Oxygen Atoms Of Nitro Group Research Articles

Structural basis of binding and justification for the urease inhibitory activity of acetamide hybrids of N-substituted 1,3,4-oxadiazoles and piperidines

In present, we have performed the Michaelis–Menten kinetics studies of urease inhibitors (6a–o), having basic skeleton of acetamide hybrids of N-substituted 1,3,4-oxadiazoles and piperidines. From the Lineweaver-Burk plot, Dixon plot and their secondary replots, it has been confirmed that all the compounds have inhibited the enzyme competitively with Ki values of in range from 3.11 ± 0.2 to 5.20 ± 0.7 μM. Compound 6a was found to have lowest Ki among the series, while compounds 6d, 6e, 6gand 6i were found subsequently the excellent Ki values after 6a. Molecular docking has supported their types of inhibitions and structure activity-relationship. Most frequently, the nitro group oxygen atoms were found in contact with nickel ions of the active site. Moreover, all the compounds were subjected to toxicity tests and were found nontoxic against human neutrophils and plants, respectively.

The equilibrium molecular structure of 3-methyl-4-nitro- and 4-methyl-3-nitrofuroxans by gas-phase electron diffraction and coupled cluster calculations

The equilibrium molecular structures of the isomeric 3-methyl-4-nitro- and 4-methyl-3-nitrofuroxans have been determined for the first time by gas-phase electron diffraction (GED) supported by coupled cluster calculations up to CCSD(T)/cc-pVTZ level of theory, in frame of dynamic model with relaxation of all structural parameters. The best fit of the experimental scattering intensities was obtained for a model of Cs symmetry. The small differences between similar geometric parameters were constrained at the theoretical values. To compare structural parameters of the titled compounds, the geometries of parent furazan and furoxan molecules were calculated at the CCSD(T)-AE/aug-cc-pVQZ and CCSD(T)-AE/cc-pVQZ levels of theory, respectively. Mean amplitudes and vibrational corrections necessary for GED analysis were computed at the B3LYP/SNDS levels of theory using quadratic and cubic force fields. Peculiar features of electronic and geometric structures of the studied isomeric nitrofuroxans were analyzed with the use of different topological, magnetic and orbital descriptors and the reasons of the significant distinctions between 4- and 3-nitroisomers structures were revealed. Due to hyperconjugation a lone electron pair of exocyclic oxygen atom in both isomers was found to delocalize into antibonding orbital of adjacent ON endocyclic bond, nπ(O)→σ∗(ON). The peculiarity of the 3-nitroisomer structure was provided with the additional interaction of exocyclic and nitro group oxygen atoms.

Pharmacophore modeling of pretomanid (PA-824) derivatives for antitubercular potency against replicating and non-replicating Mycobacterium tuberculosis

Pretomanid (PA-824) is the recently (2019) approved drug for the treatment of extensively drug-resistant (XDR) TB and the multidrug-resistant (MDR) TB by US FDA. The experimental data of antitubercular activity of 543 pretomanid derivatives (total 6 datasets) against replicating (active) and non-replicating (dormant) forms of Mycobacterium tuberculosis (strain H37Rv) are available in the literature. Such vast experimental data of pretomanid derivatives against both of these endpoints, and recent approval of pretomanid molecule as a drug encouraged us to utilize this existing experimental information for the development of the 3D-pharmacophore models. The developed model (Hypo-1, MABA) showed the three physicochemical features namely, the oxygen atom of nitro group (HBA_1), fused pyran ring of imidazopyran heterocycle (HYAl_2) and the 4-fluorophenyl moiety (HYAr_3) are crucial for the antitubercular activity against replicating M. tb. Subsequently, the pharmacophore model (Hypo-1, LORA) developed against the non-replicating form of M. tb also showed the contribution of three physicochemical features namely, the 4-tri-fluoromethyl group (HYAl_2) and both the phenyl groups (HYAr_3, HYAr_4) of biaryl moiety in increasing the antitubercular activity. Both the pharmacophoric classifier models showed the classification accuracies of 82.98 and 74.42% for the training set compounds, and 63.91 and 61.60% for the test set compounds respectively, for labelling the compounds into higher and lower active classes. Both the models were also found to be retaining the higher active compounds in top 1.00% of the total number of compounds (decoys and actives), after performing the decoy set screening. Communicated by Ramaswamy H. Sarma

