Nitroaromatic Derivatives Research Articles

Preformulation and formulation development of a bioactive nitroaromatic compound

The N-(butanoyloxyethyl)-4-(chloromethyl)-3-nitrobenzamide (BNB) is a nitroaromatic derivative with significant antitumor activity. Preformulation, forced degradation (distilled water, acid and base hydrolysis, oxidation, and light), and formulation studies were performed to investigate the chemical behavior of the molecule, the physicochemical properties, and the impact of formulation variables. Pharmacokinetic properties for BNB were estimated in silico. Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) containing BNB were developed by a hot melt homogenization method for parenteral administration. Degradation studies demonstrated that this compound is sensitive to hydrolysis. BNB was predicted to have a favorable absorption, distribution, metabolism, and excretion profile. The nanocarriers developed were characterized for particle size (PS = 61 to 85 nm), polydispersity index (PI < 0.3), zeta potential (ZP = − 22 to − 34 mV), and encapsulation efficiency (EE = 66 to 90%) and remained stable for 30 days of storage. These studies indicated that BNB (inhibitory concentration (IC50) 21.8 μM) and BNB-loaded NLC (IC50 33.7 μM) showed moderate cytotoxicity against breast cancer cell line. Blank formulations did not induce cytotoxicity and BNB-loaded SLN was able to potentiate the action of BNB (lC50 12.4 μM). BNB is a promising antitumor agent and it is possible to modulate its activity based on the particle size of the formulation.

Ratiometric fluorescence “Turn On” probe for fast and selective detection of TNT in solution, solid and vapour

Fluorescent probe UREA-TP undergoes nearly 600% increase in emission intensity at 310nm on addition of 1 equivalent of TNT, but the emission band centered at 440nm remains unchanged. UREA-TP acts as a ratiometric fluorescence “turn-on” probe and can detect TNT between 10−9 to 10−5M with limit of detection as low as 100 pM. Paper strips coated with UREA-TP on interaction with TNT become fluorescent purple under 365nm light and can determine both qualitatively and quantitatively as low as 10μl solution of 10−13M TNT, which accounts for 2.27×10−16gcm−2 TNT, significantly lower than the TNT concentration allowed in drinking water by EPA. The common nitroaromatic derivatives 2,4-DNT, 2,6-DNT, picric acid and 2,4-DNP, the pain killers, food supplements and inorganic anions show insignificant interference in the determination of TNT using UREA-TP. The aggregate size determination using dynamic light scattering analysis and morphological studies using TEM investigations reveals that UREA-TP in H2O-DMSO (98:2) remains in aggregate state with average size of 200nm, which undergo further aggregation to larger size aggregates with increasing amounts of TNT.

Nickel oxide nanoparticles grafted on reduced graphene oxide (rGO/NiO) as efficient photocatalyst for reduction of nitroaromatics under visible light irradiation

Nickel oxide nanoparticles were grafted on reduced graphene oxide via simultaneous reduction of graphene oxide and nickel salt in a single step reaction. The synthesized material (rGO/NiO) was found to be efficient visible light active photocatalyst for the reduction of nitroaromatic derivatives to their corresponding amino compounds. Hydrazine monohydrate provided necessary protons and electrons for the targeted reaction. After completion of the reaction, the photocatalyst could readily be recovered by simple external magnet and could be reused for six runs without any significant loss of its activity. More importantly, the photocatalyst did not show any leaching during the reaction as confirmed by ICP-AES analysis of the recovered catalyst.

Surface Functionalization of Metal Nanoparticles by Conjugated Metal-Ligand Interfacial Bonds: Impacts on Intraparticle Charge Transfer.

