Applications of Ionic Liquids in the Food and Bioproducts Industries

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Applications of Ionic Liquids in the Food and Bioproducts Industries Ariel A. C. Toledo Hijo,† Guilherme J. Maximo,† Mariana C. Costa,‡ Eduardo A. C. Batista,† and Antonio J. A. Meirelles*,† †

Laboratory of Extraction, Applied Thermodynamics and Equilibrium, School of Food Engineering, University of Campinas, R. Monteiro Lobato 80, 13083-862, Campinas, São Paulo, Brazil ‡ Department of Process and Products Design, School of Chemical Engineering, University of Campinas, 13083-852, Campinas, São Paulo, Brazil ABSTRACT: Ionic liquids (ILs) have been extensively used in many research and industry fields, including chemical and pharmaceutical applications. Nevertheless, during past years, some works revealed that those green solvents in fact could present certain toxicity levels. This is the reason why some biocompounds from natural sources, such as choline, amino acids, and organic acids, for synthesis of ILs have showed to be alternatives. This means that there is evidence that ILs with low or nontoxic effects could be synthesized, possibly overcoming the major drawback of using them in the food industry. Applications of these third generation ILs, or even the most common ILs, in food processes are scarce and mainly focused on extraction processes and chemical analysis methods. These works have proven that, considering the physical properties of ILs of interest for the food industry such as melting profile, solubility, viscoelasticity, and high biocompatibility, when compared to those commonly used, ILs are alternatives for use in the design of food products and processes. In this context, the present review provides an overview of applications of ILs in the food industry reported to date in the literature, disclosing their synthesis with natural biocompounds. Also, it proposes new applications in the food and bioproducts industries based on the main trends of the recent literature. KEYWORDS: Toxicity, Physical properties, Analysis, Extraction, Natural sources

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INTRODUCTION Ionic liquids (ILs) have attracted the interest of the industrial and academic community due to their potential for application in chemical, pharmaceutical, and food industries. They have been described as molten salts, which means liquids in a thermodynamic definition, but also liquid crystals, with solid phase melting temperature below 373.15 K, in reference to water boiling temperature.1 Among their properties of interest are the selfassembling ability, low vapor pressure, nonflammability, thermal stability, and wide liquid phase range.2 In the last two decades, the literature has revealed several applications of ionic liquids in the pharmaceutical and biotechnological industry, among several other interests in the chemical engineering field, such as the bioseparation processes of active compounds,3−5 development of drug delivery systems,6−8 electrochemistry,9−11 and enzymatic processes.12−14 In particular, imidazolium-based ILs have been widely employed in the formulation of emulsions for drug delivery systems,6 solubility of gases,15 and surfactants,16 due to their tuning solubility properties. However, few innovations related to the food industry have been revealed in comparison to other academic or industrial fields. Literature on food science and technology involving ILs is still scarce. [From the total number of papers involving ionic liquids © 2016 American Chemical Society

in the last two decades, 0.23% were related to the search terms “ionic liquids” and “food” at Scopus and Web of Science.] It has been mainly focused on extraction processes17−20 and food analysis,21−23 despite the fact that the ongoing access of their properties and the recent advances on the comprehension of their mixtures24−27 have presented them interesting additives for many applications in the food industry, such as surfactant,28 lubricant,29 and solvent ability30 and antimicrobial31 and enzymatic activity enhancer.32 In fact, the viability of using ILs as additives or chemicals in food applications requires studies on their physicochemical, thermodynamic, and toxicological properties. As is well known, the right choice of anions and cations promotes the tuning of IL properties for the synthesis of additives/chemicals with specific characteristics for a given process or product. In this context, the evaluation of the thermodynamic phase equilibrium has been applied as a useful tool for such a property design, taking into account specific melting temperatures,33 rheological profiles,34 or crystalline structures behavior27 that directly impact the products’ physicochemical properties or sensory quality. Received: March 19, 2016 Revised: August 4, 2016 Published: August 11, 2016 5347

DOI: 10.1021/acssuschemeng.6b00560 ACS Sustainable Chem. Eng. 2016, 4, 5347−5369

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ACS Sustainable Chemistry & Engineering

Figure 1. Prospects of IL applications and their current use in the food industry.

corncob, corn, and wheat has been also discussed. In general, imidazolium-based ILs, especially those based on the 1-alkyl-3methylimidazolium cation have been the most used in these processes. Nevertheless, it should be also remarkable that ILs obtained from natural sources, which are more interesting for the food industry, especially cholinium- and amino acids-based ILs have been also successfully employed. Extraction Processes. The replacement of conventional organic solvents by ILs in industrial processes requiring high and low temperatures or higher solvent ability have been the main focus of works on the use of ILs in food extraction processes. In fact, the ability of ILs to integrate chemical reactions or processes at low temperatures allows the decreasing of temperatures, energy costs, loss of solvents by evaporation, and especially thermal injuries, which is a fundamental target taking into account sensorial profiles and activity of nutraceutical compounds. From the point of view of food processing innovation, it is possible to obtain high value-added compounds from natural materials, such as polyphenols, essential oils, or natural dyes. Nowadays, there are several methods for extraction of such compounds from food samples, such as liquid−liquid (LLE), solid−liquid (SLE), or vapor−liquid extraction (VLE) techniques. In the past decade, the use of pure ILs or ILs mixed with other solvents for enhancing the extraction yield of natural valueadded compounds of interest for the food and bioproducts industries has increased.20,66,71,75 Despite this, their large potential still offers several possibilities with respect to the design of new extraction methods,71 optimization of processes conditions, decreasing of the toxicity of output streams, choice of best solvents, or mixtures of them. According to Passos et al.,20 solid− liquid or liquid−liquid extraction, including aqueous bi- (ABS) or triphasic systems (ATS), are the main alternatives up to date in IL-based extraction techniques in food processes, also coupled to other methods, especially ultrasound- (UAE) or microwaveassisted extraction (MAE).4

Regarding toxicological aspects, one of the main reasons for the lack of application of ILs in the food industry is the divergence in literature on such a topic.35−38 This is the reason that several studies on the use of renewable compounds for the synthesis of ILs, such as amino acids,39,40 lipidic compounds41 or other acids from natural origin42−44 have emerged gradually. In this scenario, the present review attempted to summarize the ILs applications in the food industry or in biobased processes already evaluated in the literature. Also, this work highlights the tunability of their physicochemical properties, especially taking into account the synthesis of ILs based on natural compounds, with interest in overcoming toxicity aspects. Finally, it proposes potential applications in such a field (Figure 1).

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IONIC LIQUIDS IN FOOD PROCESSES: ONGOING STEPS The discussion described in the following paragraphs focuses on the application of ILs in food and related areas based on many works available to date in the literature. It is divided into three different subsections according to the field of application of ILs in food and bioproducts industries, namely, extraction processes, food analysis, and biofuel produced from food sources (biodiesel or bioethanol). Table 1 provides a complete frame on such applications and the respective ILs used in each process. Value-added products of interest for the food industry such as phenolic compounds, essential oils, piperine, caffeine, fatty acids, and other food additives have been the main target of extraction processes. Remarkably, the extraction of biocompounds from food waste has also been reported in the last years. Food analysis has been focused on the determination of dyes, heavy metals, antibiotics, bisphenol A, herbicides, preservatives, acrylamide, phenolic compounds, vitamins, species, acidic food additives, and folic and ascorbic acids. The application of ILs in the production of biodiesel and bioethanol from vegetable oils, sugar cane bagasse, 5348


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ACS Sustainable Chemistry & Engineering Table 1. Overview of Application of Ionic Liquids in Food Industrya

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ACS Sustainable Chemistry & Engineering Table 1. continued

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ACS Sustainable Chemistry & Engineering Table 1. continued

MAE − microwave-assisted extraction; UAE − ultrasound-assisted extraction; ABS − aqueous biphasic system; SLE − solid−liquid extraction; LLE − liquid−liquid extraction; QuEChERS − quick, easy, cheap, effective, rugged and safe; SEC − size exclusion chromatography; ICP MS − inductively coupled plasma mass spectrometry; SPE − solid-phase extraction; FAAS − flame atomic absorption spectrometry; SWCNT − singlewalled carbon nanotube; HPLC − high-performance liquid chromatography; MALDI − matrix-assisted laser desorption ionization; TOF − time-offlight; UA − ultrasound assisted; DIST − distillation.

