Mixture solubilities of nitrobenzoic acid isomers in supercritical carbon dioxide

The ternary solubilities of solid isomers of nitrobenzoic acid (NBA) were experimentally determined at 308, 318 and 328K over a pressure range of 12-18 MPa in supercritical carbon dioxide (SCCO2). Compared to its binary solubility, the ternary solubilities of m-NBA increased at 308 K while it decreased at 328 K. However, the ternary solubilities of p-NBA increased at all temperatures and pressures except at 13 MPa and 328K. A new model was developed by applying solution model and activity coefficient model for the ternary solubilities of pharmaceutical and non-pharmaceutical solid mixtures in terms of temperature, density and cosolute composition. The model equation involves four temperature independent constraint-free parameters. The model equation correlates the ternary solubilities of seven pharmaceutical solid mixtures along with current data with an average AARD around 9.5% and sixteen non-pharmaceutical solid mixtures with 9% AARD. (C) 2012 Elsevier B.V. All rights reserved.

Temperature dependence of chlorine NQR in 2-chloro 5-nitrobenzoic acid and 4-chloro 3-nitrobenzoic acid

Temperature dependence of chlorine nuclear quadrupole resonance in 2-chloro 5-nitrobenzoic acid and 4-chloro 3-nitrobenzoic acid has been investigated in the region 77° K to room temperature. No phase transition has been observed. The results are analysed to obtain the torsional frequencies and their temperature dependence. A nonlinear temperature dependence is obtained for the torsional frequencies.

Inter And Intramolecular Interactions Of Porphyrins With 5,5′-Dithiobis(2-Nitrobenzoic Acid)

meso-Tetraphenylporphyrin and its metal [zinc(II) and copper(II)] derivatives form both inter and intramolecular complexes with 5,5′-dithiobis(2-nitrobenzoic acid) (DTNB). The nature of interaction is predominantly charge transfer (CT) in origin, with the porphyrin functioning as a II-donor and DTNB as an acceptor. Among the covalently linked intramolecular systems, the magnitude of CT interaction varies with the position (of one of the aryl groups of the porphyrin) to which DTNB is attached as ortho meta > para. Steady-state and time-resolved fluorescence studies revealed electron transfer to be the dominant pathway for the fluorescence quenching in these systems. Steady-state photolysis experiments probed using EPR and optical absorption studies have shown that electron transfer (from the excited singlet state of the porphyrin) to DTNB results in the formation of thiyl radical and production of free thiolate anion. It is found that the products of electrochemical reduction of covalently linked porphyrin-DTNB systems are different from those observed for the photochemical studies.

Synthesis and characterization of cobalt(II), nickel(II), copper(II) and zinc(II) complexes of 2-nitrobenzoic acid with methyl carbazate as ancillary ligand. Crystal structure of the copper(II) complex

Divalent metal complexes of general formula M(2-nb)(2)(mc)(2)].2(2-nbH), where M = Co(II), Ni(II), Cu(II) or Zn(II), 2-nbH = 2-nitrobenzoic acid and mc = methyl carbazate (NH2NHCOOCH3), have been prepared and characterized by physicochemical and spectroscopic methods. Single-crystal X-ray study of the Cu(II) complex revealed that the molecule is centrosymmetric, with two N,O-chelating mc ligands in equatorial positions and a pair of monodentate 2-nb anions in the axial positions. The lattice 2-nbH molecules help to establish the packing of monomers through hydrogen-bonding interactions. Thermal stability and reactivity of the complexes were studied by TG-DTA. Emission studies show that these complexes are fluorescent.

Chemical aspects of the hypergolic preignition reactions of some hybrid hypergols

A new class of solid compounds, viz., bisthiocarbonohydrazones and thiosemicarbazones, have been found to be hypergolic with fuming nitric acid. The observed ignition delays of these hypergols have been compared with those of the monothiocarbonohydrazones-nitric acid systems and explained in terms of the chemical reactions-neutralization, oxidation, and nitration-occurring in the preignition stage. p-Nitrobenzoic acid, benzoic acid, benzaldehyde, sulfur trioxide, nitrogen dioxide, and nitrogen have been isolated as preignition reaction intermediates in the mono- and bisbenzaldehydethiocarbonohydrazone-nitric acid systems. A scheme of reactions occurring in the preignition stage is proposed based on the formation of these products.

