Bis Imidazolium Salts Research Articles

Acceptor specificities and selective inhibition of recombinant human Gal- and GlcNAc-transferases that synthesize core structures 1, 2, 3 and 4 of O-glycans

BackgroundModifications of proteins by O-glycosylation determine many of the properties and functions of proteins. We wish to understand the mechanisms of O-glycosylation and develop inhibitors that could affect glycoprotein functions and alter cellular behavior. MethodsWe expressed recombinant soluble human Gal- and GlcNAc-transferases that synthesize the O-glycan cores 1 to 4 and are critical for the overall structures of O-glycans. We determined the properties and substrate specificities of these enzymes using synthetic acceptor substrate analogs. Compounds that were inactive as substrates were tested as inhibitors. ResultsEnzymes significantly differed in their recognition of the sugar moieties and aglycone groups of substrates. Core 1 synthase was active with glycopeptide substrates but GlcNAc-transferases preferred substrates with hydrophobic aglycone groups. Chemical modifications of the acceptors shed light on enzyme–substrate interactions. Core 1 synthase was weakly inhibited by its substrate analog benzyl 2-butanamido-2-deoxy-α-d-galactoside while two of the three GlcNAc-transferases were selectively and potently inhibited by bis-imidazolium salts which are not substrate analogs. ConclusionsThis work delineates the distinct specificities and properties of the enzymes that synthesize the common O-glycan core structures 1 to 4. New inhibitors were found that could selectively inhibit the synthesis of cores 1, 2 and 3 but not core 4. General significanceThese studies help our understanding of the mechanisms of action of enzymes critical for O-glycosylation. The results may be useful for the re-engineering of O-glycosylation to determine the roles of O-glycans and the enzymes critical for O-glycosylation, and for biotechnology with potential therapeutic applications.

Nanocarriers from dicationic bis-imidazolium amphiphiles and their interaction with anionic drugs.

Dicationic gemini surfactants based on bis-imidazolium salts with bromide counterions were synthesized and shown to self-assemble into micellar-type structures in aqueous solution. The solubilisation capability of these micelles for anionic drugs (valproate) indicates their great potential as drug nanocarriers. A range of physicochemical techniques including surface tension, fluorescence spectroscopy, small-angle neutron scattering (SANS) and pulsed-gradient spin-echo nuclear magnetic resonance (PGSE-NMR) have been used to determine the nanocarrier (micelle) structure and to quantify the interaction of the drug with the nanocarrier. The insights gained here, structural activity relationships such as hydrophobic dependence of the CMC and drug binding isotherms, will allow for a rational optimization of molecular structure.

Preparation, characterization and thermal stability of bentonite modified with bis-imidazolium salts

Sodium bentonite was modified with several organic bis-imidazolium salts. Organoclays with water soluble surfactants were prepared by the traditional cation exchange reaction. The bis-imidazolium-bentonites were characterized by Fourier transform infrared spectroscopy (FTIR), powder X-ray diffraction analysis (PXRD) and thermogravimetric analysis (TGA). The effect of chemical composition and molecular weight of the salts on the thermal stability and basal spacing were evaluated. The bis-imidazolium-bentonites showed enhanced thermal stability (300–400 °C) and may be potentially useful materials for melt processing of polymer/layered silicates nanocomposites.

Consequences of the One‐Electron Reduction and Photoexcitation of Unsymmetric Bis‐imidazolium Salts

Coupling of uronium salts with in situ generated N-heterocyclic carbenes provides straightforward access to symmetrical [4](2+) and unsymmetrical bis-imidazolium salts [6](2+) and [9](2+) . As indicated by cyclic and square-wave voltammetry, [6](2+) and [9](2+) can be (irreversibly) reduced by one electron. The initially formed radicals [6](.+) and [9](.+) undergo further reactions, which were probed by EPR spectroscopy and density functional calculations. The final products of the two-electron reduction are the two carbenes. Upon irradiation with UV light both [6](2+) and [9](2+) emit at room temperature in solution but with dramatically different characteristics. The different fluorescence behavior is analyzed by emission spectroscopy and interpreted by using time-dependent density functional calculations as largely due to different excited-state dynamics of [6](2+) and [9](2+) . The geometries of both radicals [6](.+) and [9](.+) and excited states {[6](2+) }* and {[9](2+) }* are substantially different from those of the parent ground-state molecules.

