Local ion hydration structure in aqueous imidazolium-based ionic liquids: The effects of concentration and anion nature

Accepted Manuscript Local ion hydration structure in aqueous imidazolium-based ionic liquids: The effects of concentration and anion nature

Marina V. Fedotova, Sergey E. Kruchinin, Gennady N. Chuev PII: DOI: Reference:

S0167-7322(17)33137-9 doi:10.1016/j.molliq.2017.09.087 MOLLIQ 7924

To appear in:

Journal of Molecular Liquids

Received date: Revised date: Accepted date:

13 July 2017 8 September 2017 20 September 2017

Please cite this article as: Marina V. Fedotova, Sergey E. Kruchinin, Gennady N. Chuev , Local ion hydration structure in aqueous imidazolium-based ionic liquids: The effects of concentration and anion nature. The address for the corresponding author was captured as affiliation for all authors. Please check if appropriate. Molliq(2017), doi:10.1016/ j.molliq.2017.09.087

This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

ACCEPTED MANUSCRIPT Local Ion Hydration Structure in Aqueous Imidazolium-Based Ionic Liquids: The Effects of Concentration and Anion Nature Marina V. Fedotova*1, Sergey E. Kruchinin1, and Gennady N. Chuev2 1

G.A. Krestov Institute of Solution Chemistry, the Russian Academy of Sciences, Akademicheskaya st., 1, Ivanovo, 153045 Russia

2

Institute of Theoretical and Experimental Biophysics, the Russian Academy of Sciences, Institutskaya st., Pushchino, Moscow Region, 142290 Russia

RI PT

*Email address: [email protected] (M. V. Fedotova)

The effects of concentration and anion nature on the ion hydration structure in aqueous imidazolium-based ionic liquids (IL), [EMIM][EtSO4], [EMIM][Cl], and [EMIM][Gly], were

SC

studied using integral equation theory in the one- and three-Dimensional Reference Interaction Site Model (1D- and 3D-RISM) approaches. The concentration behavior of ion hydration has

NU

been examined for the [EMIM][EtSO4]-water mixture. It was found that the main concentration effect is in significant dehydration of both the cation and the anion with increasing IL content

MA

from 0.005 M to 4.714 M. At the same time, at low IL content all ions under study are well hydrated with stronger interactions between the anions and water in comparison with the cation and water. The obtained data indicate strengthening of anion-water interactions in the sequence

PT E

D

[EtSO4]– < [Gly]– < [Cl]–.

AC

CE

Key words: ionic liquid; aqueous solution; ion; hydration structure

1

ACCEPTED MANUSCRIPT Introduction Among various ionic liquids (ILs), the biocompatible ILs capable of affecting the structural state and functioning of biocompounds attract special interest. Such ILs are expected to act as effective reaction medium for biochemistry or as a mediator for biochemical reactions as well as to dissolve proteins, carbohydrates, enzymes, and DNA. Some of these ILs, including imidazolium-based ionic liquids, have high hydrophilicity. They can mix with water in all proportions, so that their physical properties change depending on the amount of water. It has

RI PT

been established that the hydrophilic ILs are able to raise the solubility of proteins and peptides in aqueous solutions, to change enzyme selectivity and reaction efficiency. In aqueous media the hydrophilic ILs dissociate into individual ions which are involved in the hydration process. Ion hydration is crucially important in many biological and biochemical

SC

phenomena including folding/unfolding of proteins and formation of their native structure. For example, the ability of some imidazolium-based ILs to stabilize the native protein structure in

NU

aqueous solution has been found (see [1, 15]). It is assumed that in aqueous solutions of hydrophilic ILs the stability of proteins including enzymes as well as the activity, reactivity, and

MA

enantioselectivity of proteins depend on the nature of the cation and anion of IL. For some cases this dependence is defined by the Hofmeister series assigned to an establishing of the ability of ions to stabilize the protein structure. According to this series, the ions are divided into

D

kosmotropes with strong hydration properties (or structure-makers increasing the structuring of

PT E

water) and chaotropes with the weak hydration properties (or structure-breakers decreasing the structuring of water). Kosmotropes are supposed to stabilize proteins because they the formation of a strong hydrogen bond network including the water molecules, resulting in a decreased

CE

solubility of the hydrophobic parts of the protein, whereas chaotropes often unfold protein structure. From these positions the Hofmeister series can be considered as a classification of ions by the degree of their hydration. It was found (see, for instance, [15]), that the ions-stabilizers

AC

(such as kosmotropic anions) having the stronger interactions with water molecules than with proteins, do not have the direct interactions with proteins but only through water layer. As a result, they are preferentially hydrated by water molecules instead of interacting directly with the protein / enzyme surface and, thus, generally excluded from protein / enzyme surfaces. It means that the features of hydration of various ions in ILs composition can play an important role in the stabilizing effect ILs on proteins. Another factor that can affect protein functionality in aqueous media is the IL content that determines the ionic strength of solution. The change in the concentration of aqueous IL solution (and, correspondingly, in the ionic strength of solution) has a direct link with the changes in ion hydration. The features of this process in a wide concentration range are different and connected 2

ACCEPTED MANUSCRIPT with a balance of various interparticle (water-water, ion-water, ion-ion) interactions. The effect of concentration of imidazolium-based IL on the stabilization of the native structure of proteins is under intensive discussion in literature (see, for example, [15, 20-24]). Some authors indicate that the stabilization of the protein structure is possible only in aqueous solutions with low IL content [22]. At the same time, according to [21], proteins are able to keep their structure in some aqueous solutions of biocompatible ILs up to high IL content. As it was established in [23], [EMIM][Cl] was found to have the largest effect on the protein structure.

RI PT

The physical and chemical behavior of the imidazolium-based ILs is a subject for active studies during recent decades. The main attention in the literature is directed to their acoustic, thermophysical, volumetric, transport, or dielectric properties and to water structural state or ion association in these IL-water mixtures as a function of the ion (as a rule, the cation) nature or IL

SC

concentration [8, 25-31]. At the same time, the ion hydration structure in aqueous biocompatible ILs in itself as well as the effect of IL concentration or nature of IL ion (especially, the anion) on

NU

this hydration structure have been little studied. There are only a few papers on the structural parameters of ion hydration for these ILs [38-41]. To fill this gap we have investigated the

MA

mixtures of water and three ionic liquids with the 1-ethyl-3-methylimidazolium cation, [EMIM]+, and [Cl]–, [EtSO4]–, [Gly]– anions. These ILs are characterized by high hydrophilicity and the ability to stabilize the native structure of the protein. Note that [EMIM][Gly] belongs to

D

the class of ILs functionalized with amino acids.