Facile preparation and some applications of an affinity matrix with a cleavable connector arm containing a disulfide bond

A versatile affinity matrix in which the ligand of interest is linked to the matrix through a connector arm containing a disulfide bond is described. It can be synthesized from any amino-substituted matrix by successive reaction with 2-imino-thio-lane, 5, 5'-dithiobis(2-nitrobenzoic acid), and a thiol derivative of the ligand of choice. The repertoire of ligands can be significantly increased by the appropriate use of avidin-biotin bridges. After adsorption of the material to be fractionated, elution can be effected by reducing the disulfide bond in the connector arm with dithiothreitol. Examples of the preparation and use of various affinity matrices based on amino-substituted Sepharose 6MB are given. One involves the immobilization of the Fab' fragment of a monoclonal antibody against Aspergillus oryzae β-galactosidase and the specific binding of that enzyme to the resulting immunoaffinity matrix. Another involves the immobilization of N-biotinyl-2-thioethylamine followed by complex formation with avidin. The resulting avidin-substituted matrix was used for the selective adsorption and subsequent recovery of mouse hybridoma cells producing anti-avidin antibodies. By further complexing the avidin-substituted matrix with appropriate biotinylated antigens, it should be possible to fractionate cells producing antibodies against a variety of antigens.

NQR study of complexes between p-dichlorobenzene and some aromatic π acceptors

The charge-transfer complexes of p-dichlorobenzene (PDB) with some aromatic π acceptors such as m-nitrobenzaldehyde (MNB), picric acid (PA), p-nitrobenzoic acid (PNB), and m-dinitrobenzene (MDNB) were prepared by slowly adding the acceptor to the molten donor and then cooling the mass to 15°C. The NQR frequencies of these complexes were measured at room temperature. Contrary to the theoretical prediction, the NQR shift is positive, indicating that the NQR shift in donor-acceptor complexes is indirectly related to the charge-transfer interaction. Bond properties are discussed in terms of frequency shift.

Growth and characterization of L-histidinium 2-nitrobenzoate single crystals: A new NLO material

Crystals of a new nonlinear optical (NLO) material, viz., L-histidinium 2-nitrobenzoate (LHNB) (1) were grown by slow evaporation of an aqueous solution containing equimolar concentrations of L-histidine and 2-nitrobenzoic acid. The structure of the title compound which crystallizes in the non-centrosymmetric monoclinic space group P2(1) was elucidated using single crystal X-ray intensity data. The UV-Vis-NIR spectrum of 1 reveals its transparent nature while the vibrational spectra confirm the presence of the functional groups in 1. The thermal stability and second harmonic generation (SHG) conversion efficiency of 1 were also investigated. (C) 2012 Elsevier GmbH. All rights reserved.

The Role of Weak Interactions in the Phase Transition and Distinct Mechanical Behavior of Two Structurally Similar Caffeine Co-crystal Polymorphs Studied by Nanoindentation

Although weak interactions, such as C-H center dot center dot center dot O and pi-stacking, are generally considered to be insignificant, it is their reorganization that holds the key for many a solid-state phenomenon, such as phase transitions, plastic deformation, elastic flexibility, and mechanochromic luminescence in solid-state fluorophores. Despite this, the role of weak interactions in these dynamic phenomena is poorly understood. In this study, we investigate two co-crystal polymorphs of caffeine:4-chloro-3-nitrobenzoic acid, which have close structural similarity (2D layered structures), but surprisingly show distinct mechanical behavior. Form I is brittle, but shows shear-induced phase instability and, upon grinding, converts to Form II, which is soft and plastically shearable. This observation is in contrast to those reported in earlier studies on aspirin, wherein the metastable drug forms are softer and convert to stable and harder forms upon stressing To establish a molecular level understanding, have investigated the two co-crystal polymorphs I and II by single crystal X-ray diffraction, nanoindentation to quantify mechanical properties, and theoretical calculations. The lower hardness (from nanoindentation) and smooth potential surfaces (from theoretical studies) for shearing of layers in Form II allowed us to rationalize the role of stronger intralayer (sp(2))C-H center dot center dot center dot O and nonspecific interlayer pi-stacking interactions in the structure of II. Although the Form I also possesses the same type of interactions, its strength is clearly opposite, that is, weaker intralayer (sp(3))C-H center dot center dot center dot O and specific interlayer pi-stacking interactions. Hence, Form I is harder than Form IL Theoretical calculations and indentation on (111) of Form I suggested the low resistance of this face to mechanical stress; thus, Form I converts to II upon mechanical action. Hence, our approach demonstrates the usefulness of multiple techniques for establishing the role of weak noncovalent interactions in solid-state dynamic phenomena, such as stress induced phase transformation, and hence is important in the context of solid-state pharmaceutical chemistry and crystal engineering.

