Pyrrolidinium Ionic Liquid Crystals with Pendant Mesogenic Groups

New ionic liquid crystals (including ionic metallomesogens) based oil the pyrrolidinium core are presented. N-Methylpyrrolidine was quaternized with different mesogenic groups connected to a flexible, omega-bromosubstituted alkyl spacer. The length of the flexible alkyl spacer between the cationic head group and the rigid mesogenic group was varied. The substituted pyrrolidinium cations were combined with bromide, bis(trifluoromethylsulfonyl)imide, tetrakis (2-thenoyltrifluoroacetonato)europate(III), and tetrabromouranyl anions. The influence of the type of mesogenic unit, the lengths of the flexible spacer and terminal alkyl chain, the size of the mesogenic group, and the type of anion oil the thermotropic mesomorphic behavior was investigated. Furthermore, the phase behavior was thoroughly compared with the previously reported mesomorphism of N-alkyl-N-methylpyrrolidinium salts. Low-ordered smectic A phases of the de Vries type, smectic C phases, higher-ordered smectic F/I phases, as well its crystal smectic phases (E and G, J, H, or K) were observed and investigated by polarizing optical microscopy, differential scanning calorimetry, and powder X-ray diffraction.

The ammonium bromomercurates(II) (NH4)Hg5Br11 and (NH4)(4)HgBr6

The crystal structures of two ammonium bromomercurates(II), (NH4)Hg5Br11 (1) and (NH4)(4)HgBr6 (2), were determined from single-crystal X-ray diffraction data: 1: monoclinic, C2/m (no. 12), a = 1231.3(3), b = 1517.4(3), c = 680.4(2) pm, beta = 118.78(2)degrees, Z = 2, R-1 = 0.0391 for I-0 > 2 sigma(I-0); 2: tetragonal, P4/mnc (no. 128), a = 925.6(1), c = 887.2(1) pm, Z = 2, R-1 = 0.0370 for I(0 >)2a(I-0). According to (NH4)Br[HgBr2](5) and (NH4)(4)Br-4[HgBr2] they both contain [Br-Hg-Br] molecules. Additional bromide ions are only loosely attached to the mercury atoms, however involved in (NH4)(+)-Br- bonding.

Ionic liquids as solvents for near-infrared emitting lanthanide complexes

It is shown that ionic liquids are promising solvents for near-infrared emitting lanthanide complexes, because ionic liquids are polar non-coordinating solvents that can solubilize lanthanide complexes. Neodymium(III) tosylate, bromide, triflate and sulfonylimide complexes were dissolved in 1-alkyl-3-methylimidazolium ionic liquids that contain the same anion as the neodymium(III) complexes. Near-infrared luminescence spectra of these neodymium(III) salts were measured by direct excitation of the neodymium(III) ion. The absorption spectra show detailed crystal-field fine structure and Judd-Ofelt parameters have been determined. Intense near-infrared luminescence was observed upon ligand excitation for neodymium(III) complexes with 1,10-phenanthroline or beta-diketonate ligands. (C) 2004 Elsevier B.V. All rights reserved.

Palladium-mediated reductive coupling, a stereoselective approach to the 8-dehydropumiliotoxin skeleton

Reductive cyclisation of ail E-vinyl bromide with ail allylic acetate proceeds under palladium catalysis 10 give the 8-dehydropumiliotoxin skeleton, a potential advanced precursor to 8-deoxypumiliotoxin alkaloids. Control of the stereochemistry of the E-vinyl bromide precursor is achieved readily using the Kogen or Bruckner bromophosphonate reagents and the reductive cyclisation proceeds with retention of the vinyl bromide stereochemistry. The mechanism for the cyclisation involves an in situ conversion of the allylic acetate to ail allyl stannane followed by ail intramolecular Stille-type coupling.