PT E

To this end we have performed statistical mechanics calculations in the framework of the integral equation theory (IET) in 1D- and 3D-RISM (Reference Interaction Site Model) approaches. These methods provide detailed information about the solute–solvent interactions in

CE

terms of statistically averaged site–site radial distribution functions (RDFs), or molecular (ion)atom spatial distribution functions (SDFs). RISM-IET is a good method to investigate solvation phenomena including the hydration of ions and molecules or association phenomena including

AC

the ion-ion binding in aqueous solutions of ILs (see, for instance, our previous papers). We should also note that there are a set papers devoted to study of ILs with use of RISM / 3D-RISM theory [52-54] and hybrid approaches such as the self-consistent field coupling of RISM methods (RISM-SCF) (see, for instance, [55-61]. Despite they do not touch the objects and a subject of our study, nevertheless these papers demonstrate a good description of various chemical phenomena in the ILs (for instance, the hydrolysis of cellobiose [55], the glucose transformation [56], proton-transfer reaction [58], the solvent structure of neat IL [52, 54] or in IL-carbon dioxide mixture [57] as well as transport and relaxation properties of ILs [60]). The advantages of RISM-IET in comparison with other computational techniques such as MD simulations are in its low computational requirements and fast calculations. 3

ACCEPTED MANUSCRIPT Method and computational details The basic concepts of 1D- and 3D-RISM methods are well known (see, for example [62-72]). Therefore, we give only a brief outline of the aspects necessary for the purposes of this study. The basis of 1D-RISM theory is the site-site (atom-atom) Ornstein–Zernike equation [62]. For the solute (u) –solvent (v) correlations it can be written as uv hαβ ( r ) = ∑ωαγu ( r ) ∗ cγµuv ( r ) ∗ ωµβv ( r ) + ρβ hµβvv ( r ) ,

(1)

γ ,µ

ρ

v ωµβ ( r ) and ωαγu ( r ) are the intramolecular

is an average density of solvent;

RI PT

where

uv uv correlation functions of solvent and solute, respectively; hαβ (r ) and cαβ (r ) are the total and

direct site-site correlation functions of sites (atoms) α and β belonging to the molecules u and

SC

v. The symbol (*) denotes the integral convolution. The RDFs and the total correlation functions are connected as gαβ (r ) ≡ hαβ (r ) + 1 . uv

uv

NU

To make Eq. (1) complete a closure relationship is required. We have used the partially linearized hypernetted chain closure proposed by Kovalenko and Hirata (KH closure) . With the

MA

RISM/KH method the convergence of the numerical algorithm is more stable

and the

convergence rate is increased. The KH closure takes the form

(

)

uv uv exp dαβ (r ) , dαβ (r ) ≤ 0  gαβ ( r ) =  uv uv (r ) > 0 . dαβ 1 + dαβ (r ),

(2).

PT E

D

uv

uv uv uv uv dαβ (r ) = − βUαβ (r ) + hαβ (r ) − cαβ (r )

Here

β = 1 kBT , kB is the Boltzmann constant and T is the absolute temperature. Uαβuv ( r ) is the

CE

potential of interaction defined by

uv uv uv Uαβ ( r )=ϕαβ ( r ) + Φαβ (r) ,

(3)

AC

uv uv where ϕαβ ( r ) and Φ αβ ( r ) are short- (Lennard–Jones) and long- (Coulomb) range parts of the

site-site interactions, respectively. uv

The RDFs gαβ (r ) are obtained by numerically solving the above coupled 1D-RISM equations (Eqs.1 & 2) describing the molecular or ion hydration. From the ion-water RDFs one can obtain the ion-water distances and partial hydration (coordination) numbers of ions. The interatomic (ion-water atom) distances, rαβ , as the most probable ion-water distances in the ion hydration shell are defined by the positions of the first maximum of g

uv

(r ) . The partial

hydration number (HN) of the ions or solute molecules is calculated as 4

ACCEPTED MANUSCRIPT nαβ = 4πρ β

rmin

∫

uv gαβ ( r ) r 2dr .

(4)

0

The partial HN is the average number of the solvent sites/atoms of kind β in a hydration shell of radius rmin i around an

α -type site/atom of the solute molecule or ion.

To estimate the strength of ion-water interactions one can calculate the ion – water potentials of mean force (PMFs). These PMFs,

Wαβuv ( r ) , are readily obtained as a logarithm of

RI PT

the solute–solvent RDFs as

uv uv Wαβ (r ) = −kBT ln gαβ (r) .

(5)

The RISM method also gives a possibility to calculate the thermodynamic characteristics of

hydration free energy (HFE) can be expressed as

uv uv = 2π k BT ∑ ρ β ∫  −2cαβ ( r ) − hαβuv ( r ) cαβ ( r ) + ( hαβuv ( r ) ) Θ ( −hαβuv ( r ) ) r 2dr , (6)

αβ

0

NU

∆G

∞

KH hyd

SC

the hydration process. In particular, within the framework of the 1D RISM / KH theory, the



2



MA

where Θ ( x ) is the Heaviside step function.

3D-RISM approach yields the three-dimensional (3D-) distribution of atoms / sites (γ) of the

D

solvent (v) atoms around the solute (u) molecule of arbitrary shape by molecular-atom (site)

PT E

uv SDFs, gγ (r ) . The calculation of the SDFs is based on the solution of the 3D-RISM Ornstein–

Zernike integral equation [66, 68]

vv hγuv ( r ) = cαuv ( r ) * (ωαγ ( r ) + ρv hαγvv ( r ) ) ,

(7)

CE

coupled with the 3D-type Kovalenko-Hirata closure relation [68]

AC

(

)

exp d uvγ ( r ) , d uvγ ( r ) ≤ 0  g γ (r ) =  uv d uvγ ( r ) > 0 , 1 + d γ ( r ) , d uvγ ( r ) = − βU uvγ ( r ) + h uvγ ( r ) − c uvγ ( r ) uv

(8).

uv uv In the formulas (7) and (8), hγ ( r ) and cγ ( r ) are, respectively, the 3D-total and 3D-direct

molecular-atom (site) correlation functions of the solvent site γ around the solute molecule; vv hαγ ( r ) is the radial site-site total correlation function of the solvent; ωαγvv ( r ) is the

intramolecular correlation function of the solvent;

ρV

is the average solvent density, and

U uvγ ( r ) is the interaction potential between the site γ of the solvent and the whole solute. The

5

ACCEPTED MANUSCRIPT asterisk in Eq. (7) means convolution in direct space and summation over repeating indices. The uv uv SDF is defined as gγ (r ) ≡ hγ (r ) + 1 .