Noble metal nanoparticles represent a unique class of functional nanomaterials with physical and chemical properties that deviate markedly from those of their atomic and bulk forms. In order to stabilize the nanoparticles and further manipulate the materials properties, surface functionalization with organic molecules has been utilized as a powerful tool. Among those, mercapto derivatives have been used extensively as the ligands of choice for nanoparticle surface functionalization by taking advantage of the strong affinity of thiol moieties to transition metal surfaces forming (polar) metal-thiolate linkages. Yet, the nanoparticle material properties are generally discussed within the context of the two structural components, the metal cores and the organic capping layers, whereas the impacts of the metal-sulfur interfacial bonds are largely ignored because of the lack of interesting chemistry. In recent years, it has been found that metal nanoparticles may also be functionalized by stable metal-carbon (or even -nitrogen) covalent bonds. Because of the formation of dπ-pπ interactions between the transition-metal nanoparticles and terminal carbon moieties, the interfacial resistance at the metal-ligand interface is markedly reduced, leading to the emergence of unprecedented optical and electronic properties. In this Account, we summarize recent progress in the studies of metal nanoparticles functionalized by conjugated metal-ligand interfacial bonds that include metal-carbene (M═C) and metal-acetylide (M-C≡)/metal-vinylidene (M═C═C) bonds. Such interfacial bonds are readily formed by ligand self-assembly onto nanoparticle metal cores. The resulting nanoparticles exhibit apparent intraparticle charge delocalization between the particle-bound functional moieties, leading to the emergence of optical and electronic properties that are analogous to those of their dimeric counterparts, as manifested in spectroscopic and electrochemical measurements. This is first highlighted by ferrocene-functionalized nanoparticles that exhibit nanoparticle-mediated intervalence charge transfer (IVCT) among the particle-bound ferrocenyl moieties, as manifested in electrochemical and spectroscopic measurements. Such intraparticle charge delocalization has also been observed with other functional moieties such as pyrene and anthracene, where the photoluminescence emissions are consistent with those of their dimeric derivatives. Importantly, as such electronic communication occurs via a through-bond pathway, it may be readily manipulated by the valence states of the nanoparticle cores as well as specific binding of selective molecules/ions to the organic capping shells. These fundamental insights may be exploited for diverse applications, ranging from chemical sensing to (nano)electronics and fuel cell electrochemistry. Several examples are included, such as sensitive detection of nitroaromatic derivatives, metal cations, and fluoride anions by fluorophore-functionalized metal nanoparticles, fabrication of nanoparticle-bridged molecular dyads by, for instance, using nanoparticles cofunctionalized with 4-ethynyl-N,N-diphenyl-aniline (electron donor) and 9-vinylanthracene (electron acceptor), and enhanced electrocatalytic activity of acetylene derivatives-functionalized metal/alloy nanoparticles for oxygen reduction reaction by manipulation of the metal core electron density and hence interactions with reaction intermediates. We conclude this Account with a perspective where inspiration from conventional organometallic chemistry may be exploited for more complicated nanoparticle surface functionalization through the formation of diverse metal-nonmetal bonds. This is a unique platform for ready manipulation of nanoparticle properties and applications.

Carbon nanotube-supported gold nanoparticles as efficient catalyst for the selective hydrogenation of nitroaromatic derivatives to anilines

Gold nanoparticles (AuNPs) with sizes between 3 and 10nm were firmly supported on pristine multi-walled carbon nanotubes (MWCNT) in high yields by a facile linker-free deposition route using aqueous suspensions of pre-reduced gold precursors. For the first time, the resulting AuNP-MWCNT hybrid material was employed as catalyst for the hydrogenation of a series of substituted nitroarenes under mild reaction conditions. High catalytic activity with turnover frequencies (TOF) values up to 1200h−1 were achieved accompanied by a remarkable chemoselectivity. Recyclability tests did neither reveal leaching nor changes in size or oxidation states of the AuNPs. The concomitant presence of Au0 and AuI accounts for both the superior catalytic performance and the high stability of the hybrid material. Preferential orientation of nitroarenes on the MWCNT surface due to π–π interactions coupled with coulombic contact of the nitro group to the AuNPs most likely explains the high chemoselectivity of the hybrid material, and further underlines the valuable role of MWCNTs for catalytic reactions.