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for orange essential oil isolation from orange peels through distillation using pure 1-butyl-3-methylimidazolium chloride ([C4mim]Cl), 1-allyl-3-methylimidazolium chloride ([Amim]Cl), and 1-ethyl-3-methylimidazolium acetate ([C2mim][CH3COO]). The proposal is based on the low volatility of ILs and their ability to dissolve lignocellulosic material. This promotes the dissolution of the peel matrices, enhancing the efficiency of the distillation and separation of the oil. In this example, [C2mim][CH3COO] was more suitable for complete dissolution of the biomass by using low concentrations (20%−35% w/w solution). Afterward, high yield values were achieved (4.1% w/w) through vacuum distillation followed by ILs recovered using water extraction. This method was proved to be more efficient in comparison to yields of conventional methods, such as solid−liquid extraction with dichloromethane and diethyl ether (close to 1% w/w).71,141 Li et al.67 reported higher extraction yields for obtaining Farfarae flos plant essential oil (0.26% w/w) using aqueous solution of imidazolium-based ILs ([C2mim][CH3COO] as the best result) followed by distillation, which resulted in a yield increase in 62% in comparison to conventional water distillation. Flamini et al.68 studied the use of aqueous solutions of cholinium chloride ([Ch]Cl), claimed as less toxic than imidazolium-based ILs, 1-hydroxyethyl-3methylimidazolium chloride, N,N-butylmethylmorpholinium chloride, or N-methylimidazolium chloride, on the extraction of Rosmarinus of ficinalis L. essential oil by hydrodistillation. Mixtures containing 1-hydroxyethyl-3-methylimidazolium chloride at low concentration (solid:IL ratio 1:1, g mL−1) presented higher extraction yields (1.93% w/w), which is higher than conventional hydrodistillation (1.46%−1.64% w/w).

In general, the imidazolium-based ILs are the most popular choice, despite discussion about their toxicity. However, alternatives have been revealed. Taking into account the decreasing of their toxicity levels, the use of 1-butyl-3-methylimidazolium acesulfamate [C4mim][Ace],139 [N111(C2O(O)C12)]-based IL,65 [N(C1)2CO2]-based IL,140 acetate-,55,71 and amino acids-57 and cholinium-based ILs55,88,89 are some examples. Relevant advantages have been also reported in the case of using mixtures of ILs and conventional solvents, in terms of profitability, efficiency, purity, and recyclability. This is the case of aqueous solutions of ILs already used for recovering essential oils, phenolic compounds, caffeine, piperine, or food additives, for example, due to water costs and sustainability.4 The utilization of other solvents, such as ethanol and methanol, has been also reported.20,48,57,90 This is worthy because when ILs are diluted in low molecular solvent, their viscosity is decreased, promoting a higher solvent penetration in the food matrices and higher mass transfer coefficients. Also, the use of solid ILs becomes feasible. Essential oils are substances present in herbs, seeds, and fruits, commonly extracted through mechanical processes, by using solvents or hydrodistillation. Their technological importance is based on the presence of active compounds, such as esters, alcohols, and phenols, with antioxidant and antimicrobial properties, as well as their activity as promoters of fragrance and flavor. In this way, the enhancing of the extraction yield of essential oils from fruits and herbs is of interest for the food industry. On the basis of this approach, some authors reported the use of ILs associated with hydrodistillation and microwaveassisted methods with superior extraction yields when compared to conventional methods. Bica et al.71 reported a method 5351


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to be considered in this case. Cláudio et al.66 increased the efficiency of the SLE of caffeine from guarana seeds using aqueous solutions of 1-butyl-3-methylimidazolium chloride ([C4mim]Cl) at different concentrations. The authors observed a drastic increase in the extraction yield (from 3.86% to 8.18% w/w) as the IL concentration in water increased (from 0.0 to 3.0 M). Such enhancing was probably related to the biomass dissolution ability since scanning electron microscopy (SEM) showed a breaking effect on samples mixed with the IL solution. Also, the authors did not observed maximum extraction yield at the evaluated concentration of ILs, in contrast to some authors.64,81,83 It is important to consider that such maximum extraction efficiency is probably achieved when the viscosity of the solution starts to increase at a given IL concentration. Also, the diameter of guarana particles was more relevant, in this case, than the molecular structure of the IL composed of imidazolium and pyrrolidinium cations and chloride, acetate, and tosylate anions. However, in the case of 1-butyl-3-methylimidazolium tosylate ([C4mim][Tos]) (yield of 6.48% w/w), π−π interactions with caffeine could increase the effectiveness of the process. Moreover, the optimization of the operational conditions showed excellent extraction yields of caffeine (up to 9% w/w) within 30 min at 70 °C using aqueous solutions of [C4mim]Cl at 2.34 M. This is relevant when compared to Soxhlet extraction using a volatile organic solvent methylene chloride, which presented yields of caffeine up to 4.3% w/w during 270 min of extraction. Also, ILs could be recovered by a LLE using chloroform and butanol. Ma et al.86 extracted alkaloids (N-nornuciferine, O-nornuciferine, and nuciferine) from lotus leaf by MAE and conventional heat reflux extraction (HRE) by using aqueous solutions of 1-alkyl-methylimidazolium (Cnmim)based ILs (n = 2, 4, 6, 8) with different anions (Cl, Br, BF4, PF6) and cations (C2mim, C4mim, C6mim, C8mim). 1-Hexyl-3methylimidazolium bromide ([C6mim]Br) was selected as the most efficient solvent, with stronger interaction with the alkaloids through hydrogen and π−π86 bondings. The extraction efficiency increased up to n = 6 when water solubility started to decrease. Micelle-forming ability could be also a significant factor in this case, taking into account the alkyl chain length. Despite power (in MAE) did not show significant influence, the increase in the extraction efficiency was observed when the solid−liquid ratio reached 1:30 and in extraction time (from 0 to 1 min). In comparison to regular MAE and HRE, the use of an aqueous solution of IL in MAE led to a drastic reduction in extraction time (from 120 to 2 min) and higher efficiency (0.9%−43.7%). Terpenes are a class of compounds found in citrus essential oils. This is the case of limonene, the major compound that can oxidize during storage, causing undesirable off-flavors. Extraction processes of such compounds, called as deterpenation, are commonly applied in industry for improving the quality and shelf life of products.30,72−74 Lago et al.30 showed that acetate-based ILs ([C2mim][CH3COO] and [C4mim][CH3COO]) were as effective as other common ILs or other solvents for the extraction of terpenes from a model system of citrus essential oil. In this case, the longer the carbon chain of the cation is, the higher the distribution ratio and selectivity are. The liquid−liquid equilibrium of mixtures containing IL + limonene and linalool was also determined by other authors (1-ethyl-3-methylimidazolium ethylsulfate, 1-ethyl-3-methylimidazolium methanesulfonate, and 1-ethyl-3-methylimidazolium 2-(2-methoxyethoxy) ethylsulfate).72−74 Some of them found higher extraction selectivity compared to organic solvents, such as in the case of

Remarkably, [Ch]Cl also resulted in higher extraction yields (1.67% w/w) than conventional distillation. Zhai et al.75 employed MAE for obtaining dried fruits essential oils by using 1-hexyl-3-methylimidazolium hexafluorophosphate ([C6mim][PF6]). With similar yields than those obtained by conventional distillation, the use of ILs led to lower process time (reduction of 90%) and sample consumption. Similar results were obtained by Ma et al.76 for the extraction of Schisandra chinensis Baill essential oil by using 1-lauryl-3-methylimidazolium bromide ([C12mim]Br) aqueous solution. Higher extraction yields (12.12 mL/kg) and lower process time (reduction of 70%) were achieved compared to conventional distillation. Phenolic compounds are bioactive molecules obtained synthetically or naturally from foods, being the natural source more beneficial to human health than synthetic ones.57 The obtainment of phenolic compounds from natural sources has some barriers due to the complex profile of the matrices. This fact requires efficient extraction techniques, and ILs have shown good effectiveness.50,57,60 Ni et al.57 employed LLE using amino acid-based ILs mixed with dimethylformamide (DMF) for the recovery of α-tocopherol from its mixture with methyl linoleate. Tocopherols are commonly extracted from methylated oil deodorizer distillate during refining vegetable oils. Higher selectivity values (up to 29) were obtained for 1-ethyl-3-methylimidazolium alanine ([C2mim][Ala]) and 1-ethyl-3-methylimidazolium lysine ([C2mim][Lys]) at molar ratios of 15:85 IL:DMF. This value is nine times higher than pure DMF or ILs with most popular anions (bromide, tetrafluoroborate, and hexafluoroborate). The values were attributed to the hydrogen bonds between phenolic and amino acidic groups. The DMF concentration at the mixtures also led to effects on the distribution coefficients due to decreasing of the viscosity of the solvent. Ribeiro et al.55 used aqueous solutions of imidazolium- and cholinium-based ILs for the extraction of polyphenols from tea and mate. [Ch]Cl among cholinium acetate ([Ch][CH3COO]), 1-ethyl-3-methylimidazolium chloride ([C2mim]Cl), and 1-ethyl-3-methylimidazolium trifluoromethanesulfonate ([C2mim][OTf]) was the best solvent with yield values higher than that obtained for ethanolic extraction. In this case, shorter alkyl chains presented more favorable interactions with polyphenols, resulting in higher extraction efficiency. Due to their better performance, [Ch]Cl was evaluated for the optimization of the temperature condition, presenting higher extraction yields at 70 °C. Considering the set of ILs evaluated as solvents for the extraction of essential oils and phenolic compounds, ILs based on acetate ([CH3COO]) and amino acid anions, as well as ILs based on the cholinium ([Ch]) cation, seems to be promising compounds for food and bioproducts industries since besides their excellent extraction yield they can be obtained from natural sources, presenting possibly lower toxicity and biodegradability. Caffeine is an alkaloid with bioactive properties commonly found in coffee, tea, chocolate, and guarana. It has been used in the formulation of pharmaceutical products due to their stimulant effect on the muscular and nervous system and is considered bioactive product for replacement of pesticides since it has antimicrobial and antifungical properties.66,142 Moreover, their extraction from food systems is increasingly demanded for particular caffeine-sensitive consumers, especially in the case of soft drinks or decaffeinated products. Studies on the extraction of caffeine,66 but also other alkaloids, such as piperine,64,65 nuciferine,86 camptothecin,81 and catharanthine83 from food matrices were carried out with IL aqueous mixtures due to their water solubility.20 Thus, polarity and solubility are target factors 5352


