Nitro Oxygen Atoms Research Articles

CHARACTERISATION, EVALUATION AND DENSITY FUNCTIONAL ANALYSIS OF CILNIDIPINE-NICOTINAMIDE COCRYSTALS DEVELOPED BY LIQUID ASSISTED GRINDING TECHNIQUE: A SUSTAINABLE APPROACH FOR ENHANCED SOLUBILITY

Objective: Improving the solubility of poorly water-soluble drugs has always been a challenge in drug development. This study aimed to enhance the aqueous solubility of a poorly water-soluble drug, Cilnidipine, by cocrystallisation method using liquid-assisted grinding (LAG) technique with Nicotinamide as the coformer. The study also aimed to understand the mechanism of cocrystal formation by quantum mechanical calculations. Methods: The Cilnidipine-Nicotinamide cocrystals were prepared in various stoichiometric ratios using the liquid-assisted grinding (LAG) technique. The cocrystals obtained were characterised by vibrational spectroscopy, thermal methods such as differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD) and surface morphology by field emission scanning electron microscopy (FE-SEM). The cocrystals were evaluated for saturation solubility, and the mechanistic study of cocrystal formation was performed using the Gaussian 09 software package. Results: FT-IR spectra of the formulated cocrystal indicated the intermolecular hydrogen bond formation between-N-H of Nicotinamide and the nitro group of Cilnidipine. DSC analysis showed a single endotherm at 96.76 °C, PXRD patterns were different from that of the reactants, and FE-SEM analysis revealed the changes in the surface morphology of the obtained cocrystal. The prepared cocrystal showed a 26.36-fold enhancement in the aqueous solubility of Cilnidipine. The DFT study demonstrated the formation of a strong intermolecular hydrogen bonding between the nitro-oxygen atom of Cilnidipine and the amide hydrogen atom of Nicotinamide in cocrystal formed. Conclusion: This study highlights the potential of the liquid-assisted grinding method for preparing cocrystals as a sustainable and reliable approach to address the challenges posed by poorly water-soluble drugs.

N-(4-Meth-oxy-3-nitro-phen-yl)acetamide.

The title compound, C9H10N2O4, crystallizes with a disordered nitro group in twinned crystals. Both the meth-oxy group and the acetamide groups are nearly coplanar with the phenyl ring, and the C-N-C-O torsion angle [0.2 (4)°] is also insignificantly different from zero. Overall, the 12-atom meth-oxy-phenyl-acetamide group is nearly planar, with an r.m.s. deviation of 0.042 Å. The nitro group is twisted out of this plane by about 30°, disordered into two orientations with opposite senses of twist. In the crystal, the N-H group donates a hydrogen bond to a nitro oxygen atom, generating chains propagating in the [101] direction. The amide carbonyl oxygen atom is not involved in the hydrogen bonding.

Structural characterization of sodium and potassium 3-nitrohydrogenphthalate coordination polymers

Abstract The synthesis, crystal structures and properties of two alkali metal 3-nitrohydrogenphthalates obtained by a 1:2 reaction of M2CO3 (M = K or Na) with 3-nitrophthalic acid (LH2) are reported. In the anhydrous potassium coordination polymer [K(LH)] (LH = 2-carboxy-3-nitrobenzoate) 1, the K+ cation is bonded to nine oxygen atoms from six symmetry related (LH)– ligands resulting in a distorted {KO9} coordination polyhedron. Five of the six oxygen atoms including a nitro oxygen atom of the crystallographically unique 2-carboxy-3-nitrobenzoate are involved in metal binding. The μ6-bridging mode of (LH)– places the K+ cations into the layers of the two-dimensional (2D) coordination polymer. Each {KO9} polyhedron in 1 shares edges with two other polyhedra along the b and c axes. A low temperature structure redetermination of [Na(L#H)(H2O)3]·H2O (L#H = 2-carboxy-6-nitrobenzoate) 2 has revealed that the (L#H)− anion is bonded to the Na+ cation in a monodentate fashion via the carbonyl oxygen atom of the –COOH group and two of the three unique aqua ligands exhibit a bridging bidentate mode stabilizing a chain polymer. The structure of compound 2 thus consists of chains of edge-sharing {NaO6} octahedra. Thermal decomposition of 1 or 2 results in the formation of metal carbonate residues.

