Understanding the Structure and Properties of Cholinium Amino Acid

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Understanding Structure and Properties of Cholinium-Amino Acid Based Ionic Liquids Lourdes del Olmo, Isabel Lage-Estebanez, Rafael Jose Lopez, and Jose M Garcia de la Vega J. Phys. Chem. B, Just Accepted Manuscript • DOI: 10.1021/acs.jpcb.6b06969 • Publication Date (Web): 12 Sep 2016 Downloaded from http://pubs.acs.org on September 12, 2016

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The Journal of Physical Chemistry

Understanding Structure and Properties of Cholinium-Amino Acid Based Ionic Liquids Lourdes del Olmo, Isabel Lage-Estebanez, Rafael López, and José M. García de la Vega∗ Departamento de Química Física Aplicada, Facultad de Ciencias, Universidad Autónoma de Madrid, 28049 Madrid, Spain E-mail: [email protected] Phone: +34 (0)91 4974963

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Abstract The molecular structure of novel ionic liquids based on cholinum-amino acids (ChAAILs) has been analyzed. Polarization charge density for all ion pairs has been examined as a function of the hydrophobicity of the anion. The COSMO σ-profiles and σ-potentials have been obtained and used to interpret the chemical behavior of ChAAILs. Some physicochemical properties such as density and viscosity have been estimated using COSMO-RS method. Furthermore, the polarization on the molecular structure, physicochemical properties and hydrophobicities have been evaluated. Finally, the results obtained have been compared with experimental data.

Introduction Ionic liquids (ILs) are molten salts which are liquid below 100 ◦ C and whose interest in the scientific community is growing due to their unique characteristics such as low vapor pressure, renewable character, and high thermal and chemical stability 1–4 among others. They show remarkable properties as disolvents which make them a good green alternative to the organic solvents. Thus, they have been recognized as green solvents. Although some of them are toxic, 5 they can be considered to be environmentally benign, with large potential benefits for sustainable chemistry. 6 Biodegradation of ILs has been studied by several authors. 7–10 Moreover, different reactions have been studied using biodegradable ILs. 11,12 Recently, ILs consisting of quaternary amines as cations have drawn attention of the scientific community and are being object of continuous research. One particular case of quaternary amine is choline cation which is an essential nutrient for humans. 13,14 Therefore, choline cation is a good candidate to produce ILs of relatively low toxicity 15 and highly biodegradable 16 when combined with appropriate anions. Also, reactions of graphene and reactions with carbon nanotubes have been studied using the choline as cation. 17 ILs formed of α-amino acids as anions have been synthesized, and their electronic properties have been analyzed. 18–22 The combination of choline cation and the carboxylic func2


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tional group of AAs as anion results in a type of advanced ILs which are known generically as ChAA-ILs. 23 Some ChAA-ILs can be synthesized in good yields but require considerable time. Tao et al. 24 proposed the mechanism of formation for four ChAA-ILs from choline chloride, although first synthesis of these novel ILs was made by Moriel et al. 25 Previous investigations on ILs as antimicrobial and antitumor agents have been focused on ILs based on cations as imidazolium and pyridinium. 26,27 Currently, the choline cation combined with α-amino acids as anions are being investigated in studies against breast cancer. 28 In addition, these systems are used in the enzymatic extraction and biocatalysis. 29 In order to investigate the molecular structure of these compounds and its relation with their physicochemical properties, methods of Computational Chemistry can be combined with the COnductor-like Screening MOdel for Realistic Solvation (COSMO-RS) method. 30,31 Previous studies with different ILs have demonstrated the capabilities of this procedure in the prediction of physicochemical properties in the liquid phase and the analysis of their dependence on the molecular structure and interactions. 32–34 This work is focused on the analysis of the structure and some outstanding physicochemical properties of ChAA-ILs formed by choline as cation and α-amino acids as anions. For this purpose, a theoretical analysis of the molecular structure has been carried out for twenty ion pairs, and some physicochemical properties like density and viscosity have been estimated by COSMO-RS at room temperature. Polarity and hydrophobicity have also been analyzed and have been compared, also with results obtained at a different computational level 35 and with experimental data 24,36,37 when available.