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ACS Sustainable Chemistry & Engineering 1-ethyl-3-methylimidazolium methanesulfonate74 in comparison to 2-butene-1,4-diol and ethylene glycol. Food Analysis. New food analysis methods with high efficiency, sensitivity, and low cost are still necessary for determination and quantification of compounds of interest or those prohibited or limited by food legislation. In this way, food analysis using ILs has gained importance, mainly for determination of nondesirable or amount-limited compounds. This is the case of some preservatives, heavy metals, antibiotics, herbicides, and dyes in which authors have been focused. As in the case of extraction processes, 1-alkyl-imidazolium-based ILs are the most used in food analysis, and in some cases, they are used in solutions with water or ethanol. Cholinium and amino acids biobased cations have been also employed, although less frequently. In fact, microextraction processes are generally employed as the first step in food analysis methods, taking into account the biocompatibility between ILs and target biocompounds. Fluorinated anions, such as hexafluorophosphate (PF6-), tetrafluoroborate (BF4-), and bis(trifluormethylsulfonyl)imid (Tf2N-) have been the most used anion, in this context, especially for the determination of dyes and heavy metals. Moreover, works reported to date on food analysis have been focused only on the influence of the alkyl chain length. Thus, further studies on the effect of the cation−anion pair are still demanded for improving food analysis techniques. Zhang et al.117 employed 1-hexyl-3-methylimidazolium hexafluorophosphate ([C6mim][PF6]) for determination of Safranin-T content in food matrices. Safranin-T is a synthetic dye commonly used in the production of foods due to their red color and low cost but prohibited by legislation in many countries. This method was based on liquid−liquid, solid−liquid microextraction, and fluorimetry, showing efficiency, lower analysis time, and simplicity when compared to conventional methods for determination of this type of dye, such as highperformance liquid chromatography of fluorescence (HPLC-FL) and ultrahigh-performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS). Khani and Shemirani23 determined cobalt and nickel in water streams by using 1-hexyl-3-methylimmidazolium bis(trifluormethylsulfonyl)imide ([C6mim][Tf2N]). Despite such metals being nutritionally essential in trace levels, they can promote intoxication above certain quantities. Thus, the determination of the concentration of heavy metals is important for the evaluation of the food quality and customer health assurance. The method was as efficient as other methods, such as solid-phase (SPE) and cloud point extraction (CPE), using low ILs concentration, which corroborates with cost and toxicological and environmental aspects. Davudabadi Farahani et al.96 reported for the first time the determination of copper from food matrices by using a series of 1-alkyl-imidazolium (Cnmim)-based ILs (n = 2,4,6) combined with different fluorinated anions (BF4-, PF6-, Tf2N-) as carriers in ferrofluid (containing ferromagnetic particles)-based dispersive solid-phase extraction (SPE) followed by flame atomic absorption spectrometry (FAAS). Results of extraction yields showed that the effect of the structure of the anion was more relevant than the cation, increasing in this order: Tf2N-, PF6-, and BF4-based ILs. Among the evaluated ILs, 1-hexyl-3-methylimidazolium tetrafluoroborate (C6mim][BF4]) was selected as the most promising since it provides higher ferrofluid stability, which is related to the electrostatic and steric stabilization between metal nanoparticles and the supramolecular IL network. The use of BF4-based ILs

for separation and determination of heavy metals is even more interesting because of their hydrophilicity, considering the purification and analysis of aqueous solutions of food waste. Antibiotics and herbicides are chemicals prohibited or limited by food legislation and sometimes unduly present in foods. Shao et al.108 developed an analytical method for determination of sulfonamides (antibiotics) from milk samples. Antibiotics are used for treatment of animal infections or diseases, such as in the case of mastitis in cows, which leads to the risk of milk contamination. This is the reason why they must be detected and controlled in food samples before human consumption. Shao et al.108 developed an analytical method for extraction and determination of sulfonamides (antibiotics) from milk samples. The method consisted of an ABS based on 1-butyl-3methylimidazolium tetrafluoroborate ([C4mim][BF4]) and trisodium citrate dehydrate followed by HPLC, as an alternative to common methods based on spectrophotometry and gas chromatography, that are time consuming or use volatile solvents. The method was feasible and performed in one cleanup and preenrichment step, with high recovery of analytes (higher than 72.32% w/w) and accuracy (0.56%−12.20%, standard deviations). Regarding biobased ILs, Shahriari et al.109 first reported the use of cholinium-based ILs combined with different chlorate and amino acids for the separation and determination of antibiotics by using ABS followed by spectroscopy. The authors concluded that cholinium-based ILs are expected to play an important role as a purification platform for the determination of antibiotics, presenting higher partition coefficients than typical polymer-based ABS. For tetracycline HCl and ciprofloxacin HCl determination, in this case, the efficiency of the anion increased in this order: glutarate, succinate, levulinate, chlorate, and acetate. Zhang et al.114 developed a method for determination of triazine herbicides from soybeans by using MAE followed by a flotation step and HPLC, in which a set of ILs were evaluated as foaming agents, due to their amphiphilic character. The effect of the ILs’ ion structures was investigated by combining [C6mim][PF6] with three different anions (BF4-, PF6-, Cl-) and by varying the PF6-based ILs alkyl chain length (Cnmim- with n = 2,4,6). Results showed that the recovery of herbicides increased as the alkyl chain of the ILs increase. This is due to the surface tension reducing ability of long chain ILs and its relationship to the formation of foams, which promotes better recovery yields. Regarding the anion effect, PF6-based ILs was more indicated for such a technique since, according to the authors, the thermal stability of hydrophobic ILs, such as [C6mim][PF6], is higher. Thus, the method was successfully employed, and the [C6mim][PF6] was selected as the most promising ILs, achieving good recovery yields (>84.5% w/w) and accuracy (∼5.1%). Sun et al.21 reported a method for determination and quantification of sorbic, benzoic, p-hydroxybenzoic, and m-amino benzoic acid, butyl p-hydroxybenzoate, propyl p-hydroxybenzoate, ethyl p-hydroxybenzoate, and methyl p-hydroxybenzoate, commonly present as preservatives in soft drinks, fruit juices, and vitamin supplements. Preservatives can be used in limited amounts, according to food legislation, in order to increase the shelf life of foods through the inhibition of the growth of pathogens or spoilage microorganisms. The knowledge of their levels in foods is of great importance for food safety, either in the case of growth of pathogens or due to their toxicity when above the limits. The technique employed capillary electrophoresis using imidazolium-based ILs with different anions (BF4-, PF6-, Cl-) as an electrolyte additive. Among the evaluated ILs with different cations, 1-butyl-2,3-dimethylimidazolium chloride ([C4C1mim]Cl) 5353