N-(4-Hy-droxy-2-nitro-phen-yl)acetamide.

The title compound, C8H8N2O4, differs in its degree of planarity from the 3-nitro isomer and also in its hydrogen-bonding pattern. Its NH group forms an intra-molecular hydrogen bond to a nitro oxygen atom, and its OH group forms an inter-molecular hydrogen bond to an amide oxygen atom, generating [10] chains in the crystal.

Salt Formation, to Realize a Good Combination of High Energy and Low Sensitivity of Nitroform-Based Energetic Compounds

Energetic salts constitute an important issue in the field of energetic materials. In this research, the series of energetic salts 5–8 with nitroform structures were obtained by a single-displacement reaction, and their crystal structures were fully characterized by X-ray single-crystal diffraction. As energetic compounds, their energy performance and sensitivity to mechanical stimuli have been explored. These compounds not only exhibit excellent detonation performance (Dv = 8.45–9.13 km s–1 and P = 30.5–37.4 GPa) and extremely high specific impulse (Isp = 262.63–277.42 s) but also show low sensitivity to mechanical stimuli. According to the crystallographic data, the relationship between molecular structure and sensitivity has been explored. The results show that the positive electrostatic potential near the nitroform and the interaction between the intermolecular nitro oxygen atoms (O···O interaction) are significantly reduced after salt formation. In addition, this trend of change is consistent with the sensitivity distribution of these energetic salts (the impact sensitivity decreased from 5 to 15 J and the friction sensitivity decreased from 100 to 240 N). This study not only provides ideas for the molecular design of high-specific-impulse energetic compounds but also reveals the relationship between the structure and sensitivity of nitroform energetic compounds from the perspective of crystallography.

Revealing the chirality origin and homochirality crystallization of Ag14 nanocluster at the molecular level

Although chirality is an ever-present characteristic in biology and some artificial molecules, controlling the chirality and demystifying the chirality origin of complex assemblies remain challenging. Herein, we report two homochiral Ag14 nanoclusters with inherent chirality originated from identical rotation of six square faces on a Ag8 cube driven by intra-cluster π···π stacking interaction between pntp− (Hpntp = p-nitrothiophenol) ligands. The spontaneous resolution of the racemic (SD/rac-Ag14a) to homochiral nanoclusters (SD/L-Ag14 and SD/R-Ag14) can be realized by re-crystallizing SD/rac-Ag14a in acetonitrile, which promotes the homochiral crystallization in solid state by forming C–H···O/N hydrogen bonds with nitro oxygen atoms in pntp− or aromatic hydrogen atoms in dpph (dpph = 1,6-bis(diphenylphosphino)hexane) on Ag14 nanocluster. This work not only provides strategic guidance for the syntheses of chiral silver nanoclusters in an all-achiral environment, but also deciphers the origin of chirality at molecular level by identifying the special effects of intra- and inter-cluster supramolecular interactions.

Crystal structure and spectroscopic properties of (E)-1,3-dimethyl-2-[3-(4-nitro-phen-yl)triaz-2-enyl-idene]-2,3-di-hydro-1H-imidazole.

The title compound (E)-1,3-dimethyl-2-[3-(4-nitro-phen-yl)triaz-2-enyl-idene]-2,3-di-hydro-1H-imidazole, C11H12N6O2, has monoclinic (C2/c) symmetry at 100 K. This triazene derivative was synthesized by the coupling reaction of 1,3-di-methyl-imidazolium iodide with 1-azido-4-nitro benzene in the presence of sodium hydride (60% in mineral oil) and characterized by 1H NMR, 13C NMR, IR, mass spectrometry, and single-crystal X-ray diffraction. The mol-ecule consists of six-membered and five-membered rings, which are connected by a triazene moiety (-N=N-N-). In the solid-state, the mol-ecule is found to be planar due to conjugation throughout the mol-ecule. The extended structure shows two layers of mol-ecules, which present weak inter-molecular inter-actions that facilitate the stacked arrangement of the mol-ecules forming the extended structure. Furthermore, there are several weak pseudo-cyclical inter-actions between the nitro oxygen atoms and symmetry-adjacent H atoms, which help to arrange the mol-ecules.