Palladium catalysed formal 6-endo-trig approaches to pumiliotoxin alkaloids: interception of the elusive cyclopropyl intermediate

Intramolecular Heck cyclisation of (E)-vinyl bromides leads to indolizidines, related to pumiliotoxin alkaloids, in which the stereochemistry of the trisubstituted double bond undergoes inversion. A cyclopropyl intermediate, which is believed to be responsible for the double bond inversion, has been intercepted by forcing an 'early' beta-hydride elimination on this species. The relative stereochemistry of this cyclopropyl intermediate determines the regioselectivity of the final beta-hydride elimination. In this case all three beta-hydride eliminations were stereochemically permitted, giving rise to a mixture of three isomeric products, differing in the position of a double bond. (Z)-Vinyl bromides were found to be less reactive than (E)-vinyl bromides, but on cyclisation gave the required conjugated diene, with inversion of the vinyl bromide stereochemistry, as the sole reaction product. This methodology will allow rapid stereoselective access to the diene-based pumiliotoxin alkaloids.

Ionic liquid S-alkylthiouronium salts

The prepn. and characterization of a series of ionic liqs. based on S-alkylthiouronium cations prepd. from thiourea, 1,3-dimethylthiourea, 1,3-diethylthiourea and 1,3-tetramethylthiourea coupled with bis{(trifluoromethane)sulfonyl}imide, bromide, methylsulfate or ethylsulfate anions are reported. All are liqs. at room temp. or solids with m.ps. close to room temp., except for the bromide salts, which have m.ps. below 92 °C. Systematic variation in the N- and S-alkyl substituents demonstrates how the phys. properties of these ionic liqs. can be readily controlled. The mutual miscibility limits of representative examples with octane, dodecane and toluene have been detd. as a function of temp., and the extn. of dibenzothiophene from dodecane as a model for desulfurisation of diesel has been investigated.

Identification of a major GpVI-binding locus in human type III collagen

We have analyzed the adhesion of human and murine platelets, and of recombinant human and murine GpVI ectodomains, to synthetic triple-helical collagen-like peptides. These included 57 peptides derived from the sequence of human type III collagen and 9 peptides derived from the cyanogen bromide fragment of bovine type III collagen, alpha 1(III)CB4. We have identified several peptides that interact with GpVI, in particular a peptide designated III-30 with the sequence GAOGLRGGAGPOG-PEGGKGAAGPOGPO. Both human and murine platelets bound to peptide III-30 in a GpVI-dependent manner. III-30 also supported binding of recombinant GpVI ectodomains. Cross-linked III-30 induced aggregation of human and murine platelets, although with a lower potency than collagen-related peptide. Modifications of the peptide sequence indicated that the hydroxyproline residues play a significant role in supporting its GpVI reactivity. However, many peptides containing OGP/ GPO motifs did not support adhesion to GpVI. These data indicate that the ability of a triple-helical peptide to bind GpVI is not solely determined by the presence or spatial arrangement of these OGP/GPO motifs within the peptides.

Second-order NMR spectra at high field of common organic functional groups

The proton NMR spectra of aryl n-propyl sulfides gave rise to what may appear to be first-order proton NMR spectra. Upon oxidation to the corresponding sulfone, the spectra changed appearance dramatically and were clearly second-order. A detailed analysis of these second-order spectra, in the sulfone series, provided vicinal coupling constants which indicated that these compounds had a moderate preference for the anti-conformer, reflecting the much greater size of the sulfone over the sulfide. It also emerged, from this study, that the criterion for observing large second-order effects in the proton NMR spectra of 1,2-disubstituted ethanes was that the difference in vicinal coupling constants must be large and the difference in geminal coupling constants must be small. n-Propyl triphenylphosphonium bromide and 2-trimethylsilylethanesulfonyl chloride, and derivatives thereof, also exhibited second-order spectra, again due to the bulky substituents. Since these spectra are second-order due to magnetic nonequivalence of the nuclei in question, not chemical shifts, the proton spectra are perpetually second-order and can never be rendered first-order by using higher field NMR spectrometers.

