Ionic Liquids and Salts from Ibuprofen as Promising Innovative Formulations of an Old Drug

Herein we report the synthesis of novel ionic liquids (ILs) and organic salts by combining ibuprofen as anion with ammonium, imidazolium, or pyridinium cations. The methodology consists of an acid–base reaction of neutral ibuprofen with cation hydroxides, which were previously prepared by anion exchange from the corresponding halide salts with Amberlyst A-26(OH). In comparison with the parent drug, these organic salts display higher solubility in water and biological fluids and a smaller degree of polymorphism, which in some cases was completely eliminated. With the exception of [C₁₆Pyr][Ibu] and [N_1,1,2,2OH1][Ibu], the prepared salts did not affect the viability of normal human dermal fibroblasts or ovarian carcinoma (A2780) cells. Therefore, these ibuprofen-based ionic liquids may be very promising lead candidates for the development of effective formulations of this drug.     

Sulfonium-based Ionic Liquids Incorporating the Allyl Functionality

A series of sulfonium halides bearing allyl groups have been prepared and characterized. Anion metathesis with Li[Tf₂N] and Ag[N(CN)₂] resulted in sulfonium-based ionic liquids which exhibit low viscosities at room temperature. The solid state structure of one of the halide salts was determined by single crystal X-ray diffraction.     

Antitumor Activity of Ionic Liquids Based on Ampicillin

Significant antiproliferative effects against various tumor cell lines were observed with novel ampicillin salts as ionic liquids. The combination of anionic ampicillin with appropriate ammonium, imidazolium, phosphonium, and pyridinium cations yielded active pharmaceutical ingredient ionic liquids (API‐ILs) that show potent antiproliferative activities against five different human cancer cell lines: T47D (breast), PC3 (prostate), HepG2 (liver), MG63 (osteosarcoma), and RKO (colon). Some API‐ILs showed IC₅₀ values between 5 and 42 nM , activities that stand in dramatic contrast to the negligible cytotoxic activity level shown by the ampicillin sodium salt. Moreover, very low cytotoxicity against two primary cell lines—skin (SF) and gingival fibroblasts (GF)—indicates that the majority of these API‐ILs are nontoxic to normal human cell lines. The most promising combination of antitumor activity and low toxicity toward healthy cells was observed for the 1‐hydroxyethyl‐3‐methylimidazolium–ampicillin pair ([C₂OHMIM][Amp]), making this the most suitable lead API‐IL for future studies.     

Ionic liquids and plastic crystals based on tertiary sulfonium and bis(fluorosulfonyl)imide

A new series of low-melting, low-viscosity, hydrophobic ionic liquids based on relatively small tertiary sulfonium cations ([R¹R²R³S]⁺, wherein R¹, R², R³ = CH₃ or C₂H₅, R³ = CH₂CH₂OCH₃, CH₂CH₂COOCH₃, CH₂CH₂CN) and bis(fluorosulfonyl)imide (FSI⁻) anion have been prepared and characterized. The important physicochemical and electrochemical properties of these salts, such as melting point, glass transition, viscosity, density, ionic conductivity, thermal and electrochemical stability, have been determined. The influence of structure variation in the tertiary sulfonium cations on the above physicochemical properties is discussed. Among these new salts, some of them show the desirable properties including low-melting points, low viscosities, and high conductivities, to be selected as potential candidates as electrolytes in energy devices, and two salts are ionic plastic crystals.     

Enhanced electrical conductivity of polyindole prepared by electrochemical polymerization of indole in ionic liquids

The in situ electrical conductivity (resistance) of electrochemically prepared polyindole (PIn) in ionic liquids was found to be strongly dependent on the nature of the solvents, size of ionic liquid counter ions and preparation technique. Accordingly, the conductivity can be enhanced by about one order of magnitude when using a 1‐butyl‐3‐methylimidazolium tetrafluoroborate [BMIm] [BF₄^‐] or 1‐butyl‐3‐methylimidazolium hexafluorophosphate [BMIm] [PF₆^?] in comparison to acetonitrile (ACN). Moreover, the growth of polyindole in ionic liquid on gold electrode surface is faster than growth of polymer in acetonitrile. Additionally, a significant enhancement of the conductivity by using ionic liquids during the polymerization could be achieved. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 40094.     

