Monocyte-dependent oncostatin M and TNFa synergize to stimulate unopposed matrix metalloproteinase-1/3 secretion from human lung fibroblasts in tuberculosis

Leukocyte-derived matrix metalloproteinases (MMP) are implicated in the tissue destruction characteristic of tuberculosis (TB). The contribution of lung stromal cells to MMP activity in TB is unknown. Oncostatin M (OSM) is an important stimulus to extrapulmonary stromal MMP induction, but its role in regulation of pulmonary MMP secretion or pathophysiology of TB is unknown. We investigated OSM secretion from Mycobacterium tuberculosis (Mtb)-infected human monocytes/macrophages and the networking effects of such OSM on lung fibroblast MMP secretion. Mtb increased monocyte OSM secretion dose dependently in vitro. In vivo tuberculous granulomas immunostained positively for OSM. Further, conditioned media from Mtb-infected monocytes (CoMTb) induced monocyte OSM secretion (670 ± 55 versus 166 ± 14 pg/mL in controls), implicating an autocrine loop. Mtb-induced OSM secretion was prostaglandin (PG) sensitive, and required activation of surface G-protein coupled receptors. OSM induction was ERK MAP kinase dependent, p38-requiring but JNK-independent. OSM synergized with TNF-, a key cytokine in TB granuloma formation, to stimulate pulmonary fibroblast MMP-1/-3 secretion, while suppressing secretion of tissue inhibitors of metalloproteinases-1/-2. In summary, Mtb infection of monocytes results in PG-dependent OSM secretion, which synergizes with TNF- to drive functionally unopposed fibroblast MMP-1/-3 secretion, demonstrating a previously unrecognized role for OSM in TB.

Glucose solvation by the ionic liquid 1,3-dimethylimidazolium chloride: A simulation study

Simulations of beta-glucose in the ionic liquid 1,3-dimethylimidazoliurn chloride have been performed in order to examine the solvation environment of the carbohydrate. Both single molecule and 1:5 glucose:ionic liquid (16.7 wt %) solutions are Studied, and the hydrogen bonding between sugar and solvent is examined. The primary solvation shell around the perimeter of the glucose ring consists predominantly of chloride anions which hydrogen bond to the hydroxyl groups. A small presence of the cation is also found, with the association Occurring through the weakly acidic hydrogen at the 2-position of the imidazolium ring interacting with the oxygen atoms of the sugar secondary hydroxyls. An average chloride coordination number of 4 is found around the glucose for both the single molecule and high concentration Simulations, despite the reduced chloride:glucose ratio in the latter case. In relation to the cation, the glucose molecules occupy positions above and below the plane of the imidazolium ring. Importantly, even at high glucose concentrations, no significant change in the anion-cation interactions and overall liquid structure of the ionic liquid is found, indicating that the glucose is readily accommodated by the solvent at this concentration. Dominant contributions to the sugar-ionic liquid interaction energy come from favorable hydrogen bonding (electrostatic) interactions between hydroxyls and chlorides, although a small favorable van der Waals energy contribution is also seen between the sugar and cations suggesting that the cation could be tailored in order to further improve the dissolution of glucose/cellulose in ionic liquid systems.

Liquid structure of the ionic liquid 1,3-dimethylimidazolium bis{(trifluoromethyl)sulfonyl}amide

Neutron diffraction has been used to determine the liquid structure of 1,3-dimethylimidazolium bis{( trifluoromethyl) sulfonyl} amide ([dmim][NTf2]). Significantly smaller charge ordering is found in this liquid compared with analogous chloride and hexafluorophosphate salts due to the diffuse charge density and size of the [NTf2](-) anion. This is manifested in a much larger cation-cation and cation-anion separation and an overlap of the cation-cation and cation-anion shells. Comparison of the liquid structure with the crystal structure reported by Holbrey et al. ( Dalton Trans. 2004, 2267) indicates little correlation, for example, the [NTf2](-) anion adopts a trans orientation predominantly in the liquid whereas a cis orientation is found in the solid phase.

Ruthenium complexes of the 1,4-bis(diphenylphosphino)-1,3-butadiene-bridged diphosphine 1,2,3,4-Me-4-NUPHOS: Solvent-dependent interconversion of four- and six-electron donor coordination and transfer hydrogenation activity