Crystal structure of zwitterionic bisimidazolium sulfonates

Crystal structures of three zwitterionic bisimidazolium salts 1–3 in which imidazolium sulfonate moieties were connected with aromatic linkers, p-xylylene, 4,4′-dimethylenebiphenyl, and phenylene, respectively, were examined. The latter two were obtained as hydrates. An S-shaped molecular structure in which the sulfonate moiety was placed on the imidazolium ring was observed for 1. A helical array of hydrated water molecules was obtained for 2 while a linear array of hydrated water molecules was observed for 3.

Ag Complexes of NHC Ligands Bearing Polyfluoroalkyl and/or Polyfluoropolyalkoxy Ponytails. Why Are Polyethers More Fluorous Than Alkyls?

A series of fluorous silver complexes bearing two fluorous NHC ligands was synthesized from bis(polyfluoroalkylated) or bis(polyfluoropolyoxaalkylated) imidazolium salts and silver oxide in acetoni...

Chiral Ag(i) and Pt(ii) complexes of ditopic NHC ligands: synthesis, structural and spectroscopic properties

The butyl and isopropyl derivatives (4I, 5Br) of chiral pool derived bis-imidazolium dehydrohexitol salts have been prepared. The ditopic N-heterocyclic carbenes 4 and 5 form dinuclear Ag(I) and Pt(II) complexes. All compounds were fully characterised by multinuclear NMR spectroscopy. The bis-imidazolium salt 4I and platinum complexes cis-[Pt(2)(μ-2)(dmso)(2)Cl(4)] and cis-[Pt(2)(μ-4)(dmso)(2)Cl(4)] were characterised by X-ray crystallography. In the case of the Pt(II) complexes, the carbene ring is positioned in a sterically preferred orientation, approximately perpendicular to the platinum coordination plane. The (1)H, (13)C, (15)N and (195)Pt NMR spectra of the platinum complexes show the presence of rotamers due to hindered rotation about the carbene-metal bond.

Green Synthesis of Alkane Bridged Bisimidazolium Salts Under Solvent-Free Conditions

A series of N-aryl or N-methyl substituted bisimidazolium dichloride or dibromide salts with different alkyl bridge lengths (n = 1–4) have been synthesized starting from N-arylimidazoles or N-methylimidazoles with dialkyl bromides or the less expensive but less reactive dialkyl chlorides under solvent-free conditions. This green protocol provided most bisimidazolium chloride and bromide salts in good yields, and the reaction time was shortened to a few hours. In two examples, we showed either bisimidazolium dichloride (1a) or dibromide salt (3c) can be easily converted to the corresponding dihexafluorophosphate salt (1a′ or 3c′) in near quantitative yield.

Synthesis, Structures, and Reactivity of Chelating Bis-N-Heterocyclic-Carbene Complexes of Iron(II)

Distorted tetrahedral (bis-carbene)FeX2 complexes can be synthesized by direct metalation of chelating bisimidazolium salts, containing CH2 or phenylene linkers, with Fe(N(SiMe3)2)2(THF). For methylenebis(N-R-imidazole-2-ylidene) ((RC)2CH2), the high-spin complexes ((RC)2CH2)FeX2 (R = iPr or 2,6-di-isopropylphenyl (DIPP), X = I or Br) are isolated in good to excellent yield. In contrast the phenylene-linked congener ((iPrC)2Ph)FeI2 cannot be separated from two co-products, one of which was characterized by X-ray crystallography and zero-field 57Fe Mossbauer spectroscopy as the square-planar complex [((iPrC)2Ph)2Fe][I]2. The disparate reactivity toward Fe(N(SiMe3)2)2(THF) is due to the increase in linker length and decrease in linker flexibility of the phenylene-linked bis-carbene ligand relative to the methylene analogue. The short, flexible −CH2– linker projects the azole rings into the xy plane (defined as the carbene–Fe bond directions) and away from the pseudoaxial anionic substituent, whereas the inf...

