Imidazolium Core Research Articles

Synthesis and physical properties of tunable aryl alkyl ionic liquids based on 1-aryl-4,5-dimethylimidazolium cations.

We present a new class of tunable aryl alkyl ionic liquids (TAAILs) based on 1-aryl-4,5-dimethylimidazolium cations with electron-withdrawing and -donating substituents in different positions of the phenyl ring and the bis(trifluoromethylsulfonyl)imide (NTf2) anion. We investigated the effect of additional methyl groups in the backbone of the imidazolium core on the physical properties regarding viscosity, conductivity and electrochemical window. With an electrochemical window of up to 6.3 V, which is unprecedented for TAAILs with an NTf2 anion, this new class of TAAILs demonstrates the opportunities that arise from modifications in the backbone of the imidazolium cation.

Polymerized ionic liquid Co-catalysts driving photocatalytic CO2 transformation.

Photocatalytic production of CO from CO2 has the potential for safe and atom-economic production of feedstock chemicals via in situ carbonylation chemistry. We developed novel ionic liquid-based polymeric materials through radical copolymerisation of 1-butyl-3-vinylimidazolium chloride and photocatalytically active Re- and Ru-complexes that serve as the CO2 reduction catalyst and photosensitiser, respectively. The crosslinked polymeric framework allows for the facile immobilisation of molecular organometallic complexes for use as heterogenised catalysts; moreover, the involved imidazolium core units co-catalyze the reduction of CO2 via covalent interaction. The ratio of sensitiser and catalyst was analysed by laser ablation inductively coupled plasma mass spectroscopy (LA-ICP-MS) and set in relation to results from photocatalytic experiments. Ultimately, the heterogenous polymeric framework showed high selectivity for CO formation on photocatalytic CO2 reduction with improved stability to the corresponding homogenous system.

Experimental and theoretical study on the synthesis and thermophysical properties of newer tricationic ionic liquids

The synthesis of nineteen new linear symmetric tricationic ionic liquids (7a-s) with imidazolium-based structures is reported. The physicochemical properties of the new cations as morpholine, N,N-dimethyl amino pyridine, N-methylimidazole, N-methyl piperazine, also the anions as Cl−, −OSO2CH3, −OSO2Ph, CH3CO2−, CF3CO2− were evaluated. The theoretical studies employing DFT and MD simulation were used to analyze the experimental data as density, molar volume, solubility, lattice energy and ΔH. The strategy of synthesis provided the imidazolium core with different nucleophiles in good yield and diversity. The results of the density and molar volume were compared with the experimental data verifying a close agreement. The values of relative solubility and solubility parameters showed that these molecules are completely insoluble in non-polar solvents, and their affinity predominates in solvents with high dipole moments such as water, alcohols, and ketones. The lattice energy values showed a tendency towards the formation of stable ionic liquids.

Discovery and Biosynthesis of Antimicrobial Phenethylamine Alkaloids from the Marine Flavobacterium Tenacibaculum discolor sv11.

The bacterial genus Tenacibaculum has been associated with various ecological roles in marine environments. Members of this genus can act, for example, as pathogens, predators, or episymbionts. However, natural products produced by these bacteria are still unknown. In the present work, we investigated a Tenacibaculum strain for the production of antimicrobial metabolites. Six new phenethylamine (PEA)-containing alkaloids, discolins A and B (1 and 2), dispyridine (3), dispyrrolopyridine A and B (4 and 5), and dispyrrole (6), were isolated from media produced by the predatory bacterium Tenacibaculum discolor sv11. Chemical structures were elucidated by analysis of spectroscopic data. Alkaloids 4 and 5 exhibited strong activity against Gram-positive Bacillus subtilis DSM10, Mycobacterium smegmatis ATCC607, Listeria monocytogenes DSM20600, and Staphylococcus aureus ATCC25923, with minimum inhibitory concentration (MIC) values ranging from 0.5 to 4 μg/mL, and moderate activity against Candida albicans FH2173 and Aspergillus flavus ATCC9170. Compound 6 displayed moderate antibacterial activities against Gram-positive bacteria. Dispyrrolopyridine A (4) was active against efflux pump deficient Escherichia coli ATCC25922 ΔtolC, with an MIC value of 8 μg/mL, as well as against Caenorhabditis elegans N2 with an MIC value of 32 μg/mL. Other compounds were inactive against these microorganisms. The biosynthetic route toward discolins A and B (1 and 2) was investigated using in vivo and in vitro experiments. It comprises an enzymatic decarboxylation of phenylalanine to PEA catalyzed by DisA, followed by a nonenzymatic condensation to form the central imidazolium ring. This spontaneous formation of the imidazolium core was verified by means of a synthetic one-pot reaction using the respective building blocks. Six additional strains belonging to three Tenacibaculum species were able to produce discolins, and several DisA analogues were identified in various marine flavobacterial genera, suggesting the widespread presence of PEA-derived compounds in marine ecosystems.