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conventional solvents for breaking the water + ethanol azeotropy during distillation of bioethanol. ILs have been also applied as solvents in the pretreatment of sugar cane bagasse that is performed during the second generation bioethanol production. Such a pretreatment consists in the obtainment of simple sugars from cellulose, such as mono- and disaccharides, and highly volatile and toxic organic solvents are commonly employed. Zhu et al.136 evaluated the performance of cholinium-based ILs and reported that the advantages in employing ILs in the pretreatment of biomass are the use of low temperatures, the increase in enzymatic activity for the digestibility of lignocellulosic biomass, and reuse of the solvent for sequential pretreatments. In comparison to other green solvents for the pretreatment of biomass, such as supercritical CO2, the processes using ILs do not require high pressures, which reduces the manufacturing costs.129

was the most promising, presenting higher recovery values when compared to traditional capillary electrophoresis techniques. Improvements were also observed for the other imidazolium-based ILs, but they were similar for ILs with different anions. This means that other anions should be evaluated. Adulteration is another interesting focus for food analysis. It is by definition an illegal practice, consisting in a modification of food products in which a substance is intentionally added for reducing cost. In the same way, food consumers and suppliers rely on efficient analysis for adulteration detection, which is the case of adulteration of extra virgin olive oil with cheaper vegetable oils that requests highly sensitive analytical techniques.103 Calvano et al.103 developed a method for detection of extra virgin oil adulteration with hazelnut oil using tributylammonium α-cyano-4-hydroxycinnamate ([TBA][CHCA]) for liquid−liquid pre-extraction followed by mass spectrometry. It was based on determination of phospholipids and presented a very high efficiency from samples with 1% of contaminants. Besides prohibited additives, already listed above, analytical methods for the quantification of vitamins,92 such as works with folic acid93 and other nutraceutical biocompounds, are still a demand. An alternative method using ILs was reported by Zhu et al.100 The authors determined ethyl vanillin and ethyl maltol, compounds with flavor effects, in biscuits, chocolate, and milk powder by using aqueous extraction with 1-octyl-3methylimmidazolium chloride ([C8mim]Cl) followed by ion chromatography. The method was noteworthy due to their simplicity and use of low amounts of samples, and ILs showed efficiency with high recovery values (up to 95.8% w/w). Biofuel Production from Vegetable Oils and Biomass. ILs have shown to play an important role in the development of more “green” and efficient methods for biodiesel production from vegetable oils and biethanol from sugar cane. Conventionally, biodiesel, i.e., fatty esters, are produced by the transesterification of triacylglycerols, the major component of vegetable oils, by using methanol or ethanol under catalysis, with NaOH and H2SO4.143,144 However, the use of some catalysts may have drawbacks,145 such as formation of soaps, in the case of basic catalysts, when free fatty acids are present in excess in vegetable oils or corrosion and environmental pollution in case of acid catalysts. In this context, due to their catalytic properties, easy preparation, high solubility, and variable acidity, the use of ILs as catalysts for biodiesel production has revealed interesting results.125,126,146 Guo et al.126 used 1-butyl-3-methylimidazolium tosylate ([C4mim][CH3SO3]) in biodiesel production from Jatropha oil reporting up to 93% of esterification rate. Guo et al.127 used 3-(N,N,N-triethylamino)-1-propanesulfonic hydrogen sulfate and found similar yields (93.2%) for biodiesel production from soybean oil. ILs could also be used as a solvent during bioethanol production from food sources, such as sugar cane, either for distillation or fermentation. The bioethanol industry presents a promising and sustainable market appeal as one of the alternatives to fossil fuels, being successfully employed in some countries, such as in Brazil, but also used as a renewable solvent for extraction processes in food industry. Therefore, optimization of its production chain is always being demanded in order to reduce costs and environmental impacts. Several works in the literature reported that some ILs, such as 1,3-dimethylimidazolium tetrafluoroborate ([C1mim][BF4]),130 1-octyl-3-methylimidazolium tetrafluoroborate ([C 8 mim][BF 4 ]), 128 and 3-methylimidazolium tetrafluoroborate ([mim][BF4])131 could be employed in the replacement of pollutant and hazardous

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POSSIBLE EDIBLE ILS FROM NATURAL SOURCES Several authors have broadcasted toxicity as the major drawback for using ILs in food processes or as food additives. However, although some works revealed toxicity level for several ILs, a decrease in toxicity has been proven in some cases. This is because researches indicate that toxicity depends directly on IL structures, i.e., their cation−anion profile.147,148 Therefore, the search for anions and/or cations from natural sources for synthesis of new ILs has revealed an interesting way to decrease their toxicity, possibly overcoming the drawback of using them in food processes. Table 2 and Figure 2 show anions and/or cations obtained from natural sources used to date for synthesis of such new generation ILs. They mainly include amino acids, carboxylic acids, and choline derivatives, compounds that show both lower environmental impacts and toxicity. Glycine, also known as amino acetic acid, is widely employed in nutritional supplements and one of the amino acids most found in some large-scale raw materials, such as sugar cane and fruits. Glycine and other amino acids were recently used for the synthesis of ILs showing interesting properties for extraction processes57 and sweetish taste. The extractive ability of these ILs has been related to the strong hydrogen bonding with acidic compounds, making them good solvents for phenolic compounds extraction, such as tocopherols,57 for example. Cholinium is a cation, also known as belonging to the B-complex vitamins, that can be found in several foods, such as eggs and peanuts, as well as soybeans, and is considered an essential and nontoxic nutrient recommended for the human diet for normal human health assurance.155 ILs synthesized with cholinium and amino acids derivatives have been produced for biomass pretreatment in order to replace more toxic and conventional ILs, such as those containing imidazolium in their structure.39,40,151,154 Also, cholinium-based ILs seem to be cheaper than imidazolium-based ILs. This is the case of cholinium chloride ([Ch]Cl) and [Cnmim]-based ILs with industrial prices of ∼ $US 1.21 kg−1 and ∼ $US 14−34 kg−1, respectively.20 Choline derivatives have been also used in the development of sweeteners due to their ability to increase the sweetening power.156 Notably, [Ch]Cl, classically mentioned in IL literature, is classified as a safe substance by the U.S. Food and Drug Administration (FDA). Some authors have similarly reported nontoxicity of cholinium-based ILs.157 Fatty acids are long chain carboxylic acids largely produced, as coproducts, during the refining of vegetable oils, such as palm, soybean, and sunflower oil. Other natural compounds, such as fatty acid esters and phospholipids, may also be produced from such a source and usually used in the production of surfactants, 5354


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ACS Sustainable Chemistry & Engineering Table 2. Anions and/or Cations Obtained from Natural Sources for Synthesis of Ionic Liquids

for food, cosmetics, and pharmaceutical products.158 Fatty acidbased ILs have been synthesized by some authors,41,149 considering their renewable aspect and easy and low-cost production. The interest for fatty acids is related to the increasing worldwide large-scale production of vegetable oils. Moreover, their physical and functional properties seem to be an important aspect to consider when evaluating these ILs as relevant products. Toxicity Aspects. In recent years, studies on IL toxicity have grown proportionally to the interest in their application, although most of them have been used in processes not involving foods. Imidazolium- and pyridinium-based ILs are common examples of ILs with certain levels of toxicity.159−163 However, the toxicological aspects of ILs can be understood in many

perspectives as there are different types of analysis for toxicity assessments. According to Zhao et al.,36 the main toxicological analysis employed for ILs are based on aquatic ecosystems, microorganisms, animal tests, cytotoxicology, and enzyme inhibition. Most of the toxicological studies for ILs reported to date were focused on environmental hazards, especially those based on aquatic ecosystems and microorganisms, such as Vibrio f ischeri,164 Staphylococcus aureus and Escherichia coli,165 Chlorella vulgaris and Pseudokirchneriella subcapitata,164,166,167 crustaceans148,159,168 and aquatic plants, such as Lemna minor.160 Despite the fact that they are not suitable for evaluation of toxicological aspects in the case of the food industry, such analyses bring important information in the absence of it. 5355


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of IL-based additives, including those based on ions obtained from natural sources, the following toxicological tests have to be performed: genetic toxicity tests, toxicity studies with rodents and nonrodents, developmental and reproduction toxicity studies, metabolism and pharmacokinetic studies, and finally, human studies. Genotoxicity tests are used for the determination of the damage of a given substance on the human health based on gene mutation and chromosomal modification. According to some authors,172 the assessment of IL genotoxicity is very scarce, with some exceptions.172−174 Zhang et al.174 and Docherty et al.173 reported the first studies on the evaluation of imidazolium-based IL toxicity using Salmonella typhimurium, and in both studies, such ILs displayed mutagenicity, which is related to carcinogenicity. Cytotoxicity methods by using human and animal cells are important techniques for the evaluation of the potential risk of ILs in human health and are simpler when compared to oral toxicity using rodents and humans. There are many studies using rat cell line161,175−177 and human cell line148,157,178−181 and most of them evaluating those ILs with imidazolium cation. In 2010, Frade and Afonso169 reported a review on the effect of a considerable number of ILs with different anions and cations by using cancerous cell lines and enzymes assays. This work represents one of the most complete studies on the effect of the ion structure by in vitro tests: It confirmed the relationship between the structure of the ions and their toxicity and that it is dependent on the cell line. For different cations, they concluded that the toxicity of ILs toward IPC-81 cell lines increased in this order: morpholinum (Morp)-, piperidinium (Pip)-, pyridinium (Py)-, pyrrolidinium (Pyr)-, methylimidazolium (mim)-, quinolinium-, tetrabutylammonium-, and tetrabutylphosphoniumbased ILs. However, when the MCF-7 cell line was used, toxicity followed the other: Pip-, mim-, Pyr-, and Py-based ILs. Chen et al.182 evaluated the cytotoxicity of imidazolium-based ILs in the human lung carcinoma A549 cell line and concluded that the toxicity effect depends on the anion−cation association, as well as on the alkyl chain length of the structure. Stepnowski et al.180 compared ILs and organic solvents toxicity toward the human HeLa cell line, which is quite interesting taking into account their use in replacement of these conventional compounds. They found that 1-butyl-3-methylimidazolium chloride ([C4mim]Cl), 1-butyl-3-methylimidazolium hexafluorophosphate ([C4mim][PF6]), and 1-hexyl-3-methylimidazolium tetrafluoroborate ([C6mim][BF4]) are less toxic taking into account certain concentrations than some classical solvents, dichloromethane, phenol, and xylene. Cytotoxicity studies for ions from natural sources, on the other hand, seem to present more interesting results when compared to the imidazolium-based ILs. Frade et al.157 found no toxicity for cholinium saccharin and cholinium acesulfame toward human colon carcinoma HT-29 cell lines. Remarkably, saccharin and acesulfame have the approval of the FDA as high-intensity sweetener food additives. For cholinium-based ILs, the alkyl chain of the anion seems to influence their cytotoxicity.183 Patinha et al.183 reported the toxicity dependence with the alkyl chain length for six cholinium perfluoroalkanoate ILs using three cell lines (MRC-5, Huh-7, and HEK 293), but no toxic effect was found for cholinium-based ILs with a shorter alkyl chain (cholinium trifluoroacetate and perfluoropropanoate) in the case of concentrations up to 10−2 M. Gouveia et al.148 studied the toxicity of a group of amino acidbased ILs composed of cholinium, imidazolium, and pyridinium