Our calculations were carried out for IL–water systems at different concentrations (СМ([EMIM][Cl] = 0.005 mol/l; СМ([EMIM][EtSO4]) = 0.005, 1.0, 2.0, 3.0, 4.0, 4.714 mol/l; and aqueous [EMIM][Gly] solution at infinite dilution) at ambient conditions (298 K, 0.1 МPa). The modified version of the SPC/E model (MSPC/E) was used for water . The structures of [EMIM]+ and [EtSO4]– & [Gly]– were obtained by the DFT (Density

RI PT

Functional Theory) method at the B3LYP/6-31++G(d,p) level using GAUSSIAN 09 program package . The optimized geometries in the form of atom coordinates are presented in the Tables S1-S3 of Supporting Information. Figure 1 demonstrates their schematic representation with atom labeling. Note that in ILs under study, the negative charge of the anions is mainly distributed

SC

among the oxygen atoms of the sulfate-OSO3 group of [EtSO4]–, or the oxygen atoms of the carboxylate group of [Gly]– whereas the positive charge of the cation is located in the

NU

imidazolium ring. Corresponding LJ parameters and partial charges for [EMIM]+, Cl– and [EtSO4]– were taken from Ref. and for [Gly]– were adopted from Ref. .

MA

The 1D- and 3D-RISM calculations were performed using the “rism1d” and “rism3d.snglpnt” computer programs from the AmberTools package (version 14) . The numerical solution of the 1D- and 3D-RISM integral equations was found using the MDIIS (Modified Direct

AC

CE

PT E

D

Inversion in the Iterative Subspace) iterative scheme . The 1D-RISM-KH

Figure 1. Schematic representation with atom labeling for [EMIM]+ (a), [EtSO4]– (b), and [Gly]– (c). equations were solved on a 1D grid of 16384 points with the spacing of 2.5*10–3 nm with 10 MDIIS vectors. The 3D-RISM equations were solved on a 3D-grid of 256 × 270 × 256 points with 6

ACCEPTED MANUSCRIPT 4 MDIIS vectors and with the spacing of 0.025 nm. It corresponds to the parallelepiped cell of size 6.375 nm × 6.725 nm × 6.375 nm. A residual tolerance of 10–6 was chosen. These parameters are large enough to accommodate the solute together with sufficient solvation space around it so that the obtained results are without significant numerical errors.

Results and discussion 1. Effect of concentration: [EMIM][EtSO4] – water system

RI PT

The RDFs characterizing the cation and anion hydration at the lowest (0.005 mol/l) and highest (4.7 mol/l) concentrations as examples are shown in Figures 2-4. The full set of characteristic values of all these functions is listed in Tables 1 and 2. The subscript w in the text, tables, and figures below denotes water molecule. The SDFs characterizing water distribution

SC

around [EMIM]+ and [EtSO4]– are presented in Figure 5 a,с.

NU

1.1. Hydration of [EMIM]+

Imidazole ring. According to the spatial distribution of water around the [EMIM]+ cation

MA

(Fig. 5a), the water molecules are oriented to the imidazole ring by oxygen atoms. At the lowest IL concentration in the solution (0.005 mol/l), they are located at the distances of 0.300-0.313 nm and of 0.217-0.253 nm from the carbon and the hydrogen atoms of the ring, respectively

D

(Table 1, Fig. 2). Note that the rCi Ow value is in satisfactory agreement with the value of 0.32

PT E

nm obtained by MD simulation [75]. Moreover, the first peaks of the RDFs g H1Ow ( r ) are slightly shifted to the lower interatomic distances (by ~0.035 nm) in comparison with the first

g H3Ow ( r ) (Table 1, Fig. 2). As stressed in the literature , this

CE

peaks of the RDFs g H2Ow ( r ) &

fact is connected to the enhanced acidity of H1, and, therefore, the affinity for Ow, when compared to H2 or H3.

AC

At c = 0.005 M the RISM calculations for the nearest environment of the imidazole ring give, on average, ~ 4-5water molecules per each ring carbon and ~ 2-3 water molecules Hbonded with the ring per each ring hydrogen (Table 1). The total number of water molecules in the nearest environment of the ring is 15.38 (Table 1). This value is close to the hydration number of imidazole ring, 14.6, obtained by MD simulation for the diluted aqueous solution of imidazolium-based IL [35].

7

ACCEPTED MANUSCRIPT

RI PT

Figure 2. Cation-water RDFs g C1Ow (r ) & g H1Ow (r ) (a), g C2Ow (r ) & g H2Ow (r ) (b), g C3Ow (r ) & g H3Ow (r ) (c) at the lowest and highest concentrations of [EMIM][EtSO4]. Atom labeling corresponds to Figure 1a. An increase in the IL concentration to 4.7 mol/l leads to a sharp growth of the main peaks of the RDFs but without significant changes in their positions, and, respectively, in the distances

SC

between the ring atoms and water molecules (Fig. 2, Table 1). The concentration effect causes a decrease of the number of water molecules near the carbon ring atoms by 8-9 times, and of the

NU

number of H-bonds formed between the ring hydrogens and water molecules by ~ 7-8 times (Table 1). In this case, all water molecules remaining in the nearest environment of the ring are

MA

H-bonded. Our results are in agreement with the MD simulations for imidasolium-based ILs where the same concentration behavior for the ring-water RDFs and the hydration numbers was found.

D

Methyl group. The RDFs gC4Ow ( r ) and g H 4,5,6Ow (r ) describing the hydration of the methyl

PT E

group are presented in Figure 3a. The data obtained show that ~6 water molecules at an average distance of 0.333 nm are arranged in the nearest environment of the methyl group at c = 0.005 M (Table 1). An increase of the IL content to 4.7 mol/l leads to an increase of the first peaks of

CE

RDFs without the change of their positions. As a result, a number of water molecules near the methyl group decreases by a factor of ~8 (Table 1).

