Gabriela Gurau

Demonstration of Chemisorption of Carbon Dioxide in 1,3‐Dialkylimidazolium Acetate Ionic Liquids

Driven by increasing environmental concerns about greenhouse gas emissions (particularly carbon dioxide) and global warming, a growing amount of research has been carried out over the last decade on the use of ionic liquids (ILs), among other options, as a potential alternative to conventional processes based on aqueous amine solutions for CO2 capture. The tethering of an amine functional group to the cation was one of the initial possibilities investigated, while more recently, absorption of CO2 in ILs with amine functionality in the anion has also been reported. Still, even without amine functionalization, ILs do generally dissolve CO2 to a certain extent and CO2 is generally much more soluble than other gases such as N2 or O2. [4] In most cases, solubilization of CO2 in the nonfunctionalized IL occurs through physisorption, although chemisorption has been suggested for ILs with anions of remarkable basicity (e.g., carboxylate-derived anions). The mechanisms proposed have typically involved an interaction between the acidic CO2 and the basic anion; the only exception being a grant report by Maginn in 2005 where, to explain the absorption of CO2 in 1-butyl-3methylimidazolium acetate, he used NMR results to propose the abstraction of the proton at the C(2) position of the imidazolium ring by the basic acetate anion, followed by reaction of CO2 with the carbene species thus formed. [5a] Interestingly, we could not find any further reference to this mechanism in the literature and we assume the idea was not pursued due to concerns about the lack of explanation for the presence of an a priori unstable N-heterocyclic carbene in a relatively stable IL. The weak acidity of the proton at the C(2) position of 1,3dialkylimidazolium rings is one of the major pathways for reactivity of imidazolium species, in particular of imidazolium ILs. Wang et al. made use of this to achieve an equimolar CO2 capture in 1,3-dialkylimidazolium ILs by addition of a superbase, 1,8-diazabicyclo[5.4.0]undec-7-ene, with formation of the corresponding 1,3-dialkylimidazolium-2-carboxylate. We have recently shown that the C(2) proton can be abstracted to some extent in neat 1,3-dialkylimidazolium ILs if they are paired with a basic enough anion such as acetate even in the absence of any external base. For example, the carbene concentration in 1-ethyl-3-methylimidazolium acetate ([C2mim][OAc]) and 1-butyl-3-methylimidazolium acetate ([C4mim][OAc]) is high enough to enable formation of imidazole-2-chalcogenones by the direct addition of elemental chalcogens to these ILs. However, we also realized that complex anion formation (e.g., acetic acid/ acetate) resulted in stabilization of the volatile acetic acid thus formed, preventing further decomposition reactions and allowing these ILs to act as stable reservoirs of carbenes for direct carbene-based chemistry. Recently reported quantum chemical calculations support this concept. Here, we report direct experimental evidence in the form of single-crystal X-ray structures of solid-state products resulting from the reaction of CO2 with acetate ILs, which confirm both the reaction mechanism and the role of complex anion formation. Since to the best of our knowledge there were no reported crystal structures of 1,3-dialkylimidazolium acetate salts, we first investigated the crystal structure of 1,3diethylimidazolium acetate ([C2C2im][OAc]), an off-white crystalline solid with a melting temperature of 30 8C (Figure 1

Reaction of elemental chalcogens with imidazolium acetates to yield imidazole-2-chalcogenones: direct evidence for ionic liquids as proto-carbenes

Mechanistic analysis of the reaction between elemental sulfur or selenium and 1,3-dialkylimidazolium acetate ionic liquids, in the absence of an external base or solvent, affords evidence for the equilibrium presence of carbene species in these ionic liquids. It demonstrates the potential to control, through anion selection, the concentration of carbene in stable ionic liquids.

Ionic liquid forms of the herbicide dicamba with increased efficacy and reduced volatility

Twenty eight new dicamba (3,6-dichloro-2-methoxybenzoic acid)-based herbicidal salts, have been synthesized and characterized in order to attempt to improve the efficacy of this widely known herbicide used to protect maize, grassland, and other cultures. The new compounds, most of which are ionic liquids by definition and three of which are solids melting above 100 °C, were prepared by pairing quaternary tetraalkyl- or alkoxyammonium, piperidinium, imidazolium, pyridinium, morpholinium, quinolinium, and phosphonium cations with the dicamba anion. Growth chamber and field test data suggested that ionic liquid forms of dicamba offer substantially increased efficacy which would allow less to be applied in the field. Compared to the commercial dicamba free acid product, improved physical properties were observed including higher decomposition temperatures and reduced volatilities, suggesting a potential reduction of overall environmental impact of this herbicide.