Imidazolium-based ILs, used in several applications involving food systems, as mentioned before, have been widely studied through ecotoxicity methods. According to some authors, the alkyl chain length is a relevant factor for their toxicity.167,169 On the other hand, these ILs and those with pyridinium cations could present lower toxicity when synthesized with lower toxic anions. This is the case, for example, for imidazolium- and pyridinium-based ILs synthesized with mandelic acid derivatives,43 naturally found in almond extracts (Figure 2). Moreover,

Figure 2. Ions obtained from natural sources and used for ILs synthesis.

Nockemann et al.170 synthesized lower toxic ILs with lower toxic ions, cholinium saccharinate, and cholinium acesulfamate, finding lower ecotoxicity levels toward crustaceans, when compared to most common ILs, and related this to the natural origin of the ions. Similarly, Peric et al.44 found no toxicity for ILs with organic acid anions when compared to classical imidazolium molecules, through ecotoxicity and biodegradability tests toward aquatic systems. In other words, could ILs be edible? In this context, a well-established FDA designation of a safe substance or chemical has gained attention. This is the Generally Recognized as Safe (GRAS) concept, designated for a substance added to food that by scientific procedures has been determined as safe under the conditions of intended use. This means that there is considerable scientific evidence to conclude that the substance does not present toxicological hazards or safety concerns at the intended use levels. In terms of toxicological safety, there is no difference between a GRAS substance and an approved food additive.171 The importance of GRAS substances is based on their well-known safety recognition by the scientific community.171 Regarding the ions obtained from natural sources reported in this work, some of them or their sources have been approved by FDA as GRAS substances and/or food additives. This is the case for cholinium chloride, carboxylic acids (e.g., acetic acid), and the non-nutritive sweeteners saccharin and acesulfame potassium. The FDA has recommended a list of toxicity tests as rules for the evaluation of the safety of a substance potentially used as a food additive and to determine its addition limits. This FDA guidance for the food industry represents a summary of toxicological testing based on the 1993 draft Redbook II [Toxicological Principles for the Safety Assessment of Direct Food Additives and Color Additives Used in Food − Redbook II (US Food and Drug Administration, 1993)]. In the case of development of a novel food additive, that could be the case 5356


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Considering that the toxicity of ILs depends on the model of toxicological assay as well as the nature and structure of the ions, there is still a large lacuna in the literature. This is especially for case of ILs synthesized with biocompounds from natural sources and toxicological studies based on human and/or animal oral exposure. Nevertheless, this could provide important information on the synthesis of nontoxic ILs, enabling their application in food products and processes.

cations toward HeLa cells (from cervical carcinoma) but also performed tests with living organisms (crustacean Artemia salina, Bacillus subtilis, and Escherichia coli). The authors also showed that the use of the cholinium cation instead of the methylimidazolium cation lead to a drastic decrease in toxicity. This suggests that the use of cholinium and amino acid ions, as natural ions, could present less hazards to human health and environment. Despite the fact that in vitro tests have shown important results taking into account the nature and structure of the ions on toxicity of ILs, in vivo tests are also recommended by the FDA. The FDA recommends the use of rodents (usually rats and mice) for carcinogenicity, reproductive, developmental, metabolism, short-term, subchronic, and chronic toxicity studies. On the other hand, nonrodents (usually dogs) are recommended for subchronic and one-year toxicity studies. Nevertheless, toxicity studies of ILs to mammals are still scarce in the literature.150 Despite this, metabolism and pharmacokinetic studies have been applied to evaluate enzyme inhibition in the presence of ILs. Metabolism tests provide valuable information on how ILs are metabolized, i.e., their metabolic pathways and rates, their effects on enzymes activity, and their effects on tissues and organs. Also, they can be used for planning the deepest toxicological evaluations, such as subchronic and chronic toxicity studies. They were already applied, for example, for 1-alkyl-3-methylimidazolium-,184,185 pyrrolidinium-, and phosphonium-based ILs,186 as well as for tetrabutylammonium chloride187. Although scarce, some works on oral toxicity have been published. Landry et al.37 evaluated oral toxicity toward Fischer 344 rats in the case of 1-butyl-3-methylimidazolium chloride ([C4mim]Cl) and concluded that toxicological response was a function of concentration. Xu et al.188 also evaluated the oral toxicity of 1-alkyl-3-methylimidazolium tetrafluoborate [Cnmim][BF4] toward mice and found medium levels of toxicity short-term potential of 56.16−214.18 mg kg−1 for n = 10, 12, 14, and 18. Over again, conclusions pointed to an alkyl chain length effect. Similarly, medium toxicity toward mice (short-term potential of 98.91−220.16 mg kg−1) was also reported for 1-alkyl-3-methylimidazolium borate [Cnmim]Br.189 On the context of ILs formed by natural ions, Jodynis-Liebert et al.150 and Jodynis-Liebert et al.190 studied rats oral exposure (subchronic toxicity) and cytotoxicity for didecyldimethylammonium saccharinate and didecyldimethylammonium acesulfamate, respectively. The authors concluded that both ILs presented no evidence of treatment-related toxicity effect on rats after being exposed for 28 days at doses up to 100 mg/kg/day. This is quite noteworthy, considering that this IL is an active agent for cosmetics, toothpaste, and antiseptics manufacturing. Imidazolium-based ILs have been also evaluated through developmental toxicity, which is addressed to study fetal development and maternal toxicity of animals, preferably rats and rabbits. In 2008, Bailey et al.191 evaluated the prenatal exposure of mice to 1-butyl-3-methylimidazolium chloride ([C4mim]Cl) at high concentration of 225 mg kg−1 d−1 and found morphological defects, indicating the negatively effect of such compounds on the embryonic development. Then, Bailey et al.192 reinforced the developmental toxicity of 1-alkyl-3-methylimidazolium chloride ([Cnmim]Cl) by studying the influence of the alkyl chain of such ILs ([C2mim]Cl, [C4mim]Cl and [C10mim]Cl). Results showed that [C4mim]Cl and [C10mim]Cl seem to be more harmful, which corroborates with many works that concluded about the influence of alkyl chains.

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IONIC LIQUIDS TUNABILITY Food additives or ingredients with targeted physical properties are increasingly in demand for manufacturing high quality standardized products in the food industry. In the context of innovation, and considering the potential of ILs as additives, solvents, catalysts, or supporting mediums for bioprocesses, they are good choices for product and process design. This means that new ILs could be readily synthesized from the right choice of a pair of ions in order to optimize their physical properties. Therefore, their properties can be intentionally modified through it. This is what several authors in the literature call “tunability”.193−195 The tunability of ILs has been the subject of several studies in order to evaluate the effect of the chemical structure of their ions on their physical properties, such as viscosity,196−198 density,199,200 melting temperature,26,41,201 solubility,195,202,203 surface tension,204,205 and conductivity.206 Despite the existence of a considerable number of studies involving the tunability of ILs, there is still a high number of ILs to be discovered, taking into account the possible combinations of cations and anions, as well as the formulation of new ILs through binary or ternary mixtures,1,130 representing almost one quintillion of new ILs with different properties. In this scenario, the physical properties of ILs composed of natural ions, with particular interest in the food industry, are still few explored. Therefore, they are the major focus of the following sections, even though the most common ILs, such as those with imidazolium cations, have been widely studied in food and bioproduct processes. Viscosity and Solubility. In the context of bioprocesses, some authors have been recently evaluating the tuning of viscosity and solubility of ILs by using natural ions in their synthesis. In the case of food processes, the properties adjustment should be focused on enhancing IL biocompatibility with food matrices and/or with biocompounds of interest. In this context, some works have shown that the adjustment of IL properties by using ions from natural sources can promote enhancing process yields. For example, cholinium and amino acid ions have presented interesting extraction abilities in the case of phenolic compounds.20 Almeida et al.199 used acetate ions (a derivative of GRAS acetic acid) to design ILs with more favorable viscosity, density, and surface tension profiles by using different common cations, such as N,N-dimethyl-N-ethylammonium and 1-ethylimidazolium, 1-ethyl-3-methylimidazolium, 1-butyl-3-methylimidazolium, and 1-butyl-1-methylpyrrolydinium. They found promising solvents for biomass dissolution, depending on the cation used. Hou et al.40 also used cholinium and amino acidic ions (lysine, glycine, alanine, serine, phenylalanine, tryptophane, proline, and glutamic acid) in order to synthesize ILs with a higher solubility ability and favorable viscosity profile for lignin extraction. Although low viscosity ILs are considered more efficient solvents for extraction processes,30,109 high viscous ILs can be also used by dissolving them in other solvents, especially in water. This promotes the reduction of viscosity, leading to enhanced 5357


