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Four imidazolium-based ionic liquids (IL; 1-butyl-3-methylimidazolium chloride, 1-carboxymethyl-3-methylimidazolium chloride, 1,3-dicarboxymethylimidazolium chloride and 1-(2-hydroxyethyl) -3-methylimidazolium chloride) were tested as compatibilizers of microcrystalline cellulose (MCC). Subsequently, ethanolic IL solutions were prepared; MCC was mixed, and the mixtures were left to evaporate the ethanol at ambient conditions. These modified MCC were characterized and applied as reinforcements (5.0 and 10 phr) in an epoxy resin aiming to manufacture biobased composites with enhanced performances. The IL did not significantly modify the morphological and structural characteristics of such reinforcements. Regarding the thermal stability, the slight increase was associated with the MCC-IL affinity. The IL-modified MCC-epoxy composites presented improved mechanical responses, such as flexural strength (≈22.5%) and toughness behavior (≈18.6%), compared with pure epoxy. Such improvement was also obtained for the viscoelastic response, where the storage modulus at the glassy state depended on the MCC amount and IL type. These differences were associated with stronger hydrogen bonding between IL and epoxy hardener or the IL with MCC, causing a "bridging" effect between MCC and epoxy matrix.

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Due to the increase in life expectancy worldwide, age-related disorders such as neurodegenerative diseases (NDs) have become more prevalent. Conventional treatments comprise drugs that only attenuate some of the symptoms, but fail to arrest or delay neuronal proteotoxicity that characterizes these diseases. Due to their diverse biological activities, imidazole rings are intensively explored as powerful scaffolds for the development of new bioactive molecules. By using C. elegans, our work aims to explore novel biological roles for these compounds. To this end, we have tested the in vivo anti-proteotoxic effects of imidazolium salts. Since NDs have been largely linked to impaired antioxidant defense mechanisms, we focused on 1-Mesityl-3-(3-sulfonatopropyl) imidazolium (MSI), one of the imidazolium salts that we identified as capable of improving iron-induced oxidative stress resistance in wild-type animals. By combining mutant and gene expression analysis we have determined that this protective effect depends on the activation of the Heat Shock Transcription Factor (HSF-1), whereas it is independent of other canonical cytoprotective molecules such as abnormal Dauer Formation-16 (DAF-16/FOXO) and Skinhead-1 (SKN-1/Nrf2). To delve deeper into the biological roles of MSI, we analyzed the impact of this compound on previously established C. elegans models of protein aggregation. We found that MSI ameliorates ß-amyloid-induced paralysis in worms expressing the pathological protein involved in Alzheimer's Disease. Moreover, this compound also delays age-related locomotion decline in other proteotoxic C. elegans models, suggesting a broad protective effect. Taken together, our results point to MSI as a promising anti-proteotoxic compound and provide proof of concept of the potential of imidazole derivatives in the development of novel therapies to retard age-related proteotoxic diseases.

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In this study we explored the previously established leishmanicidal activity of a complementary set of 24 imidazolium salts (IS), 1-hexadecylimidazole (C16Im) and 1-hexadecylpyridinium chloride (C16PyrCl) against Leishmania (Leishmania) amazonensis and Leishmania (Leishmania) infantum chagasi. Promastigotes of L. amazonensis and L. infantum chagasi were incubated with 0.1 to 100 µM of the compounds and eight of them demonstrated leishmanicidal activity after 48 h - C10MImMeS (IC50 L. amazonensis = 11.6), C16MImPF6(IC50 L. amazonensis = 6.9), C16MImBr (IC50 L. amazonensis = 6), C16M2ImCl (IC50 L. amazonensis = 4.1), C16M4ImCl (IC50 L. amazonensis = 1.8), (C10)2MImCl (IC50 L. amazonensis = 1.9), C16Im (IC50 L. amazonensis = 14.6), and C16PyrCl (IC50 L. amazonensis = 4).The effect of IS on reactive oxygen species production, mitochondrial membrane potential, membrane integrity and morphological alterations of promastigotes was determined, as well as on L. amazonensis-infected macrophages. Their cytotoxicity against macrophages and human erythrocytes was also evaluated. The IS C10MImMeS, C16MImPF6, C16MImBr, C16M2ImCl, C16M4ImCl and (C10)2MImCl, and the compounds C16Im and C16PyrCl killed and inhibited the growth of promastigote forms of L. amazonensis and L. infantum chagasi in a concentration-dependent manner, contributing to a better understanding of the structure-activity relationship of IS against Leishmania. These IS induced ROS production, mitochondrial dysfunction, membrane disruption and morphological alterations in infective forms of L. amazonensis and killed intracellular amastigote forms in very low concentrations (IC50 amastigotes ≤ 0.3), being potential drug candidates against L. amazonensis.