Ionic Liquid Confined in Nafion: Toward Molecular‐Level Understanding

In this article, multiscale simulation methods were used to study structural and transport properties of Nafion–ionic liquid composite membranes that are novel proton conducting materials for fuel cells. Coarse‐grained model for 1‐butyl‐3‐methylimidazolium tetrafluoroborate ([bmim][BF₄]) ionic liquid was first developed in the framework of BMW‐MARTINI force field. Coarse‐grained simulation results of bulk [bmim][BF₄] ionic liquid show good agreement with all‐atom simulation results and experimental data. Nafion–[bmim][BF₄] composite membranes were then simulated using all‐atom and coarse‐grained models. Ionic liquid cluster formation inside Nafion was revealed by coarse‐grained simulations. Diffusion coefficients of both [bmim]⁺ cations and anions are reduced by one to two orders of magnitude depending on their concentrations in Nafion membrane. [Bmim]⁺ cations have faster self‐diffusion coefficient than anions, while this phenomenon is more pronounced when ionic liquids are confined in Nafion. This work provides molecular basis for understanding Nafion–ionic liquid composite membranes. © 2013 American Institute of Chemical Engineers AIChE J, 59: 2630–2639, 2013     

Electropolymerization and characterization of ionic diffusion in poly(diphenyldithieno[3,2‐b;20,30‐d]thiophene)

Poly(diphenyldithieno[3,2‐b;20,30‐d]thiophene) was synthesized by electropolymerization on Pt quartz crystal and on an indium tin oxide electrode by cyclic voltammetry. Ionic diffusion through the electronic conducting film (for the p‐doping process) was studied by cyclic voltammetry coupled to a quartz crystal microbalance (E‐QCM) and electrochemical impedance spectroscopy (EIS), using different electrolyte salts such as LiTFSI, LiClO₄ or LiCF₃CO₂. The molar ratio of insertion/expulsion of anions and cations was estimated from E‐QCM. By comparison between E‐QCM and EIS, the intrinsic ionic diffusion mechanisms in the electronic conducting film were highlighted depending on the salts used in acetonitrile. Moreover, the different mechanisms are in good agreement with the molar ratio of anion/cation insertion/expulsion. © 2018 Society of Chemical Industry     

Synthesis and characterization of iron (III) complexes of N4 schiff base macrocycles

Iron(III) complexes of the diprotic N₄ Schiff base macrocycles, 7,8,15,16,17,18-hexahydro-dibenzo[e,m] [1,4,8,11]tetraazacyclotetradecine (H₂(2,2mac)) and 8,9,16,17,18,19-hexahydro-7H-dibenzo[e,n][1,4,8,12]tetraazacyclopentaadecine(H₂(3,2mac)), were prepared by the metathesis reaction of anhydrous iron (III) bromide with the disodium or magnesium complexes of the dianionic ligands in THF under an inert atmosphere. The complexes exhibit the intermediate spin state as evidenced by magnetic susceptibility and Mössbauer spectroscopy. Fe(3,2 mac)Br is structurally characterized as a distorted square pyramid with the four nitrogen atoms in the basal positions and the bromide occupying the axial site. The average iron to nitrogen bond distance is 1.921 Å.     

Phase equilibria and structural properties of thiophene/[Bmim][BF4]: A molecular insight from monte carlo simulations

The phase equilibria of thiophene in 1‐butyl‐3‐methylimidazolium tetrafluoroborate ([Bmim][BF₄]) is calculated by Monte Carlo simulation in Gibbs ensemble using a united atom force field. The liquid density of studied ionic liquid and the vapor pressure of thiophene in [Bmim][BF₄] were compared with corresponding experimental data reported in the literature, and a good agreement was obtained. In order to describe the solubility of thiophene in this ionic liquid, we have calculated the radial distribution functions and spatial distribution functions of thiophene/IL mixtures to study the interaction of thiophene with cations and anions of [Bmim][BF₄] in the liquid phase. The local composition concept in fluid was also examined to give further insight into the liquid structure. The results show that thiophene is well organized around the terminal carbon atom of the butyl or methyl chain attached to the imidazolium ring of cations and tends to adopt a symmetrically distribution on the anions. © 2014 American Institute of Chemical Engineers AIChE J, 60: 3916–3924, 2014     