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ACS Sustainable Chemistry & Engineering yields, depending on the concentration of the mixture.20 Mixtures of cholinium-based ILs with water are good examples in this context, taking into account systems with lower viscosity and also lower toxicity, especially due to their high solubility in water.55,183 On the other hand, hydrophobicity of choliniumbased ILs can be also altered by the right choice of the anion. This is the case of perfluoroalkanoate anions as recently reported by Patinha et al.183 in which such ILs were used for the design of purification processes based on aqueous biphasic systems. Remarkably, aqueous solutions of ILs are quite interesting, taking into account water safety for food processes and its low cost. Critical Micellar Concentration. ILs with hydrophilic and hydrophobic moieties tend to self-organize in a solution, at a given concentration, in different micelles structures, e.g., spherical, cylindrical, hexagonal, or bilayers. Such self-assembling profiles can be determined by critical micellar concentration (CMC).41 The self-assembling ability of amphiphilic compounds is a valuable resource for the food industry. On the basis of this property, they can be used as emulsifiers, stabilizers, or encapsulation agents for the formulation of many foods such as mayonnaise, dairy drinks, bakeries, ice creams, and flavorings. The determination of CMC values indicates the surfactant ability of the compound, and the lower the CMC value is, the higher their ability to form micelles is. The tunability of CMC is related to size effects for both anions and cations as well as to the presence of unsaturations in the structure of the compound. According to some works, the CMC values for ILs decrease as the alkyl chain increases207−209 and can also increase in the presence of unsaturation.41 Furthermore, this property can be enhanced by mixing or using blends of amphiphilic surfactants with different chain sizes, especially different alkyl chain lengths as reported for common surfactants.210 CMC is also an important parameter for the optimization of extraction processes. Aqueous solutions of [Cnmim]-based ILs (with n = 10 to 14) were recently used for the extraction of pepper from piperine at different concentrations above and below the CMC values.65 According to the authors,65 the self-aggregation of the ILs in micelles was relevant since higher extraction yields (4.0% w/w) were obtained above CMC values when compared to that obtained at lower concentrations (0.2% w/w). Melting Profile. One of the most important properties for the design of ILs in the food industry is usually the melting temperature. The relative low ILs’ melting point, in comparison to inorganic salts, is related to structural and charge effects.211 Basically, the asymmetry and long length of the cation could decrease the intermolecular interactions and the corresponding energy of cohesion, consequently diminishing their melting temperatures. Increasing the temperature range in which ILs can be at the liquid state is one of the most important features from a manufacturing point of view. In this state, it can be easily transported and handled and also more suitable for mixing with food matrices. In the case of ILs formed by natural ions, the melting profile of fatty acid-based ILs41,44,212,213 have been well evaluated, showing a similar behavior when compared with their origin compounds. It is known that fatty acids with longer alkyl chain length have higher melting temperatures than those with shorter ones. On the other hand, the increase in the degree of unsaturation decreases the melting temperature proportionally. However, their properties could be significantly changed with the cationic component, promoting new electrostatic interactions and hydrophilic−lipophilic balance profiles.41 This could be quite

interesting in the case of using them as emulsifiers in the production of chocolate, biscuits, or other fatty-based foods. The evaluation of the melting profile of ILs and their mixtures with other solvents requires an accurate study of the solid−liquid equilibrium (SLE).212,214 The method of differential scanning calorimetry (DSC) has been used by many authors for the study of SLE of pure ILs,24,215,216 IL-based products,217−220 and IL mixtures,26,206 being the most efficient method for determination of transition temperatures. Other methods, such as infrared spectroscopy, first reported by Pudney et al.213 on the characterization of stearate-based ILs mixtures, and microscopy have been also applied. The characterization of ILs and their mixtures using DSC consists in the determination of enthalpies and temperatures for both solid−liquid and solid−solid transitions158 by means of sequential cooling−heating cycles with low rates. This is important in order to create a quasiequilibrium state, to delete the thermal history of the sample, in the case of polymorphism of the solid phase, and to determine the most thermodynamic stable profile during the melting analysis taken in the last heating ramp. A typical thermogram, with the most common thermal events, in the case of ILs is presented in Figure 3.

Figure 3. Schematic thermogram obtained by DSC representing possible thermal events for ILs during their solid−liquid transitions. SS, solid−solid; SLC, solid−liquid crystal; LC, liquid crystal; L, liquid.

An interesting event observed during the melting profile of some ILs is the formation of liquid crystalline phases, which gives rise to what authors in the literature called ionic liquid crystals (ILCs). Such mesophases have a high potential for technological applications in the food industry. Above the solid-phase melting temperature, some ILs, especially those with long alkyl chains, tend to form crystalline structures with a nonisotropic liquid state.221 The presence of electrostatic interactions promotes the formation of stable mesophases with direct influence on physicochemical properties.222 This enhances their thermal stability, in comparison to conventional ILs,223 their non-Newtonian profiles and viscosity, which is interesting in emulsifying or tribological applications,34,224,225 and their conductivity values.26,41 According to Pogodina et al,.225 mesophase transitions (solid− liquid crystal and liquid crystal−liquid transitions) can be evaluated by DSC (Figure 3). The authors studied the characterization of three imidazolium-based ILs by DSC and found two phase transition peaks for 1-tetradecyl-3-methylimidazolium tetrafluoroborate ([C14mim][BF4]) and 1-tetradecyl-3-methylimidazolium hexafluorophosphate ([C14mim][PF6]), corresponding to solid−liquid crystal and liquid crystal−liquid phase transitions. More detailed studies on phase transitions of ILs presenting crystalline structures can be performed by using polarized light 5358


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ACS Sustainable Chemistry & Engineering optical microscopy (POM).27,41,212,214 Through this technique, the liquid crystalline phase range above melting temperatures can be determined. Typical textures indicate the structure of mesophase, typically lamellar, hexagonal, or cubic ensembles. This kind of study is quite important, taking into account the applicability of ionic liquid crystals as additives, since it depends on the type of crystalline structure. This is the case of 2-hydroxy ethylammonium oleates and stearates, for example. Such fatty acid-based ILs tend to show bilayered lamellar structures above melting temperature with a marked non-Newtonian behavior.41,212 Also, they can present hexagonal structures in mixtures with polar or nonpolar substances, which is interesting for the formulation of surfactants or microcapsules of bioactives. DSC is also applied for determining solid−solid transitions below melting temperature. ILs can present solid−solid transitions with different polymorphic structures, which is the case for 1-methyl-1-propylpyrrolidinium hexafluorophosphate ([C3mpyr][PF6]), 1-methyl-1-propylpiperidinium hexafluorophosphate ([C3mpip][PF6]), tetrabutylammonium hexafluorophosphate ([N4444][PF6]), and tetrabutylphosphonium hexafluorophosphate ([P4444][PF6]).26 The influence of temperature in the formation of polymorphic structures is especially important for the development of additives since products with different mechanical behavior require specific time−temperature expositions in order to promote the formation or disruption of specific polymorphs.158 Determining the melting temperature profile for mixtures of ILs and other compounds could be necessary for designing products and solid-phase extractions. Mixtures with tris(2-hydroxy ethyl)ammonium salts and fatty acids, for example, have shown an interesting liquid crystalline profile that is useful in the case of formulating soaps24,212,213 or design fatty acid separation processes in liquid media. The use of N,N′,N″,N‴-hexadecyltrimethylammonium bis(trifluoromethylsulfonyl)imide ([C16tma][NTf2]) is another example in this case. This IL was successfully employed for the production of food flavor esters.13 This is because its melting temperature (64 °C) is higher than the temperatures of the final step of the process (20, 10, and 4 °C), leading to its recovery by crystallization. Recently, some works in the literature have shown that mixtures of ILs could be an interesting alternative for the adjustment of melting temperatures and other properties. Through this strategy, new ILs, i.e., ILs formed by two or more cations and/or anions, are synthesized, presenting new properties profiles. Considering the set of ILs known to date, information about the phase behavior of ILs mixtures is still scarce.206 Binary mixtures of ILs have their physical properties directly related to anion−cation interactions and composition, in particular, the liquid-phase temperature range, and viscosity. These changes play an important role for process design. Fox et al.206 reported the property profile for binary mixtures of N-alkyl-N-methylpyrrolidinium bis(trifluoromethanesulfonyl)imide ILs. According to the authors, similar cation structures did not lead to a decrease in the melting temperature of the mixture, but shorter alkyl chain length resulted in mixtures with higher conductivity. Maximo et al.26 reported the reduction of the melting temperatures of hexafluorophosphate-based ILs by formulating binary mixtures with the same anion and showed that mixing ILs is an alternative for generating ionic liquids from solid salts. Rheology and Food Properties. Mechanical and sensorial properties of food products are quite affected when submitted to different shear stresses. In fact, most such products exhibit