Drug specific, tuning of an ionic liquid's hydrophilic–lipophilic balance to improve water solubility of poorly soluble active pharmaceutical ingredients

Amphotericin B and itraconazole were used to demonstrate that ionic liquids can be designed or chosen to provide tunable hydrophilicity in one ion and lipophilicity in the other allowing one to match the structural requirements needed to solubilize poorly water soluble active pharmaceutical ingredients. These liquid, amphiphilic excipients could be used as both drug delivery systems and solubilization agents to improve the aqueous solubility of many drugs. The solubility in deionized water, simulated gastric fluid, simulated intestinal fluid, and phosphate buffer solution was greatly improved over current methods for drug delivery by utilizing designed ionic liquids as excipients.

Chemistry: Develop ionic liquid drugs

A new realm of potential drugs is hiding in plain sight. Pharmaceutical research, manufacture and regulation focuses on solid active ingredients, delivered as powders or tablets. Liquid forms are neglected and viewed as an intermediate step, rather than an endpoint. Yet many promising solid drug candidates are too insoluble for the body to absorb. Of Develop ionic liquid drugs Update regulation to spur research into drugs that the body absorbs more easily and that could reach market more quickly, urge Julia L. Shamshina and colleagues. the compounds entering development, 40–70% fail because they cannot be modified simply to allow effective release into the bloodstream 1. Meanwhile, ionic liquids, an exciting class of chemical that could bypass these delivery problems, are being ignored 2. Half of all drugs sold are salts 3 that are held together by ionic bonds, among other forces. Salts that are liquid at room or body temperature can have dramatically better solubility, absorba-bility and stability than do solid forms 4. Ionic liquids can also be configured to deliver two or more active ingredients at once. For example, combining active ions from the pain reliever procaine and the non-steroidal anti-inflammatory drug (NSAID) salicylic acid generates a liquid salt, procainium salicylate. It could deliver the medical benefits of both compounds more efficiently and cheaply while opening up new treatment options. With the drug-discovery pipeline clogged, it is time to try alternatives. We call on chemists and the pharmaceutical industry to develop liquid salt forms of drugs. Chemists will need to learn more about the spectrum of interactions in ionic liquids, how to engineer ionic bonds, and how the choice of ions changes the chemical, physical and biological properties of ionic compounds. Regulations must be updated to consider active ingredients in liquid as well as solid states. Why are ionic liquids being ignored? First, most academic and industrial chemists lack understanding and experience of working with them. Chemistry courses and textbooks teach that new molecules are made by manipulating covalent bonds (where electrons are shared between atoms) rather than ionic ones. Second, pharmaceutical companies are conservative. Ionic liquids are unfamiliar , unregulated and felt to be too risky to develop commercially. And there is a perception problem. Over the past 20 years many researchers (including us) have demonstrated the value of ionic liquids as solvents, electrolytes and com-pressor fluids that are reusable, non-volatile and safe. Yet many researchers and journalists …

Molecular interactions in aqueous biphasic systems composed of polyethylene glycol and crystalline vs. liquid cholinium-based salts