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Chitosan/chondroitin sulfate (CHT/CS) curcumin-charged hydrogels were prepared through polyelectrolytic complexation (PEC) following two methodologies (PEC-CUR and PEC-T-CUR) and were applied on apoptosis of HeLa, HT29 and PC3 cancer cells. PEC-T-CUR (ionic liquid (IL) mixed using ultraturrax homogenizer) results show to be far better than for PEC-CUR (IL mixed using magnetic stirring), with IC50 being improved 5.13 times to HeLa cancer cells (from 1675.2 to 326.7 µg mL-1). PECs produced by this methodology presented favorable characteristics, such as particle size, hydrophobicity, pH swelling. Beyond this, the IL was quantitatively recovered in both cases. CUR entrapment levels were hugely loaded into PEC at around 100%. Swelling, dissolution/degradation, and pHpzc assays showed that PECs may positively act in several environments, releasing the CUR, the CHT and CS as well. Characterization through FTIR, SEM, TEM, TGA, DSC, and WAXS confirmed CUR presence in both types of PECs, and cytotoxic studies showed the significant anticancer effects of CUR-containing PECs.

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BACKGROUND: In the therapy of cancer, several treatments have been designed using nanomaterials, among which gold nanoparticles (AuNPs) have been featured as a promising antitumoral agent. Our research group has developed the synthesis of gold nanoparticles L-AuNPs and D-AuNPs stabilized with zwitterions of imidazolium (L-1 and D-1) derived from L-methionine and D-methionine. Because the stabilizer agent is chiral, we observed through circular dichroism that AuNPs also present chirality; such chirality as well as the fact that the stabilizing agent contains fragments of methionine and imidazolium that are commonly involved in biological processes, opens up the possibility that this system may have biological compatibility. Additionally, the presence of methionine in the stabilizing agent opens the application of this system as a possible antitumor agent because methionine is involved in methylation processes of molecules such as DNA. OBJECTIVE: The aim of this research is the evaluation of the antitumor activity of gold nanoparticles stabilized with zwitterions of imidazolium (L-AuNPs) derived from L-methionine in the model of BALB/c mice with lymphoma L5178Y. METHODS: Taking as a parameter cell density, the evaluation of the inhibitory effect of L-AuNPs was carried out with a series of in vivo tests in BALB/c type mice; three groups of five mice each were formed (Groups 1, 2 and 3); all mice were i.p. inoculated with the lymphoblast murine L5178Y. Group 1 consisted of mice without treatment. In the Groups 2 and 3 the mice were treated with L-AuNPs at 0.3 mg/Kg on days 1, 7 and 14 by orally and intraperitonally respectively. RESULTS: These results show low antitumor activity of these gold nanoparticles (L-NPsAu) but interestingly, the imidazolium stabilizing agent of gold nanoparticle (L-1) displayed promising antitumor activity. On the other hand, the enantiomer of L-1, (D-1) as well as asymmetric imidazole derivate from L-methionine (L-2), do not exhibit the same activity as L-1. CONCLUSION: The imidazolium stabilizing agent (L-1) displayed promising antitumor activity. Modifications in the structure of L-1 showed that, the stereochemistry (like D-1) and the presence of methionine fragments (like L-2) are determinants in the antitumor activity of this compound.