AC

Ethyl group. The figures 3b & 3c demonstrate the functions gC5,6Ow ( r ) , g H7,8Ow (r ) , and g H9,10,11Ow ( r ) characterizing the hydration of the ethyl group. According to the results of the calculations, at the lowest IL concentration (0.005 mol/l) the nearest environment of this group includes ~ 4-5 water molecules at an average distance of ~0.340 nm (Table 1). Under an increase of the IL content in the solution to 4.7 mol/l, one can see an increase in the height of the RDF peaks (Fig. 3b & c). As a result, a number of water molecules near the carbons of ethyl group decreases by a factor of 9 (Table 1).

8

ACCEPTED MANUSCRIPT

RI PT

Figure 3. Cation-water RDFs g C4Ow (r ) & g H4,5,6Ow (r ) (a), g C5Ow (r ) & gH7,8Ow (r ) (b), g C6Ow (r ) & g H9,10,11Ow (r ) (c) at the lowest and highest concentrations of [EMIM][EtSO4]. Atom labeling corresponds to Figure 1a. As it follows from Table 1, the distances between the water oxygens and the carbons of the

SC

methyl and ethyl groups of the cation are rather large compared to the distances rC1,2,3Ow in the

rC2Ow

nC2Ow rC3Ow

nC3Ow rH1Ow

n H1Ow rH2Ow

4.7

0.297 3.58

0.297 1.26

0.297 0.47

0.313 5.64

0.313 4.78

0.313 3.76

0.315 2.85

0.315 1.71

0.318 0.67

0.313 5.43

0.313 4.61

0.313 3.62

0.315 2.75

0.315 1.66

0.318 0.65

0.217 2.10

0.217 1.77

0.217 1.45

0.217 1.14

0.217 0.71

0.215 0.27

0.253 3.55

0.253 3.03

0.250 2.45

0.250 1.88

0.250 1.16

0.250 0.46

rH3Ow

0.250 3.32

0.250 2.77

0.250 2.24

0.250 1.72

0.248 1.08

0.248 0.44

n H3Ow rC4Ow

0.333 6.17

0.333 4.90

Methyl group 0.333 4.00

0.333 4.05

0.333 2.21

0.330 0.77

nC4Ow

0.342 3.93

0.342 3.32

Ethyl group 0.340 2.66

rC5Ow

0.342 1.83

0.342 1.11

0.342 0.41

nC5Ow rC6Ow

0.340 5.07

0.340 3.29

0.340 2.13

0.342 1.49

0.342 0.83

0.342 0.55

nC6Ow

MA

4.0

AC

n H2Ow

0.300 4.31

Concentration of IL (mol/l) 2.0 3.0 Imidazole ring 0.297 0.297 2.87 2.11

D

nC1Ow

1.0

PT E

rC1Ow

0.005

CE

Structural parameters

NU

Table 1. Structural parameters of [EMIM]+ hydration in aqueous [EMIM][EtSO4] solutions. The subscript w denotes water molecule. Atom labeling corresponds to Figure 1a.

9

ACCEPTED MANUSCRIPT case of the imidazole ring. Moreover, the total amount of water molecules in the nearest environment of the ring ( n C1Ow + n C2Ow + n C3Ow ) is much higher than near other functional groups ( n C5Ow or n C6Ow ) of [EMIM]+. In addition, one can see the accumulation of water molecules near the hydrogens of the imidazole ring from the cation-water SDFs (Fig. 5a). All these observations indicate the preferential interaction of water with the ring in comparison with other groups of the cation. This result agrees with the EXAFS spectroscopy study indicated that the interaction of water has been found to be localized at the imidazole ring hydrogen atoms that

RI PT

are able to form hydrogen bonds with water. Our conclusion is also in line with the MD simulation data for imidazolium-based IL-water mixtures , where it was shown that as the ring moiety of the cation is more polar than the alkyl tails, therefore, because of strong electrostatic

SC

interactions, favorable binding of water with the imidazole ring of the cation is observed.

1.2. Hydration of [EtSO4]–

NU

-SO4 group. As it follows from Fig. 1b, only the О1, О2, О3 atoms of the -SO4 group are able to interact with water. At the same time, О4 and S atoms can not interact with water

MA

molecules due to the steric limitations.

One can see from the spatial distribution of water around the [EtSO4]– anion (Fig. 5с) that the water molecules are oriented toward the -SO4 group by the hydrogen atoms acting as H-bond

D

donors. At the lowest IL concentration in the solution (0.005 mol/l) the distances between the

PT E

oxygens of the -SO4 group and the water oxygens or water hydrogens are 0.295 nm or 0.173 nm, respectively (Table 2, Fig. 4a). The number of water molecules in the nearest environment of the

AC

CE

-SO4 group is ~ 6 but only ~2 water molecules are H-bonded with the group (Table 2).

Figure 4. Anion-water RDFs gO1,2,3W (r ) (a), g C1Ow (r ) & gH4,5Ow (r ) (b), g C2Ow (r ) & g H1,2,3Ow (r ) (c) at the lowest and highest concentrations of [EMIM][EtSO4]. Atom labeling is corresponding to Figure 1b. An increase of the IL content in the solution leads to a small effect on the RDFs gO1,2,3O ( r ) but to an appreciable growth of the first peaks of gO1,2,3 H ( r ) (Fig. 4a) without significant changes in the 10

ACCEPTED MANUSCRIPT positions of all these peaks (Table 2). When the IL content in the solution increases to 4.7 mol/l, the number of water molecules in the nearest environment of the -SO4 group and the number of H-bonds formed by this group with water decreases by a factor of ~9.5 and ~5, respectively

SC

RI PT

(Table 2). The concentration change of H-bonds means weakening of H-bonding between

Figure 5. Spatial distribution functions of the oxygen (red) and hydrogen (white) atoms of water

NU

around: a. EMIM+ (the isodensity surfaces correspond to SDF values of g EMIM-Ow ( r ) = 3.0 &

MA

g EMIM-Hw ( r ) = 1.7); b. Cl– (the isodensity surfaces correspond to SDF values of g Cl-Ow ( r ) = 1.9 & g Cl-Hw ( r ) = 2.1); c. EtSO4– (the isodensity surfaces correspond to SDF values of g EtSO -Ow ( r ) = 3.2 & g EtSO -Hw ( r ) = 2.7); d. Gly– (the isodensity surfaces correspond to SDF values of g Gly-Ow ( r ) = 3.3 & g Gly-Hw ( r ) = 4.1). 4