Colorimetric Detection of Nitroaromatics Using Organic Photochromic Compounds

An organic photochromic compound is explored as a new portable colorimetric sensor for nitroaromatics. This photochromic compound switches from colourless to pink upon exposure to ultraviolet light. In the presence of nitroaromatic explosive derivatives the photoswitching behaviour of the dithienylethene is suppressed, while a potential false positive (toluene) has little effect. The degree of photoswitching inhibition was determined by comparing the integrated visible absorption with the concentration of the analyte to give the pseudo Stern–Volmer constant (KPSV). The KPSVs measured varied from 12900 (p-nitrotoluene) to 236 M–1 (toluene), which were directly related to the analyte absorption at the excitation wavelength.

Multifunctional Benzothiadiazole-Based Small Molecules Displaying Solvatochromism and Sensing Properties toward Nitroarenes, Anions, and Cations.

Aryl or heteroaryl 5-substituted imidazo-benzothiadiazole derivatives were synthesized and shown to display remarkable solvatofluorochromism and selectively sense mercury(II) cations, acetate anions, and nitroaromatic derivatives, with discrimination between p-nitrophenol and picric acid. These novel sensors are of importance these days, as the detection of explosives is a high priority in issues of national security and environmental protection. To determine the ion binding properties of the sensors, their absorption and fluorescence emission spectra upon binding different cations and anions were compared. Significant shifts in the spectra were only observed for mercury(II) and acetate. The binding of these two ions was further studied using 1H NMR. The binding properties of different nitroaromatic compounds were also determined, and the results showed the importance of the presence of a phenol group in the guest molecule. Specifically, the two sensors were shown to discriminate between p-nitrophenol and picric acid. Finally, the mechanism of fluorescence quenching upon addition of nitrophenols was determined by computational methods.

Plasticization of a polymer layer harnessed to a silicon microcantilever as a highly sensitive and selective means to detect nitroaromatic derivatives

A new approach to the chemo-mechanical detection of trace amounts of nitroaromatics, even in the presence of high concentrations of background materials, is presented. The detection scheme is based on the plasticization of an aminopropyl silane layer that is harnessed to a silicon beam following its reaction with nitroaromatic systems. The reactioninduced plasticization attenuates the temperature induced bending of the polymer-beam sandwich, offering a simple and very sensitive tool for the detection of nitroaromatic systems. Using this approach, it was possible to detect a sample of 100 pg TNT even in the presence of a 10 fold excess of a background material such as acetonitrile. VC 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014, 52, 2124–2130

ZnO nanowires as effective luminescent sensing materials for nitroaromatic derivatives

We report on the efficient room-temperature photoluminescence (PL) quenching of ZnO in the presence of 2,4-dinitrotoluene (DNT) vapor and for concentration as low as 180 ppb. Compared to ZnO thin films, ZnO nanowires exhibit a strong (95%) and fast (41 s) quenching of the PL intensity in the presence of DNT vapor. Assuming that the PL quenching is due to a trapping of the ZnO excitons by adsorbed DNT molecules, Monte-Carlo calculations show that the nanometric dimensions as well as the better crystallographic quality (longer mean free path) of the ZnO nanowires result in an enhanced trapping process at the origin of the improved sensing properties of the nanowires. The results demonstrate the importance of nanostructures in improving the sensitivity of ZnO. The study also reveals the sensing capability of ZnO nanowires and paves the path towards the potential realization of low-cost sub-ppb nitroaromatic derivative sensors.