Ionic liquids in electrosynthesis and characterization of a polyazulene-fullerene composite

Polyazulene (PAz) was electrosynthesized in the ionic liquid N,N-butyl-methyl-pyrrolidinium bis(trifluoromethylsulfonyl)imide ([BMP][Tf₂N]) and characterized using electrochemical methods. By using [BMP][Tf₂N] as the electrolyte we obtained films with improved electrochemical and morphological properties compared to films electrosynthesized in an acetonitrile-based electrolyte solution. Composite films consisting of drop cast C₆₀ and electrosynthesized PAz were also investigated in [BMP][Tf₂N] using electrochemical methods, UV–vis and SEM and the results were compared to similar films prepared in acetonitrile. The use of ionic liquids made it possible to study the redox reactions of C₆₀ at room-temperature and in an extended cathodic potential range. In comparison to pure PAz the presence of C₆₀ in the composite film improved the charge storing ability. Electrosynthesis in [BMP][Tf₂N] resulted in composite films with a lower degree of charge trapping compared to composite films synthesized in organic media.     

Synthesis and characterization of Ru doped CuO thin films for supercapacitor based on Bronsted acidic ionic liquid

The synthesis of nanostructured ruthenium (Ru) doped copper oxide (CuO) thin films by colloidal solution method and ionic liquid are presented. The prepared colloidal solution was spin coated on the stainless steel substrates. The coated films were used to measure the specific capacitance in the task specific Bronsted acidic that is in 3-carboxymethyl-1-methylimidazolium bisulfate [CMIM] [HSO₄] ionic liquid (IL). Further, the films were characterized by X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), Fourier transform Raman spectroscopy (FT-Raman) and cyclic voltammetry (CV). The Ru doped CuO films exhibit higher specific capacitance, C_sp (C_sp = ratio of average current in CV and a product of scan rate and mass deposited on the film) with the larger potential window as compared to undoped CuO film. The highest C_sp of 406 F g⁻¹ was observed for 15 volume percent of Ru doping concentration. This is the first successful step towards development of ecofriendly CuO based supercapacitors in task specific IL synthesized by green technology.     

Rational design of double salt ionic liquids as extraction solvents: Separation of thiophene/n-octane as example

Although double salt ionic liquids (DSILs) offer significant advantages over classical two-ion ionic liquids as separation solvents, relevant studies are still scarce and a systematic DSIL selection method is thus highly desirable. In this contribution, a rational method for designing DSILs as extraction solvents is proposed and exemplified by the thiophene/n-octane separation. The effects of additional degrees of freedom for DSIL design (i.e., double cations and/or anions and the ion ratio) on the thermodynamic properties are first analyzed by COSMO-RS. Then, a multilevel DSIL design method combining the prediction of infinite dilution thermodynamic properties, the estimation of physical properties, the evaluation of phase equilibrium behavior, and the experimental validation is proposed. By applying this method, [C₂MIm][OAc] _x[NO₃]_1-x (x = [0, 1]) and [C₂MIm][OAc] _x[SCN]_1-x (x = [0.70, 1]) are identified as promising DSIL solvents for the thiophene/n-octane separation. Correspondingly, the liquid–liquid equilibria of {DSILs + thiophene + n-octane} with the designed DSILs are experimentally studied.     

Screening of ionic liquids as entrainers for the separation of 1-propanol + water and 2-propanol + water mixtures using COSMO-RS model