4

D

the -SO4 group and water. The same result was also obtained by ATR-IR, 1H NMR

PT E

spectroscopy, and quantum chemical calculations . Ethyl group. The RDFs gC1,2Ow ( r ) , g H1,2,3Ow ( r ) , and g H 4,5Ow ( r ) characterizing the hydration

CE

of ethyl group of the anion are presented in Figure 4 b & c. At the lowest IL concentration (0.005 mol/l), the nearest environment of this group includes 4-5 water molecules distributed at the

AC

distances of 0.342-0.360 nm from the group (Table 2). These long distances indicate the hydrophobic hydration of the ethyl group compared to the -SO4 group. An increase of the IL content to 4.7 mol/l causes a decrease in the number of water molecules in the environment of ethyl group by almost an order of magnitude: from ~4 down to 0.3 in the environment of the C1 atom and from ~5.7 to ~0.7 in the environment of the C2 atom (Table 2). As we have stressed in subsection 1.1 for the cation, the distances between water and methyl or ethyl groups are rather large compared to the distances between water and imidazole ring (Table 1). One can see the same situation with the anion [EtSO4]– when the distances between the water oxygens and the carbons of the ethyl group are much larger than the distances rO1,2,3Ow in the case of the -SO4 group (Table 2). It is also indicative from Figure 5c, where the main distribution is arranged 11

ACCEPTED MANUSCRIPT Table 2. Structural parameters of [EtSO4]– hydration in aqueous [EMIM][EtSO4] solutions. Subscript w denotes water molecule. Atom labeling corresponds to Figure 1b. Structural parameters

0.005

1.0

rO1,2,3Ow

0.295

0.295

n O1,2,3Ow

5.87

4.84

3.81

rO1,2,3Hw

0.173

0.173

n O1,2,3Hw

2.16

rC2Ow

0.300

0.304

2.87

1.64

0.62

0.173

0.170

0.170

0.169

1.94

1.66

1.38

0.94

0.44

0.360 4.02

0.360 3.35

Ethyl group 0.360 2.60

0.362 1.85

0.362 0.96

0.360 0.30

0.342 5.65

0.342 5.02

0.345 4.33

0.345 3.41

0.345 1.96

0.342 0.67

NU

nC2Ow

4.7

RI PT

nC1Ow

4.0

SC

rC1Ow

Concentration of IL (mol/l) 2.0 3.0 -SO4 group 0.296 0.297

close to the -SO4 group. It means that in the nearest environment of the cation and the anion the water molecules are localized, mainly, close to the polar (charged) groups (imidazole ring and -

MA

SO4 group). This result is in line with the IR spectroscopy study where it was indicated that water is strongly bonded to [Emim][EtSO4] due to the high polarity of this IL when compared

D

with other hydrophilic ILs. Moreover, as it follows from Figure 2 and Figure 4a, the intensity of the first peaks for the anion-water RDFs is slightly higher than those observed for the cation-

PT E

water RDFs. These features were also found in the MD simulation data for this IL . This suggests stronger interactions between [EtSO4]– and water than between [EMIM]+ and water, in agreement with the results for other imidazolium-based ILs . Our suggestion is confirmed by the

AC

CE

deeper minimum of the PMF [EtSO4]–-Ow in comparison with the PMF [EMIM]+-Ow (Fig. 6).

Figure 6. Ion-water potentials of mean force for systems under study.

12

ACCEPTED MANUSCRIPT The main trend of the IL concentration effect from our study is a significant dehydration of both the cation and the anion without significant change in the size of their hydration shells. As a consequence of this effect, a possibility for ion-ion aggregation in the solution appears as it was shown in the MD simulation [41].

2. Effect of anion nature: [EMIM][X] – water system ([X] = [Cl], [EtSO4], [Gly]) 2.1. Anion hydration

RI PT

Here we present the analysis of the ion hydration structure in aqueous solutions of [EMIM][Cl] and [EMIM][EtSO4] with IL concentration of 0.005 mol/l as well as of [EMIM][Gly] at infinite dilution (the water-rich solutions).

According to the data obtained from the RDFs for the chloride ion (Fig. 7), its hydration

SC

shell has a radius of 0.338 nm and consists of 6 H-bonded water molecules retained by the OH…Cl– interactions. Strong hydrogen bonding O-H…Cl- interactions between the chloride ions

NU

and the water molecules are considered in literature as the feature characterizing the structure of imidazolium chloride ILs. The number of water molecules H-bonded with Cl- obtained by us is

MA

greater than the value of ~4.8 calculated by Car-Parinello MD simulation . However, this discrepancy can be connected with the higher concentration of IL in the mixture studied in . Moreover, the authors

are stressed that the anion hydration is not complete under IL

AC

CE

PT E

D

concentration in their study.

Figure 7. Cl–-water RDFs gCl− -W ( r ) for aqueous [EMIM][Cl] solution. The analysis of the RDFs characterizing the [EtSO4]– hydration was done in Subsection 2.1. Here we stress once again that the water molecules in the aqueous solution of [EMIM][EtSO4] interact preferably with the polar -SO4 group of the anion. The average number of water molecules in the nearest surroundings of the -SO4 group is ~ 6 but only ~2 molecules are H-bonded with this group (Table 2). 13

ACCEPTED MANUSCRIPT From the RDFs for the glycine anion (Fig. 8) we have found that the average number of the water molecules in the nearest surroundings of the –СОО– group is ~6.5 at an average distance of 0.295 nm. However, only 3 water molecules are able to form the H-bonds with the carboxylate moiety with the bond length of ~0.168 nm. At the same time, the spatial configuration of the –

СОО– group (Fig. 1с) suggests that the water molecules should be partly “collectivized” by the oxygen atoms of the carboxylate group, i.e. the water molecules will be shared by the О1 and О2 atoms of [Gly]– anion. Thus, the total number of water molecules in the nearest environment of

RI PT

the –СОО- group will not be equal to the sum of the partial hydration numbers nO1OW and

nO2OW . The nearest environment of the –NH2 group of [Gly]– anion includes ~7 water molecules at the average distance of 0.308 nm. From these waters only 3 molecules are H-bonded to this

SC

group with the bond length of ~0.180 nm. Taking into account the structural feature of the carboxylate moiety to “collectivize", the total hydration number of the glycine anion will be

NU

close to 17, which is comparable with the number ~ 16.3 obtained for [EMIM][Gly] in Ref. [31]. It is well known from the literature that in the IL/water mixtures the anion-water interactions play an important role . The anions under study possess a strong ability to keep a