N-Alkoxyimidazolylidines (NOHCs): nucleophilic carbenes based on an oxidized imidazolium core.

We report the first preparation of N-alkoxyimidazolylidene (NOHC), a nucleophilic carbene based on an oxidized imidazolium core. The Arduengo-type analogous carbene center shows the most upfield 13C NMR shift compared to common NHCs. The obtained gold(I) complex of the carbene follows the 13C NMR upfield trend and shows the marked influence the alkoxy substituents. Similarly, the 77Se and 15N NMR shifts of a range of NOHC-selenium adducts show increased σ-donation and decreased π-back donation in the bonding with the nucleophile. This extension of the NHC family provides altered electronic properties for the use of such carbenes as ligands or catalysts.

Synthesis of cationic π-extended imidazolium salts by sequential Cu-catalyzed arylation/annulation and photocyclization.

A series of cationic π-extended imidazolium salts were synthesized by a sequential Cu-catalyzed arylation/annulation and photocyclization strategy in a simple but efficient way. Among them, a nine-fused-ring compound with a doubly aza[5]helical geometry is by far the largest cationic polycyclic heteroaromatic with a central imidazolium core.

Diazapentabenzocorannulenium: A Hydrophilic/Biophilic Cationic Buckybowl.

Polycyclic aromatic molecules are promising functional materials for a wide range of applications, especially in organic electronics. However, their largely hydrophobic nature has impeded further applications. As such, imparting high solubility/hydrophilicity to polycyclic aromatic molecules leads to a breakthrough in this research field. Herein, we report the synthesis of diazapentabenzocorannulenium, a cationic nitrogen-embedded buckybowl bearing a central imidazolium core, by a bottom-up strategy from polycyclic aromatic azomethine ylide. X-ray crystallography analyses have revealed a bowl-shaped molecular structure that is capable of forming charge-segregated one-dimensional columns by bowl-in-bowl packing. In addition to its fluorescence capabilities and high dispersibility in water, the molecule was found to selectively localize in the mitochondria of various tumor cells, showing potential as viable mitochondria-selective fluorescent probes.

Diazapentabenzocorannulenium: A Hydrophilic/Biophilic Cationic Buckybowl

AbstractPolycyclic aromatic molecules are promising functional materials for a wide range of applications, especially in organic electronics. However, their largely hydrophobic nature has impeded further applications. As such, imparting high solubility/hydrophilicity to polycyclic aromatic molecules leads to a breakthrough in this research field. Herein, we report the synthesis of diazapentabenzocorannulenium, a cationic nitrogen‐embedded buckybowl bearing a central imidazolium core, by a bottom‐up strategy from polycyclic aromatic azomethine ylide. X‐ray crystallography analyses have revealed a bowl‐shaped molecular structure that is capable of forming charge‐segregated one‐dimensional columns by bowl‐in‐bowl packing. In addition to its fluorescence capabilities and high dispersibility in water, the molecule was found to selectively localize in the mitochondria of various tumor cells, showing potential as viable mitochondria‐selective fluorescent probes.

Tetrakis(pentafluoroethyl)gallate, [Ga(C2 F5 )4 ]- , Ionic Liquids.

We synthesized new imidazolium‐based tunable aryl alkyl ionic liquids (TAAILs) with the weakly coordinating tetrakis(pentafluoroethyl)gallate anion, [Ga(C2F5)4]−. Phenyl and phenyl derivatives (2‐Me, 4‐OMe, 2,4‐F) were combined with varying alkyl chain lengths at the imidazolium core leading to TAAILs, which were investigated with regard to their viscosity, conductivity, and electrochemical window and compared to EMIM and BMIM standard cations. Remarkable low viscosities of 29 cP at 25 °C for [BMIM][Ga(C2F5)4] were achieved. However, the EMIM and BMIM gallates show electrochemical instability, releasing pentafluoroethane at a voltage of 1.5 V. The 2‐Me‐substituted gallate‐TAAILs slowly decompose over several weeks, whereas all other gallate‐TAAILs showed no decomposition at all. With electrochemical windows of up to 5.15 V and low viscosities in a range of 66–162 cP, the gallate‐TAAILs are promising candidates as electrolytes in electrochemical applications.