Structural Systematics of Lanthanide(III) Picrate Solvates: Neutral, Mononuclear Ln(pic)3(dimethylsulfoxide)3 Arrays

Adducts of dimethylsulfoxide, dmso=Me2SO, with lanthanide(iii) picrates (picrate=2,4,6-trinitrophenoxide, pic) of stoichiometry Ln(pic)3·3dmso have been prepared and characterised by single-crystal X-ray structure determinations as discrete, neutral, mononuclear molecular species. Such complexes have been obtained across the gamut of Ln, specifically for Ln=La, Pr, Nd, Sm, Gd, Dy, Yb, Lu, and Y, presumably also accessible for other intermediate members, the series being isomorphous (monoclinic, C2/c, Z=8); a second triclinic P form has also been identified for Ln=La, Pr. In both forms, the metal atom coordination environments are nine-coordinate, tricapped trigonal prismatic, [Ln(dmso-O)3(pic-O,O′)3], two of the three unidentate ligands lying in one of the trigonal planes and one in the other (an isomer we have termed meridional, mer). A hydrated form of Ln(pic)3·2dmso·H2O stoichiometry has also been defined for Ln=Sm, Gd, Lu, the metal atom environment again nine-coordinate, [Ln(dmso-O)2(H2O)(pic-O,O′)3], but now fac, with the three unidentate ligands occupying one triangular face of the tricapped trigonal prism and involved in a centrosymmetric H-bonding array with the three similar ligands of an adjacent complex; the three capping atoms are nitro-oxygen atoms, the phenoxy-O triad occupying the other face.

Crystal structure of (N,N'-ethyl-enebis{3-[2-(3-nitro-phen-yl)hydrazin-1-yl-idene]-4-oxo-pentan-2-iminato})copper(II)-3-[2-(3-nitro-phen-yl)hydrazin-1-yl-idene]pentane-2,4-dione (1/1).

In the title 1:1 co-crystal, [Cu(C24H24N8O6)]·C11H11N3O4, each of the crystal components forms undulating layers which stack alternately along the b-axis direction. Mol-ecules of the CuII complex are connected via C-H⋯O hydrogen bonds involving the nitro and keto oxygen atoms, thus forming supra-molecular networks. Mol-ecules of the aryl-hydrazone component are linked by C-H⋯O inter-actions into zigzag strands showing no inter-strand association.

Two Achiral Isomers of Chloronitropyridine Crystallize as Polar Materials with Different Molecular Packing Motifs Based on Similar Intermolecular Interactions

The molecular structures of two of the ten possible isomers of chloronitropyridine have been studied by spectroscopic techniques and single crystal X-ray diffraction. The structures of 2-chloro-4-nitropyridine (1) [monoclinic, Pc, a = 3.7711(14) A, b = 8.919(3) A, c = 9.324(3) A, β = 99.506(5)°] and 5-chloro-2-nitropyridine (2) [triclinic, P1, a = 3.7559(13) A, b = 6.071(2) A, c = 6.939(2) A, α = 85.703(5)°, β = 89.619(5)°, γ = 75.189(5)°] reveal that the isomers crystallize in non-centrosymmetric space groups with different molecular packing motifs based on similar intermolecular interactions. Each compound packs into molecular sheets via short chlorine–oxygen contacts and C–H⋯X (X = O, N) interactions of the nitro oxygen atoms and the pyridine nitrogen atom. The sheets further pack with an offset face-to-face π-stacking geometrical arrangement of the aromatic rings to form the three-dimensional structures. Achiral 2-chloro-4-nitropyridine (1) crystallizes as a polar material in the non-centrosymmetric and non-enantiomorphous space group Pc while the isomeric achiral compound 5-chloro-2-nitropyridine (2) forms a polar material that approximates inversion symmetry in the non-centrosymmetric enantiomorphous space group P1. The molecular structures of achiral 2-chloro-4-nitropyridine and 5-chloro-2-nitropyridine have been studied by X-ray diffraction revealing that they crystallize as polar materials. The structures have different packing motifs based on similar intermolecular interactions consisting of π-stacked molecular sheets formed by chlorine–oxygen contacts and C–H⋯X (X = O, N) interactions.