MA

significant amount of water molecules in concordance with the obtained values of the anion hydration numbers. The anion-water SDFs (Fig. 5 b, c) show a uniform distribution of water

D

around the chloride ion due to its spherical shape and the preferential localization of water near

AC

CE

PT E

the -SO4 group of [EtSO4]– due to the polarity of this group. In the case of [Gly]– (Fig. 5 d),

Figure 8. Gly–-water RDFs gO1,2W ( r ) (a) and g N1W ( r ) & g H1,2W ( r ) (b) for aqueous [EMIM][Gly] solution. Atom labeling corresponds to Figure 1c. the simultaneous arrangement of water around -COO- and -NH2 groups with the prevailing distribution of water around the charged polar carboxylate moiety is observed. As it can be seen from the anion-water PMFs (fig. 6), the strength of these interactions is increased in the sequence [EtSO4]– < [Gly]– < [Cl]– that is in line with the Hofmeister series and reflects the decreasing 14

ACCEPTED MANUSCRIPT affinity of these ions for water and, thus, a decrease of the ion effect on protein stability . According to the Hofmeister series, this trend should correspond to a decrease of ion hydration anion energy . Our calculations of the hydration free energy of anions, ∆Ghyd in aqueous solutions of

[EMIM][Cl], [EMIM][EtSO4], and [EMIM][Gly] show this correspondence by means of the [EtSO ] [Gly] [Cl] series ∆Ghyd 4 ( –52.91 kcal/mol) > ∆Ghyd (–81.02 kcal/mol) > ∆Ghyd (–84.81 kcal/mol). −

−

−

2.2. Cation hydration

RI PT

The presence of the water-cation interactions in the mixtures of water with imidazoliumbased ILs having different anions are detected experimentally by the analysis of H and 13C NMR spectra and EXAFS spectroscopy data . The structural parameters of [EMIM]+ hydration in the

SC

aqueous ILs with [Cl]–, [EtSO4]–, [Gly]– anions under our study are presented in Table 3. The set of corresponding RDFs is shown in Figure 9 as an example.

NU

As it follows from the obtained data (Table 3, Fig. 5), the structural parameters of the cation hydration in aqueous solutions of ILs with various anions are very close. Moreover, the ( ∆Ghyd

[EMIM]+

MA

calculated hydration free energy of the cation is practically the same for all solutions under study ~ 14 kcal/mol). Such results were quite expected if to take into account very low

content of ILs in the systems studied here. These solutions are under high dilution and even

D

under infinite dilution (the case of [EMIM][Gly]), therefore the ions are completely dissociated

PT E

there due to their own strong hydration. As a result, in these solutions the interionic interactions are absent, and a mutual influence of counterions is practically excluded. Thus, it is not a surprise that there is no significant difference in the cation hydration structure as it follows from

CE

the data in Table 3. The absence of anion effect on the cation hydration indirectly confirms once more the complete dissociation of ions in the diluted solutions. Summarizing the results in the section 2, one can state that all ions in the IL-water mixtures

AC

under study are well-hydrated with the stronger interactions between anions and water than between the cation and water.

Figure 9. Cation-water RDFs g H1Ow (r ) (a), g C4Ow (r ) (b), and g C6Ow (r ) (c) of [EMIM]+ in imidazolium-based ILs with various anions. 15

ACCEPTED MANUSCRIPT Table 3. Structural parameters of [EMIM]+ hydration in aqueous solutions of imidazolium-based ILs with different anions. Subscript w denotes water molecule. Atom labeling corresponds to Figure 1. Structural parameter

0.300 4.30

rC2Ow

nC2Ow rC3Ow

nC3Ow rH1Ow

n H1Ow n H2Ow

0.313 5.62

0.313 5.42

0.313 5.43

0.313 5.42

0.217 2.09

0.217 2.10

0.217 2.09

0.253 3.55

0.253 3.54

0.250 3.32

0.250 3.31

Methyl group 0.333 6.17

0.333 6.14

Ethyl group 0.342 3.93

0.342 3.91

0.340 5.07

0.340 5.05

0.333 6.15

rC4Ow

nC4Ow

0.342 3.91

D

rC5Ow

MA

n H3Ow

NU

0.250 3.31

rH3Ow

PT E

nC5Ow

0.340 5.05

rC6Ow

CE

nC6Ow

0.300 4.30

0.313 5.64

0.253 3.54

rH2Ow

Gly–

0.313 5.62

RI PT

nC1Ow

SC

rC1Ow

Conclusions

Anion EtSO4– Imidazole ring 0.300 4.31

Cl–

Understanding the ion hydration in biocompatible IL-water mixtures is important for

AC

establishing of its role in some biological phenomena including stabilization of proteins or enzymes. One of the approaches to improve the protein / enzyme stability is optimization of the solvent (water) environment [39]. It can be performed by two ways [93] that connected directly with the features of ion hydration. The first possibility is to use the additives including biocompatible ILs with the corresponding tuning by the proper selection of cations and anions. This selection is often following to the Hofmeister series that define a classification of ions by the degree of their hydration. The second way is the changes in the ionic strength (concentration) of aqueous solution leading to the changes in ion hydration. The presented work touches upon both these issues and reports the effects of concentration and anion nature on the local ion

16

ACCEPTED MANUSCRIPT hydration structure for three biocompatible hydrated imidazolium-based ionic liquids, [EMIM][EtSO4], [EMIM][Cl], and [EMIM][Gly]. We have found that the water molecules in the nearest environment of the cation and anion are localized, mainly, close to the polar (charged) groups. The concentration trend exhibits a significant dehydration of both the cation and the anion as a response to the increase of IL content that was shown by the example of [EMIM][EtSO4]-water mixture. As a consequence of this effect, a possibility for ion-ion aggregation in the solution appears.

RI PT

Our results for the water-rich systems with the chaotropic [EMIM]+ cation [94] and Cl–, EtSO4–, Gly– anions have shown that all ions under study are well-hydrated with the stronger interactions between anions and water than between the cation and water. Moreover, the strength of the ion-water interactions is increased in the sequence [EtSO4]– < [Gly]– < [Cl]– that is an

SC

indication of a decrease of their kosmotropicity according to the Hofmeister series and, thus, reflects a decrease of the anion effect on protein stability. However, we should note that both the

NU

cation and the anion of an IL should act cooperatively to affect the protein stability.

MA

Acknowledgements

This work was supported by the Russian Foundation for Basic Research (grant No. 16-3350094).

AC

CE

PT E

D

Conflict of interest The authors declare that they have no conflict of interest.