New N-heterocyclic carbene mercury(II) complexes: Close mercury–arene interaction

Mononuclear mercury complexes ( 1, 2, and 3) bearing bis- N-heterocyclic carbene (NHC) ligands of the form [(NHC) 2-μ-Hg] +2 have been prepared and structurally characterised. The complexes were derived from three bis-imidazolium salts as precursors to NHC; either 1,3-bis( N-methylimidazolium-1-ylmethyl)benzene bis(hexafluorophosphate) ( I·2PF 6), 1,3-bis( N-butylimidazolium-1-ylmethyl)benzene bis(hexafluorophosphate) ( II·2PF 6) or 3,5-bis( N-butylimidazolium-1-ylmethyl)toluene bis(hexafluorophosphate) ( III·2PF 6) treated with mercury(II) acetate. Interestingly X-ray crystal structure analysis revealed a close interaction between the Hg metal centre with one carbon atom of the aryl linker in addition to coordination with two NHCs.

Synthesis of Novel Phasmidic, Gemini-Type Bisimidazolium Salts

New bisimidazolium salts based on pyrogallol with flexible ethyland P-xylyl spacers and with a seriesof different counter-ions were prepared. ¹ H NMRstudies showed a good linear correlation of the chemical shift withthe radius of the anion.

Size Selective Supramolecular Cages from Aryl-Bisimidazolium Derivatives and Cucurbit[8]uril

A series of bisimidazolium salts were synthesized as novel guests for the macrocyclic host molecule cucurbit[8]uril (CB[8]). These bisimidazolium-CB[8] binary complexes exhibited a unique cage structure with the imidazolium rings acting as lids, leading to a size-dependent binding selectivity by altering the hydrophobic linker between the two imidazolium moieties. This new class of CB[8] complexes was also capable of binding small solvent molecules, including acetone, acetonitrile, diethyl ether, and tetrahydrofuran (THF) in an aqueous environment.

Synthesis and Structure of Dinuclear Silver(I) and Palladium(II) Complexes of 2,7-Bis(methylene)naphthalene-Bridged Bis-N-Heterocyclic Carbene Ligands

We synthesized a series of new Ag2(bis-NHC)2 complexes from the corresponding bisimidazolium salts tethered with 2,7-dimethylnaphthalene-bridged bis-NHC ligands. The reaction proceeded in a selective manner, and the Ag2(bis-NHC)2 complexes were isolated in good to high yields. The Ag complexes were converted to the Pd2(bis-NHC)2 complexes efficiently. It is important to choose proper conditions for the conversion of the silver complexes to the palladium complexes, depending on the structure of the ligand: the effect of the counteranion was significant. The structures of the complexes were studied by X-ray crystallographic analyses and compared with the corresponding monodentate NHC complexes. The catalytic activity of the Pd complexes for the Mizoroki−Heck reaction was examined.

1,2-Bis[N-(N′-alkylimidazolium)]ethane salts: a new class of organic ionic plastic crystals

A new class of organic ionic plastic crystals was discovered. A series of alkylene 1,2-bis[N-(N′-alkylimidazolium)] salts with Br− and PF6− anions was prepared and most of the ethylene (C2) linked compounds undergo multiple solid–solid phase transitions as determined by differential scanning calorimetry (DSC). The salts with longer spacers (C3 or C4) between the imidazolium units do not display any solid–solid transitions. The PF6− salts with terminal C10 and C12n-alkyl moieties are “classical” organic ionic plastic crystals by Timmermans' definition; they have low ΔSf (11 J K−1 mol−1 for C10 and 12 J K−1 mol−1 for C12). Additionally, the C2 linked bis-imidazolium salts with n-butyl, n-hexyl, n-heptyl and n-octyl termini all undergo two, three or four solid state transitions and exhibit ΔSf values in the range of 36–49 J K−1 mol−1, which are similar to those of other known ionic plastic crystalline materials. These materials were additionally characterized via ionic conductivity and solid state NMR. These ionic plastic crystals are presumably single-ion conductors, but the ionic conductivities appear to be too low for practical applications. The activation energy for conduction decreases as these compounds are heated through each solid–solid transition. The lack of any change in solid state 2H NMR spectra with temperature indicates that there is no change in phenyl ring flipping, suggesting no change in the imidazolium local environment. A resolution of this apparent dichotomy is perhaps that the counterions reside with the ethylene spacers between imidazolium moieties.