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INTRODUCTION: Several strains of the free-living genus Acanthamoeba can cause granulomatous amoebic encephalitis (GAE), a rare chronic and slowly progressive infection of the central nervous system (CNS), and Acanthamoeba keratitis (AK), a sight-threatening eye infectious disease. AK incidence has increased with the popularization of the contact lens wear and its treatment is currently limited and frequently unsuccessful. As imidazolium salts (IS), cationic imidazole derivatives, have promising antimicrobial potential. MATERIALS AND METHODS: The present study evaluated the amoebicidal activity of four IS; 1-n-hexadecyl-3-methylimidazolium methanesulfonate (C16MImMeS), chloride (C16MImCl) and bis (triluoromethylsulfonyl) imide (C16MImNTf2 ), and 1-methyl-3-n-octadecylimidazolium chloride (C18MImCl), against the Acanthamoeba castellanii (ATCC30010) environmental strain and a clinical isolate (genotype T4). RESULTS: Three IS showed being lethal to 100% of the Acanthamoeba trophozoites at the minimum inhibitory concentrations of 125 and 62.5 µg/mL (C16MImMeS), 31.25 and 62.5 µg/mL (C16MImCl), and 125 and 125 µg/mL (C18MImCl) for ATCC30010 and isolate T4, respectively. C16MImNTf2 did not demonstrate amoebicidal activity. All active IS caused the hemolysis of erythrocytes. The cytotoxic effect of the IS was tested in RAW macrophages and human brain microvascular endothelial cells, which demonstrated cytotoxicity in all concentrations tested against both cell lines. As a consequence, these IS with amoebicidal activity presented low selectivity index values (SI) (SI < 1.0), demonstrating lack of parasite selectivity. CONCLUSION: Thus, C16MImMeS, C16MImCl, and C18MImCl seem to hold greater promise as components for contact lens cleaning and disinfection solutions, instead of direct human application.

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This work studied the effect of the cation alkyl chain length of 1-alkyl-n-methylimidazolium chloride ([Cnmim]Cl)-based ILs on the activity of Aspergillus niger lipase. First, the lipase activity in the presence of different ILs concentration over time was determined. ILs with shorter cation alkyl side chain length, namely [C4mim]Cl and [C6mim]Cl, promoted an increase of lipase activity; while, [C8mim]Cl, depending on its concentration, maintained or decreased the enzyme activity. In the presence of ILs with longer cation alkyl chain length, i.e., [C10mim]Cl and [C12mim]Cl, the lipase relative activity was reduced with 0.1 (%v/v) and until suppressed ([C12mim]Cl at 0.3 (%v/v)) as a result of irreversible changes in its secondary structure. Fluorescence and circular dichroism spectroscopy analysis confirmed the results achieved. These findings show that [Cnmim]Cl-based ILs can exert different behavior on the lipase' activity (enhance, maintain or even inhibit) and structural conformation, depending on the cation alkyl chain length and their relative concentration.

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BACKGROUND: Aedes aegypti is an important mosquito species that can transmit several arboviruses such as dengue fever, yellow fever, chikungunya and zika. Because these mosquitoes are becoming resistant to most chemical insecticides used around the world, studies with new larvicides should be prioritized. Based on the known biological profile of imidazolium salts (IS), the objective of this study was to evaluate the potential of six IS as larvicides against Ae. aegypti, as tested against Ae. aegypti larvae. Larval mortality was measured after 24 and 48 h, and residual larvicidal activity was also evaluated. RESULTS: Promising results were obtained with aqueous solutions of two IS: 1-n-octadecyl-3-methylimidazolium chloride (C18 MImCl) and 1-n-hexadecyl-3-methylimidazolium methanesulfonate (C16 MImMeS), showing up to 90% larval mortality after 48 h exposure. C18 MImCl was more effective than C16 mIMeS, causing mortality until day 15 after exposure. An application of C18 MImCl left to dry under ambient conditions for at least 2 months and then dissolved in water showed a more pronounced residual effect (36 days with 95% mortality and 80% mortality up to 78 days). CONCLUSION: This is the first study to show the potential of IS in the control of Ae. aegypti. Further studies are needed to understand the mode of action of these compounds in the biological development of this mosquito species. © 2017 Society of Chemical Industry.