The COSMO-RS model was used to screen potential ionic liquids for the separation of aqueous azeotropic mixtures 1-propanol?+?water and 2-propanol?+?water. A combination of 22 cations (involving imidazolium, pyridinium, pyrrolidinium, quinolinium, and ammonium) and 36 anions were investigated. The anions chloride [Cl] and dihydrogen phosphate [H₂O₄P] were found to strongly influence the vapor liquid equilibrium behavior, whereas the ammonium-based cations diethanol ammonium [(Et)₂AMM]⁺ and tetra methyl ammonium [M₄AMM]⁺ were the most promising cations. In addition, the study of mixing enthalpy and excess Gibbs free energy confirmed that the molecular interaction of ionic liquids with water was found to be much larger than that with alcohols 1-propanol and 2-propanol, indicating the presence of a strong hydrogen bonding between the ionic liquids and water. Further, the addition of ionic liquids to the alcohol–water mixture reduces the activity coefficient of water and increases the relative volatility of the mixture, facilitating easier separation. Ionic liquids [(Et)₂AMM][Cl], [(Et)₂AMM][H₂O₄P], [M₄AMM][Cl], and [M₄AMM][H₂O₄P] are expected to be effective entrainers for the separation of the industrially important 1-propanol?+?water and 2-propanol?+?water systems.     

A new reaction of dithiocarbamates: CS2 elimination and two C–C bond formations leading to formation of cyclic ammonium salts

Sodium salts of N,N-dibenzyldithiocarbamate, N,N-diisopropyldithiocarbamate and pyrrolidine-1-carbodithioate gave cyclic products, 4-oxo-2,6-diphenyl-piperidinium, 2,2,6,6-tetramethyl-4-oxo-piperidinium and 3-oxo-8-azonia-bicyclo[3.2.1]octane cations, respectively, when treated with aluminum trichloride in acetone. The 2,2,6,6-tetramethyl-4-oxo-piperidinium thiocyanate salt has been characterized by X-ray crystallography. A plausible mechanism has also been suggested on the basis of preliminary DFT calculations.     

Synthesis and antibacterial activity of alkylated chitosan under basic ionic liquid conditions

A novel method to synthesize alkylated chitosan with [Bmim]OH basic ionic liquid as alkaline reagent is reported for the first time. Chitosan was alkalized by [Bmim]OH basic ionic liquid before it was reacted with various alkyl halides, and a series of alkylated chitosans with different carbon chain substituents were prepared. The structure of alkylated product was characterized by IR, ¹H‐NMR, and XRD. The reusability of the ionic liquid was also investigated, and the experimental results indicated that there was no noticeable change for the degree of substitution (DS) of alkylated chitosan after the ionic liquid was reused for three times. The antibacterial activities of the target products were investigated according their minimum inhibitory concentration (MIC) against K. pneumoniae, P. aeruginosa, E. aerogenes, E. coil, S. epidermidis, and S. aureus, and the results indicated that E‐CTS, B‐CTS, and D‐CTS could exhibit excellent antibacterial activities against P. aeruginosa, and their MIC were 128, 128, and 256 μg mL^?1, respectively. Meanwhile, the antibacterial activities of alkylted chitosans were decreased with the growth of the DS or the growth of the carbon chain. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 40052.     

Physical and potentiometric properties of polyurethane‐based cation‐selective membranes

Lipophilic salts based on tetraphenylborate derivatives [e.g., potassium tetrakis(p‐chlorophenyl)borate (KTpClPB), sodium tetraphenylborate (NaTPB), and cesium tetrakis(3‐methylphenyl)borate are essential ingredients used in the preparation of solvent polymeric cation‐selective membranes. The effects of such lipophilic salts on the physical properties of a polyurethane (PU) matrix comprising 4,4′‐diphenylmethane diisocyanate, 1,4‐butanediol, and poly(tetramethylene ether glycol) were examined. Differential scanning calorimetry measurements revealed that the sodium and potassium salts doped in PU increased the glass‐transition temperatures (T_g) of the matrix, while the film containing cesium salt exhibited slightly decreased T_g. The temperature dependence of the ionic conductivity for PU60 films doped with KTpClPB is well described by the Arrhenius‐type equation, and that doped with NaTPB is described by the Vogel–Tammann–Fulcher (VTF)‐type equation. The temperature dependence of the ionic conductivity on the VTF‐type equation suggests that the transport of sodium ions in the PU60 matrix is more strongly coupled to the soft segmental motion, and potassium ions are decoupled from the polymer host and transported by activated hopping. The effect of added salt on the internal structure of PU membranes was investigated by measuring the ratio between the free and hydrogen‐bonded CO bands at 1703 and 1730 cm⁻¹, respectively. The results showed that the ether oxygens in the soft segment chains are strongly coupled to the potassium or sodium, but much less to cesium. The potentiometric properties of these lipophilic additive doped PU membranes were characterized by incorporating valinomycin and 4‐tert‐butylcalix[4]arene‐tetraacetic acid tetraethylester as potassium‐ and sodium‐selective ionophores, respectively. Their response behavior could be explained by the observed physical characteristics. © 2001 John Wiley & Sons, Inc. J Appl Polym Sci 80: 618–625, 2001     