Crystal structure of 6-(4-chloro-phen-yl)-6a-nitro-6a,6b,8,9,10,12a-hexa-hydro-6H,7H-spiro[chromeno[3,4-a]indolizine-12,11'-indeno-[1,2-b]quinoxaline

The title compound, C35H27ClN4O3, crystallized with two independent mol-ecules (A and B) in the asymmetric unit. In both mol-ecules, the pyran and pyridine rings adopt envelope and chair conformations, respectively. The conformation of the pyrrolidine and cyclo-pentene rings differ in the two mol-ecules; twisted and flat, respectively, in mol-ecule A, but envelope and twisted, respectively, in mol-ecule B. In both mol-ecules, there is a C-H⋯N intra-molecular hydrogen bond present. In both mol-ecules, the oxygen atoms of the nitro groups are disordered as is the chlorine atom in mol-ecule B. In the crystal, the B mol-ecules are linked by C-H⋯O hydrogen bonds, forming -B-B-B- chains along [010], and by C-H⋯π inter-actions. The A and B mol-ecules are also linked by a number of C-H⋯π inter-actions, resulting in the formation a supra-molecular three-dimensional structure. In mol-ecule A, the nitro group oxygen atoms are disordered over two positions with refined occupancy ratios of the nitro group oxygen atoms O3A and O4A in 0.59 (2):0.41 (2) while in molecule B one of the nitro O atoms is disordered over two positions with a refined occupancy ratio of 0.686 (13):0.314 (13) and the chlorine atoms is disordered over two positions with a refined occupancy ratio of 0.72 (3):0.28 (3).

Structural study of three heteroaryl oximes, heteroaryl-N=OH: Compounds forming strong C3 molecular chains

In order to further investigate the structural chemistry of oximes and to further establish the main structural arrangements adopted, we have determined the crystal structure of and carried out Hirshfeld surface calculations on three heteroaryl oximes, namely (Z)-thiophene-2-carbaldehyde oxime (1), (Z)-1H-pyrrole-2 carbaldehyde oxime (2) and (Z)-5-nitrofuran-2-carbaldehyde oxime (3). As confirmed by both techniques, the major intermolecular interactions in each compound are classical N—H···O hydrogen bonds, which link the molecules into C3 chains. Such an arrangement has been previous reported as an important aggregation mode for oximes. Secondary interactions, C—H···π and C—H···O interactions, in compounds 1 and 2, and interactions involving the nitro group oxygen atoms in compound 3 link the chains into three dimensional arrays.

Crystal structures of 3-(2H-1,3-benzodioxol-5-ylmethyl)-2-(m- and p-nitrophenyl)-1,3-thiazolidin-4-ones: different roles of the oxygen atoms

Abstract The crystal structures of two isomeric 3-(2H-1,3-benzodioxol-5-ylmethyl)-2-(aryl)-1,3-thiazolidin-4-one compounds (1: aryl=4-O2NC6H4; 2: aryl=3-O2NC6H4) are reported. In both these nonplanar, compounds, the carbonyl oxygen is involved in intramolecular C–H···O hydrogen bonds. However, there are significant differences in the sets of intermolecular interactions, in particular the roles of the oxygen atoms, exhibited by the two compounds. Thus in 1, a dioxolyl oxygen and the two nitro group oxygen atoms are each involved in different chain forming C–H···O intermolecular hydrogen bonds, while the carbonyl oxygen atom is not involved in any intermolecular interaction. In 2, the dioxolyl oxygen atom is involved in the formation of centrosymmetric dimers, the carbonyl oxygen in three different C–H···O hydrogen bonds and the nitro group oxygens in two N–O···π(aryl) interactions. Compound 2 exhibits also C–H···π(phenyl), π(phenyl)···π(phenyl) and π(benzodioxolyl)···π(benzodioxolyl) interactions, while in 1 only the latter interaction is present. Compound 1 crystallizes in the monoclinic space group, P21/a with Z=4, while compound 2 crystallizes in the triclinic space group, P1̅, with Z=2.