The relative ability of cholinium-([Ch](+))-based salts, including ionic liquids (ILs), to form biocompatible aqueous biphasic systems (ABS) with polyethylene glycols (PEGs) was deeply scrutinized in this work. Aqueous solutions of low molecular weight PEG polymers (400, 600, and 1000 g mol(-1)) and [Ch](+) salts of chloride, acetate, bicarbonate, glycolate, lactate, dihydrogenphosphate, dihydrogencitrate, and bitartrate can undergo liquid-liquid demixing at certain concentrations of the phase-forming components and at several temperatures. Cholinium butanoate and propanoate were also studied; however, these long alkyl side chain ILs are not able to promote an immiscibility region with PEG aqueous solutions. The ternary liquid-liquid phase diagrams, binary water activities, PEG-salt and salt-H2O solubility data, and binary and ternary excess enthalpies estimated by COSMO-RS (COnductor-like Screening MOdel for Realistic Solvation) were used to obtain new insights into the molecular-level mechanisms responsible for phase separation. Instead of the expected and commonly reported salting-out phenomenon induced by the [Ch](+) salts over the polymer, the formation of PEG-[Ch](+) salt ABS was revealed to be an end result of a more intricate molecular scenario. The multifaceted approach employed here reveals that the ability to promote an ABS is quite different for the higher melting salts vs. the lower melting or liquid ILs. In the latter systems, the ABS formation seems to be controlled by the interplay of the relative strengths of the ion-ion, ion-water, ion-PEG, and water-PEG interactions, with a significant contribution from specific hydrogen-bonding between the IL anion and the PEG hydroxyl groups.

Coagulation of Chitin and Cellulose from 1‐Ethyl‐3‐methylimidazolium Acetate Ionic‐Liquid Solutions Using Carbon Dioxide

Chemisorption of carbon dioxide by 1-ethyl-3-methylimidazolium acetate ([C2 mim][OAc]) provides a route to coagulate chitin and cellulose from [C2 mim][OAc] solutions without the use of high-boiling antisolvents (e.g., water or ethanol). The use of CO2 chemisorption as an alternative coagulating process has the potential to provide an economical and energy-efficient method for recycling the ionic liquid.

Prodrug ionic liquids: functionalizing neutral active pharmaceutical ingredients to take advantage of the ionic liquid form

Neutral, non- or not easily-ionizable active pharmaceutical ingredients can take advantage of the unique property sets of ionic liquids by functionalization with hydrolyzable, charged (or ionizable) groups in the preparation of ionic liquid prodrugs as demonstrated here with the synthesis, characterization, and hydrolysis of cationic acetaminophen prodrugs paired with the docusate anion.

Metsulfuron-Methyl-Based Herbicidal Ionic Liquids

Ten sulfonylurea-based herbicidal ionic liquids (HILs) were prepared by combining the metsulfuron-methyl anion with various cation types including quaternary ammonium ([bis(2-hydroxyethyl)methyloleylammonium](+), [2-hydroxyethyltrimethylammonium](+)), pyridinium ([1-dodecylpyridinium](+)), piperidinium ([1-methyl-1-propylpiperidinium](+)), imidazolium ([1-allyl-3-methylimidazolium](+), [1-butyl-3-methylimidazolium](+)), pyrrolidinium ([1-butyl-1-methylpyrrolidinium](+)), morpholinium ([4-decyl-4-methylmorpholinium](+)), and phosphonium ([trihexyltetradecylphosphonium](+) and [tetrabutylphosphonium](+)). Their herbicidal efficacy was studied in both greenhouse tests and field trials. Preliminary results for the greenhouse tests showed at least twice the activity for all HILs when compared to the activity of commercial Galmet 20 SG, with HILs with phosphonium cations being the most effective. The results of two-year field studies showed significantly less enhancement of activity than observed in the greenhouse; nonetheless, it was found that the herbicidal efficacy was higher than that of the commercial analog, and efficacy varied depending on the plant species.

Chitin–calcium alginate composite fibers for wound care dressings spun from ionic liquid solution

Chitin-calcium alginate composite fibers were prepared from a solution of high molecular weight chitin extracted from shrimp shells and alginic acid in the ionic liquid 1-ethyl-3-methylimidazolium acetate by dry-jet wet spinning into an aqueous bath saturated with CaCO3. The fibers exhibited a significant proportion of the individual properties of both calcium alginate and chitin. Ultimate stress values were close to values obtained for calcium alginate fibers, and the absorption capacities measured were consistent with those reported for current wound care dressings. Wound healing studies (rat model, histological evaluation) indicated that chitin-calcium alginate covered wound sites underwent normal wound healing with re-epithelialization and that coverage of the dermal fibrosis with hyperplastic epidermis was consistently complete after only 7 days of treatment. Using a single patch per wound per animal during the entire study, all rat wounds achieved 95-99% closure by day 10 with complete wound closure by day 14.