In chloroform, [RuCl2(nbd)(py)(2)] (1) (nbd = norbornadiene; py = pyridine) reacts with 1,4-bis(diphenylphosphino)-1,2,3,4-tetramethyl-1,3-butadiene (1,2,3,4-Me-4-NUPHOS) to give the dimer [Ru2Cl3(eta(4)-1,2,3,4-Me-4-NUPHOS)(2)]Cl (2a), whereas, in THF [RuCl2(1,2,3,4-Me-4-NUPHOS)(PY)(2)] (3) is isolated as the sole product of reaction. Compound 2 exists as a 4:1 mixture of two noninterconverting isomers, the major with C, symmetry and the minor with either C, or C-2 symmetry. A single-crystal X-ray analysis of [Ru2Cl3 (eta(4)-1,2,3,4-Me-4-NUPHOS)(2)] [SbF6] (2b), the hexafluoroantimonate salt of 2a, revealed that the diphosphine coordinates in an unusual manner, as a eta(4)-six-electron donor, bonded through both P atoms and one of the double bonds of the butadiene tether. Compounds 2a and 3 react with 1,2-ethylenediamine (en) in THF to afford [RuCl2(1,2,3,4-Me-4-NUPHOS)(en)] (4), which rapidly dissociates a chloride ligand in chloroform to give [RuCl(eta(4)-1,2,3,4-Me-4-NUPHOS)(en)] [Cl] (5a). Complexes 4 and 5a cleanly and quantitatively interconvert in a solvent-dependent equilibrium, and in THF 5a readily adds chloride to displace the eta(2)-interaction and re-form 4. A single-crystal X-ray structure determination of [RuCl(eta(4)-1,2,3,4-Me-4-NUPHOS)(en)][ClO4] (5b) confirmed that the diphosphine coordinates in an eta(4)-manner as a facial six-electron donor with the eta(2)-coordinated double bond occupying the site trans to chloride. The eta(4)-bonding mode can be readily identified by the unusually high-field chemical shift associated with the phosphorus atom adjacent to the eta(2)-coordinated double bond. Complexes 2a, 2b, 4, and 5a form catalysts that are active for transfer hydrogenation of a range of ketones. In all cases, catalysts formed from precursors 2a and 2b are markedly more active than those formed from 4 and 5a.

Liquid and solid-state structures of 1,3-dimethylimidazolium salts

Using neutron and single crystal X-ray diffraction the structures of 1,3-dimethylimidazolim chloride and hexafluorophosphate salts have been determined in the liquid and the solid-state. The relative hydrogen bonding characteristics and sizes of the two anions force the ions to pack differently. In each case, a strong correlation between the crystal structure and liquid structure is found.

Liquid structure of 1, 3-dimethylimidazolium salts

The structure of liquid 1, 3-dimethylimidazolium hexafluorophosphate is described in detail and compared with the structure of 1, 3-dimethylimidazolium chloride. In each case, the data were obtained from neutron diffraction experiments and analysed using an empirical potential structure refinement process. Overall, the structures are similar; however, significant differences arise from the variation in anion size.

Formation of Novel Di-Nuclear Lanthanide Luminescent Sm(III), Eu(III) and Tb(III) Triple Stranded Helicates from a C2 Symmetrically 2,6-Dicarboxylic Amide based 1,3-Xylene Ligand in CH3CN

The synthesis of the C2-symmetrical ligand 1 consisting of two naphthalene units connected to two pyridine-2,6-dicarboxamide moieties linked by a xylene spacer and the formation of LnIII-based (Ln1/4 Sm, Eu, Tb, and Lu) dimetallic helicates [Ln2 · 13] in MeCN by means of a metal-directed synthesis is described. By analyzing the metal-induced changes in the absorption and the fluorescence of 1, the formation of the helicates, and the presence of a second species [Ln2 · 12] was confirmed by nonlinear- regression analysis. While significant changes were observed in the photophysical properties of 1, the most dramatic changes were observed in the metal-centred lanthanide emissions, upon excitation of the naphthalene antennae. From the changes in the lanthanide emission, we were able to demonstrate that these helicates were formed in high yields (ca. 90% after the addition of 0.6 equiv. of LnIII), with high binding constants, which matched well with that determined from the changes in the absorption spectra. The formation of the LuIII helicate, [ Lu2 · 13 ] , was also investigated for comparison purposes, as we were unable to obtain accurate binding constants from the changes in the fluorescence emission upon formation of [Sm2 · 13], [Eu2 · 13], and [Tb2 · 13].

Development of a QSPR correlation for the parachor of 1,3-dialkyl imidazolium based ionic liquids

Ionic liquids have received significant interest from both academia and industry for a wide range of applications which often requires knowledge of their thermophysical properties. Quantitative structure-property relationship correlations and group contribution methods for thermophysical properties of ionic liquids are a basic necessity for the development of computer aided molecular design approaches for these liquids and subsequently offer the potential for designing an ionic liquid having a desirable set of thermophysical properties. However, the limited availability of experimental thermophysical data and their quality have prevented the development of such tools. Based on previously reported experimental surface tension data, a correlation of the parachors with the molar volume of the ionic liquids has been developed. The predicted parachor values have been shown to be in good agreement with the experimental data. A maximum deviation of

Rapid annulation of tropolone units via a pyrylium ylide 1,3-dipolar cycloaddition reaction

The tropolone subunit of the naturally occurring alkaloid rubrolone aglycon is synthesized via a short reaction sequence starting with a 1,3-dipolar cycloaddition of a pyrylium ylide and indenone, followed by enone oxidation, oxygen bridge elimination and finally hydroxy group oxidation.