Multicomponent Adducts of Pyridoxine: An Evaluation of the Formation of Eutectics and Molecular Salts

Cocrystallization of pyridoxine (vitamin B6) with several biologically important molecules was undertaken with the intent of successfully designing various hydrogen bonded adducts such as salts, cocrystals, and eutectics. Pyridoxine formed eutectics with isoniazid (an antitubercular drug) and nicotinic acid (vitamin B3) and molecular salts with para-aminobenzoic acid (a bioactive) and saccharin (an artificial sweetener), respectively, in accordance to our design strategy. A salt cocrystal, a precisely conjugate acid-base cocrystal, was obtained for the pyridoxine-para-nitrobenzoic acid combination. The role of supramolecular affinity of hydrogen bonding functional groups and Delta pK(a) differences leading to the formation of above diverse adducts was discussed. This study underpins the need for full-fledged supramolecular compatibility studies of multivitamin/drug combinations toward the development of optimal and/or synergistic combination formulations.

Estimating successive pK(a) values of polyprotic acids from ab initio molecular dynamics using metadynamics: the dissociation of phthalic acid and its isomers

Estimation of the dissociation constant, or pK(a), of weak acids continues to be a central goal in theoretical chemistry. Here we show that ab initio Car-Parrinello molecular dynamics simulations in conjunction with metadynamics calculations of the free energy profile of the dissociation reaction can provide reasonable estimates of the successive pK(a) values of polyprotic acids. We use the distance-dependent coordination number of the protons bound to the hydroxyl oxygen of the carboxylic group as the collective variable to explore the free energy profile of the dissociation process. Water molecules, sufficient to complete three hydration shells surrounding the acid molecule, were included explicitly in the computation procedure. Two distinct minima corresponding to the dissociated and un-dissociated states of the acid are observed and the difference in their free energy values provides the estimate for pK(a), the acid dissociation constant. We show that the method predicts the pK(a) value of benzoic acid in good agreement with experiment and then show using phthalic acid (benzene dicarboxylic acid) as a test system that both the first and second pK(a) values as well, as the subtle difference in their values for different isomers can be predicted in reasonable agreement with experimental data.

Aspects of tautomerism 12-Some causes and consequences of participation in the solvolysis of acid chlorides

Solvolysis of nine representative half ester acid chlorides in aqueous acetone have been studied. Isomers solvolyse at distinctly different rates and furnish the original acids. Contrary to the well accepted views, no evidence for tautomerism or isomerism between the isomeric pairs of acid chlorides could be detected. In a number of cases alkoxy group participates in the solvolysis of neighbouring acid chlorides. This results in (a) rate enhancement and (b) partial or total shift of the reaction pattern from SN2 to SN1. Isomeric half ester acid chlorides, in the presence of a sufficiently strong Lewis acid, could give the same oxonium salt. Rearrangements observed in the reactions of unsymmetrical 1,2- and 1,3-dicarboxylic acid derivatives could be ascribed to the prior formation of common oxonium salt intermediates in the presence of Lewis acids.