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Herein we describe the synthesis of gold nanoparticles (Au-NPs) in presence of sulphonated imidazolium salts [1,3-bis(2,6-diisopropyl-4-sodiumsulfonatophenyl)imidazolium (L1), 1-mesityl-3-(3-sulfonatopropyl)imidazolium (L2) and 1-(3-sulfonatopropyl)imidazolium (L3)] in water and in a confinement environment created by reverse micelles (RMs). The Au-NPs were characterized-with an excellent agreement between different techniques-by UV-vis spectroscopy, transmission electron microscopy (TEM), dynamic light scattering (DLS) and zeta potential. In homogeneous media, the Au-NPs interact with the imidazolium ring and the sulphonate groups were directed away from the NPs' surface. This fact is responsible for the Au-NPs' stability-over three months-in water. Based on the obtained zeta potential values we assume the degree of coverage of the Au-NPs by the imidazolium salts. In n-heptane/sodium 1,4-bis (2-ethylhexyl) sulfosuccinate (AOT)/water RMs, the Au-NPs formed in presence of sulphonated imidazolium salts present different patterns depending on the ligand used as stabilizer. Interestingly, the Au-NPs are more stable in time when the salts are present in AOT RMs (three weeks) in comparison with the same RMs system but in absence of ligands (less than an hour). Clearly, the sulphonated imidazolium salts are very effective Au-NPs stabilizers in a different medium and this generates a plus to be able to use them for multiple purposes.

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Zeolite synthesis is a wide area of study with increasing popularity. Several general reviews have already been published, but they did not summarize the study of imidazolium species in zeolite synthesis. Imidazolium derivatives are promising compounds in the search for new zeolites and can be used to help understand the structure-directing role. Nearly 50 different imidazolium cations have already been used, resulting in a variety of zeolitic types, but there are still many derivatives to be studied. In this context, the purpose of this short review is to help researchers starting in this area by summarizing the most important concepts related to imidazolium-based zeolite studies and by presenting a table of recent imidazolium derivatives that have been recently studied to facilitate filling in the knowledge gaps.

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Forthcoming applications in electronics and optoelectronics make phosphorene a subject of vigorous research efforts. Solvent-assisted exfoliation of phosphorene promises affordable delivery in industrial quantities for future applications. We demonstrate, using equilibrium, steered and umbrella sampling molecular dynamics, that the 1-ethyl-3-methylimidazolium tetrafluoroborate [EMIM][BF4] ionic liquid is an excellent solvent for phosphorene exfoliation. The presence of both hydrophobic and hydrophilic moieties, as well as substantial shear viscosity, allows [EMIM][BF4] simultaneously to facilitate separation of phosphorene sheets and to protect them from getting in direct contact with moisture and oxygen. The exfoliation thermodynamics is moderately unfavorable, which indicates that an external stimulus is necessary. Unexpectedly, [EMIM][BF4] does not coordinates phosphorene by π-electron stacking with the imidazole ring. Instead, the solvation proceeds via hydrophobic side chains, while polar imidazole rings form an electrostatically stabilized protective layer. The simulations suggest that further efforts in solvent engineering for phosphorene exfoliation should concentrate on use of weakly coordinating ions and grafting groups that promote stronger dispersion interactions and on elongation of nonpolar chains.

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ABSTRACT Unsymmetrically substituted imidazolium salts were synthesized and characterized using 1H-NMR and 13C-NMR. The antimicrobial activities of the salts were evaluated using the agar-well diffusion method against 14 bacteria and five yeasts. The minimal inhibitory concentrations (MIC) against seven bacteria and one yeast were also determined. Among the test compounds applied, 1, 2, 3, 6 and 11 showed activities against Micrococcus luteus ATCC 9341, Staphylococcus aureus ATCC 25923, Staphylococcus epidermidis ATCC 12228, Bacilllus cereus ATCC 11778, Bacillus subtilis ATCC 6633, Bacillus thuringiensis, Listeria monocytogenes ATCC 19112 and Candida trophicalis. However, compounds 1, 2 and 3 showed the highest antimicrobial activities against Micrococcus luteus ATCC 9341, Stapylococcus aureus ATCC 25923, Staphylococcus epidermidis ATCC 12228, Bacilllus cereus ATCC 11778 and Bacillus subtilis ATCC 6633 with inhibition zones of 14-20 mm. In addition, compound 6 have only demonstrated activities against Candida trophicalis while compounds 4, 5, 7, 8, 9, 10, 12, 13 and 14 had no effect on test microorganisms.