Methods and computational details Full geometries have been optimized at DFT level. In all cases, the absence of imaginary frequencies in optimized structures has been checked. The calculations have been made using the B3LYP functional. 38–40 In order to test the effect of dispersion in structures and esti-

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mations of the physicochemical properties, further calculations have been performed using Grimme’s dispersion treatment with the original D3 damping function. 41 All calculations have been carried out with the 6-311+G** basis set. 42,43 This is a triple zeta basis set including polarization functions for all atoms, and difuse functions 44 for heavy atoms. 45 All calculations have been carried out using Gaussian09 package, 46 and stabilization energies have been corrected from the Basis Set Superposition Error by using the CounterPoise method. 47 In spite of its use is controversial, in this case it is justified by the application of diffusion functions. 48 Also, an analysis of their chemical behavior and predictions of physicochemical properties have been made within the COSMO model framework. Density and viscosity have been estimated by COSMO-RS method at room temperature using COSMOtherm program. 49 In this case, BP_TZVP_C30_1201 parameterization level has been chosen for estimating these properties.

Results and discussion Conformational analysis Twenty systems have been selected to analyze their molecular structures, taking as starting point the background acquired by our group in this type of studies. 32–34 In addition, the effect of dispersion on these molecular structures has been evaluated. All the systems considered in this work are composed of choline as cation and α-AAs as anions. Although many AAs are currently known, only twenty of them are codified by standard DNA molecules. Figure 1 (a) shows the molecular structure of choline cation and Figure 1 (b) represents the general structure of AA anions. There are different classifications for AAs although only two types have been considered in this work. First, according to their origin, they are classified as essential and non-essential. Essential AAs are considered those that cannot be synthesized in our body and must be obtained from diet. These are: arginine (Arg), phenylalanine (Phe), histidine (His), isoleucine 4


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(a) Choline cation

(b) AA anion

Figure 1: General molecular structure of ChAA-ILs (Ile), leucine (Leu), lysine (Lys), methionine (Met), threonine (Thr), tryptophan (Trp), valine (Val). On the other hand, non-essential AAs are those that can be synthesized in the body from other substances. This group includes: alanine (Ala), asparagine (Asn), aspartic acid (Asp), cysteine (Cys), glutamic acid (Glu), glutamine (Gln), glycine (Gly), proline (Pro) serine (Ser), tyrosine (Tyr). The other classification of the AAs considered herein is based on the hydrophobicity function of their lateral chain. 50,51 Hydrophobic AAs are inside the protein core and they do not ionize nor participate in the formation of hydrogen bonds, unlike hydrophilic AAs which are often involved in the formation of hydrogen bonds and are on the surfaces of proteins. All molecular structures of the ChAA-ILs have been optimized using the functional B3LYP and the functional B3LYP-D3 for taking into account the dispersion in the calculation (see Figure S1 in Supporting Information (SI)). In this figure the orientation of the carboxylic group AA to the hydroxyl group of the cation is similar in all cases irrespective when dispersion is considered (see “B3LYPD3” column) or not (see “B3LYP” column). All ion pairs show this behavior except ChAla and ChGly. An example of the different orientation betwen two ion pairs (ChAla and ChAsn) is shown in Figure 2. A dispersion energy around 50 kJ.mol−1 in the optimization process using B3LYP-D3/6-311+G** is found. Thus, these results confirm that the molecular structure is sensitive to the dispersion in the calculations. Figures 2 (a), (c) show the molecular structures of ChAla and ChAsn optimized without dispersion, whereas Figures 2 (b), (d) are the corresponding structures when dispersion is taken into account.