Voltammetric platform for detection of 2,4,6-trinitrotoluene based on a molecularly imprinted polymer

New methods for determination of explosive substances as, for example, 2,4,6-trinitrotoluene (TNT), in a rapid way and at low cost are highly required. An electrochemical platform has been here developed with good characteristics of low dimension, fast response, low cost, and high selectivity. It is based on a commercially available screen printed cell with graphite ink working and auxiliary electrodes and a silver ink quasi-reference electrode. The whole cell is covered with a thick layer of cation exchanging acrylic polymer molecularly imprinted with 2,4,6-trinitrotoluene. The polymeric layer acts at the same time as electrolytic medium and selective receptor. It has been demonstrated that, in this medium, 2,4,6-trinitrotoluene is electroactive at graphite electrode, being reduced by a non-reversible reaction. The peak current (differential pulse voltammogram) is proportional to TNT concentration with limit of detection for TNT around 5 × 10(-7) M and linearity range up to 2 × 10(-5) M. The selectivity for TNT relative to other reducible compounds as, for example, nitroaromatic derivatives, and to other possible interfering substances, as negatively charged ions, is good. Measurements can be performed in not de-aerated solution and in small volumes (20 μl), so that the proposed platform is very promising for in situ determinations.

Enantiomeric separation in high-performance liquid chromatography using novel β-cyclodextrin derivatives modified by R-configuration groups as chiral stationary phases

Two new chiral stationary phases (CSP) were successfully prepared through bonding β-cyclodextrin (CD) derivatives modified by R-configuration groups (R-CPGCD, R-HMPGCD) to silica gel. Nineteen chiral nitro aromatic alcohol derivatives were separated under the polar organic and the reversed phase modes. Better enantioseparation was obtained in the reversed phase mode. The resolution values of the analytes ranged from 1.98 to 7.57 and from 2.19 to 8.14 on R-CPGCD and R-HMPGCD CSPs, respectively, using a mobile phase composed of methanol/water (v/v, 40/60). Better enantioseparation was obtained on R-HMPGCD CSP than on R-CPGCD CSP because of stronger hydrogen bonding and π–π interactions between the substituents on the cyclodextrin derivatives and the analytes. For different analytes, the increasing electronic density of the benzene ring was found to be favorable to the enantioseparation of the test analytes. The thermodynamic parameters showed that the enantioseparation of analytes was enthalpy-controlled and a lower temperature aided the enantiomeric separation of the solutes on the two CSPs. MD simulations were used to investigate the recognition mechanism between the chiral selectors and the analyte using R-, S-2-naphthalenemethanol and R-CPGCD and R-HMPGCD complexes as examples. S-2-naphthalenemethanol had the stronger interactions with R-CPGCD and R-HMPGCD than the R-isomer. The substituent derivatized on R-CPGCD and the cyclodextrin cavity contributed to the discrimination of the S-isomer, but only the derivatized group on R-HMPGCD was found to play a major role in separating prosess. In addition, the larger free energy deviation of the R- and S-isomers in the R-HMPGCD system brought about a higher resolution value (Rs=8.14).

Prediction of toxicity of nitroaromatic compounds through their molecular structures

In this paper, a new simple method is presented for the estimation of the toxicity of nitroaromatic compounds including some well-known explosives. This method can predict the 50% lethal dose concentration for rats (LD50) as the estimation of toxicity in vivo. The prediction of LD50 of nitroaromatics through a new general correlation is based on the number of alkyl and nitro groups per molecular weight of the nitroaromatic compound as a core function. The existence of some specific structural parameters can decrease or increase the predicted results on the basis of the core function. The predicted results of various nitroaromatic compounds afford reliable prediction of LD50 with respect to experimental data. Prediction of toxicity for 28 nitroaromatic compounds, where the experimental data were available, and new nitroaromatic derivatives produce comparable results to those of several models of Quantitative Structure Activity Relation (QSAR).