marked non-Newtonian profiles. Therefore, taking into account the utilization of ILs in the food industry, the comprehension of their rheological behavior is relevant for designing new applications. Nevertheless, studies on the evaluation of ILs’ viscoelasticity are scarce and mostly focused on ILs reported as toxic.226−228 In the case of these ILs, Wang et al.27 showed that long alkyl chain lengths, such as presented in 1,3-didodecylimidazolium tetrafluoroborate [C12C12im][BF4], are the inducers for the appearance of a non-Newtonian profile due to the tendency to the formation of liquid crystalline structures. In this way, works on rheology and phase behavior of ILs based on natural compounds, such as those presenting a liquid crystalline profile, are to date highly expected. The 2-hydroxy ethylammonium oleates are a single example. They show a unique non-Newtonian rheological profile, taking into account the temperature due to the formation of very stable mesophases.41 Food products shelf life and sensorial quality, as well as the flow, mass, and heat transfer processes in which they are submitted, are a straight function of their physical properties and their rheological and phase behavior. Thus, in the perspective of future works on ILs based on natural ions, possibly applicable in the food industry, Valencia-Marquez et al.131 suggested that their design could be more effectively accomplished through a simultaneous study of the processes in which they will be used. This is because such an interaction is important information for the technical and economic viability of the project.

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PROSPECTS Surfactants and Lubricants. Several research studies about the micelle-forming ability (amphiphilic characteristic) of ILs were published mostly since 2004,229 being a field still little explored. IL-based surfactants can present low values of CMC, which makes them more efficient in modifying the interfacial tension of the system. Also, their ionic profile can interfere in the balance between electrostatic and hydrophobic interactions, leading to important changes in the micellar structure.230 According to some authors,41,207,208 the amphiphilic character of some ILs, such as imidazolium-based ILs,207,209,231 fatty acidderived ILs,41 and other ILs with long chains,208 is relevant to considered them as a new group of surfactants. The prospects to produce IL surfactants compatible for food are based on natural ions with surfactant ability and lower toxicity. Future studies should be focused on their emulsifying ability in oil + water model systems and more complex mixtures. By presenting low CMC values, the emulsification of a system can be achieved using low concentrations of ILs.207−209 This is quite important since surfactants can be added in low concentrations according to food legislation. In fact, emulsifiers are used to improve texture, stability, softness, aeration, and shelf life of foods. Therefore, the surfactant ability and electrostatic profile of ILs suggest that they could improve the thermodynamic stability of emulsions, modify the crystallization profile of the oil droplets, and influence the coalescence process of fat globules. Besides their properties as surfactants, some ILs, such as imidazolium-225 and phosphonium-based ILs,232 have a frictionreducing ability with high thermal stability. In this context, 1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide ([C2mim][TFSI]) and 1-butyl-3-methylimidazolium iodide ([C4mim]I) were successfully used as lubricants with lower ecotoxicity and higher biodegradability than conventional lubricants,29 such as the petroleum derivatives. Nevertheless, when aiming the design of more safe and more efficient lubricants for the food industry for sanitary plants accessories, 5359


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is an expensive and important antioxidant (∼$US 320/mg). 1-Propylamine-3-methylimidazolium bromide ([C3NH2mim]Br) presented the higher extraction efficiency (80 μg of astaxanthin/g of dried shrimp), which is 66% higher compared to extraction by using pure ethanol. Lateef et al.91 used 1-(2-cyanoethyl)-3methylimidazolium bromide ([CyanoC2mim]Br) and 1-propyl3-methylimidazolium bromide ([C3mim]Br) in recovering fats from discarded foods. Bica et al.71 explored the dissolution of fruit peels (as previously discussed in the Extraction Processes Section), a largescale waste in the juice industry, and a high valuable source of nutritional substances by using 1-ethyl-3-methylimidazolium acetate ([C2mim][CH3COO]). Wang et al.88 used cholinium and amino acid−based ILs for the extraction of flavonoids from citrus peels.88 Garcia et al.89 extracted suberin from corks, which is a waste from the wine industry, using cholinium- and imidazolium-based ILs. The process was based on biomass dissolution at high temperatures. Cholinium hexanoate ILs presented the higher extraction efficiency (65% w/w), which was a promising IL considering their sustainable character when compared to imidazolium-based ILs and conventional solvents. Qin et al.87 used ILs for the extraction of vitamin E (tocopherol) from deodorizer distillate, a food waste obtained from the refining process of vegetable oils. ILs composed of 1-butyl-3-methylimidazolium ([C4mim]) cation and different anions, such as acetate ([CH3COO]), tetrafluoroborate ([BF4]), and hexafluorophosfate ([PF6]), were evaluated. 1-Hexyl-3methylimidazolium acetate ([C6mim][CH3COO]) was considered the best solvent with a high selectivity value of 108.23. Ni et al.57 used cholinium- and amino acid-based ILs as solvents for the same case (as previously discussed in the Extraction Processes Section), also containing good results. Antimicrobial and Enzymatic Activity. The antimicrobial properties of some ILs could be studied to inhibit or decrease the growth rate of pathogens and spoilage microorganisms in foods, ensuring high quality and safe products production. Some imidazolium- and pyridinium-based ILs, depending on their alkyl-chain length, presented efficient antimicrobial activity for Gram-negative and -positive bacteria as well as for fungi.31 According to the authors, these ILs are similar or better than cetyltrimethylammonium chloride (CTAC), commonly used as an antimicrobial agent against Gram-positive microorganisms. Pernak et al.165 studied the antimicrobial activity of ILs with 3-alkoxymethyl-1-methylimidazolium as the cation against cocci, bacilli, and fungi. The authors also showed that the increase in the alkyl length of the cation increased their antimicrobial activity. Being an unexplored field, more efficient sanitizers could be formulated using ILs with good antimicrobial properties. The increase in the kinetic of enzymatic reactions, as well as the enzymatic stability, is another target of few studies in the literature involving ILs but with promising and relevant results. Processes involving enzymes generally lead to high-cost production and purification steps. Because of this, the surfactant ability of ILs has been evaluated for enhancing enzyme activity and stability,32,248−251 while avoiding industry waste production due to the possibility of recycling such catalysts.252 Ventura et al.32 developed an aqueous solution formed by 1-decyl-3methylimidazolium chloride ([C10mim]Cl), whose self-aggregation ability and micelle formation were the key to increasing the activity of Candida antarctica lipase B enzyme. Another example is the production of food flavoring esters13,253−255 by fermentative processes. This is the case of ethyl acetate, naturally formed during beer manufacturing, and one of those responsible

valves, or pumps, further studies on renewable ILs have to be performed. Recently, ILs derived from fatty acids,233,234 amino acids,235,236 and saccharin (sweetener)237 have been reported as efficient lubricants for low friction and wear. Surfactant and lubricant properties are related to the formation of liquid crystalline structures. When submitted to a determined shear stress/strain value, the interactions and orientation of the molecules can be changed, influencing their rheological characteristics. In this context, imidazolium-based ILs225 and ammonium-based ILs41 revealed a complex shear stress/strain flow. Although there are many studies available in the literature about the physical properties of ILCs,214,238,239 their rheological behavior is far from being fully evaluated in order to determine their application in industrial processes. Solubility Enhancer. Another interesting application of ILs in the food industry is the modification of the solubility of food ingredients, especially in the case of low water-soluble biocompounds, such as dyes, vitamins, flavors, and essential oils. In recent approaches, ILs were reported as solubility enhancers for hydrophobic biocompounds. Claudio et al.240 evaluated the solubility of vanillin and gallic acid in water by using 22 different hydrotropes, among imidazolium-, [N4444]-, and [P4444]-based ILs and [Ch]Cl. The solubility was enhanced up to 46 times for [C4mim]Cl at 303 K when compared to common Na-based hydrotropes, such as sodium citrate Na[C6H5O7], sodium benzoate Na[C7H5O7], sodium thiocyanate Na[SCN], and sodium dyacianamide Na[N(CN)2]. Shamshina and Rogers241 successfully used ILs as solubility enhancers of poorly soluble pharmaceutical components, such as transdermal systems. An active pharmaceutical presents better absorption when at a liquid state, taking into account the body temperature. In this work, ILs promoted the decrease in the melting temperature of the system, enhancing chemicals solubility. These results suggest that food matrices can be modified in order to enhance not only the solubility of biocompounds but also their nutraceutical ability by improving their biodisponibility in body. Biofunctionality. Recently, physical properties of mixtures of cholinium-based ILs and phenolic compounds were evaluated.242−244 Their very low melting point and possible low toxicity suggest their potential for use in the food industry as additives due to their multifunctional character by presenting high solvent and nutraceutical ability as antioxidants and acetylcholinestearase inhibitors.245 Such deep eutetic mixtures have been reported as good extractants,242−244,246 especially in the case of mixtures of cholinium-based ILs, such as [Ch]Cl, and hydrogen bond donors, such as phenols and poly(carboxylic acid)s.243 Their use as extractants could avoid purification steps of the extract steam being a potential functional product for food and bioproducts industries. Treatment of Food Industry Waste. The use of ILs in the treatment of food industry waste is another possible application that is still little evaluated. The efficient management of the waste produced by food processing is still a challenge for industries. Also, the reduction in production costs with the reuse of waste has encouraged the development of processes to recover bioactive compounds. Passos et al.20 reported that ILs can be successfully employed for the extraction of value-added compounds from biomass. In the context of the food industry, Bi et al.90 studied the performance of imidazolium-based ILs in ethanol in the UAE of astaxanthin from shrimp waste. In fact, seafood processing produces a considerable amount of waste with values above 50% of the weight of the initial product.247 Shrimp waste presents a high concentration of astaxanthin that 5360


