Nitrophenyl Substituent Research Articles

Design, Synthesis, and In Vitro and In Vivo Bioactivity Studies of Hydrazide-Hydrazones of 2,4-Dihydroxybenzoic Acid.

In this research, twenty-four hydrazide-hydrazones of 2,4-dihydroxybenzoic acid were designed, synthesized, and subjected to in vitro and in vivo bioactivity studies. The chemical structure of the obtained compounds was confirmed by spectral methods. Antimicrobial activity screening was performed against a panel of microorganisms for all synthesized hydrazide-hydrazones. The performed assays revealed the interesting antibacterial activity of a few substances against Gram-positive bacterial strains including MRSA-Staphylococcus aureus ATCC 43300 (compound 18: 2,4-dihydroxy-N-[(2-hydroxy-3,5-diiodophenyl)methylidene]benzohydrazide-Minimal Inhibitory Concentration, MIC = 3.91 µg/mL). In addition, we performed the in vitro screening of antiproliferative activity and also assessed the acute toxicity of six hydrazide-hydrazones. The following human cancer cell lines were used: 769-P, HepG2, H1563, and LN-229, and the viability of the cells was assessed using the MTT method. The HEK-293 cell line was used as a reference line. The toxicity was tested in vivo on Danio rerio embryos using the Fish Embryo Acute Toxicity (FET) test procedure according to OECD No. 236. The inhibitory concentration values obtained in the in vitro test showed that N-[(4-nitrophenyl)methylidene]-2,4-dihydroxybenzhydrazide (21) inhibited cancer cell proliferation the most, with an extremely low IC50 (Inhibitory Concentration) value, estimated at 0.77 µM for LN-229. In addition, each of the compounds tested was selective against cancer cell lines. The compounds with a nitrophenyl substituent were the most promising in terms of inhibition cancer cell proliferation. The toxicity against zebrafish embryos and larvae was also very low or moderate.

Leveraging Coupled Solvatofluorochromism and Fluorescence Quenching in Nitrophenyl-Containing Thiazolothiazoles for Efficient Organic Vapor Sensing.

Solvatofluorochromic molecules provide strikingly high fluorescent outputs to monitor a wide range of biological, environmental, or materials-related sensing processes. Here, thiazolo[5,4-d]thiazole (TTz) fluorophores equipped with simple alkylamino and nitrophenyl substituents for solid-state, high-performance chemo-responsive sensing applications are reported. Nitroaromatic substituents are known to strongly quench dye fluorescence, however, the TTz core subtly modulates intramolecular charge transfer (ICT) enabling strong, locally excited-state fluorescence in non-polar conditions. In polar media, a planar ICT excited-state shows near complete quenching, enabling a twisted excited-state emission to be observed. These unique fluorescent properties (spectral shifts of 0.13 - 0.87eV and large transition dipole moments Δµ = 20.4 - 21.3 D) are leveraged to develop highly sought-after chemo-responsive, organic vapor optical sensors. The sensors are developed by embedding the TTz fluorophores within a poly(styrene-isoprene-styrene) block copolymer to form fluorescent dye/polymer composites (ΦF = 70 - 97%). The composites respond reversibly to a comprehensive list of organic solvents and show low vapor concentration sensing (e.g., 0.04% solvent saturation vapor pressure of THF - 66ppm). The composite films can distinguish between solvent vapors with near complete fluorescent quenching observed when exposed to their saturated solvent vapor pressures, making this an extremely promising material for optical chemo-responsive sensing.

Realization of nitroaromatic chromophores with intense two-photon brightness.

Strong fluorescence is a general feature of dipyrrolonaphthyridinediones bearing two nitrophenyl substituents. Methyl groups simultaneously being weakly electron-donating and inducing steric hindrance appear to be a key structural parameter that allows for significant emission enhancement, whereas Et2N groups cause fluorescence quenching. The magnitude of two-photon absorption increases if 4-nitrophenyl substituents are present while the contribution of Et2N groups is detrimental.

Photophysical properties of BODIPYs with sterically-hindered nitrophenyls in meso-position

During recent years, the BODIPY core became a popular scaffold for designing of dyes with desirable properties. In this paper, we extend the library of possible modification of BODIPYs, presenting experimental data for a new family meso-substituted with nitrophenyl groups. We also present quantum chemical calculations, which complement the experimental data and give additional insight in the underlying photochemical and photophysical processes. Optical properties of novel compounds are characterized. It is shown that the fluorescence quantum yield and the efficiency of singlet oxygen generation differs by two orders of magnitude across the family. In aqueous solution, red-shifted fluorescence emission band is detected, corresponding to aggregates. This band has shorter decay time and wide excitation spectrum. We show that photolysis is not accompanied by the release of nitric oxide (NO) which was observed earlier for some dyes with nitrophenyl substituents. The experimental data presented in this paper may be useful for further designing of BODIPY dyes and NO photodonors.