17

ACCEPTED MANUSCRIPT References [1] K. Fujita, D. R. MacFarlane and M. Forsyth, Protein solubilising and stabilising ionic liquids, Chem. Commun. 38 (2005) 4804-4806. [2] M. Naushad, Z. A. Alothman, A. B. Khan and M. Ali, Effect of ionic liquid on activity, stability, and structure of enzymes: A review, Int. J. Biol. Macromol. 51 (2012) 555-560. [3] K. R. Seddon, A. Stark and M.-J. Torres, Influence of chloride, water, and organic solvents on the physical properties of ionic liquids, Pure Appl. Chem. 72 (2000) 2275-2287.

RI PT

[4] B. D. Fitchett, T. N. Knepp and J. C. Conboy, 1-Alkyl-3-methylimidazolium Bis(perfluoroalkylsulfonyl)imide Water-Immiscible Ionic Liquids: The Effect of Water on Electrochemical and Physical Properties, J. Electrochem. Soc. 151 (2004) E219-E225.

SC

[5] S. Pandey, K. A. Fletcher, S. N. Baker and G. A. Baker, Correlation between the fluorescent response of microfluidity probes and the water content and viscosity of ionic liquid and water mixtures, Analyst. 129 (2004) 569-573.

NU

[6] J. A. Widegren, A. Laesecke and J. W. Magee, The effect of dissolved water on the viscosities of hydrophobic room-temperature ionic liquids, Chem. Commun. 12 (2005) 1610-

MA

1612.

[7] D. Chakrabarty, A. Chakraborty, D. Seth and N. Sarkar, Effect of Water, Methanol, and Acetonitrile on Solvent Relaxation and Rotational Relaxation of Coumarin 153 in Neat 1-Hexyl-

D

3-methylimidazolium Hexafluorophosphate, J. Phys. Chem. A. 109 (2005) 1764-1769.

PT E

[8] R. L. Gardas, D. H. Dagade, J. A. P. Coutinho and K. J. Patil, Thermodynamic Studies of Ionic Interactions in Aqueous Solutions of Imidazolium-Based Ionic Liquids [Emim][Br] and [Bmim][Cl], J. Phys. Chem. B. 112 (2008) 3380-3389.

CE

[9] M. G. Freire, P. J. Carvalho, A. M. Fernandes, I. M. Marrucho, A. J. Queimada and J. A. P. Coutinho, Surface tensions of imidazolium based ionic liquids: Anion, cation, temperature and

AC

water effect, J. Colloid Interface Sci. 314 (2007) 621-630. [10] C. G. Hanke and R. M. Lynden-Bell, A Simulation Study of Water−Dialkylimidazolium Ionic Liquid Mixtures, J. Phys. Chem. B. 107 (2003) 10873-10878. [11] D. Sate, M. H. A. Janssen, G. Stephens, R. A. Sheldon, K. R. Seddon and J. R. Lu, Enzyme aggregation in ionic liquids studied by dynamic light scattering and small angle neutron scattering, Green Chem. 9 (2007) 859-867. [12] T. De Diego, P. Lozano, S. Gmouh, M. Vaultier and J. L. Iborra, Understanding Structure−Stability Relationships of Candida antartica

Lipase B in

Ionic Liquids,

Biomacromolecules. 6 (2005) 1457-1464. [13] F. Franks, Solute-Water interactions: Do polyhydroxy compounds alter the properties of water?, Cryobiology. 20 (1983) 335-345. 18

ACCEPTED MANUSCRIPT [14] Water and the Cell, G. H. Pollack, I.L. Cameron, D. N. Wheatley, Springer, Dordrecht, The Netherlands, 2006. [15] H. Zhao, Protein stabilization and enzyme activation in ionic liquids: specific ion effects, J. Chem. Technol. Biotechnol. 91 (2016) 25-50. [16] P. M. Wiggins, Hydrophobic hydration, hydrophobic forces and protein folding, Physica A. 238 (1997) 113-128. [17] K. D. Collins, Ions from the Hofmeister series and osmolytes: effects on proteins in solution

RI PT

and in the crystallization process, Methods. 34 (2004) 300-311. [18] R. L. Baldwin, How Hofmeister ion interactions affect protein stability, Biophys. J. 71 (1996) 2056-2063.

interfaces, Q. Rev. Biophys. 18 (1985) 323-422.

SC

[19] K. D. Collins and M. W. Washabaugh, The Hofmeister effect and the behaviour of water at

[20] N. Kaftzik, P. Wasserscheid and U. Kragl, Use of Ionic Liquids to Increase the Yield and

Process Res. Dev. 6 (2002) 553-557.

NU

Enzyme Stability in the β-Galactosidase Catalysed Synthesis of N-Acetyllactosamine, Org.

MA

[21] H. Noritomi, K. Minamisawa, R. Kamiya and S. Kato, Thermal stability of proteins in the presence of aprotic ionic liquids J. Biomed. Sci. Eng. 4 (2011) 94-99. [22] R. K. Desai, M. Streefland, R. H. Wijffels and M. H. M. Eppink, Extraction and stability of

D

selected proteins in ionic liquid based aqueous two phase systems, Green Chem. 16 (2014) 2670-

PT E

2679.

[23] R. Buchfink, A. Tischer, G. Patil, R. Rudolph and C. Lange, Ionic liquids as refolding additives: Variation of the anion, J. Biotechnol. 150 (2010) 64-72.

CE

[24] H. Zhao, Methods for stabilizing and activating enzymes in ionic liquids—a review, J. Chem. Technol. Biotechnol. 85 (2010) 891-907. [25] L. Gaillon, J. Sirieix-Plenet and P. Letellier, Volumetric Study of Binary Solvent Mixtures

AC

Constituted by Amphiphilic Ionic Liquids at Room Temperature (1-Alkyl-3-Methylimidazolium Bromide) and Water, J. Solution Chem. 33 (2004) 1333-1347. [26] X.-M. Lu, W.-G. Xu, J.-S. Gui, H.-W. Li and J.-Z. Yang, Volumetric properties of room temperature ionic liquid 1. The system of {1-methyl-3-ethylimidazolium ethyl sulfate + water} at temperature in the range (278.15 to 333.15 K), J. Chem. Thermodyn. 37 (2005) 13-19. [27] W. Liu, T. Zhao, Y. Zhang, H. Wang and M. Yu, The Physical Properties of Aqueous Solutions of the Ionic Liquid [BMIM][BF4], J. Solution Chem. 35 (2006) 1337-1346. [28] M. G. Freire, C. M. S. S. Neves, P. J. Carvalho, R. L. Gardas, A. M. Fernandes, I. M. Marrucho, L. M. N. B. F. Santos and J. A. P. Coutinho, Mutual Solubilities of Water and Hydrophobic Ionic Liquids, J. Phys. Chem. B. 111 (2007) 13082-13089. 19