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AIMS: This study demonstrates the development of a mouthwash formulation containing the imidazolium salt (IMS) 1-n-hexadecyl-3-methylimidazolium chloride (C16 MImCl), considering its stability and efficacy against Candida sp. Biofilm formation. METHODS AND RESULTS: A variety of in vitro test methods were applied, assessing contaminated acrylic resin strip specimens before and after applying the mouthwash formulations. The formulation using C16 MImCl presented a similar antibiofilm activity to cetylpyridinium chloride one and a commercial mouthwash, but at a 10 times lower concentration. Scanning electron microscopy imaging demonstrated that the selected mouthwash preparation fully destroys the biofilm cells, while with the hypoallergenicity test no irritant effect was observed in ex vivo model. CONCLUSIONS: The results presented herein indicate a high potential for imidazolium salts application as mouthwash agents that can eliminate Candida biofilm growth at very low concentrations. SIGNIFICANCE AND IMPACT OF THE STUDY: This study demonstrates a new and effective antibiofilm formulation containing the IMS C16 MImCl. These findings suggest the IMS' use as mouthwash formulations active ingredient against Candida biofilms on oral surfaces, as it outperforms the often used cetylpyridinium chloride at a 10 times lower concentration.

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AIMS: Evaluate the in vitro effect of imidazolium salts (IMS) on the conidia germination and mycelial growth of Fusarium graminearum and their in vivo efficacy for suppressing the symptoms of the disease and infection of kernels in wheat plants. METHODS AND RESULTS: The minimum inhibitory concentrations (MIC) of three IMS (C16 MImCl, C16 MImMeS and C16 MImNTf2 ) were determined for four F. graminearum isolates using serial broth dilution method. The MICs found for all IMS were either 3·12 or 6·25 µg ml(-1) across the isolates, with the former as the most frequent. In the mycelial growth assay on potato dextrose agar media, only the C16 MImCl among the IMS reduced 50% of mycelial growth of one isolate at an estimated concentration of 0·32 mg ml(-1) . The time-kill curves showed a strong fungicidal effect starting 1 h after incubation at a concentration of 12·5 µg ml(-1) , representing a fourfold increase in the most frequent MIC. The C16 MImCl sprayed onto the spikes of potted wheat plants during the flowering stage reduced disease intensity at levels comparable to the commercial fungicide when applied preventatively (1 h prior to fungal inoculation), rather than curatively, and at the higher dosage (2 mg ml(-1) ) rather than lower dosage (0·5 mg ml(-1) ). CONCLUSIONS: C16 MImCl proved to be a potent inhibitor of F. graminearum growth and provided good levels of control of the disease at levels comparable to a commercial fungicide, in wheat plants treated prior to fungal infection during flowering stages. SIGNIFICANCE AND IMPACT OF THE STUDY: This study suggests the potential of using IMS as alternative to the hazardous standard fungicides in the management of Fusarium head blight of wheat.

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UNLABELLED: Although the use of catheters in critically ill patients is mostly inevitable, this invasive procedure comes together with several health risks. Within this context, the contamination with Candida tropicalis is a primary concern as this highly prevalent pathogenic yeast can develop an extensive polymeric matrix that hinders the drugs' penetration and its effective treatment. This study addresses the potential for the 1-n-hexadecyl-3-methylimidazolium methanesulfonate (C16 MImMeS) and chloride (C16 MImCl) salts for eliminating the viable cells of biofilms of Candida tropicalis, compared to the performance of chlorhexidine (CHX) and fluconazole (FLZ). The minimum concentration required of C16 MImMeS, C16 MImCl, CHX and FLZ for elimination of the biofilm's viable cells (MBEC) was evaluated through microtitre plate biofilm exposure with different concentrations of these substances. These concentrations were determined at 80% of effective activity against the biofilm's viable cells by using the MTT reduction assay. C16 MImMeS and C16 MImCl were able to eliminate the viable cells at much lower concentrations (15·6 and 0·45 µg ml(-1) respectively) than CHX (1250 µg ml(-1) ) and FLZ (resistance of the viable cells). This demonstrates the high potential of these substances for nosocomial infections control. SIGNIFICANCE AND IMPACT OF THE STUDY: The 1-n-hexadecyl-3-methylimidazolium methanesulfonate (C16 MImMeS) and chloride (C16 MImCl) salts are extremely effective in eliminating the viable cells of Candida tropicalis biofilms, which allows the use of much lower concentrations than with the antimicrobial of choice (chlorhexidine) in hospital practices. These findings indicate these imidazolium salts as high-potential candidates for asepsis of medical environments and materials, including implants.