ChemInform Abstract: Synthesis of Bis(polyfluoroalkylated)imidazolium Salts as Key Intermediates for Fluorous NHC Ligands.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Formation of Inclusion Complexes between 1,1′-Dialkyl-3,3′-(1,4-phenylene)bisimidazolium Dibromide Salts and Cucurbit[7]uril

N,N'-Dialkyl-(1,4-phenylene)bisimidazolium salts form inclusion complexes with cucurbit[7]uril (CB[7]) with high association constants. The stoichiometry of the complexes depends on the alkyl chains and on the relative concentration of the imidazolium salt and CB[7]. The binding interactions of CB[7] with these bisimidazolium salts were studied experimentally by (1)H NMR, high resolution mass spectroscopy, and UV spectroscopy, and theoretically by semiempirical molecular modeling. Nonlinear regression analysis was used to calculate or estimate the binding parameters for the supramolecular inclusion complexes present in solution. The detailed study of the binding association of these imidazolium salts may allow us to understand the exact role of each recognition site in these salts and to assemble higher supramolecular complexes.

Synthesis of bis(polyfluoroalkylated)imidazolium salts as key intermediates for fluorous NHC ligands

1,3-Bis(polyfluoroalkyl)- and 1-mesityl-3-(polyfluoroalkyl)imidazolium salts differing in the length of a polyfluorinated chain and a non-fluorinated spacer were synthesized as key building blocks for fluorous NHC ( N-heterocyclic carbene) ligands. A new approach using polyfluoroalkyl triflates instead of the corresponding iodides was employed allowing fine tailoring of fluorous properties, as well as of the electron density of the imidazolium ring. Using bis(polyfluoroalkylated)imidazolium salt, a fluorous analogue of the PEPPSI™ catalyst was synthesized and its structure confirmed by X-ray diffraction. The catalyst was employed in model Heck and Suzuki couplings with moderate yields, however, its recycle was not successful. Fluorophilicity of bis(polyfluoroalkylated)imidazolium salts was found to be surprisingly low compared with the analogous perfluoropolyether-based salts.

Dicationic bis-imidazolium molten salts for efficient dye sensitized solar cells: Synthesis and photovoltaic properties

New dicationic bis-imidazolium salts based ionic liquids were synthesized to develop new electrolytes to improve photovoltaic properties of dye sensitized solar cells. Various properties of electrolytes such as viscosities, ion diffusion coefficients, charge transfer resistances and photovoltaic properties were studied. Electrochemical impedance spectroscopy has been performed to investigate diffusion coefficients and charge transfer resistances. Influence of polarity and chain length on the photovoltaic performance, was investigated. A DSSC employing the K34 (butyl-1,4-bis(3-methyl imidazolium iodide) gives an open-circuit voltage of 0.64 V, a short-circuit current of 17.11 mA/cm 2 and conversion efficiency of 5.60% under light intensity of 100 mW/cm 2 while the DSSC based on 1-butyl-3-methyl imidazolium iodide which is a reference ionic liquid exhibited 5.64% efficiency due to the lowest viscosity, highest diffusion coefficient.

Use of a silicon carbide multi-well plate in conjunction with microwave heating for rapid ligand synthesis, formation of palladium complexes, and catalyst screening in a Suzuki coupling

The preparation of a library of bis-imidazolium salts and corresponding palladium complexes is reported. These complexes are screened as catalysts in the Suzuki reaction between 4-bromoanisole and phenylboronic acid. Each step is performed in parallel using a 24-position silicon carbide plate and microwave heating. The plate allows for use of standard glass vials as reaction vessels. The ease and speed of operation show the potential for microwave heating in conjunction with the silicon carbide plate as a tool for catalyst screening.

Chiral bisimidazolium salts derived from amino acids and their palladium(II)- and platinum(II)-biscarbene complexes

We report new chiral bisimidazolium salts synthesized from naturally occurring l-amino acids. They served as precursors for bidentate N-heterocyclic carbene metal complexes. The chiral imidazoles could be synthesized in good yields via a one-pot ring closing reaction, followed by esterification. The methylene bridged bisimidazolium iodide salts are accessible in moderate yields. Corresponding palladium(II)- and platinum(II)-NHC complexes could be synthesized and fully characterized, but do not show optical activity. We also report a solid state structure of one of the synthesized palladium(II) biscarbene compounds derived from alanine.