TIME-RESOLVED ABSORPTION, INFRARED, AND RESONANCE RAMAN-SPECTRA OF THE COMPLEXES [RU(X)(R)(CO)(2)(ALPHA-DIIMINE)] (X=HALIDE R=ALKYL) - INFLUENCE OF X ON THE CHARGE-TRANSFER CHARACTER OF THE LOWEST EXCITED-STATE

Nanosecond time-resolved absorption (TA), resonance Raman (TR(3)), and infrared (TRIR) spectra are reported for several complexes [Ru(X)(R)(CO)(2)(alpha-diimine)] (X = Cl, Br, I; R = Me, Et; alpha-diimine = N,N'-diisopropyl-1,4-diaza-1,3-butadiene (iPr-DAB), pyridine-2-carbaldehyde-N-isopropylimine (iPr-PyCa), 2,2'-bipyridine (bpy)). This is the first instance in which the TA, TR(3), and TRIR techniques have been used to probe excited states in the same series of complexes. The TA spectra of the iodide complexes show a transient absorption between 550 and 700 nm, which does not depend on the solvent but shifts to lower energy in the order iPr-DAB > bpy > iPr-PyCa. This band is assigned to an intraligand transition. For the corresponding chloride and bromide complexes this band occurs at higher energy, most probably because of a change of character of the lowest excited state from XLCT to MLCT. The TRIR spectra show an increase in v(CO) (and k(CO)) on promotion to the excited state; however, the shifts Delta v(CO) show a decrease in the order Cl- > Br- > I-. The TR(3) spectra of the excited complexes [Ru(X)(R)(Co)(2)(iPr-DAB)] show v(s)(CN) of the iPr-DAB ligand 50-80 cm(-1) lower in frequency than for the complexes in their ground state. This frequency shift decreases in the order Cl- > Br- > I-, indicating a decrease of CT character of the lowest excited state in this order. However, going from X = Br to I, the effect on Delta v(CO) is much larger than the decrease of Delta v(s)(CN). This different effect on the CO- and CN-stretching frequencies is assigned to a gradual change in character of the lowest excited state from MLCT to XLCT when Cl- is replaced by Br- and I-. This result confirms a similar conclusion derived from previous resonance Raman and emission experiments on these complexes.

On the self-aggregation and fluorescence quenching aptitude of surfactant ionic liquids

The aggregation behavior in aqueous solution of a number of ionic liquids was investigated at ambient conditions by using three techniques: fluorescence, interfacial tension, and H-1 NMR spectroscopy. For the first time, the fluorescence quenching effect has been used for the determination of critical micelle concentrations. This study focuses on the following ionic liquids: [C(n)mpy]Cl (1-alkyl-3-methylpyridinium chlorides) with different linear alkyl chain lengths (n = 4, 10, 12, 14, 16, or 18), [C(12)mpip]Br (1-dodecyl-1-methylpiperidinium bromide), [C(12)mpy]Br (1-dodecyl-3-methylpyridinium bromide), and [C(12)mpyrr]Br (1-dodecyl-1-methylpyrrolidinium bromide). Both the influence of the alkyl side-chain length and the type of ring in the cation (head) on the CMC were investigated. A comparison of the self-aggregation behavior of ionic liquids based on 1-alkyl-3-methylpyridinium and 1-alkyl-3-methylpyridinium cations is provided. It was observed that 1-alkyl-3-methylpyridinium ionic liquids could be used as quenchers for some fluorescence probes (fluorophores). As a consequence, a simple and convenient method to probe early evidence of aggregate formation was established.

Nitrile-Functionalized Pyridinium, Pyrrolidinium, and Piperidinium Ionic Liquids

Two series of 1-alkylpyridinium and N-alkyl-N-methylpiperidinium ionic liquids fiinctionalized with a nitrile group at the end of the alkyl chain have been synthesized. Structural modifications include a change of the alkyl spacer length between the nitrile group and the heterocycle of the cationic core, as well as adding methyl or ethyl substituents on different positions of the pyridinium ring. The anions are the bromide and the bis(trifluoromethylsulfonyl)imide ion. All the bis(trifluoromethylsulfonyl)imide salts as well as the bromide salts with a long alkyl spacer were obtained as viscous liquids at room temperature, but some turned out to be supercooled liquids. In addition, pyrrolidinium and piperidinium ionic liquids with two nitrile functions attached to the heterocyclic core have been prepared. The crystal structures of seven pyridinium bis(trifluoromethylsulfonyl)imide salts are reported. Quantum chemical calculations have been performed on model cations and ion pairs with the bis(trifluoromethylsulfonyl)imide anion. A continuum model has been used to take solvation effects into account. These calculations show that the natural partial charge on the nitrogen atom of the nitrile group becomes more negative when the length of the alkyl spacer between the nitrile functional group and the heterocyclic core of the cation is increased. Methyl or methoxy substituents on the pyridinium ring slightly increase the negative charge on the nitrile nitrogen atom due to their electron-donating abilities. The position of the substituent (ortho, meta, or para) has only a very minor effect on the charge of the nitrogen atom. The N-15 NMR spectra of the bis(trifluoromethylsulfonyl)imide ionic liquids were recorded with the nitrogen-15 nucleus at its natural abundance. The chemical shift of the N-15 nucleus of the nitrile nitrogen atom could be correlated with the calculated negative partial charge on the nitrogen atom.