Synthesis and crystal structure characterization of (E)-2,2,2-Trifluoro-N-[2-(2-nitrovinyl)phenyl]acetamide

ABSTRACTThe title compound, (E)-2,2,2-trifluoro-N-[2-(2-nitrovinyl)phenyl]acetamide, was synthesized and characterized by 1H and 13C NMR and HRMS spectroscopy. Its molecular configuration was investigated by X-ray crystallography. The crystal structure analysis revealed that the structure exhibits intermolecular hydrogen bonds of the type N–H…O and intermolecular hydrogen bonds of the type N–H…F, and molecules are linked by weak C–H…O contacts. Furthermore, the two oxygen atoms of nitro group are disordered over two positions, respectively, with site occupancy factors of 0.8:0.2 and 0.6:0.4. Three fluorine atoms are also disordered over two positions, respectively, one fluorine atom with site occupancy factors of 0.6:0.4 and the other two fluorine atoms with site occupancy factors of 0.5:0.5.

Theoretical anharmonic Raman and infrared spectra with vibrational assignments and NBO analysis for 1-methyl-4-nitropyrazole

Both experimental and calculated spectral and electronic properties of 1-methyl-4-nitropyrazole have been demonstrated. Experimental values have been compared with theoretical computations and also new hybrid density functionals, APF (Austin–Petersson–Frisch) and APF(D), have been tested and compared to B3LYP hybrid functional. The theoretical wavenumbers of fully anharmonic infrared and Raman spectra with anharmonic intensities of 1-methyl-4-nitropyrazole are in very good agreement with the experimental observations. The detailed interpretation of the infrared and Raman spectra is reported based on potential energy distribution (PED). The ring N1N2 bond distance of 1-methyl-4-nitropyrazole, calculated with both APF/6-311++G(df,pd) and APF-D/6-311++G(df,pd) models, is much underestimated in comparison with X-ray experimental value. Overall results point that B3LYP functional with 6-311++G(df,pd) basis function better predicts the bond lengths and angles of titled compound than both APF and APF-D ones. As a key factor for biological activity of nitro compounds, the redox potential of 1-methyl-4-nitropyrazole in water solution was also measured and then was set against the calculated electronic properties. The analysis of the calculated components of HOMO and LUMO orbitals has shown that nitrogen and oxygen atoms of nitro group are the most probable site of acceptance of electron. Hence, nitro group should be the most sensitive fragment of 1-methyl-4-nitropyrazole molecule to the reduction process. Moreover, the stability of the 1-methyl-4-nitropyrazole arising from hyper conjugative interactions has been studied using natural bond orbital (NBO) analysis. Unambiguous assignment of values of proton chemical shifts to appropriate protons has been finally made thanks to two dimensional (2D) 1H–1H NMR spectroscopy.

A Reaction of 4, 5-Diphenylimidazole Nitration in the Presence of Some 3d-Metals Nitrates

By interaction of cobalt(II), nickel(II), or zinc(II) nitrate with 4,5- diphenylimidazole in methanol in solvotermal conditions the new derivative of imidazole (4,5-diphenyl-2-nitroimidazole) and three new coordinative compounds [M(4,5-Ph2ImNO2)2(CH3OH)2] have been synthesized and investigated. Metal ions have a distorted octahedral environment with N2O4. Coordination number of metal is six. Ligand is coordinated to metal ion by one oxygen atom of nitrogroup and one nitrogen atom of imidazole.