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Figure 2: Optimized molecular structure for (a) ChAla - B3LYP/6-311+G**, (b) ChAla - B3LYP-D3/6-311+G**, (c) ChAsn - B3LYP/6-311+G**, (d) ChAsn - B3LYP-D3/6311+G** Table 1 collects the most significant geometrical parameters for all molecular structures and includes the data reported by Benedetto et al., 35 using a different functional (M062X/D3), for comparison. The most significant distances are d(OAA OCh ), d(OAA NCh ), and angle θ(OAA HOCh ) for all ChAA-ILs. In Table 1, geometrical parameters obtained using Grimme’s dispersion are printed in boldface. For all ChAA-ILs, the difference of the distance values between ions -d(OAA OCh )- yielded by both methods is around 2-3 Å, unlike the difference of the distances d(OAA NCh ) that is less than 1 Å. Different distances between ions and orientations are observed. For most ChAA-ILs, θ(OAA HOCh ) is close to 170 ◦ , both with and without dispersion, although high differences can be found in five cases: ChAla, ChAsp, ChCys, ChGly and ChPhe. In particular, a maximum difference of 90

◦

in the values of this

angle is found for ChGly. In this case, the difference is due to the different orientation of the carboxylic group AA towards the hydroxyl group of the cation. The effect of dispersion on the interaction energy and dipole moment is shown in Table 2, (results with dispersion again boldfaced). The interaction energy is defined as the difference of the total electronic energy between the ChAA and its separated ions, ∆Eint = EChAA − (ECh + EAA ). Results for these systems of interaction energy are found between 20-60 kJ.mol−1 when dispersion is taken into account in the calculation, and 5-15 kJ.mol−1 when 6


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Table 1: Geometrical parameters: distances [Å] and angle [◦ ] of ChAA-ILs using B3LYP/6-311+G** (up), B3LYP-D3/6-311+G** in boldface (bottom) and data reported by Benedetto et al. 35 using M06-2X/D3 ChAA-IL ChAla ChArg ChAsn ChAsp ChCys ChGln ChGlu ChGly ChHis ChIle ChLeu ChLys ChMet ChPhe ChPro ChSer ChThr ChTrp ChTyr ChVal

d(OAA OCh ) 2.74 4.05 2.65 2.58 2.76 2.75 2.66 3.82 2.64 3.75 2.64 2.69 2.61 2.61 2.61 4.42 2.63 2.65 2.61 2.63 2.61 2.65 2.72 2.72 2.61 2.66 2.66 3.51 2.73 2.65 2.66 2.61 2.74 2.66 2.73 2.66 2.74 2.74 2.61 2.64

da (OAA OCh ) 2.68 2.72 2.74 2.70 2.70 2.69 2.70 2.68

d(OAA NCh ) 4.26 3.44 4.08 4.76 4.38 4.27 4.12 4.63 4.66 4.66 4.68 4.91 4.64 4.59 4.61 3.78 4.70 4.65 4.62 4.20 4.60 3.99 4.29 4.23 4.60 4.33 4.05 4.73 4.21 4.03 4.07 4.59 4.03 3.93 4.33 4.12 4.27 4.27 4.61 4.14

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da (OAA NCh ) 3.28 3.36 3.41 3.33 3.36 3.32 3.34 3.28


θ(OAA HOCh ) 165 121 170 171 168 161 170 108 172 110 172 175 172 169 172 82 170 162 172 171 173 168 165 160 173 163 169 114 163 168 169 169 153 165 167 170 165 165 172 170

θa (OAA HOCh ) 166 166 166 165 162 165 163 166


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it is not. Moreover, maximum difference around 8 D in dipole moment is observed. Most data reported by Benedetto et al. 35 yield values different from our estimations showing a maximum difference around 10 D for ChAsn.