Investigation of redox mechanism and DNA binding of novel 2-(x-nitrophenyl)-5-nitrobenzimidazole (x = 2, 3 and 4)

The present study describes the investigation of the binding modes of potential anti-cancerous nitrophenyl derivatives of 2-(x-nitrophenyl)-5-nitrobenzimidazole with calf thymus DNA. The -2-(x-nitrophenyl)-5-nitrobenzimidazoles under investigation differ only in position x of nitro group in nitrophenyl substituent relative to benzimidazole moiety leading to 1-NPNB (x = 2), 2-NPNB (x = 3) and 3-NPNB (x = 4). The DFT calculations predicted that derivatives were electrochemically reducible which was then confirmed by cyclic voltammetry. In cyclic voltammetry, the second reversible peak was dependent on first irreversible reduction. This revealed that electrochemical irreversible process was governed by some other process which was then followed by reversible second electron transfer. Thus, ECE (electron transfer leading to coupled chemical reaction followed by another electron transfer process) mechanism was attributed for electrochemical reduction. Experimental results based on UV–Vis spectroscopy vaguely showed intercalation of 1-NPNB, 2-NPNB and 3-NPNB into DNA which was assisted by cyclic voltammetry. However, thermal melting and florescence spectroscopy unambiguously established intercalation for all three compounds. Molecular docking analysis ascertained in pocket stacking of 5-nitrobenzimidazole moiety in 1-NPNB and 2-NPNB while nitro phenyl substitution in 3-NPNB stacks between DNA base pair during intercalation which was in agreement with DFT computed molecular geometry. Therefore, the relative positions of nitro group and 5-nitrobenzimidazole moieties in 2-(x-nitrophenyl)- 5-nitrobenzimidazole influenced the DNA binding pattern of compounds during intercalation. The cytotoxicity of these compounds was comparable to standard drug doxorubicin against both cancerous (MCF-7) and normal (MCF-10A) breast cells which depicts their anti-cancerous potential.

Synthesis and crystallographic characterization of a brominated porphyrin with a nitrophenyl substituent and its iron derivative

2,3,7,8,12,13,17,18-Octabromo-5-(2-nitrophenyl)-10,15,20-triphenyl porphyrin (H[Formula: see text]OBP-NO[Formula: see text] and its metallic complexes have been designed and synthesized. Both the free-base porphyrin and its iron(III) complex have been characterized by X-ray crystallography. Structures confirm there are three phenyl groups and one 2-nitrophenyl at meso positions and eight bromine atoms at [Formula: see text]-pyrrole positions. The crowded substituents cause the porphyrin plane to be distorted and become saddle shaped. The complexes were also characterized by NMR and UV-vis spectra. The UV-vis spectrum of the free-base porphyrin shows that substitution by eight bromine atoms at [Formula: see text]-pyrrole positions leads to a red shift of the bands.

Highly refractive thiazole-containing polyimides: a structural property comparison

Highly refractive, thermally stable, and solution processable polyimides (PIs) were synthesized by the introduction of thiazole units, thioether linkages, and phenyl or nitrophenyl groups into the polymer backbones. These PIs were prepared via the polycondensation of two diamine monomers, 5,5′-thiobis(2-amino-4-phenyl-thiazole) (DA-1) or 5,5′-thiobis(2-amino-4-(3-nitrophenyl)thiazole) (DA-2), with various aromatic dianhydrides(a–d). The bulky pendant phenyl or nitrophenyl units as well as the non-coplanar conformations because of ortho-sulfide linkages endowed the resulting PIs with excellent solubility in organic solvents. These PIs showed outstanding thermal stability, with 10% weight loss temperatures exceeding 492 °C under nitrogen and 475 °C in air atmosphere, while their glass transition temperatures were in the range of 239–278 °C. In general, the synergic effects of thiazole groups, phenyl or nitrophenyl substituents, and thioether linkages provided PIs with very high refractive indices of up to 1.7646 at 632.8 nm, along with small birefringences (<0.0085) and high Abbe’s numbers. The structure–property relationships of the analogous PIs containing phenyl or nitrophenyl substituents groups were also studied in detail by comparing the results.

