target to detect the hypoxic status of cancer cells and potential bacterial infections. To evaluate the specific activation level of NTR, great efforts have been devoted to the development of fluorescent probes to detect NTR activities using fluorogenic methods to probe its behaviour in a cellular context; however, NTR-responsive MRI contrast agents are still by far underexplored. In this study, para-nitrobenzyl substituted T1-weighted magnetic resonance imaging (MRI) contrast agent Gd-DOTA-PNB (probe 1) has been designed and explored for the possible detection of NTR. Our experimental results show that probe 1 could serve as an MRI-enhanced contrast agent for monitoring NTR activity. The in vitro response and mechanism of the NTR catalysed reduction of probe 1 have been investigated through LC–MS and MRI. Para-nitrobenzyl substituted probe 1 was catalytically reduced by NTR to the intermediate para-aminobenzyl substituted probe which then underwent a rearrangement elimination reaction to Gd-DOTA, generating the enhanced T1-weighted MR imaging. Further, LC–MS and MRI studies of living Escherichia coli have confirmed the NTR activity detection ability of probe 1 at a cellular level. This method may potentially be used for the diagnosis of bacterial infections.

Urea Metal-Organic Frameworks for Nitro-Substituted Compounds Sensing.

Urea groups are known to form strong hydrogen bonds with molecules containing atom(s) that can act as hydrogen bond acceptor(s). Thus, urea is a particularly interesting building block for designing receptors for neutral or charged guests. In the quest for new sensors with enhanced performance for the detection of nitro-substituted compounds, two pillared metal-organic frameworks containing urea functional groups were synthesized and structurally characterized. The sensing properties of these frameworks toward nitro-analytes were investigated and compared to each other. The study clearly reveals the importance of urea groups orientation inside the pore cavity of MOFs, as well as the supramolecular interactions between the interpenetrated networks. This work is interesting as it represents the first example of urea-functionalized MOFs for nitro-analytes recognition.

Straightforward synthesis of diverse dipyrazolylmethane derivatives and their application for fluorescence sensing of Cu2+ ions

Various dipyrazolylmethanes were synthesized and nitro-substituted compound displayed an excellent turn-off fluorescence sensing property for the detection of Cu2+ ions.

Novel pyrazine analogs of chalcones: synthesis and evaluation of their antifungal and antimycobacterial activity.

Infectious diseases, such as tuberculosis and invasive mycoses, represent serious health problems. As a part of our long-term efforts to find new agents for the treatment of these diseases, a new series of pyrazine analogs of chalcones bearing an isopropyl group in position 5 of the pyrazine ring was prepared. The structures of the compounds were corroborated by IR and NMR spectroscopy and their purity confirmed by elemental analysis. The susceptibility of eight fungal strains to the studied compounds was tested. The results have been compared with the activity of some previously reported propyl derivatives. The only strain that was susceptible to the studied compounds was Trichophyton mentagrophytes. It was found that replacing a non-branched propyl with a branched isopropyl did not have a decisive and unequivocal influence on the in vitro antifungal activity against T. mentagrophytes. In vitro activity against Trichophyton mentagrophytes comparable with that of fluconazole was exhibited by nitro-substituted derivatives. Unfortunately, no compound exhibited efficacy comparable with that of terbinafine, which is the most widely used agent for treating mycoses caused by dermatophytes. Some of the prepared compounds were assayed for antimycobacterial activity against M. tuberculosis H37Rv. The highest potency was also displayed by nitro-substituted compounds. The results of the present study are in a good agreement with our previous findings and confirm the positive influence of electron-withdrawing groups on the B-ring of chalcones on the antifungal and antimycobacterial activity of these compounds.

Non-symmetrical aryl- and arylethynyl-substituted thioalkyl-porphyrazines for optoelectronic materials: synthesis, properties, and computational studies.