Pyrene-Functionalized Ruthenium Nanoparticles as Effective Chemosensors for Nitroaromatic Derivatives

Pyrene-functionalized Ru nanoparticles were synthesized by olefin metathesis reactions of carbene-stabilized Ru nanoparticles with 1-vinylpyrene and 1-allylpyrene (the resulting particles were denoted as Ru=VPy and Ru=APy, respectively) and examined as sensitive chemosensors for the detection of nitroaromatic compounds, such as 2,4,6-trinitrotoluene (TNT), 2,4-dinitrotoluene (2,4-DNT), 2,6-dinitrotoluene (2,6-DNT), 1-chloro-nitrobenzene (CNB), and nitrobenzene (NB), by their effective quenching of the nanoparticle fluorescence. It was found that the detection sensitivity increased with increasing nitration of the molecules. Additionally, in comparison to monomeric pyrene derivatives, both Ru=VPy and Ru=APy nanoparticles exhibited markedly enhanced performance in the detection of nitroaromatic explosives, most probably as a result of the enhanced collision frequency between the fluorophores and the quencher molecules. Furthermore, Ru=VPy nanoparticles displayed much higher sensitivity (down to the nanomolar regime for TNT) than Ru=APy in the detection of these nitroaromatic explosives, which was ascribed to the extended intraparticle conjugation that provided efficient pathways for energy/electron transfer and consequently amplified the analyte binding events.

The effects of characteristics of substituents on toxicity of the nitroaromatics: HiT QSAR study

The present study applies the Hierarchical Technology for Quantitative Structure-Activity Relationships (HiT QSAR) for (i) evaluation of the influence of the characteristics of 28 nitroaromatic compounds (some of which belong to a widely known class of explosives) as to their toxicity; (ii) prediction of toxicity for new nitroaromatic derivatives; (iii) analysis of the effects of substituents in nitroaromatic compounds on their toxicity in vivo. The 50% lethal dose concentration for rats (LD50) was used to develop the QSAR models based on simplex representation of molecular structure. The preliminary 1D QSAR results show that even the information on the composition of molecules reveals the main tendencies of changes in toxicity. The statistic characteristics for partial least squares 2D QSAR models are quite satisfactory (R2 = 0.96-0.98; Q2 = 0.91-0.93; R2 (test) = 0.89-0.92), which allows us to carry out the prediction of activity for 41 novel compounds designed by the application of new combinations of substituents represented in the training set. The comprehensive analysis of toxicity changes as a function of substituent position and nature was carried out. Molecular fragments that promote and interfere with toxicity were defined on the basis of the obtained models. It was shown that the mutual influence of substituents in the benzene ring plays a crucial role regarding toxicity. The influence of different substituents on toxicity can be mediated via different C-H fragments of the aromatic ring.

Differences in the Biotransformation of 2,4,6-Trinitrotoluene (TNT) Between Wild and Axenically Grown Isolates of Myriophyllum aquaticum

The aim of this study was to demonstrate the potential for aquatic plants and their associated microbes to bioremediate wetland sites contaminated with 2,4,6-trinitrotoluene (TNT). The transformation of TNT was studied using both wild and axenically grown isolates of Myriophyllum aquaticum (parrot feather). Differences in TNT transformation rates and nitroaromatic metabolites were observed between different plants. The wild isolates, containing a consortium of associated microorganisms, transformed TNT into 2-amino- 4,6-dinitrotoluene (2-A-DNT) and 4-amino-2,6-dinitrotoluene (4-A-DNT) via 2- and 4-hydroxylamino-dinitrotoluene, which were detected as intermediates. The wild M. aquaticum also converted the metabolites, 2-A-DNT and 4-A-DNT, into low levels of 2,4-diaminotoluene (2,4-DAT). The axenically grown plants, containing no cultureable microorganisms, also transformed TNT into 2-A-DNT and 4-A-DNT, but at a much lower rate than that observed for the wild isolates. Unlike the wild plants, axenically grown M. aquaticum could not transform either 2-A-DNT or 4-A-DNT into 2,4-DAT over the incubation period. The differences in the performance between these plants could indicate that plant-associated microorganisms assisted in the overall transformation of TNT. For each plant, unidentifiable metabolites were observed and the soluble monoamino-derivatives present in the wild and axenic medium accounted for 14 and 7% of the initial TNT concentration, respectively. Thus, the majority of nitroaromatic derivatives remained associated with the plant tissues. Furthermore, only 7 and 3% of the initial TNT concentration were extracted as monoamino-derivatives from the tissues of the wild and axenically grown plants, respectively.