Solid-state entrapment of water clusters by 26-membered pentamide unclosed cryptands – probing the para-substituent effect

Twenty six membered unclosed cryptands end-capped with nitrophenyl (1), phenyl (2), and methoxyphenyl (3) amide substituent (lariat arm) were characterized by single crystal X-ray analysis to reveal the role of para-substituent on the solid-state stabilization of water clusters. Host molecules 1 and 3 crystallize in the same space group (P-1) forming isostructural assemblies with the same entrapped octameric water cluster build from a cyclic tetramer connected with four up-and-down positioned pendulous water molecules. In striking contrast, the host molecule 2 bearing the unsubstituted amido-phenyl group crystallizes in P21/c space group in which two host molecules stabilize acyclic water chain. This distinct crystallization behavior may be rationalized by differences in the electrostatic potential surfaces between hosts 1 and 3 as compared with 2 (para-substituent effect).

Copper(II) Complexes of Cyclams Containing Nitrophenyl Substituents: Push-Pull Behavior and Scorpionate Coordination of the Nitro Group.

The three nitrophenyl-cyclam derivatives (nitrocyclams): 1-(4-nitrophenyl)-1,4,8,11-tetraazacyclotetradecane (2), 1-(2-nitrophenyl)-1,4,8,11-tetraazacyclotetradecane (3), and 1-(2,4-dinitrophenyl)-1,4,8,11-tetraazacyclotetradecane (4), in an MeCN solution, specifically incorporate the Cu(II) ion according to an irreversible process signaled by disappearance of the yellow color for a concentration c < 1 × 10(-4) M and by a yellow-to-red color change for c ≥ 1 × 10(-3), and must be considered efficient and specific dosimeters of copper(II) salts. When present in the ortho position of the nitrophenyl substituent, the -NO2 group coordinates the Cu(II) according to a scorpionate mode, while the metallocyclam system exhibits a trans-I configuration. In an MeCN solution the red trans-I-[Cu(II)(3)](2+) and trans-I-[Cu(II)(4)](2+) scorpionate complexes slowly convert into the violet trans-III scorpionate complexes. Kinetic aspects of the trans-I-to-trans-III configurational rearrangement were investigated in detail for the [Cu(II)(4)](2+) system. In particular, the conversion is spectacularly accelerated by catalytic amounts of Cl(-), NCO(-), and F(-). While for Cl(-) and NCO(-) the effect can be associated with the capability of the anion to stabilize through coordination a possible dissociative intermediate, the amazingly powerful effect of F(-) must be related to the preliminary deprotonation of one N-H fragment of the macrocycle, driven by the formation of the HF2(-) ion. Most of the metal complex species studied in solution were isolated in a crystalline form, and their molecular structures were elucidated through X-ray diffraction studies. This study documents the first examples of effective metal coordination by the nitro group.

Europium triple-decker complexes containing phthalocyanine and nitrophenyl-corrole macrocycles.

A series of europium triple-decker complexes containing phthalocyanine and nitrophenyl-corrole macrocycles were synthesized and characterized by spectroscopic and electrochemical methods in nonaqueous media. The examined compounds are represented as Eu2[Pc(OC4H9)8]2[Cor(Ph)n(NO2Ph)3-n], where n varies from 0 to 3, Pc(OC4H9)8 represents the phthalocyanine macrocycle, and Cor indicates the corrole macrocycle having phenyl (Ph) or nitrophenyl (NO2Ph) meso substituents. Three different methods were used for syntheses of the target complexes, two of which are reported here for the first time. Each examined compound undergoes five reversible one-electron oxidations and 3-5 one-electron reductions depending upon the number of NO2Ph substituents. The nitrophenyl groups on the meso positions of the corrole are highly electron-withdrawing, and this leads to a substantial positive shift in potential for the five oxidations and first reduction in CH2Cl2, PhCN, or pyridine as compared to the parent triple-decker compound with a triphenylcorrole macrocycle. The measured E1/2 values are linearly related to the number of NO2Ph groups on the corrole, and the relative magnitude of the shift in potential for each redox reaction was used in conjunction with the results from thin-layer spectro-electrochemistry to assign the initial site of oxidation or reduction on the molecule. The nitrophenyl substituents are also redox-active, and each is reduced to [C6H4NO2](-) in a separate one-electron transfer step at potentials between -1.12 and -1.42 V versus saturated calomel electrode.

Topochemical polymerization of unsymmetrical aryldiacetylene supramolecules with nitrophenyl substituents utilizing C-H∙∙∙π interactions.