Unusual coordination modes of ligand 2-chloro-5-nitrobenzene sulfonate: Synthesis, spectroscopic characterization, thermal and X-ray structural studies of metal 2-chloro-5-nitrobenzene sulfonate complexes, metal = Tl(I), Cu(II), Ag(I) and Pb(II)

Using metal ions thallium(I), copper(II), silver(I) and lead(II) and ligand 2-chloro-5-nitrobenzenesulfonate(cnb), four new metal complexes [Tl(cnb)]n(1), [Cu(en)2(H2O)2](cnb)2.2H2O(2), where en = ethylenediamine, [Ag(cnb)]n(3) and [Pb(cnb)2]n(4) have been synthesized and characterized by elemental analyses, spectroscopic methods (FT-IR, multinuclear NMR), single crystal X-ray structure analyses (except 4) and TGA analyses. Complexes 1 and 3 crystallize in monoclinic crystal system in P21/c space group having unit cell dimensions, a = 13.849(2) Å, b = 9.449(2) Å, c = 7.506(2)Å, β = 105.3°, V = 947.1 Å3, Z = 4 and a = 15.197(13)Å, b = 5.136(4)Å, c = 24.058(18)Å, β = 106.86°, V = 1797.1 Å3, Z = 4 respectively. Complex 2, crystallizes in triclinic crystal system with PI¯ having unit cell parameters; a = 6.888 Å, b = 7.835 Å, c = 13.227 Å, α = 80.20°, β = 83.15°, γ = 78.18°, V = 945.6 Å3, Z = 1. X-ray structure determination revealed that complexes 1 and 3 are polymeric in nature, whereas complex 2 has ionic structure. Remarkably, cnb ligand is coordinating through sulfonato oxygen atoms and nitro oxygen atoms in thallium complex but coordinates through sulfonato oxygen atoms and chloro group in silver complex, thereby showing the flexible/versatile coordinating behaviour of anionic ligand. This is unusual.

Coordination complexes built with 3-nitrophthalate and different pyrazine derivatives: Syntheses, structures and photoluminescence

Three Ag(I) coordination complexes (CCs), namely {Ag2(epyz)(npt)}n (1), {Ag2(tpyz)(npt)}n (2), {Ag2(npt)(NH3)2}n (3), [epyz=2-ethyl-3-methylpyrazine, H2npt=3-nitro-1,2-benzenedicarboxylic acid, tpyz=2,3,5-trimethylpyrazine, mpyz=2,3,5,6-tetramethylpyrazine] have been synthesized by solution phase ultrasonic reactions of Ag2O with H2npt and various pyrazine derivatives ligands under the ammoniacal condition. All the complexes have been characterized by X-ray diffraction, elemental analyses and IR spectra. Complexes 1 and 2 show two-dimensional network. Compound 3 exhibits 1D-chain structure. However, complex 3 shows 3D supramolecular structure results from the linkage of neighboring layers through a rich hydrogen-bonding system involving the ammonia molecules with carboxyl oxygen atoms and the nitro oxygen atoms. Zigzag Ag4 subunits (SBUs) were observed in compounds 1 and 3, while the complex 2 only shows Ag2⋯Ag2 interactions. The structural diversity of the compounds indicated the Ag⋯Ag argentophilicity, the coordination modes of carboxyl groups and the difference pyrazine derivatives play an important role in the formation of such coordination architectures. The thermogravimetric analyses and photoluminescence of the complexes were also investigated.