Activation of (un)regulated cell death as a new perspective for bispyridinium and imidazolium oximes.

Oximes, investigated as antidotes against organophosphates (OP) poisoning, are known to display toxic effects on a cellular level, which could be explained beyond action on acetylcholinesterase as their main target. To investigate this further, we performed an in vitro cell-based evaluation of effects of two structurally diverse oxime groups at concentrations of up to 800μM, on several cell models: skeletal muscle, kidney, liver, and neural cells. As indicated by our results, compounds with an imidazolium core induced necrosis, unregulated cell death characterized by a cell burst, increased formation of reactive oxygen species, and activation of antioxidant scavenging. On the other hand, oximes with a pyridinium core activated apoptosis through specific caspases 3, 8, and/or 9. Interestingly, some of the compounds exhibited a synergistic effect. Moreover, we generated a pharmacophore model for each oxime series and identified ligands from public databases that map to generated pharmacophores. Several interesting hits were obtained including chemotherapeutics and specific inhibitors. We were able to define the possible structural features of tested oximes triggering toxic effects: chlorine atoms in combination with but-2(E)-en-1,4-diyl linker and adding a second benzene ring with substituents such as chlorine and/or methyl on the imidazolium core. Such oximes could not be used in further OP antidote development research, but could be introduced in other research studies on new specific targets. This could undoubtedly result in an overall improved wider use of unexplored oxime database created so far in OP antidotes field of research in a completely new perspective.

Degradation of imidazolium ionic liquids in a thermally activated persulfate system

Thermally activated persulfate (PS) oxidation, a clean source of sulfate radicals (SO4•–), has been used as a promising advanced oxidation method for the treatment of organic contaminants. In this study, the degradation of ionic liquids (ILs) by thermally activated PS was investigated with 1-alkyl-3-methylimidazolium bromides (C4mimBr) as a model compound. The effects of various factors including temperature, initial IL and PS concentrations, solution pH, alkyl chain length of imidazolium cation, and common water constituents such as humic acid (HA), HCO3-and Cl- were evaluated. Results showed that C4mimBr can be completely degraded in 2 h at 60 °C, indicating effective removal of C4mimBr by thermally activated PS oxidation. The oxidation followed a pseudo-first-order kinetics model, and the rate constant increased with increasing temperature, PS concentration and initial solution pH. Alkyl chain length had no effect on the degradation. HA and Cl- had negative effects on C4mimBr removal, while 5 mM HCO3- increased C4mimBr degradation. Multiple intermediate products were identified by HPLC-MS/MS and the degradation pathway and mechanism were proposed. The free radicals generated in the activated PS system (e.g., SO4•– and •OH) showed different effects on the degradation. SO4•– radicals select to attack the substituted side chain of ILs cation, producing more chance for •OH to attack the imidazolium core. Moreover, toxicity tests using bioluminescent bacteria Vibrio Qinghaiensis sp.-Q67 and nematode C. elegans demonstrated efficient detoxification of CnmimBr treatment. These findings may offer an environmentally friendly approach for ILs treatment in aqueous solution.

Water-soluble silver(i) complexes with N-donor benzimidazole ligands containing an imidazolium core: stability and preliminary biological studies.

Herein, we report the synthesis, characterisation and preliminary biological evaluation of two novel silver(i) complexes of type [AgL2](NO3)3 (3 and 4) with ionic N-donor benzimidazoles. The complexes have been synthesized by the reaction of 1.5 equivalents of silver nitrate and N-donor benzimidazoles containing an imidazolium core at the 2-position (1 and 2) in ethanol. The X-ray analysis of 4 shows that it has two free imidazolium cores and the charge is balanced with three nitrate anions. A study by the combination of NMR, IR, LC-MS and elemental analysis techniques also suggests that the complexes have this structure both in the solid-state and solution. The complexes are highly soluble and stable in water. Cytotoxicity evaluation against four cancerous human cells and one non-cancerous human cell revealed that the complexes have no significant anti-growth effect. However, the complexes showed a remarkable antimicrobial effect at normalized minimum inhibitory concentrations (normalized MICs) in the range of 33-268 μM against a panel of microorganisms consisting of Gram-negative and Gram-positive bacteria, and fungi.

NMR Spectroscopic Studies of Cation Dynamics in Symmetrically-Substituted Imidazolium-Based Ionic Liquid Crystals.