Solid-state analysis of low-melting 1,3-dialkylimidazolium hexafluorophosphate salts (ionic liquids) by combined x-ray crystallographic and computational analyses

The interactions of ions in the solid state for a series of representative 1,3-dialkylimidazolium hexafluorophosphate salts (either ionic liquids or closely related) have been examined by crystallographic analysis, combined with the theoretical estimation of crystal-packing densities and lattice-interaction energies. Efficient close-packing of the ions in the crystalline states is observed, but there was no compelling evidence for specific directional hydrogen-bonding to the hexafluorophosphate anions or the formation of interstitial voids. The close-packing efficiency is supported by the theoretical calculation of ion volumes, crystal lattice energies, and packing densities, which correlated well with experimental data. The crystal density of the salts can be predicted accurately from the summation of free ion volumes and lattice energies calculated. Of even more importance for future work, on these and related salts, the solid-state density of 1,3-dialkylimidazolium hexafluorophosphate salts can be predicted with reasonable accuracy purely on the basis of on ab initio free ion volumes, and this allows prediction of lattice energies without necessarily requiring the crystal structures.

Ionic liquids via reaction of the zwitterionic 1,3-dimethylimidazolium-2-carboxylate with protic acids. Overcoming synthetic limitations and establishing new halide free protocols for the formation of ILs

The previously reported preparation of 1,3-dimethylimidazolium salts by the reaction of 1,3-dialkylimidazolium-2-carboxylate zwitterions with protic acids has been reinvestigated in detail, leading to the identification of two competing reactions: isomerisation and decarboxylation. The ability to control both pathways allows this methodology to be used as an effective, green, waste-free approach to readily prepare a wide range of ionic liquids in high yields. Additionally, this reaction protocol opens new possibilities in the formation of other imidazolium salts, whose syntheses were previously either very expensive (due to ion exchange protocols involving metals like Ag) or difficult to achieve (due to multiple extractions and large quantities of hard to remove inorganic by-products).

The structure of [Co(H-tptz)Cl-3] center dot H2O (tptz=2,4,6-tri(2-pyridyl)-1,3,5-triazine) prepared by crystallization from the ionic liquid, N-butyl-N-methyl-pyrrolidinium bis(trifluoromethanesulfonyl)imide

The structure of tris-chloro[2,6-bis(2'-pyridyl)-4-(2'-pyridinium)-1,3,5-triazine]cobalt(II) monohydrate, [Co(C18H13N6)Cl-3]center dot H2O (C2/c (No. 15), a = 7.783(11), b = 22.42(3), c = 11.001(15) angstrom, beta = 90.05(2)degrees), crystallized from the open air reaction of CoCl2 and 2,4,6-tri(2-pyridyl)-1,3,5-triazine in the ionic liquid, N-butyl-N-methyl-pyrrolidinium bis(trifluoromethanesulfonyl)imide is reported. The structure consists of six coordinate cobalt in an octahedral geometry bonded to the tridentate tptz ligand and three chlorines. The non-coordinating pyridyl group in the tptz ligand is protonated (with the protonated nitrogen crystallographically disordered over two possible sites), providing overall charge neutrality for the complex.

Efficient, halide free synthesis of new, low cost ionic liquids: 1,3-dialkylimidazolium salts containing methyl- and ethyl-sulfate anions

New low-cost ionic liquids containing methyl- and ethyl-sulfate anions can be easily and efficiently prepared under ambient conditions by the reaction of 1-alkylimidazoles with dimethyl sulfate and diethyl sulfate. The preparation and characterization of a series of 1,3-dialkylimidazolium alkyl sulfate and 1,2,3-trialkylimidazolium alkyl sulfate salts are reported. 1,3-Dialkylimidazolium salts containing at least one non-methyl N-alkyl substituent are liquids at, or below room, temperature. Three salts were crystalline at room temperature, the single crystal X-ray structure of 1,3-dimethylimidazolium methyl sulfate was determined and shows the formation of discrete ribbons comprising of two anion-cation hydrogen-bonded chains linked via intra-chain hydrogen-bonding, but little, or no inter-ribbon hydrogen-bonding. The salts are stable, water soluble, inherently 'chloride-free', display an electrochemical window of greater than 4 V, and can be used as alternatives to the corresponding halide salts in metathesis reactions to prepare other ionic liquids including 1-butyl-3-methylimidazolium hexafluorophosphate.

1,3-dimethylimidazolium-2-carboxylate: the unexpected synthesis of an ionic liquid precursor and carbene-CO2 adduct

1,3-Dimethylimidazolium-2-carboxylate is formed in good yield, rather than the anticipated organic salt, 1,3-dimethylimidazolium methyl carbonate, as the reaction product resulting from both N-alkylation and C-carboxylation of 1-methylimidazole with dimethyl carbonate; the crystal structure of the zwitterion exhibits pi-stacked rings and two-dimensional sheets constructed by hydrogen-bonds from imidazolium-ring hydrogens to the carboxylate group.