Health benefits provided by omega-3 polyunsaturated fatty acids (PUFAs), including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in particular are noteworthy to the society as it reduces the risk of cancer, autoimmune, cardiovascular disease, inflammatory disorders, cystic fibrosis, disrupted neurological function, bowel disease, and mental illness [1
]. The use of PUFA as health prospects has gained great attention in last years. Current dietary health organization recommends a daily intake of 250–500 mg of EPA + DHA for primary and secondary prevention of coronary heart disease [7
]. Additionally, according to Shahidi and Ambigaipalan human bodies requires the supplementary sources of EPA and DHA as they are vulnerable to shortages of necessary enzymes to place a double bond at the omega-3 position and hence are unable to synthesize them to a sufficient extent [9
]. Those are one of the two classes of essential fatty acids that have such characteristics and therefore must be taken from diet and supplements. Thus, the external source of omega-3 PUFA is necessary.
Lately, the main supply of both EPA and DHA are provided from fish, however, the intake of fish oil for long period may cause a deficiency of vitamin E due to the high level of vitamin A and D involved in fish lipids [10
]. Many harmful contaminants such as methylmercury, copper, and organic pollutants as polychlorinated biphenyls (PCBs) or dioxins are also found in some species of fish especially in salmon, sardine, anchovy, and tuna, which may impose toxic effects on human health [11
], and therefore, alternative sources of omega-3 PUFA are required. Microalgae oil and fish oil have the same amount of omega-3 but microalgae oil has more advantages in terms of health and less toxicity compared to fish oil [13
]. The oil derived from microalgae contains squalene and phytosterols, which indicates several health benefits to the human body and it not having an unpleasant smell and cholesterol. The process of converting microalgae into omega-3 PUFA mainly consists of four steps, including microalgae cultivation, harvesting, cell disruption (lipid extraction), and transesterification (GC/FID analysis). There are numerous methods that have been used for lipid extraction, but most of them using conventional solvents, which are mostly volatile, aromatic, thermally unstable, and environmentally unfriendly, in addition to causing health and safety problems [14
]. For instance, the use of solvents such as hexane or isopropanol in Soxhlet extraction likewise chloroform, methanol, and water in the Bligh and Dyer method (both methods are considered to be the most widely used techniques for lipid extraction) introduced a few concerns due to the toxicity associated with the solvents that brings biosafety issues and is required to be replaced by environmentally friendly, biocompatible, and less toxic solvents.
Therefore, solvent extraction using ionic liquids (ILs) are preferable and has potential in the extraction of the microalgae lipids as an alternative to traditional solvents that use toxic solvent, long duration time, and demand a huge amount of energy [15
]. In solvent extraction, it is crucial to have high capacity to extract the targeted solute. ILs are salts with low melting point and consist of large asymmetric organic cations and smaller organic or inorganic anions [16
]. The cations of ILs are generally composed of nitrogen contacting ring like imidazolium, pyrrolidinium to which different functional groups can be added [17
]. Additionally, ILs are often considered to be “green” solvents because of their very low vapor pressure, great thermal stability with a broad electrochemical window, and high ionic conductivity compared to conventional solvents [18
]. In a study by Pan et al. [19
], the microwave-assisted extraction with [BMIM][HSO4
] as IL was observed to have higher yield rather than the conventional method of oil bath using an organic solvent for the extraction of lipid from Nannochloropsis salina
, Chlorella sorokiniana,
and Galdieria sulphuraria
. Moreover, Kim et al. [20
] used the mixture of IL like [BMIM][CF3
] with methanol to extract lipid (biodiesel purpose) from microalgae C.vulgaris,
which obtained 19%. According to the literature, ILs in general have prominent advantages over organic solvent like hexane, chloroform, however, there are only a few studies available to use ILs for extraction of long chain fatty acids such as EPA and DHA. It is noticeable that using ILs for processing is costly and time-consuming, and thus a reasonable screening of different cations and anions combination is obligatory prior to selecting the appropriate ILs. Therefore, it seems crucial to predict ILs behavior before the experimental application. The conductor like screening model for real solvent (COSMO-RS) proposed by Klamt is a model that can be used for such fast prior prediction [21
]. COSMO-RS is a new method to predict the thermodynamic properties of fluid and liquid mixture based on quantum chemistry concept of density functional theory (DFT) [23
]. Chosen the suitable IL for the extraction efficiency, some thermodynamic properties are important. The solvent capacity, selectivity at infinite dilution and performance index was used many times by previous studies for solvent liquid-liquid extraction prediction, which was calculated under the activity coefficient at the infinite dilution. For instance, Mansoure et al. [24
] used the COSMO-RS tool for the prediction of ammonium ILs capacity and then selectivity values for β-carotene separation from n-hexane. Additionally, the study reported by Zeeshan et al. [25
] COSMO-RS software used for the calculation of activity coefficient at infinite dilution and then selectivity, capacity, and performance index to predict different types of ILs potential for asphaltene extraction as a part of liquid-liquid extraction. Moreover, in a recent study by Xing et al. [26
], it has been used COSMO-RS for prediction and exploring the potential separation mechanism of long chain fatty acids (EPA, DHA, CLAs, OA, and SA) through the calculation of different solvents capacity, selectivity, and performance index values. In another study, adjustable parameters were re-optimized in COSMO-RS to fit for the systems containing ionic liquids (ILs), whereby a vast numbers of activity coefficients and at infinite dilution and CO2
solubility were collected from references and used as a training set. The results showed that the predicted results by COSMO-RS model with the new optimized parameters are in agreement with experimental data [27
]. As pointed out by previous literatures, COSMO-RS only require the structural information of interacting species in order to calculate their related thermodynamic properties through a set of defined mathematical equations and hence one does not need to perform any experimentations in advance [28
]. It is noteworthy to mention that, although COSMO-RS is a powerful screening tool, this software has been addressed by a number of authors as a mean field model that does not account for solvent molecular structure and correlations. Therefore, it is suggested that when using COSMO-RS, the important effects of explicit interactions between organic molecules and water, which can lead to charge transfer between the solute and water, must also be considered [30
While the ILs screening potential seems crucial for extraction of omega-3 (EPA, DHA and ALA) compounds from biomass, however to the best of the author’s knowledge, no significant report has been published yet to concern the application of COSMO-RS in that particular regard. Therefore, this study strictly help and open a new horizon about ILs interaction toward valuable omega-3 compound for researchers who seek to replace the conventional solvent with proper green solvent (ILs) without any requirement to perform expensive and time consuming lab experimentations. Moreover, what makes the COSMO-RS screening even more valuable is that it provides the facility to study over the variety of 352 combination of cations and anions as ILs to act as solvents in interaction with EPA compounds.
In this study, COSMO-RS has been used as the screening methodology to select the most suitable ILs as a part of solid-liquid extraction of EPA from microalgae. This work aims to predict infinite capacity values of ILs for EPA extraction and without the use of any experimental data.