Structural, spectroscopic and theoretical studies on 3,4,7,8-tetramethyl-1,10-phenantroline complex with picric acid

The almost planar molecular complex, formed by 3,4,7,8-tetramethyl-phenantroline (Me4phen) and picric acid (2,4,6-trinitrophenol, PA), has been investigated by using X-ray diffraction, vibrational spectroscopy, tunnel splitting and theoretical analysis. In the crystal of Me4phen·PA two short bifurcated hydrogen bonds N+–H···O− [2.6238(14)Å] and N+–H···N [2.6898(15)Å] are created. Infra-red spectra show the hydrogen bonds are short. The neutron backscattering spectrum of Me4phen⋅PA at 3K shows two tunneling peaks at ca. 1 and 3μeV. The number of the peaks is consistent with X-ray diffraction studies, which disclosed the inequivalence of methyl groups in the crystal structure. The comparison of the tunnel splitting for neat Me4phen and for its complex with picric acid indicates that in the latter case the methyl groups are more strongly engaged in the intermolecular interactions, particularly with nitro group oxygen atoms of picric acid, leading to an increase of the CH3 rotational barrier height.

A B3LYP and MP2(full) theoretical investigation into explosive sensitivity upon the formation of the molecule-cation interaction between the nitro group of 3,4-dinitropyrazole and H+, Li+, Na+, Be2+ or Mg2+

The explosive sensitivity upon the formation of molecule-cation interaction between the nitro group of 3,4-dinitropyrazole (DNP) and H(+), Li(+), Na(+), Be(2+) or Mg(2+) has been investigated using the B3LYP and MP2(full) methods with the 6-311++G** and 6-311++G(2df,2p) basis sets. The bond dissociation energy (BDE) of the C3-N7 trigger bond has also been discussed for the DNP monomer and the corresponding complex. The interaction between the oxygen atom of nitro group and H(+) in DNP…H(+) is partly covalent in nature. The molecule-cation interaction and bond dissociation energy of the C3-N7 trigger bond follow the order of DNP…Be(2+) > DNP…Mg(2+) > DNP…Li(+) > DNP…Na(+). Except for DNP…H(+), the increment of the trigger bond dissociation energy in comparison with the DNP monomer correlates well with the molecule-cation interaction energy, natural charge of the nitro group, electron density ρ(BCP(C3-N7)), delocalization energy E(2) and NBO charge transfer. The analyses of atoms in molecules (AIM), natural bond orbital (NBO) and electron density shifts have shown that the electron density of the nitro group shifts toward the C3-N7 trigger bond upon the formation of the molecule-cation interaction. Thus, the trigger bond is strengthened and the sensitivity of DNP is reduced.

Thermodynamic stability of 2,4,6-tris(nitromethyl)-1,3,5-triazine: an experimental and theoretical study

The molecular geometries and electronic structures of 2,4,6-tris(nitromethyl)-1,3,5-triazine isomers were investigated by the density functional method DFT/B3LYP/6-311++G** to elucidate the structural factors responsible for the stability of these systems. It was shown that a characteristic feature of the nitromethyl tautomer (1) of 2,4,6-tris (nitromethyl)-1,3,5-triazine consists in nonvalence interactions between an oxygen atom of nitro group and a carbon atom of triazine ring, which are probably due to Coulomb attraction between them. The tautomer with the 2,4,6-tris (nitromethylene)-hexahyrdo-1,3,5-triazine structure (2) is stabilized trough direct polar conjugation between the amino and nitro groups at the double bond. Structural strain of the molecule with the 2,4,6-tris(aci-nitromethyl)-1,3,5-triazine structure (3) is the reason for its thermodynamic instability. X-ray data indicate that the compound under study exists in the triazine tautomeric form 1 and the distances between oxygen atoms of nitro group and carbon atom of the triazine ring are shortened. NMR data suggest the existence of triazine in the nitromethyl form 1 in acetonitrile and acetone and a tautomeric equilibrium between the nitromethyl and nitromethylene forms in a more polar solvent (DMSO). The results obtained suggest a Coulomb-type stabilization of the 2,4,6-tris(nitromethyl)-1,3,5-triazine molecule in the gas phase, in the crystal, and in nonpolar solvents.