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AIMS: To investigate the antidermatophytic action of a complementary set imidazolium salts (IMS), determining structure-activity relationships and characterizing the IMS toxicological profiles. METHODS AND RESULTS: The susceptibility evaluation of 45 dermatophytic clinical isolates, treated in vitro with eleven different IMS (ionic compounds) and commercial antifungals (nonionic compounds), was performed by broth microdilution, following the standard norm of CLSI M38-A2. All dermatophytes were inhibited by IMS, where the lowest minimum inhibitory concentration (MIC) values were observed for salts with n-hexadecyl segment in the cation side chain, containing either the chloride or methanesulfonate anion. 1-n-Hexadecyl-3-methylimidazolium chloride (C16 MImCl) and 1-n-hexadecyl-3-methylimidazolium methanesulfonate (C16 MImMeS) acted as fungicides, even in extremely low concentrations, wherein C16 MImMeS exerted this effect on 100% of the tested dermatophytes. Some of these IMS provoked evident alterations on the fungi cell morphology, causing a total cell damage of ≥ 70%. Importantly, none of the screened IMS were cytotoxic, mutagenic or genotoxic to human leucocyte cells. CONCLUSIONS: This report demonstrates for the first time the strong antifungal potential of IMS against multidrug-resistant dermatophytes, without presenting toxicity to human leucocyte cells at MIC. SIGNIFICANCE AND IMPACT OF THE STUDY: The expressive antifungal activity of IMS, combined with the in vitro nontoxicity, makes them promising compounds for the safe and effective treatment of dermatophytoses, mainly when this skin mycosis is unresponsive to conventional drugs.

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UNLABELLED: The in vitro activity of the imidazolium salt C16 MImCl against planktonic and biofilm cells of multidrug-resistant isolates of Candida tropicalis was evaluated, both in solution and applied on a commercial catheter surface. This was determined by inhibition and susceptibility assays of biofilm and planktonic cells. In both cases, C16 MImCl prevented in vitro biofilm formation of C. tropicalis strains, including multidrug-resistant ones. Outstanding performances were observed, even at extremely low concentrations. Furthermore, this is the first report of the antifungal lock property of C16 MImCl, using a tracheal catheter as the test specimen to mimic a clinical in vivo condition. As such, C16 MImCl has been identified as a promising antimicotic pharmaceutical candidate for the treatment of candidiasis infections. SIGNIFICANCE AND IMPACT OF THE STUDY: The imidazolium salt 1-n-hexadecyl-3-methylimidazolium chloride (C16 MImCl) strongly prevents, in concentrations as low as 0·028 µg ml(-1) , the biofilm formation of multidrug-resistant Candida tropicalis isolates, either in solution or applied on the surface of commercial catheters. This presents an effective antimicotic candidate and alternative for invasive clinical procedure toolset asepsis.

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Imidazolium salts are best known for their applications in organic synthesis as room-temperature ionic liquids, or as precursors of stable carbenes, but they also show important biological properties such as anti-oxidative effects, induction of mitochondrial membrane permeabilisation and inhibition of the infection cycle of Plasmodium falciparum. For these reasons, and since chemotherapy for Chagas disease is inefficient, the aim of this study was to test the use of imidazolium compounds against the kinetoplastid haemoflagellate aetiological agent for this disease, namely Trypanosoma cruzi. The results show that five of the tested compounds are more effective than the reference drug benznidazole against the epimastigote and trypomastigote forms of T. cruzi. Moreover, intracellular amastigotes were also affected by the compounds, which showed lower toxicity in host cells. Transmission electron microscopy analysis demonstrated that the tested agents induced alterations of the kinetoplast and particularly of the mitochondria, leading to extraordinary swelling of the organelle. These results further demonstrate that the test agents with the best profile are those bearing symmetrical bulky substituents at N(1) and N(3), displaying promising activity against all forms of T. cruzi, interesting selectivity indexes and exceptional activity at low doses. Accordingly, these agents represent promising candidates for the treatment of Chagas disease.

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