A series of novel non-symmetrically substituted mono β-aryl and β-arylethynyl (alkylsulfanyl)porphyrazines and the corresponding Ni(ii) complexes have been prepared by the Suzuki-Miyaura and Sonogashira cross-coupling reactions with the aim to investigate substituent effects on their electronic and aggregation properties. Spectroscopic, electrochemical and computational investigations show that in both aryl and arylethynyl compounds efficient electron transfer between the aryl and macrocycle moieties occurs. The highest perturbation of the porphyrazine π-electron core is provided by strong electron-donating (NMe2) and electron withdrawing (NO2) aryl substituents, which increase and decrease the macrocycle electron density, respectively. Moreover, while in most of the compounds the LUMOs and HOMOs are mainly localized on the porphyrazine ring, in the amino-substituted derivatives the HOMO is localized on the peripheral aryl moieties and the LUMO is localized on the macrocycle. Charge-transfer electronic excitations give rise to absorptions in UV-Vis spectra of both amino- and nitro-substituted compounds. In the former such excitations occur from aryl-localized to macrocycle-localized orbitals, while backward excitations occur in the latter. Therefore, the porphyrazine ring shows an ambivalent behavior, acting as an electron acceptor in the case of the NMe2-substituted compounds and as an electron donor in the NO2-substituted derivative. In these derivatives, even macrocycle mono-substitution provides unconventional "push-pull" systems suitable for NLO. Columnar discotic mesophases are also shown by thio-octyl arylethynyl derivatives, allowing us to envisage the possibility to achieve compounds both suitable for optoelectronic applications and endowed with self-aggregation properties.

Nitro and dinitroamino N-oxides of octaazaanthracene as high energy materials

The present study undertook the design of nitro and dinitroamino compounds from the skeleton of isomeric N-oxides of octaazanaphthalene, using computational methods to predict their degradation and explosive characteristics. The atom equivalent method was employed to evaluate the gas phase heats of formation of the designed species. Condensed phase heats of formation were also determined and found to be in the range of 220-286 kcal mol(-1). Crystal densities of all the designed molecules were calculated and found to be in the range of 1.91-1.98 g cm(-3). Detonation pressure (P) and detonation velocity (D) determined using the Kamlet-Jacobs equation showed that the performance of nitro-substituted compounds was comparable to that of RDX while that of dinitroamino compounds (P ≈ 43.4-43.7 GPa; D ≈ 9.6-9.7 km s(-1)) showed their superiority over HMX (P ≈ 39.3 GPa and D ≈ 9.10 km s(-1)). Impact sensitivity (h 50) of the designed molecules was compared with nitro- and nitramino-based commercial explosives on the basis of the available free space (∆V) per molecule in their crystal lattice estimated using wave function analysis. The study showed that dinitroamino compounds were more sensitive compared to their nitro analogs. Reactivity or chemical stability of the designed molecules were measured in terms of charge distribution, molecular electrostatic potential and frontier molecular orbital energy. The nitro compounds of N-oxides of octaazaanthracene were found to be more stable than their dinitroamino analogs.

Synthesis and characterisation of benzoxazole-based liquid crystals possessing 3,5-difluorophenyl unit

Series of fluorinated compounds, 2-(3′,5′-difluoro-4′-alkoxybiphenyl-4-yl)-benzoxazole derivatives (nFBx), were prepared and characterised. Their phase transition behaviour was investigated by differential scanning calorimetry and polarising optical microscopy. In the case of carbon atoms in the alkoxy chain between 4 and 10, they exhibited enantiotropic mesophases with the mesophase ranges of 12–119°C and 23–152°C on heating and cooling for compounds bearing different substituents (H, CH3, Cl, and NO2). With the exception of nitro-substituted compounds, the nFBx series displayed intense photoluminescence emission at 380–385 nm in methylene chloride solution when they were excited at their absorption maxima. Compared to non-fluorinated analogues, fluorinated compounds nFBx (apart from nitro-substituted compounds) exhibited much lower melting points, but comparable or slightly narrower mesophase ranges during both heating and cooling, which were attributed to the disruption of the side-to-side intermolecular packing caused by the two lateral fluoro substituents.

Biodegradation of organic pollutants in saline wastewater by halophilic microorganisms: a review.

Agro-food, petroleum, textile, and leather industries generate saline wastewater with a high content of organic pollutants such as aromatic hydrocarbons, phenols, nitroaromatics, and azo dyes. Halophilic microorganisms are of increasing interest in industrial waste treatment, due to their ability to degrade hazardous substances efficiently under high salt conditions. However, their full potential remains unexplored. The isolation and identification of halophilic and halotolerant microorganisms from geographically unrelated and geologically diverse hypersaline sites supports their application in bioremediation processes. Past investigations in this field have mainly focused on the elimination of polycyclic aromatic hydrocarbons and phenols, whereas few studies have investigated N-aromatic compounds, such as nitro-substituted compounds, amines, and azo dyes, in saline wastewater. Information regarding the growth conditions and degradation mechanisms of halophilic microorganisms is also limited. In this review, we discuss recent research on the removal of organic pollutants such as organic matter, in terms of chemical oxygen demand (COD), dyes, hydrocarbons, N-aliphatic and N-aromatic compounds, and phenols, in conditions of high salinity. In addition, some proposal pathways for the degradation of aromatic compounds are presented.