Phase equilibria and structural phase transformations in the furazano[3,4-e]tetrazine-4,6-dioxide-2,4-dinitro-2,4-diazapentane system

The phase diagram of the binary furazano[3,4-e]tetrazine-4,6-dioxide (1)-2,4-dinitro-2,4-diazapentane (2) system was studied by differential thermal analysis and microcalorimetry. The branches of the liquidus lines of this system were calculated. The eutectic point coordinates and monoeutectic equilibrium lines were refined. The components of the system under study were shown to interact with each other to form two low-melting-point eutectics E 1 and E 2 and a stoichiometric (in a 1: 1 molar ratio) molecular compound, viz., crystalline complex 1·2. According to the single-crystal X-ray diffraction data, complex 1·2 belongs to the orthorhombic crystal system (space group P212121, a = 10.4264(17) A, b = 10.8490(18) A, c = 10.9878(19) A, V = 1242.9(4) A3; Z = 4). In the structure of 1·2, molecules 1 and 2 are ordered. The nitro oxygen atoms form close contacts with the nitrogen atoms of the N→O groups and the system of the tetrazine ring, as well as with the carbon atoms of bicyclic compound 1. The reversible crystallization—melting processes of complex 1·2 and the eutectic E 2 were studied by turbidimetry. The sensitivity of molecular complex 1·2 to mechanical and thermal effects and its tendency to detonation were studied in relation to compound 1. The formation of the complex was found to lead to an increase in the critical diameter of detonation from 0.04 to 0.7 mm, in the minimum drop height for the determination of the impact sensitivity from 30–70 to 150–200 mm (P = 2 kg), and in the temperature of extensive decomposition from 135 to 168 °C.

Molecular modeling of the adsorption and initial photocatalytic oxidation step for para-nitrophenol on nano-sized TiO2 surface

In the present work, the non-constrained optimization for three proposed models of PNP molecule onto TiO2 (100) surface has resulted in three molecular adsorption conformations; a vertical alignment via bridged NO2, a parallel alignment bridges via NO2 and OH groups, and a monodentate vertical alignment bridged via OH. The first configuration is the dominant adsorption structure. The adsorption energy for the bridging geometries is found to be much more stable than that of the monodentate conformer. The predicted VDOS spectra indicate that the main interaction between PNP molecule and the surface of TiO2 takes place through a linkage between the Lewis acid sites, fivefold Ti (V) and fourfold Ti (IV) coordinated titanium surface atoms, and the nitro or phenolic oxygen atoms. Frontier electron theory (FET) and Wheland localization approach (WLA) have been applied for the prediction of the primary •OH initiated oxidation intermediates. These approaches highlight similar expectations for the variation in the reactivity of the ring positions, towards the hydroxyl radical attack. By comparison with the available experimental data and other theoretical calculations, it is shown that MSINDO can reproduce literature data with acceptable accuracy.

Structure-based evaluation of the resonance interactions and effectiveness of the charge transfer in nitroamines

Structural data for five nitroamines of general formula Me2N–G–NO2 show effectiveness of the ground-state charge transfer to be most and least efficient in N,N-dimethylnitramine and in 4-N,N-dimethylamino-β-nitrostyrene, respectively. Electron-donor power of the amino nitrogen atom in the latter compound is less than that in 4-nitro-β-N,N-dimethylaminostyrene (these two compounds are isomers). Natural population analysis shows that the charge transfer from the amino to the nitro oxygen atoms is most effective in N,N-dimethylnitramine, Me2N–NO2. The nitro oxygen atoms are not the only acceptors of the negative charge lost by the amino nitrogen atom. The nitro group in two substituted nitrobenzenes studied was found to be independent on substituent (nitro group attached to the benzene ring withdraws a constant electron density regardless the substitution).

Synthesis and structure of alkyl-α-arylamino-β-bromo-β-nitroacrylates, new functionalized β-nitroenamines

New bromonitroenamine compounds, alkyl-2-arylamino-3-bromo-3-nitroacrylates, were synthesized and characterized using IR, UV, 1H and 13C NMR spectroscopy, and X-ray analysis. Their molecules were found to have the E-configuration and to exist as highly conjugated structures. According to the X-ray analysis, in the ethyl-3-bromo-2-(p-bromophenylamino)-3-nitroacrylate molecule the bromonitroenamine moiety is almost planar, the ester group is located completely out of the C=C double bond plane, amino hydrogen and nitro oxygen atoms form an intramolecular hydrogen bond.