Density functional computational studies on (E)-2-[(2-Hydroxy-5-nitrophenyl)-iminiomethyl]-4-nitrophenolate

Density functional calculations of the structure, atomic charges, molecular electrostatic potential and thermodynamic functions have been performed at B3LYP/6-31G(d,p) level of theory for the title compound (E)-2-[(2-hydroxy-5-nitrophenyl)-iminiomethyl]-4-nitrophenolate. The results show that the phenolate oxygen atom and all of the nitro group oxygen atoms have bigger negative charges, and the coordination ability of these atoms differs in different solvents. The energetic behavior of the title compound in solvent media has been examined using B3LYP method with the 6-31G(d,p) basis set by applying the Onsager method and the isodensity polarized continuum model (IPCM). The results obtained with these methods reveal that the IPCM method yielded a more stable structure than Onsager's method. In addition, natural bond orbital and frontier molecular orbital analysis of the title compound were performed using the B3LYP/6-31G(d,p) method.

Pharmacophore mapping and electronic feature analysis for a series of nitroaromatic compounds with antitubercular activity

A five point pharmacophore was generated using PHASE for a series of nitroaromatic compounds and their congeners as antitubercular agents. The generated pharmacophore yielded significant 3D-QSAR model with r(2) of 0.890 for a training set of 92 molecules. The model also showed excellent predictive power with correlation coefficient Q(2) of 0.857 for a test set of 31 compounds. The pharmacophore indicated that presence of a nitro group, a piperazine moiety, one aromatic ring feature and two acceptor features are necessary for potent antitubercular activity. The pharmacophore was supported by electronic property analysis using density functional theory (DFT) at B3LYP/3-21*G level. Molecular electrostatic profile of the compounds was consistent with the generated pharmacophore model, particularly appearance of localized negative potential regions near both the oxygen atoms of nitro group extending laterally to the isoxazole ring system/amide bond in the most active compounds. Calculated data further revealed that all active compounds have smaller LUMO energies located over the nitro group, furan ring, and isoxazole ring/amide bond attached to it. Higher negative values of LUMO energies concentrated over the nitro group are indicative of the electron acceptor capacity of the compounds, suggesting that these compounds are prodrugs and must be activated by TB-nitroreductase. The results obtained from this study should aid in efficient design and development of nitroaromatic compounds as antitubercular agents.

Molecular electrostatic potentials and electron densities in nitrocubanes C 8H 8− α(NO 2) α ( α=1–8): ab initio and density functional study

Charge distributions in nitro derivatives of cubane, C 8H 8− α(NO 2) α ( α=1–8) have been derived employing the ab initio Hartree-Fock and hybrid density functional calculations using the topography of the molecular electrostatic potential (MESP) and the electron density as a tool. The electron-rich regions around the oxygen atoms of the nitro group emerged from the electrostatic potential get smaller with increasing number of nitro groups in the series. Within different isomers of nitrocubane, the lowest energy isomer engender large electron-rich regions relative to the other isomers, which has been supported by the shallow MESP minima near oxygen atoms of nitro group. The electrostatic potential at the center of the cube (cage critical point) on the other hand increases on encompassing from mono- to octa-nitrocubane. Thus it has been inferred that the successive replacement of cubyl hydrogens by NO 2 groups pushes the added electrons along a cube with an increase of curvature of the C–C bonds. It has been found that the higher value of the dipole moment for the most destabilized isomer stems from the large electron-rich regions in the electrostatic potential. Further the lowest frequency vibration and energy gap of the highest occupied and the lowest unoccupied molecular orbital in the series of octa-nitrocubane suggest it to be most labile in the series. The electron density at the bond critical point and the curvature of the C–C bonds in a cubanoid increases from mono- to octa-nitrocubane. Heats of formation derived from the isodesmic reaction approach increase with increased destabilization in the nitrocubane isomers.