Chemical behavior ChAA-ILs The chemical behavior of these ChAA-ILs has been analyzed in terms of the σ-potential of the ion pairs. This potential was obtained from the σ-profile, which is related to the polarization charge density over the cavity of each ion pair, according to COSMO methodology in the ion pairs model. 32–34 Most proteins have a hydrophobic core that is inaccessible to the solvent, and a polar surface in contact with the aqueous medium. Hydrophobic AAs tend to accumulate in the nucleus of the protein, whereas hydrophilic AAs tend to remain on the surface so that they keep contact with the solvent. Different classifications of AAs are found in the literature depending on the author. 50,51 Nonetheless, the most common division of AAs is based on their preference to be in aqueous solution or not. Betts and Russell 50 arrange AAs according to the hydrophobic character as highly hydrophobic AAs, less hydrophobic AAs, and AAs containing both hydrophilic and hydrophobic parts. The miscibility of ILs in water often depends more on the solubility of the anion than in that of the cation. 52 Therefore, in this work ChAA-ILs have been arranged according to the hydrophobicity of AA. Polarization charge distribution AA solubility mainly depends on the nature of their side chain, so that, if this is ionizable, the AA will be more soluble than if it is not. AAs with non-polar chains are: Ala, Ile, Leu, Met, Phe, Trp, Val. The side chains of Ala, Ile, Leu, Val are aliphatic; and those of Met, Phe, Trp, are aromatic. AAs with polar chains are: Arg, Asn, Asp, Gln, Glu, Lys, Ser, Thr. On the one hand, Arg, Asp, Glu, Lys are charged; on the other hand, Asn, Gln have amide 8


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Table 2: Interaction energy [kJ.mol−1 ], dipole moment [D] of ChAA-ILs using B3LYP/6-311+G** (up), B3LYP-D3/6-311+G** in boldface (bottom), and data reported by Benedetto et al. 35 using M06-2X/D3 ChAA-IL ChAla ChArg ChAsn ChAsp ChCys ChGln ChGlu ChGly ChHis ChIle ChLeu ChLys ChMet ChPhe ChPro ChSer ChThr ChTrp ChTyr ChVal

a ∆Eint

∆Eint -419.0 -454.4 -408.2 -453.5 -378.8 -403.3 -417.7 -398.5 -425.4 -412.2 -387.2 -429.4 -411.3 -436.8 -433.3 -414.1 -419.7 -430.1 -423.5 -449.6 -423.5 -454.3 -414.6 -443.1 -416.8 -431.9 -416.8 -412.0 -418.3 -452.4 -418.4 -444.2 -380.7 -432.7 -410.7 -467.9 -405.6 -413.8 -425.1 -453.2

-443.1 -446.4 -438.9 -443.1 -395.0 -434.7 -445.2 -438.1

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µ 12.1 8.4 16.0 10.4 17.4 16.8 11.7 11.6 10.9 11.0 18.2 10.6 15.1 14.6 12.9 11.5 8.7 9.8 13.3 12.9 13.2 12.8 13.4 12.9 13.2 11.6 13.0 11.7 12.1 12.3 13.8 13.4 13.7 11.1 12.9 11.2 12.6 13.2 13.1 11.9


µa 11.1 6.9 4.8 7.6 15.2 11.1 8.0 11.1


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side chains which make them very polar; Ser, Thr are hydroxyamino because they have a hydroxyl group giving them the ability to form hydrogen bonds. Finally, Cys, His and Tyr are AAs with an ambiguous polarity. Cys and His have a pKa close to neutral pH and they can be charged (His) or not (Cys) according to the pH of the medium in which it is located. Tyr can be considered less polar despite the hydroxyl group due to the electron resonance of the aromatic ring which reduces its dipole moment. Gly and Pro are considered as special AAs because Gly has no side chain, and Pro is an imino acid that forms a pyrrolidine ring with its own side chain. In this work, two groups of ChAA-ILs have been considered. A group of AAs with nonpolar character (hydrophobic) and another group of AAs with polar character (hydrophilic). According to COSMO model, polarization charge over the cavity of each ion pair allows us to predict their chemical behavior. 30 Figure 3 shows the polarization charge in case of hydrophobic AAs when dispersion is taken into account with Grimme’s treatment, and Figure 4 displays it for hydrophilic AAs. The difference on the polarization charge distribution over the surface of the cavity, caused by the polarity of the side chain of each AA, is appreciated in these figures. The region of negative polarization charge (blue) is susceptible to attack by nucleophilic reagents whereas regions with positive values (red) are not because of the presence of electronegative atoms. More blue regions can be observed for hydrophobic AAs (Figure 3) than for hydrophilic AAs (Figure 4). Plots corresponding to both cases when dispersion is not considered can be found in Figures S2 and S3 of the SI. No significant differences can be found when dispersion is taken into account and when it is not.