Substituent effect on quantum efficiency in 4-aryloxy-N-(2′,6′-diisopropylphenyl)-1,8-naphthalimides: Experimental and computational investigations

A series of potential optical brightening agents – 4-aryloxy-N-(2′,6′-diisopropylphenyl)-1,8-naphthalimides – are synthesized and their photo-physical properties are experimentally determined. Interestingly, it is found that their quantum efficiencies or quantum yields are exclusively dependent on the substituents on the aryloxy group at the 4-position. It is postulated that the electronic effect of the substituents influences the photo-induced electron transfer process, which causes a variation in quantum efficiencies. Due to analysis of charge transfer from 1,8-naphthalimide molecular part to its substituents in dichloromethane based on the time-dependent density functional theory at Becke 3-parameters Lee-Yang-Parr level coupling with the 6–31G(d) basis set in the conductor-like polarizable continuum model with the united atom topological model computations, it is found that computed charge transfers of these serial compounds correspond well with their experimental quantum yields. Validation of the calculation method is performed by experimental determination of the quantum yield of the nitro-substituted compound.

Confirmation of Frm2 as a novel nitroreductase in Saccharomyces cerevisiae

Nitroreductases comprise a group of FMN- or FAD-dependent enzymes that reduce nitrosubstituted compounds by using NAD(P)H, and are found in bacterial species and yeast. Although there is little information on the biological functions of nitroreductases, some studies suggest their possible involvement in oxidative stress responses. In the yeast Saccharomyces cerevisiae, a putative nitroreductase protein, Frm2, has been identified based on its sequence similarity with known bacterial nitroreductases. Frm2 has been reported to function in the lipid signaling pathway. To study the functions of Frm2, we measured the nitroreductase activity of purified Frm2 on 4-nitroquinoline-N-oxide (4-NQO) using NADH. LC-MS analysis of the reaction products revealed that Frm2 reduced NQO into 4-aminoquinoline-N-oxide (4-AQO) via 4-hydroxyaminoquinoline (4-HAQO). An Frm2 deletion mutant exhibited growth inhibition in the presence of 4-NQO. Thus, in this study, we demonstrate a novel nitroreductase activity of Frm2 and its involvement in the oxidative stress defense system.

Green emissive salicylaldimine-based polar Schiff bases with short alkoxy tails and their copper(II)/oxovanadium(IV) complexes: synthesis and mesomorphism

A series of salicylaldimine-based copper(II) and oxovanadium(IV) complexes of the type [ML2] (M = Cu and VO, L = N,N′-bis-(4-X-amino phenyl (4′-n-alkoxy)-salicylaldiminato), n = 4, 6; X = Cl, NO2) have been synthesised. The mesomorphic behaviour of the ligands and their complexes was probed by polarising optical microscopy and differential scanning calorimetry. The formation of mesophases was dependent not only on the electronic or the steric factors of the substituents but also on metal centre. The ligands all showed a smectic or nematic mesophase. However, nitro-substituted compounds with (n = 4) lacked any mesomorphism. Complexes (X = Cl, NO2, n = 4, 6 and M = Cu) exhibited smectic A phases. The vanadyl complexes did not show any mesogenicity. Variable temperature magnetic susceptibility measurements were carried out for the copper and vanadyl complexes. The complexes obey the Curie–Weiss law. Cyclic voltammetry showed a single electron quasireversible response for the complexes. Density functional theory analysis study revealed a distorted square planar and square pyramidal geometry for the copper(II) and vanadyl complexes, respectively. At 330 nm excitation, the ligands showed green emission in the solid state (∼ 516–559 nm, Φ = 12–9%) at room temperature.

Study of the spontaneous attachment of polycyclic aryldiazonium salts onto amorphous carbon substrates

Diazonium salts of two nitro-substituted polycyclic aromatic compounds were synthesized and their spontaneous covalent attachment onto amorphous carbon surfaces was studied via electrochemical and spectroscopic techniques. In situ spectroscopic monitoring of the grafting of these compounds at amorphous carbon surfaces via attenuated total internal reflection Fourier transform infrared spectroscopy (ATR-FTIR) highlighted a marked difference in adsorption rates, which was also evident via ex situ electrochemical analysis. We show that adsorption rate differences cannot be explained based on differences in the solvolysis rates of these two molecules. It was found instead that the relative position of the –N2+ groups with respect to the –NO2 groups affected the reduction potential of the diazonium cations and in turn their adsorption rate at amorphous carbon surfaces. We conclude that differences in the electron density at the carbon atom bound to the diazonium group are responsible for the differences observed in the spontaneous attachment at carbon.