Binding of HgCl2 by a Nitro Functionalized Tripodal Receptor and Its Decomplexation Controlled by Anion Complexation

AbstractThe presence of a nitro functionality on N‐bridged tripodal receptors has an effect on its binding ability towards HgCl2 by coordination through one of the nitro oxygen atoms, ethereal oxygen and the bridgehead nitrogen atom. Decomplexation of HgCl2 and recovery of the receptor L can be accomplished by the formation of anion complexes with [L·HgCl2]. The complexation of different anions with multiple protonated receptor units is attributable to intramolecular (N–H)+···anion interactions, at the same time the presence of multiple C–H···anion and interligand C–H···Onitro hydrogen bonds provide added stabilization. Protonation at the bridgehead nitrogen atom and the presence of the nitro functionality render the aliphatic and aryl protons sufficiently acidic for their active participation in moderate to weak C–H···anion and C–H···Onitro interactions. Spectroscopic studies provide evidence for the formation of anion complexes from [L·HgCl2] by extrusion of HgCl2.

A Density Functional Theory Study of Adsorption and Decomposition of Nitroamine Molecules on the Al(111) Surface

The density functional theory generalized gradient approximation has been used to study the adsorption of nitroamine molecules on the Al(111) surface. The calculations employ a 4 × 4 aluminum slab with three layers and three-dimensional periodic boundary conditions. There exist both physical and chemical adsorptions associated with different NH2NO2 molecule orientations and particular aluminum surface sites. For the nondissociative adsorption, the nitro oxygen atom orients to the Al surface. In the case of dissociative chemisorption, the O and N atoms bind with the Al surface. The O and N atoms of broken down N−O and N−N bonds form strong Al−O and Al−N bonds with the neighboring Al sites around the dissociation sites. Moreover, the radical species obtained as a result of N−O and N−N bond dissociation remains bonded to the surface. The largest adsorption energy is −893.8 kJ/mol. For the dissociation adsorption configurations, a significant charge transfer occurs. The most charge transfer is 3.04 e from the Al surface to the NH2NO2 molecule. The change of the electronic structures is obvious due to the dissociation of the N−O and N−N bonds and the formation of strong Al−O and Al−N bonds. It can be inferred that the aluminum surface is readily oxidized by the adsorbate of nitroamine, by dissociation of either the O and N atoms from the nitro group or the N atom from the amino group.

4-Nitroaniline–picric acid (2/1)

In the title adduct, C6H3N3O7·0.5C6H6N2O2, the complete 4-nitro­aniline mol­ecule is generated by a crystallographic twofold axis with two C atoms and two N atoms lying on the axis. The mol­ecular components are linked into two dimensional corrugated layers running parallel to the (001) plane by a combination of inter­molecular N—H⋯O and C—H⋯O hydrogen bonds. The phenolic oxygen and two sets of nitro oxygen atoms in the picric acid were found to be disordered with occupancies of 0.81 (2):0.19 (2) and 0.55 (3):0.45 (3) and 0.77 (4):0.23 (4), respectively.

Pharmacophore of neonicotinoid insecticides

Our recent study related to neonicotinoid pharmacophore was presented. The first topic described on the QSAR study with 17 variants of 2-nitroiminoimizolidine. The insect neuroblocking potency is proportionally related both to the Mulliken charge on the nitro oxygen atom and log P. The second raised the functional possibility of the 3-fluoropropyl group as an H-bond acceptor for the neonicotinoid skeleton. Its 2-nitroiminoimidazolidine derivative actually showed the insecticidal tendency common to the neonicotinoids bearing a 6-chloro-3-pyridylmethyl group, although the activating strength was not as high as expected. The third introduced a new type of neonicotinoid compounds of alkylene-tethered twin-structure. The insecticidal activity against American cockroaches was dependent on the tether length and maximized at the hexamethylene with the minimum lethal dose of 2.2 nmol/insects, comparable to that of imidacloprid.