Diacetylenes are versatile building blocks, in which many functional groups can be incorporated for the construction of new materials with desirable properties. In this study, 6-(p or m-nitrophenyl)-3,5-hexadiyne-1-ol (4a or 4b) containing nitrophenyl groups (host) and 2-hydroxyethyl groups (guest) in different diacetylene terminals were designed to establish an ordered supramolecular assembly that is complied with the strict requirements for the topochemical polymerization of diacetylenes. Crystal film and bulk crystals of compound 4b were obtained successfully by cast film and re-precipitation methods. Both of these could photopolymerize to the corresponding regular poly(diacetylene) polymer, as evidenced by UV-vis, IR, FL and Raman spectroscopy. The electrochemical properties and behaviors of 4a and 4b were also investigated, and the results show that the differences between the para and meta positions of the mono-phenylacetylene substituents probably result from the topochemical polymerization. Thus, m-nitrophenylbutadiyne derivatives with sizeable C-H∙∙∙π interactions seemed to be effective for the formation of a polymerizable packing, which is appropriate for topochemical polymerization.

Fabrication of flowerlike supramolecular architectures of fullerene derivatives bearing a small nitrophenyl substituent

Flowerlike supramolecular architectures were fabricated from fulleropyrrolidines bearing a small para-, meta-, or ortho-nitrophenyl group. The self-assembled architectures were characterized by scanning electron microscopy(SEM) and X-ray diffraction(XRD). It was found that these flowerlike architectures were assembled from nanoplates that formed from fundamental subunit of interdigitated lamellar bilayer structure.

Crystal structure of meso-tetra-kis-(4-nitro-phen-yl)porphyrin nitro-benzene disolvate.

The porphyrin core of the title centrosymmetric compound, C44H26N8O8·2C6H5NO2, is approximately planar, the maximum deviation being 0.069 (3) Å. The planes of the benzene rings of the nitro­phenyl substituents are almost perpendicular to the porphyrin mean plane, making dihedral angles of 73.89 (9) and 89.24 (9)°. The two pyrrole ring H atoms are equally disordered over the four pyrrole ring N atoms. In the crystal, weak C—H⋯O and C—H⋯N hydrogen bonds link the porphyrin mol­ecules into a three-dimensional supra­molecular network. The nitro­benzene solvent mol­ecules are linked by weak C—H⋯O hydrogen bonds into supra­molecular chains propagating along the a-axis direction.

Synthesis of new unsymmetrical imidazolinium salts with mesityl and nitrophenyl substituents

An efficient five-step procedure for synthesis of unsymmetrical imidazolinium salts with mesityl and nitrophenyl substituents was elaborated. The starting nitroaniline was acylated with chloroacetyl chloride followed by Finkelstein displacement by iodide and coupling with mesitylamine. The key step was reduction of the amide carbonyl group with BH3·S(CH3)2. Finally, an imidazoline ring was constructed by reaction with trimethyl orthoformate. A different approach was attempted for 2,6-dinitroaniline, but final cyclization failed in this case.

CYCLOCONDENSATION OF 2-PHENACYL-1H-BENZIMIDAZOLE WITH ACYLHYDRAZINES: SYNTHESIS AND TAUTOMERISM OF 2-(PYRAZOL-4-YL)-1H-BENZIMIDAZOLES

The previously unknown 2-(pyrazol-4-yl)benzimidazoles containing aryl groups in the pyrazolyl ring have been obtained by the reaction of 2-phenacyl-1H-benzimidazole with aroylhydrazines. The compounds with nitrophenyl and pyridyl substituents in the pyrazole ring show pyrazolyl tautomerism with differences in the 1 H NMR spectra. A semi-empirical method is proposed to determine the tautomeric composition of the synthesized pyrazoles. Authors: I. B. Dzvinchuk, A. V. Vypirailenko, V. V. Pirozhenko, and M. O. Lozinsky. English Translation in Chemistry of Heterocyclic Compounds , 1999, 35 (11), pp 1319-1324 http://link.springer.com/article/10.1007/BF02252001

Genotoxicity risk assessment of diversely substituted quinolines using the SOS chromotest