Figure 3: Polarization charge density for hydrophobic AAs using B3LYP-D3/6-311+G**. The polarities of the cavity can be negative (blue), neutral (green) and positive (red )

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Figure 4: Polarization charge density for hydrophilic AAs using B3LYP-D3/6-311+G**. The polarities of the cavity can be negative (blue), neutral (green) and positive (red ) Choline cation and AA anions are combined to form ChAA-ILs. Thus, ChAla, ChGly, ChIle, ChLeu, ChMet, ChPhe, ChPro, ChTrp, ChTyr and ChVal are ChAA-ILs based on hydrophobic AAs. And ChArg, ChAsn, ChAsp, ChCys, ChGln, ChGlu, ChHis, ChLys, ChSer and ChThr are ChAA-ILs based on hydrophilic AAs. Figure S4 (see SI) shows similar polarization charge density for all ChAA-ILs using both computational levels. σ-profile and σ-potential The σ-profiles are obtained from polarization charge densities. In the case of ChAA-IL their shape greatly depends on the nature of the lateral chain of each AA. Figure 5 (a) shows the σ-profiles of ion pairs formed by the choline cation and hydrophilic AAs, whereas those corresponding to ChAA-ILs based on hydrophobic AAs are displayed in Figure 5 (b). ChAA-ILs composed of hydrophobic AAs display values significantly greater than those of hydrophilic AAs in the central region of the histogram. This area among 0.000-0.010 e/Å2 is characteristic of non-polar surfaces. The existence of aromatic rings in the molecular structure causes higher intensities in this region, 53 which is typical of more hydrophobic compounds. This behavior is observed with more intense peaks at 0.006-0.012 e/Å2 in the Figure 5 (b). Figure S5 in SI shows σ-profiles when dispersion is not considered in computation. When both methods are compared, we can be observe that the peaks in Figure 5 are less intense with respect to the peaks obtained without dispersion in Figure S5. Further insight on the chemical behavior of ChAA-ILs, as well as estimations of their physicochemical properties, can be attained from the σ-potential which is obtained from 11



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Figure 5: σ-profiles for water and ChAA-ILs based on (a) hydrophilic AAs, and (b) hydrophobic AAs using B3LYP-D3/6-311+G** the σ-profile. All σ-potentials of ChAA-ILs show a similar shape, which can be interpreted as an attractive behavior with negative charge density surfaces and hydrogen bond donors. However, some ChAA-ILs have repulsive behavior with negative charge density surfaces (nucleophiles), whereas other do not. The fact that in all cases σ-potential shows the same behavior with respect to hydrogen bonding donors involves a decrease in hydrophobic character with respect to AA not combined. Thus, in these cases an increase in solubility is observed. The σ-potentials of ChAA-ILs consisting of hydrophilic AAs are displayed in Figure 6 (a). Only one cross with the σ-potential of water is found. Although all ion pairs show the same behavior, ChAA-ILs formed by acid AAs (negatively charged) show less negative potentials than those based on basic AAs (positively charged). Thus, the lower ability to interact with hydrogen donors is predicted to occur for ChThr when dispersion is taken into account in calculations (B3LYP-D3/6-311+G**), and for ChAsp and ChGlu when it is not 12


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(B3LYP/6-311+G**) (see Figure S6 in SI). This makes them more hydrophobic than for the basic AAs. Potentials corresponding to ChAA-ILs formed by AAs with non-charged polar chains appear between those of acid and basic systems.