Formation of N-methyl-2-nitroso-4,6-dinitroaniline from methyl ester of N-methyl-N-(2,4,6-trinitrophenyl)glycine

The reaction of methyl ester of N-methyl-N-(2,4,6-trinitrophenyl)glycine with methoxide in methanol produces N-methyl-2-nitroso-4,6-dinitroaniline. The kinetics of formation of the nitroso compound have been studied, and a mechanism of its formation has been suggested consisting in the intramolecular attack of CH2 group of aziridinone intermediate by oxygen atom of nitro group and in subsequent E2 elimination reaction. The aziridinone intermediate is formed by the attack of carbon atom of carboxylic group of 1,3-adduct of the starting ester with methoxide by the formally electroneutral tertiary nitrogen. In methoxide solution, N-methyl-2-nitroso-4,6-dinitroaniline undergoes another reduction-oxidation reaction giving 2-amino-2'-methylamino-3,3',5,5'-tetranitroazoxybenzene.

LIGAND COUPLING THROUGH HYPERVALENT INTERMEDIATES. REACTION OF HETEROARYL SULFOXIDES WITH ORGANOMETALLICS REAGENTS AND THEIR IMPLICATIONS

Abstract Earlier, pentacoordinate phosphorus and sulfur compounds were presumed to be of 3sp3d hybridization.1 However, a three-centered-four-electron bond, called a hypervalent bond by Musher,2 was suggested by Rundle and others3 to be consistent with p-orbitals in the early 1950s. The structure of one such compound, SF4, is shown below. Although the original theoretical treatment of hypervalent structure using three sp2- and a p-orbital was modified slightly by introduction of 3d orbitals into the calculation,4,5 the structural feature of such hypervalent compounds has remained the same. Following two stable sulfuranes, one by Kapovits et al. 6 and another by Martin and his coworkers7, are the first organic σ-sulfuranes which have both two polar and longer S[sbnd]O bonds nearly at 180°. Hypervalent interaction was noticed in the extremely short distance between the neutral divalent sulfenyl sulfur atom and the weakly nucleophilic oxygen atom of nitro group of the following compounds, we prepared for X-ray crystallographic analyses. Thus the hypervalent bonding is considered to be quite common and readily formed.

Application of the 18O isotope shift in 15N n.m.r. spectra to a biosynthetic problem: experimental evidence for the origin of the nitro group oxygen atoms of 3-nitropropanoic acid

Both oxygen atoms of the nitro group of 3-nitropropanoic acid produced by the fungus Penicillium atrovenetum are derived from molecular oxygen.

Reduction of Nitrobenzenes on Thin Aluminium Oxide Utilized in Inelastic Electron Tunneling Spectroscopy

Abstract Chemical interactions between aromatic nitro compounds and thin aluminium oxide grown on aluminium film were studied by the combined use of inelastic electron tunneling spectroscopy (IETS) and X-ray photoelectron spectroscopy (XPS). IET spectra of nitrobenzoic acids and nitrophenols show that nitro groups of these compounds are reduced on the oxide and result in the corresponding amino compounds. In this conversion reaction, oxygen atoms of nitro group are consumed for the growth of the oxide layer and hydrogen atoms of the surface hydroxyl groups are used for the amidation reaction. The intermediate of the reaction is identified to the corresponding nitroso compounds from the XPS analysis.

Crystal structure of 4,6-dinitro-1-(5-tetrazolyl)-1H-indazole trihydrate

The title compound, C8H4N8O4·3H2O, crystallizes in space groupP¯1 with cell constantsa=7.022(1),b=9.507(2),c=10.906(2) A,α=84.99(1),β=71.89(1),γ=72.56(1)°,Z=2, andV c =660.2 A3. The structure was solved by direct methods using diffractometer data and was refined by full-matrix least-squares methods to anR value of 0.060 for 2112 observed reflections. The molecule, consisting of a phenyl ring fused to a pyrazole ring with a tetrazole ring connected to it equatorially, is planar except for the N(7) nitro-group oxygen atoms. The structure is stabilized by a three-dimensional network of O-H⋯O, O-H⋯N, and N-H⋯O hydrogen bonds through the water molecules.