A novel dianionic seven-coordinate complex of tungsten(II), [WCl3(GeCl3)(CO)3]2−: Synthesis,spectroscopic properties and X-ray crystal structure

A new dianionic complex of tungsten(II), [(WCl₃(GeCl₃)(CO)₃]²⁻ (1²⁻), containing the piperidinium cations [Hpip]⁺ as the counter ions, has been obtained from the reaction between [W(CO)₄(pip)₂] and GeCl₄ in dichloromethane solution, and its molecular structure has been elucidated by single-crystal X-ray diffraction studies. The chemical properties of complex 1 were investigated by IR and NMR spectroscopy in solution.     

An Unprecedented Iridium(III) Catalyst for Stereoselective Dimerisation of Terminal Alkynes

A novel iridium(III) hydride complex, IrHCl(TIMP₃) {HTIMP₃=tris[1‐(diphenylphosphino)‐3‐methyl‐1H‐indol‐2‐yl]methane} was prepared and fully characterized in both the solid state and in solution. Chloride abstraction by silver cations provides a more reactive compound, [IrH(TIMP₃)][BF₄], which can react with pyridine (py) and phenylacetylene to yield the complexes [IrH(TIMP₃)(py)][BF₄] and [Ir(PhCHC CHCHPh)(TIMP₃)][BF₄], respectively. Interestingly, IrH(TIMP₃)(py)][BF₄] efficiently catalyses the stereoselective dimerisation of model terminal alkynes to the 1,4‐disubstituted (E)‐but‐1‐en‐3‐yne only.     

4,4-Bipyridinium ionic liquids exhibiting excellent solubility for metal salts: Potential solvents for electrodeposition

Newly synthesised 4,4-bipyridinium based ionic liquids exhibit good metal coordinating abilities and are able to dissolve metal salts at high concentrations. The ability to capture metal salts into the ionic liquid media facilitates the application of ionic liquids in many areas such as metal extraction or electrochemistry. The ionic liquid n-butyl-4,4-bipyridinium bis(trifluoromethyl)sulfonylamide ([C₄Bipyr][Tf₂N]) exhibits a large liquidus range and a wide electrochemical window. The successful electrodeposition of Cu (II) to Cu (0) from a solution of Cu(NO₃)₂ in [C₄Bipyr][Tf₂N] shows the potential of this new type of ionic liquids for electrodeposition.     

Structural and physicochemical studies of hydration of crosslinked TBA polyacrylates with different substitution degrees of H+ ions with TBA+ ions

X‐ray powder diffraction studies and physicochemical studies have been carried out of the hydrate phases formed in binary water systems with crosslinked tetrabutylammonium (TBA) polyacrylates (n = 1%) in mixed [x(C₄H₉)₄N + (100?x)H] form with low degrees of substitution of proton ions of the carboxylic groups in poly(acrylic acid) for TBA cations x = 40%, 30%, and 20%. As was shown by structural studies, the clathrate hydrate is formed in the water system with the polyacrylate in the mixed form with x = 40%. The structure is analogous to that of earlier studied hydrates formed by crosslinked polyacrylates in mixed [x(C₄H₉)₄N + (100?x)H] form with higher values of x = ～100%, 80%, and 60% and can be related to the tetragonal structure I, characteristic of the ionic clathrate hydrates of TBA salts with monomeric anions. Decomposition temperature and fusion enthalpy of the studied hydrate were determined using differential thermal analysis and calorimetric methods. It was revealed that the further decrease of x led to the destruction of clathrate hydrate framework. According to the results of X‐ray powder diffraction research, the phase of ice is crystallized instead of the hydrate phase in water systems with the polyacrylates with x = 30% and 20%. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018 , 135, 46209.