Figure 6: σ-potentials for water and ChAA-ILs based on (a) hydrophilic AAs, and (b) hydrophobic AAs using B3LYP-D3/6-311+G** The σ-potentials of ChAA-ILs consisting of hydrophobic AAs are depicted in Figure 6 (b), besides that of water. The shape of σ-potential is similar except for ChAla and ChTyr when dispersion is considered and only for ChTyr when it is not (see Figure S6 in SI). Tyr AA has an ambiguous polarity that is affected by the electronic resonance of the aromatic ring. This AA behaves like little polar despite having a hydroxyl group. ChAA-ILs based on AAs with an aromatic ring show a σ-potential with less negative values than ChAA-ILs based on AAs with aliphatic chains. Therefore, ChAA-ILs based on AAs with an aromatic ring have more hydrophobic character and less interaction with hydrogen bond donors than ion pairs based on AAs with aliphatic chains.

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Density and viscosity Some physicochemical properties have been estimated using COSMO-RS method. In this regard, it is useful to classify ChAA-ILs, according to the nature of the chain of AA, as: aliphatic, cyclic (imino acid), containing at least one carboxyl group or sulfur, acids and other amides, aromatic, and basic. Estimations of density and viscosity are compared with experimental data 24,36,37 found in the literature in order to evaluate the predictive capability of this methodology in such systems. Figure 7 collects estimations of the molar volume with COSMO-RS method using B3LYP/6-311+G** and B3LYP-D3/6-311+G** besides experimental data. 37 Estimations of molar volume with and without dispersion in the calculation yield values comparable to experimental data. 37 Thus, results show a linear relationship between molar volume and molecular weight. Therefore, the same relationship appears between our density estimations and molecular weight.

Figure 7: Molar volume for ChAA-ILs as function of their molecular weight including experimental data 37 Values of density and viscosity predicted by COSMO-RS with B3LYP-D3/6-311+G** are collected in Table 3. That shows that the density is predicted within the range 1.05-1.20 g.cm−3 , which is the same interval reported by De Santis et al. 37 Hydrogen bond interaction can explain the high values of density, as Tao et al. 24 reported for ChGly. Aliphatic and basic ChAA-ILs show low lying values of density, except for ChHis which has ambiguous 14


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polarity. Additional calculations of density from molecular structures reported by Benedetto et al. 35 have been performed using COSMO-RS method. These predictions on density result closer to our estimations. Maximum differences of 0.009 g.cm−3 and 0.027 g.cm−3 have been observed in comparison to our estimated density using B3LYP/6-311+G** and B3LYPD3/6-311+G**, respectively. Estimations of the density using B3LYP/6-311+G** show results similar to those with B3LYP-D3/6-311+G** except for the viscosity (see Table S1 in SI). Table 3: Experimental density [g.cm−3 ] and viscosity [cP], and estimations by COSMO-RS method arranged in category for ChAA-ILs using B3LYP-D3/6311+G** Category

Aliphatic

Cyclic Containing hydroxyl group or sulfur Acids and other amides Aromatic

Basic

ChAA-IL ChAla ChGly ChIle ChLeu ChVal ChPro ChCys ChMet ChSer ChThr ChAsn ChAsp ChGln ChGlu ChPhe ChTrp ChTyr ChArg ChHis ChLys

ρ 1.086 1.120 1.027 1.022 1.039 1.118 1.176 1.120 1.147 1.106 1.150 1.188 1.150 1.168 1.132 1.195 1.181 1.121 1.170 1.046 a b

ρaexp 1.130 1.156 1.068 1.052 1.138 1.180 1.145 1.201 1.143 1.204 1.152 Ref. 37 Ref. 36

η 62 3164 106 114 83 100 2966 217 1082 75 438 55662 331 12792 3179 4668 36258 6372 614 444

a ηexp 720 1230 11200 7980 9810 31200 4300 12500 55300 7063000 187000

b ηexp 163 121 480 476 372 500 330 402 454 1903 2060 2589 2308 520 5640 1002 980 460

A general trend for viscosity is found in its rise with the increase of the anion size. This fact can be interpreted in terms of dispersion forces that are highly dependent on the system size. Moreover, very different experimental values (and, in some cases, most striking) have 15