Functional and biochemical characterisation of the Escherichia coli major facilitator superfamily multidrug transporter MdtM

Multidrug resistance (MDR) occurs when bacteria simultaneously acquire resistance to a broad spectrum of structurally dissimilar compounds to which they have not previously been exposed. MDR is principally a consequence of the active transport of drugs out of the cell by proteins that are integral membrane transporters. We characterised and purified the putative Escherichia coli MDR transporter, MdtM, a 410 amino acid residue protein that belongs to the large and ubiquitous major facilitator superfamily. Functional characterisation of MdtM using growth inhibition and whole cell transport assays revealed its role in intrinsic resistance of E. coli cells to the antimicrobials ethidium bromide and chloramphenicol. Site-directed mutagenesis studies implied that the MdtM aspartate 22 residue and the highly conserved arginine at position 108 play a role in proton recognition. MdtM was homologously overexpressed and purified to homogeneity in dodecyl maltopyranoside detergent solution and the oligomeric state and stability of the protein in a variety of detergent solutions was investigated using size-exclusion HPLC. Purified MdtM is monomeric and stable in dodecyl maltopyranoside solution and binds chloramphenicol with nanomolar affinity in the same detergent. This work provides a firm foundation for structural studies on this class of multidrug transporter protein.

Bromate removal from drinking water by semiconductor photocatalysis

The semiconductor photocatalyst, platinised titanium dioxide, Pt/TiO2, is used to promote the destruction of bromate ions to bromide and oxygen by 254 nm ultraviolet light. The kinetics of bromate removal are first order with respect to [BrO3-] and are inhibited, although not completely, by competitive adsorption by other anions, including bromide and sulfate ions. The Pt/TiO2 can be used not only as a powder dispersion, but also as a thin film in a flow reactor for the destruction of bromate ions. Copyright (C) 1996 Elsevier Science Ltd

Synthesis of the putative structures of homopumiliotoxins 235C and 233F

A novel approach to diene based quinolizidines, using an intramolecular Heck reaction in which the vinyl bromide double bond undergoes inversion of configuration, is reported. These quinolizidines have previously been proposed as tentative structures for homopumiliotoxin alkaloids 233F and 235C. The mass spectral data of the synthetic materials were different to those of the natural products confirming that the original structures need to be revised. (C) 2004 Elsevier Ltd. All rights reserved.

Synthesis and in Vitro and in Vivo Evaluation of a Series of Dihydroisocoumarin Derivatives Conjugated with Fatty Acids, Alcohols, and Amines as Potential Anticancer Agents

In this paper, we report the synthesis and biological activity of a series of dihydroisocoumarin analogues Conjugated with fatty acids, alcohols, or amines, of varying hydrocarbon chain length and degree of unsaturation, to (he dihydroisocoumarins, kigelin and mellein, at the C-7 and C-8 positions on the core dihydroisocoumarin structure. These compounds were evaluated for their antiproliferative activity against human breast cancer (MCF-7 and MDA-MB-468) and melanoma cells (SK-MEL-28 and Malme-3M) using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. Two compounds Conjugated with gamma-linolenyl alcohol (18:3 n-6) demonstrated potent antiproliferative activity in vitro with one of these 4-hydroxy-3-oxo-1.3-dihydro-isobenzofuran-5-carboxylic acid octadeca-6,9,12-trienyl ester, demonstrating significant antitumor activity in vivo ill a number of human tumor xenograft models.