Ionic liquid crystals (ILCs) present a new class of non-molecular soft materials with a unique combination of high ionic conductivity and anisotropy of physicochemical properties. Symmetrically-substituted long-chain imidazolium-based mesogenic ionic liquids exhibiting a smectic liquid crystalline phase were investigated by solid state NMR spectroscopy and computational methods. The aim of the study was to reveal the correlation between cation size and structure, local dynamics, and orientational order in the layered mesophase. The obtained experimental data are consistent with the model of a rod-shaped cation with the two chains aligned in opposite directions outward from the imidazolium core. The alignment of the core plane to the phase director and the restricted conformations of the chain segments were determined and compared to those in single-chain counterparts. The orientational order parameter S~0.5–0.6 of double-chain ionic liquid crystals is higher than that of corresponding single-chain analogues. This is compatible with the enhanced contribution of van der Waals forces to the stabilization of smectic layers. Increased orientational order for the material with Br− counterions, which exhibit a smaller ionic radius and higher ability to form hydrogen bonds as compared to that of BF4−, also indicated a non-negligible influence of electrostatic and hydrogen bonding interactions. The enhanced rod-shape character and higher orientational order of symmetrically-substituted ILCs can offer additional opportunities in the design of self-assembling non-molecular materials.

Binding study on 1-adamantylalkyl(benz)imidazolium salts to cyclodextrins and cucurbit[n]urils

Adamantane-based imidazolium salts with flexible linkers between the adamantane cage and imidazolium core were prepared. Their supramolecular behaviour towards the natural cyclodextrins α-CD, β-CD and γ-CD and cucurbit[n]urils (n = 7, 8) was studied.

Improved Photovoltaic Efficiency and Amplified Photocurrent Generation in Mesoporous n = 1 Two-Dimensional Lead–Iodide Perovskite Solar Cells

We utilized two organic dications containing, respectively, a pyridinium and an imidazolium core to construct new n = 1 (where n refers to the number of contiguous two-dimensional (2D) inorganic la...

3-[2-(Oxiran-2-yl)ethyl]-1-{4-[(2-oxiran-2-yl)ethoxy]benzyl}imidazolium bis(Trifluoromethane)sulfonimide

The synthesis of 3-[2-(oxiran-2-yl)ethyl]-1-{4-[(2-oxiran-2-yl)ethoxy]benzyl}imidazolium bis(trifluoromethane)sulfonimide was achieved in seven steps with an overall yield of 63%. This ionic liquid monomer is based on an imidazolium core containing a phenoxy moiety and aliphatic chains with a reactive epoxide at both ends. This imidazolium was obtained by an efficient, reproducible, and scalable synthesis from inexpensive reagents. In the last step, a powerful oxidative agent was successfully used to generate two epoxy functions with only acetone as a byproduct. The monomer structure and intermediates were analyzed by NMR experiments, infrared, and mass spectra. In addition, the thermal properties of the diepoxide were evaluated by thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC).

Synthesis and electrochemical evaluation of 2‐substituted imidazolium salts

AbstractHerein, we report the synthesis, electrochemical, and computational evaluation of six 2‐substituted imidazolium bromides and six 2‐substituted imidazolium triflates. All final compounds were obtained in 2 or fewer synthetic steps from inexpensive starting materials and display a single, irreversible electrochemical reduction. The reduction potentials span a range greater than 1 V depending on the electron withdrawing power of the 2‐substituent. Imidazolium bromides such as Bn2(H)ImBr reduce with E1/2 = −2.70 V vs Fc/Fc+, whereas the electron‐withdrawing Br‐containing analog Bn2(Br)ImBr reduces at only −1.58 V vs Fc/Fc+. The reduction potential of imidazolium bromides obeys a linear free energy relationship to σm Hammett constants, whereas imidazolium triflates correlate better with the σp Hammett constants. These results indicate that the stabilizing effect of the 2‐substituent is anion‐sensitive, changing from induction to resonance upon exchanging bromide for triflate. Predicted electron affinities from density functional theory–optimized structures of imidazolium cations and reduced species more closely match experimental data for the triflates, suggesting that a triflate anion does not electronically perturb the imidazolium core as much as a bromide. Taken together, these data highlight the dual modularity of imidazolium salts by changing both 2‐substituent and anion.