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been reported for the same compound, which gives an idea of the difficulty of measuring this property. Liu et al. 36 reported a range of viscosities at room temperature from 121 cP to 5640 cP, unlike 182-11544 cP and 720-7063000 cP reported by Tao et al. 24 and De Santis et al., 37 respectively. ChAA-ILs based on simple anions (ChAla and ChGly) show low lying experimental viscosities of 163 cP and 121 cP, respectively. 36 Viscosity estimated by COSMO-RS for ChAla (58 cP) and ChGly (60 cP) are also the low lying values with a difference greater than 60 cP in comparison to experimental data 36 when dispersion is not considered (see Table S1 in SI). When a hydroxyl group is added to the anion (ChSer), it causes strong hydrogen bond interactions producing higher viscosities. Table 3 collects viscosity estimated when dispersion is taken into account in the calculations. Liu et al. 36 reported the highest viscosity for ChTrp (5640 cP) but this compound does not correspond to the ChAA-IL with the greatest value estimated by COSMO-RS (ChTyr), although both belong to the aromatic category. Tao et al. 24 reported the highest viscosity for ChSer (11544 cP), and De Santis et al. 37 found it for ChHis (7063000 cP). This proves the disparity in experimental data.

Conclusions The molecular structure of twenty ILs based on cholinium-amino acid has been analyzed. Also, the effect of including dispersion in the calculations has been examined for all them. In all cases, the orientation of the carboxylic group of the AA towards the hydroxyl group of the cation is similar except for ChAla and ChGly. An analysis of their geometrical parameters confirm their geometric similarity except for ChAla and ChGly. Dipole moment is similar among them around 12 D whether dispersion is taken into account or not in the calculation except for ChIle, and in the case of ChAla with dispersion. Differences in the values of interaction energy are found showing a dispersion energy around 50 kJ.mol−1 . Negligible differences with respect to experimental data are observed.

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ChAA-ILs have been classified as hydrophobic and hydrophilic depending on the nonpolar or the polar character of the anion, respectively. Polarization charge distribution over the surface of hydrophobic ChAA-ILs show more area of values close to zero than in case of the hydrophilic ChAA-ILs. The σ-profile of ChAA-ILs displays significant differences depending on their hydrophobicity showing an increase of intensity in the central region of the σ-profile in the case of ChAA-ILs based on hydrophobic AAs. The analysis of σ-potential suggests that the chemical behavior is the same for all ChAA-ILs, independently of the hydrophobicity of the anion. Low values of density are reported for ChAA-ILs whose side chain is aliphatic. Viscosity increases with the size of the anion. Similar results in density are observed whether dispersion is taken into account or not. Density estimated with COSMO-RS results close to the experimental data revealing that COSMO-RS is suitable for estimating the density of ChAA-ILs. This is not the case of viscosity, where significant differencies between theoretical predictions and reported experimental values are found. Nevertheless, given the high discrepancies between experimental values themselves, we conclude that more reliable (experimental) references will be necessary to test the actual quality of the theoretical predictions.

Acknowledgement The authors thank the ”Ministerio de Ciencia e Innovación” (Project: CTQ2010-19232) and ”Comunidad de Madrid” (Project: LIQUORGAS-S2013/MAE-2800) for financial support. We also acknowledge CCC-UAM for computational facilities.

Supporting Information Available • Optimized molecular structures of ChAA-ILs using B3LYP/6-311+G** and B3LYPD3/6-311+G**; Polarization charge density for hydrophobic AAs and hydrophilic AAs 17



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using B3LYP/6-311+G**; Polarization charge density for ChAA-ILs using B3LYP/6311+G** and B3LYP-D3/6-311+G**; σ-profiles and σ-potentials for ChAA-ILs based on hydrophilic AAs, hydrophobic AAs using B3LYP/6-311+G**; Experimental density and viscosity, and estimations by COSMO-RS for ChAA-ILs using B3LYP/6-311+G** This material is available free of charge via the Internet at http://pubs.acs.org/.

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An estimation of properties of ChAA-ILs, like density and viscosity using quantum chemical calculations, the effect of dispersion on these properties and the chemical behavior as a function of the hydrophobicity of the amino acid involved have been analyzed.

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Understanding the Structure and Properties of Cholinium Amino Acid

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