Quinolines are aromatic nitrogen compounds with wide therapeutic potential to treat parasitic and microbial diseases. In this study, the genotoxicity of quinoline, 4-methylquinoline, 4-nitroquinoline-1-oxide (4-NQO), and diversely functionalized quinoline derivatives and the influence of the substituents (functional groups and/or atoms) on their genotoxicity were tested using the SOS chromotest. Quinoline derivatives that induce genotoxicity by the formation of an enamine epoxide structure did not induce the SOS response in Escherichia coli PQ37 cells, with the exception of 4-methylquinoline that was weakly genotoxic. The chemical nature of the substitution (C-5 to C-8: hydroxyl, nitro, methyl, isopropyl, chlorine, fluorine, and iodine atoms; C-2: phenyl and 3,4-methylenedioxyphenyl rings) of quinoline skeleton did not significantly modify compound genotoxicities; however, C-2 substitution with α-, β-, or γ-pyridinyl groups removed 4-methylquinoline genotoxicity. On the other hand, 4-NQO derivatives whose genotoxic mechanism involves reduction of the C-4 nitro group were strong inducers of the SOS response. Methyl and nitrophenyl substituents at C-2 of 4-NQO core affected the genotoxic potency of this molecule. The relevance of these results is discussed in relation to the potential use of the substituted quinolines. The work showed the sensitivity of SOS chromotest for studying structure-genotoxicity relationships and bioassay-guided quinoline synthesis.

Origin of Ultrafast Radiationless Deactivation Dynamics of Free-Base Subpyriporphyrins

In this study, we have investigated the photophysical properties of free-base subpyriporphyrins by changing the peripheral substituents from phenyl to nitrophenyl groups. While the electron withdrawing nature of nitrophenyl substituent gives rise to a noticeable perturbation in the absorption spectrum arising from the charge-transfer (CT) transition, both molecules show similar excited state dynamics at ambient temperature. This feature is mainly due to the fact that the CT transitions caused by the nitrophenyl substituent in free-base subpyriporphyrin are located higher in energy than the lowest excited S1 state. Moreover, through the temperature dependence and protonation experiments, we have demonstrated that the NH-tautomerization is a key factor in determining the excited state dynamics of free-base subpyriporphyrins. In this sense, we can suggest that the control of substituent and solvents in free-base subporphyrinoids could be a new strategy for the fine-tuning of photophysical properties. Furthermore, to the best of our knowledge, this is the first study to illustrate the photophysical properties of free-base subporphyrinoids.

A critical pocket close to the glutamate binding site of mGlu receptors opens new possibilities for agonist design

A recent publication from Ogawa et al. suggested a possible allosteric chloride binding site in the extracellular domain of metabotropic glutamate receptors (mGluRs) by comparison with a similar site found in atrial natriuretic peptide receptor. We simultaneously reported about ( S)-PCEP an agonist of subtype 4 mGluR that would bind to a similar pocket, adjacent to the glutamate binding site. Here we disclose LSP1-2093, a new derivative of ( S)-PCEP that holds a nitrophenyl substituent. Docking experiments predict that the nitro group binds to the receptor at the putative chloride ion site. It is thus possible to take advantage of this putative chloride binding site to develop new types of mGluR agonists. This pocket is present in the structural family of Leucine Isoleucine Valine Binding Protein that includes class C GPCRs, suggesting that extended agonists may be identified at receptors bearing such a structural domain.

ChemInform Abstract: Vasodilating and Antiarrhythmic Activity of Heteryl Lactones.

A new series of unsaturated γ- and δ-lactones with pyridyl, quinolyl and nitrophenyl substituents (9, 10) have been synthesized by the condensation of unsaturated methyl lactones with heteryl aldehyde or nitrobenzaldehyde in the base-catalysed aldol reaction. The antiarrhythmic, vasodilating and cardiotonic activities of the synthesized compounds have been studied in vivo and ex vivo. 3-Cyano-5,5-dimethyl-4-[4'-(4-pyridyl)-1',3'-butadienyl)]-2(5H)-furanone (9e) displayed a significant vasodilating activity. The antiarrhythmic activity of this compound was higher, but its toxicity lower than that of the procainamide reference drug. Five-membered lactones, particularly 3-cyano-4-(4-pyridylvinyl)-5,5-dimethyl-2(5H)-furanone (9c), exhibited a remarkable cardiotonic activity. The replacement of a pyridyl substituent by a nitrophenyl group in the pyranone derivative did not change the cardiovascular activity and toxicity.

ChemInform Abstract: Cyclocondensation of 2-Phenacyl-1H-benzimidazole with Acylhydrazines: Synthesis and Tautomerism of 2-(Pyrazol-4-yl)-1H-benzimidazoles.

The previously unknown 2-(pyrazol-4-yl)benzimidazoles containing aryl groups in the pyrazolyl ring have been obtained by the reaction of 2-phenacyl-1H-benzimidazole with aroylhydrazines. The compounds with nitrophenyl and pyridyl substituents in the pyrazole ring show pyrazolyl tautomerism with differences in the1H NMR spectra. A semi-empirical method is proposed to determine the tautomeric composition of the synthesized pyrazoles.