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synthesis of food additives and design of products with better physical and sensorial properties.

for sensorial quality. However, their synthesis could be also induced. Gubicza et al.254 reported the good performance of 1-butyl-3-methylimidazolium hexafluorophosphate ([C4mim][PF6]) as a reaction media of an enzyme-catalyzed esterification of acetic acid in the presence of ethanol. In this case, ILs could avoid a significant drawback of this process, in which the enzymatic activity could be impaired in acidic media. Lozano et al.13 synthesized geranyl acetate and neryl propionate by using N,N′,N″,N‴hexadecyltrimethylammonium bis(trifluoromethylsulfonyl)imide ([C16tma][NTf2]). The IL biocatalyst could be also easily recycled by centrifugation and cooling below IL melting temperature. Taking into account these results, biocatalysis using ILs is still an unexplored field for building more efficient methods and synthesis of specific biocompounds for the food industry.

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AUTHOR INFORMATION

Corresponding Author

*Fax: + 55 19 3521 4027. Tel: + 55 19 3521 4097. E-mail: [email protected]. Notes

The authors declare no competing financial interest. Biographies

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FINAL REMARKS Considering works to date, the future applications of ionic liquids in the food and bioproducts industries seems to be quite promising. Despite this, there is a relevant demand for denoting them as nontoxic additives. This is because toxicological studies still present large gaps, especially those concerning toxicity toward mammals or human cells, among a list of requirements suggested by the FDA in order to use them in food processes. To deal with such a claim, ILs based on ions obtained from natural sources, such as cholinium, amino acids, organic acids derivatives, and other biocompounds, have emerged. Some works have considered them as nontoxic or less toxic than common ILs, such as imidazolium derivatives. Besides this, many authors have also proved that, due to the biocompatibility of these renewable ILs with organic systems, they can be more efficient in several applications, as well as for the replacement to conventional ILs or other common solvents. Among the set of biobased ILs reviewed in this work, those synthesized with the acetate and amino acid anions, as well as ILs based on the cholinium cation, seem to be the most promising compounds for extraction and determination of phenolic compounds, terpenes, essential oils, and value-added biocompounds from vegetable and food waste matrices. Also, they are expected to play an important role in the pretreatment of sugar cane bagasse and corncob for the production of bioethanol. An opportunity for their application in the production of biodiesel based on food matrices is still open since works have focused on exploring conventional ILs. Despite that imidazolium-based ILs have been mostly employed in food processes, they have presented toxicological concerns, and thus, they are not recommended for their application in the food industry. ILs have shown that their tunable character, achieved by the right choice of a cation−anion pair or by the formation of IL mixtures, could induce better properties in order to meet food quality standards. Also, their ionic characters have shown that some properties, especially for food application, such as surfactant and solvent ability and viscoelasticity, are improved when compared to common additives. The recent advances have also proven that the great potential of ILs for food and biocompound processes and product formulation is still unexplored. This means that, inspired by the more recent works showing their solubility-enhancing ability, antimicrobial and biocatalytic profile, emulsifying character, use in treatment of food waste, and for increasing enzymatic activities, future studies are highly demanded. Moreover, considering an infinite number of natural biocompounds potentially used as a cation−anion pair, these results should encourage the synthesis of new nontoxic and possible edible ILs. This could enlarge their applications not only for bioprocesses but also for

Ariel A. C. Toledo Hijo is currently a Ph.D. student in food engineering at the University of Campinas (Unicamp), Brazil, working at the Extraction, Applied Thermodynamics and Equilibrium (ExTrAE) laboratory at the same university. He graduated as a food engineer at the Federal University of Lavras (UFLA), Brazil, in 2014, and he obtained his master’s degree in food engineering at Unicamp, in 2016. His master’s thesis was on phase equilibrium of systems composed of new ionic liquids based on lipidic compounds and the application of such compounds in the food industry. In 2012, he worked at the ́ Department D’enginyeria Quimica of the University of Barcelona (UB), Spain, as a visiting intern researcher. His current research focus is on thermodynamics applied to the development of bioproducts and synthesis of ionic liquid crystals obtained from natural sources. He published six papers in international scientific journals. His research interest is on the application of renewable ionic liquids, suitable for the production of biochemicals and biofuels for the food and bioproducts industries, as well as the study of the phase equilibrium of systems based on such compounds.

Guilherme J. Maximo is professor doctor of the School of Food Engineering, University of Campinas, Brazil, since 2015 and researcher of the Extraction, Applied Thermodynamics and Equilibrium (ExTrAE) laboratory at the same institution. His bachelor and doctoral degrees were obtained at the same school. He received the award for best 5361


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ACS Sustainable Chemistry & Engineering academic performance in 2005 granted by the Regional Council of Engineering and Architecture. During his doctoral period, he worked in the Process and Applied Thermodynamic (PaTh) group at University of Aveiro, Portugal, administered by Prof. João A. P. Coutinho, were he established links between ionic liquids and food processing. His main works have been focused on phase equilibrium of food systems, especially considering solid and semisolid mixtures, applied to the modeling of food processes and formulation. In this context, he has been working on mechanical and physicochemical properties of ionic liquids synthesized by natural compounds for applications in the food industry.

Antonio J. A. Meirelles is a full professor and the director of the School of Food Engineering of University of Campinas (Unicamp), Brazil, where he is also one of the heads of the Laboratory of Extraction, Applied Thermodynamics and Equilibrium (ExTrAE). He obtained his Ph.D. degrees in process engineering at Technische Hochschule Merseburg (nowadays part of the Martin Luther Universität), Germany, in 1987, and in economic sciences at Unicamp, in 1997. He has published over 200 papers in international scientific journals, eight book chapters, and six patents awarded/applied. He has received distinguished awards for his work, including Young Scientist Award (1989) from the National Council for Scientific and Technological Development (CNPq) and Top Ethanol Award (2013) from national sugar mill companies. He has research experience on phase equilibrium and separation processes, acting on the following subjects: vapor−liquid, liquid−liquid, and solid−liquid equilibrium of fatty systems and aqueous solutions, distillation, liquid−liquid extraction, adsorption, vegetable oil refining, alcoholic distillation, and purification of biomolecules.

Mariana C. Costa is currently a professor and researcher at the School of Chemical Engineering at University of Campinas (Unicamp), Campinas, Brazil. She graduated as a chemical engineer at the School of Engineering of Lorena at the University of São Paulo in 2002. She obtained her master’s (2004) and Ph.D. degrees both in chemical engineering at the School of Chemical Engineering of Unicamp. During her Ph.D., she stay attached to the University of Aveiro, Portugal, and to the Université de Pau et des Pays de l′Adour, France, as a part of her Ph.D. research. After her Ph.D. conclusion, she started a postdoctoral project at the School of Food Engineering of Unicamp until 2011 when she started as a professor at School of Applied Sciences at Unicamp in Limeira, Brazil. Her main research interests are on thermodynamics, particularly the study of solid−liquid equilibrium of fatty compounds, including biodiesel. Currently, she is the author and coauthor of 25 journal papers, publishing mainly in the area of phase equilibrium.

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ACKNOWLEDGMENTS The authors thank the national funding agencies CNPq (National Council for Scientific and Technological Development) (133152/ 2014-6, 483340/2012-0, 305870/2014-9, 309780/2014-4, 406856/2013-3), UNICAMP/PAPDIC (Project number 12516) and FAPESP (Research Support Foundation of the State of São Paulo) (2014/03992-7, 2012/05027-1) for financial support and scholarships.

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