Aqueous pKa and Hydroxide Stability of Imidazolium Derivatives

Organic cations based on the imidazolium core constitute a promising class of covalently bonded cations for use in anion exchange membranes (AEM). The durability of AEM in alkaline fuel cells is largely determined by the stability of the cationic moiety. Despite tremendous research efforts, the commonly employed cations still have limited alkaline stability. A hydroxide-mediated C-H deprotonation is a possible initial step of degradation of organic cations. Another possible degradation mechanism of imidazolium derivative is the ring opening of the imidazole. In this study, we have developed computational methodologies based on density functional theory (DFT) to identify organic cations capable of withstanding extreme alkaline conditions under high temperatures for prolonged periods of time. We look at several aspects of stability, including pKa calculations and prediction of the activation energies for hydroxide nucleophilic attack on the imidazolium central carbon (carbon atom between the two nitrogen atoms, (C-2)). Eighteen organic cations from different families were selected and used in this study; these include imidazolium, guanidinium, phosphonium, ammonium, oxygen, and sulfur containing organic cations. We performed DFT calculations using three different functionals: viz. B3LYP, M06, and M06-2X, and solvation models: viz. SMD, CPCM and IEFPCM, in conjunction with the 6-311++G** basis set. The results from these computations were gauged against high-level MP2 and coupled-cluster calculations as well as the available experimental data. Altogether, we considered 21 computational protocols for predicting the pKa values of organic cations. The most accurate protocols, as compared to the experimental data, employ CCSD(T) and M06-2X methods with solvent effects computed using the SMD solvation model. The combination of B3LYP functional and the SMD solvation model also gave results of comparable accuracy. Also, we used B3LYP/6-31+G* level of theory and SMD implicit solvation model to benchmark the experimental alkaline stability of a series imidazolium cations against nucleophilic attack by hydroxide. It is observed that the calculated activation energies can correctly predict the relative stability for a series of imidazolium cations. In agreement with previous experimental and theoretical studies, we find that a replacement of the C-2 hydrogen by a methyl group substantially increases the barrier height for both the nucleophilic addition and the ring opening steps. These results provide intrinsic details into the design of stable imidazolium based cations for anion exchange membranes that are currently being investigated in our group. Acknowledgements This work was funded by the Laboratory Directed Research and Development Program of Oak Ridge National Laboratory, managed by UT-Battelle, LLC, for the U.S. Department of Energy. This research used resources of the National Energy Research Scientific Computing Center, a DOE Office of Science User Facility supported by the Office of Science of the U.S. Department of Energy under Contract No. DE-AC02-05CH11231

Anti-tumor activity and cytotoxicity in vitro of novel 4,5-dialkylimidazolium surfactants

Natural monoalkylated imidazolium derivatives exhibit significant anti-tumor activity as well as general cytotoxicity. In the present study, we used a series of newly synthesized imidazolium derivatives bearing two alkyl chains in the backbone of the imidazolium core in 4- and 5-position and either dimethyl- or dibenzyl-substituents at 1- and 3-position. Their anti-tumor activity and cytotoxicity were determined in vitro using the lactate dehydrogenase (LDH) assay. The tumor cell line C6 from rat glioma, the non-tumor MDCK cell line (Madin–Darby canine kidney) as well as the mouse embryonic fibroblast cell line (NIH3T3) were used as cellular targets. Surface activity measurements were performed leading to the determination of their critical micelle concentration (CMC) of these new lipid analogues to evaluate the molecular mechanism of the observed cellular effects. We found that 4,5-dialkylation of the imidazole ring enhances the anti-tumor activity compared to simple 1-alkylated imidazoles. The corresponding C7 homologues are found to be the most potent compounds. Furthermore dibenzyl-substituted imidazolium surfactants exhibit higher surface activity and increased toxicity against tumor cells compared to dimethyl-substituted imidazolium surfactants. In summary the dibenzyl-derivative carrying the two C7 chains was found to exhibit a drastically increased anti-tumor activity especially compared to so far known monoalkylated species.

A Remarkably Simple Class of Imidazolium-Based Lipids and Their Biological Properties.

A series of imidazolium salts bearing two alkyl chains in the backbone of the imidazolium core were synthesized, resembling the structure of lipids. Their antibacterial activity and cytotoxicity were evaluated using Gram-positive and Gram-negative bacteria and eukaryotic cell lines including tumor cells. It is shown that the length of alkyl chains in the backbone is vital for the antibiofilm activities of these lipid-mimicking components. In addition to their biological activity, their surface activity and their membrane interactions are shown by film balance and quartz crystal microbalance (QCM) measurements. The structure-activity relationship indicates that the distinctive chemical structure contributes considerably to the biological activities of this novel class of lipids.