X-ray studies on crystalline complexes involving amino acids and peptides. XXV. Structures of DL-proline hemisuccinic acid and glycyl-L-histidinium semisuccinate monohydrate and a comparative study of amino-acid and peptide complexes of succinic acid

DL-Proline hemisuccinic acid, C5H9NO2.1/2C4H6O4, M(r) = 174.2, P2(1/c) a = 5.254 (1), b = 17.480 (1), c = 10.230 (i) angstrom, beta = 119.60 (6)-degrees Z = 4, D(m) = 1.41 (4), D(x) = 1.42 g cm-3, R = 0.045 for 973 observed reflections. Glycyl-L-histidinium semisuccinate monohydrate, C8H13N4O3+.C4H5O4-.H2O, M(r) = 348.4, P2(1), a = 4.864 (1), b = 17.071 (2), c = 9.397 (1) angstrom, beta = 90.58-degrees, Z = 2, D(m) = 1.45 (1), D(x) = 1.48 g cm-3, R = 0.027 for 1610 observed reflections. Normal amino-acid and dipeptide aggregation patterns are preserved in the structures in spite of the presence of succinic acid/semisuccinate ions. In both the structures, the amino-acid/dipeptide layers stack in such a way that the succinic acid molecules/semisuccinate ions are enclosed in voids created during stacking. Substantial variability in the ionization state and the stoichiometry is observed in amino-acid and peptide complexes of succinic acid. Succinic acid molecules and succinate ions appear to prefer a planar centro-symmetric conformation with the two carboxyl (carboxylate) groups trans with respect to the central C=C bond. Considerable variation is seen in the departure from and modification of normal amino-acid aggregation patterns produced by the presence of succinic acid. Some of the complexes can be described as inclusion compounds with the amino acid/dipeptide as the 'host' and succinic acid/semisuccinate/succinate as the 'guest'. The effects of change in chirality, though very substantial, are not the same in different pairs of complexes involving DL and L isomers of the same amino acid.

An Approach Toward Homocalystegines and Silyl-homocalystegines. Acid-Mediated Migrations of Acetates in Seven-Membered Ring Systems

A short access to homocalystegine analogues silylated at C7 is described. The synthesis involves the desymmetrization of a (phenyldimethylsilyl)methylcycloheptatriene using osmium-mediated dihydroxylation, followed by the diol protection and a cycloaddition involving the remaining diene moiety and an acylnitroso reagent. Additions of the osmium and acylnitroso reagents were shown, through X-ray diffraction studies of the resulting major isomers, to occur anti and syn, respectively, relative to the SiCH2 substituent. N-O bond cleavage on the resulting cycloadduct then produces the aminopolyol having a silylmethyl substituent. Oxidation of the C-Si bond also afforded an access to unusual amino-heptitols having five contiguous stereogenic centers. In the course of this work, we finally observed a unusual rearrangement taking place on cycloheptanone 18 substituted by two acetyl groups and a neighboring Boc-protected amine. A profound reorganization of the substituents on the seven-membered ring effectively took place under acidic conditions (TFA) leading to the thermodynamically more stable homocalystegine-type compound., DFT calculations of the conformational energy of isomeric silyl homocalystegines indicated that the product observed upon the acid-mediated rearrangement was the most stable of a series of analogues with various distributions of substituents along the seven-membered ring backbone. A tentative mechanism is proposed to rationalize the acetate migrations and inversions of the stereochemistry at various stereocenters.

Diffusion ordered spectroscopy for resolution of double bonded cis, trans-isomers

NMR spectroscopic separation of double bonded cis- and trans-isomers, that have different molecular shapes but identical mass have been carried out using Diffusion Ordered Spectroscopy (DOSY). The mixtures of fumaric acid and maleic acid, that have similar hydrodynamic radii, have resolved been on the basis of their diffusion coefficients arising due to their different tendencies to associate with micelles or reverse micelles. Sodium dodecyl sulfate (SDS) and Dioctyl sulfosuccinate sodium salt (AOT) have been used as the media to mimic the chromatographic conditions, modify the average mobility and to achieve differential diffusion rates. The best separation of the components has been achieved by Dioctyl sulfosuccinate sodium salt (AOT) in D2O solution. (C) 2012 Elsevier B.V. All rights reserved.