Supported Bismuth(III) Nitrate on Silica Sulfuric Acid as Useful Reagent for Nitration of Aromatic Compounds under Solvent-Free Conditions

A number of aromatic compounds were nitrated to the corresponding nitroaromatic derivatives with the use of supported bismuth(III) nitrate on silica sulfuric acid under solvent-free conditions.

Cyclopropyl‐ and Allyl‐Substituted Arenes in Reaction with Dinitrogen Tetroxide. Effect of Substrate Oxidation Potential on Reaction Direction.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Surface plasmon resonance immunosensor for highly sensitive detection of 2,4,6-trinitrotoluene

We have examined the sensing characteristics of a surface plasmon resonance (SPR) immunoassay for the detection of 2,4,6-trinitrotoluene (TNT) using an immunoreaction between 2,4,6-trinitrophenol–ovalbumin (TNP–OVA) conjugate and anti-2,4,6-trinitrophenol antibody (anti-TNP antibody). TNP–OVA conjugate was attached to a SPR-gold sensing surface by means of physical immobilization, which undergoes binding interaction with anti-TNP antibody. Both the immobilization and binding processes were studied from a change in the SPR-resonance angle. The quantification of TNT is based on the principle of indirect competitive immunoassay, in which the immunoreaction between the TNP–OVA conjugate and anti-TNP antibody was inhibited in the presence of free TNT in solution. The decrease in the resonance angle shift is proportional to an increase in concentration of TNT used for incubation. The immunoassay exhibited excellent sensitivity for the detection of TNT in the concentration range from 0.09 to 1000 ng/ml with good stability and reproducibility. The immunosensor developed could detect TNT as low as 0.09 ng/ml, within a response time of ∼22 min. The sensor surface was regenerated by a brief flow of pepsin solution, which disrupts the antigen–antibody complex without destroying the conjugate biofilm. Cross-reactivity of the SPR sensor to some structurally related nitroaromatic derivative and the detection of TNT in the presence of these nitroaromatic compounds were investigated. The cross-reactivity of the SPR sensor to 2,4-dinitrotoluene (2,4-DNT), 1,3-dinitrobenzene (1,3-DNB), 2-amino-4,6-dinitrotoluene (2A-4,6-DNT) and 4-amino-2,6-dinitrotoluene (4A-2,6-DNT) were very low (≤1.1%). The analytical characteristics of the proposed immunosensor are highly promising for the development of new field-portable sensors for on-site detection of landmines.

Cyclopropyl- and Allyl-substituted Arenes in Reaction with Dinitrogen Tetroxide. Effect of Substrate Oxidation Potential on Reaction Direction

A correlation was found between oxidation potentials of acylcyclopropanes in solution (in CH2Cl2 and CH3CN) and their HOMO energies calculated by semiempirical (AM1) and nonempirical (HF/6-31G and HF/6-31G**) methods. The correlation provides a possibility to forecast the reaction direction of the mentioned substrates and N2O4. The correlation possesses a general character. It was established for instance that arylcyclo-propanes, cyclopropylmethyl- and allylbenzenes oxidized at more positive potentials than reduction potential of NO+ and having more positive eHOMOthan 9.0 eV (AM1), 8.4 eV (HF/6-31G), and 8.3 eV (HF/6-31 G**) reacted with N2O4 following the mechanism "electron transfer radical pair recombination" affording nitroaromatic derivatives retaining the cyclopropane (or allyl) fragments. Substrates of the same type where the electron transfer to NO+ should be endothermic process and whose HOMO values are less than the above critical numbers react with N2O4 by the mechanism of electrophilic cyclopropane ring opening (with aryl and benzylcyclopropanes) or by electrophilic addition across the double C=C bond (with allylbenzenes).

A New Paclitaxel Prodrug for Use in ADEPT Strategy.

AbstractFor Abstract see ChemInform Abstract in Full Text.