ACCEPTED MANUSCRIPT [29] W. Guan, L. Li, X.-X. Ma, J. Tong, D.-W. Fang and J.-Z. Yang, Study on the enthalpy of solution and enthalpy of dilution for the ionic liquid [C3mim][Val] (1-propyl-3methylimidazolium valine), J. Chem. Thermodyn. 47 (2012) 209-212. [30] M. Bešter-Rogač, J. Hunger, A. Stoppa and R. Buchner, 1-Ethyl-3-methylimidazolium Ethylsulfate in Water, Acetonitrile, and Dichloromethane: Molar Conductivities and Association Constants, J. Chem. Eng. Data. 56 (2011) 1261-1267. [31] D. H. Dagade, K. R. Madkar, S. P. Shinde and S. S. Barge, Thermodynamic Studies of Ionic

RI PT

Hydration and Interactions for Amino Acid Ionic Liquids in Aqueous Solutions at 298.15 K, J. Phys. Chem. B. 117 (2013) 1031-1043.

[32] C. Spickermann, J. Thar, S. B. C. Lehmann, S. Zahn, J. Hunger, R. Buchner, P. A. Hunt, T. Welton and B. Kirchner, Why are ionic liquid ions mainly associated in water? A Car–Parrinello

SC

study of 1-ethyl-3-methyl-imidazolium chloride water mixture, J. Chem. Phys. 129 (2008) 104505(1-13).

NU

[33] G. Dimitrakis, I. J. Villar-Garcia, E. Lester, P. Licence and S. Kingman, Dielectric spectroscopy: a technique for the determination of water coordination within ionic liquids, Phys.

MA

Chem. Chem. Phys. 10 (2008) 2947-2951.

[34] M. Bester-Rogac, M. V. Fedotova, S. E. Kruchinin and M. Klähn, Mobility and association of ions in aqueous solutions: the case of imidazolium based ionic liquids, Phys. Chem. Chem.

D

Phys. 18 (2016) 28594-28605.

PT E

[35] V. Migliorati, A. Zitolo and P. D’Angelo, Using a Combined Theoretical and Experimental Approach to Understand the Structure and Dynamics of Imidazolium-Based Ionic Liquids/Water Mixtures. 1. MD Simulations, J. Phys. Chem. B. 117 (2013) 12505-12515.

CE

[36] P. D’Angelo, A. Zitolo, G. Aquilanti and V. Migliorati, Using a Combined Theoretical and Experimental Approach to Understand the Structure and Dynamics of Imidazolium-Based Ionic Liquids/Water Mixtures. 2. EXAFS Spectroscopy, J. Phys. Chem. B. 117 (2013) 12516-12524.

AC

[37] F. C. Marincola, C. Piras, O. Russina, L. Gontrani, G. Saba and A. Lai, NMR Investigation of Imidazolium-Based Ionic Liquids and Their Aqueous Mixtures, ChemPhysChem. 13 (2012) 1339-1346.

[38] M. Haberler, C. Schröder and O. Steinhauser, Hydrated Ionic Liquids with and without Solute: The Influence of Water Content and Protein Solutes, J. Chem. Theory Comput. 8 (2012) 3911-3928. [39] H. Weingartner, C. Cabrele and C. Herrmann, How ionic liquids can help to stabilize native proteins, Phys. Chem. Chem. Phys. 14 (2012) 415-426.

20

ACCEPTED MANUSCRIPT [40] L. I. N. Tomé, M. Jorge, J. R. B. Gomes and J. o. A. P. Coutinho, Molecular Dynamics Simulation Studies of the Interactions between Ionic Liquids and Amino Acids in Aqueous Solution, J. Phys. Chem. B. 116 (2012) 1831-1842. [41] C. E. S. Bernardes, M. E. Minas da Piedade and J. N. Canongia Lopes, The Structure of Aqueous Solutions of a Hydrophilic Ionic Liquid: The Full Concentration Range of 1-Ethyl-3methylimidazolium Ethylsulfate and Water, J. Phys. Chem. B. 115 (2011) 2067-2074. [42] M. V. Fedotova and S. E. Kruchinin, 1D-RISM study of glycine zwitterion hydration and

RI PT

ion-molecular complex formation in aqueous NaCl solutions, J. Mol. Liq. 169 (2012) 1-7. [43] G. N. Chuev, M. Valiev and M. V. Fedotova, Integral Equation Theory of Molecular Solvation Coupled with Quantum Mechanical/Molecular Mechanics Method in NWChem Package, J. Chem. Theory Comput. 8 (2012) 1246-1254.

SC

[44] M. V. Fedotova and S. E. Kruchinin, Hydration of para-aminobenzoic acid (PABA) and its anion—The view from statistical mechanics, J. Mol. Liq. 186 (2013) 90-97.

NU

[45] M. V. Fedotova and S. E. Kruchinin, The hydration of aniline and benzoic acid: Analysis of radial and spatial distribution functions, J. Mol. Liq. 179 (2013) 27-33.

MA

[46] M. V. Fedotova and S. E. Kruchinin, Ion-binding of glycine zwitterion with inorganic ions in biologically relevant aqueous electrolyte solutions, Biophys. Chem. 190–191 (2014) 25-31. [47] M. V. Fedotova and O. A. Dmitrieva, Ion-selective interactions of biologically relevant

D

inorganic ions with alanine zwitterion: a 3D-RISM study, Amino Acids. 47 (2015) 1015-1023.

PT E

[48] M. V. Fedotova and O. A. Dmitrieva, Characterization of selective binding of biologically relevant inorganic ions with the proline zwitterion by 3D-RISM theory, New J. Chem. 39 (2015) 8594-8601.

CE

[49] A. Eiberweiser, A. Nazet, S. E. Kruchinin, M. V. Fedotova and R. Buchner, Hydration and Ion Binding of the Osmolyte Ectoine, J. Phys. Chem. B. 119 (2015) 15203-15211. [50] M. V. Fedotova and O. A. Dmitrieva, Proline hydration at low temperatures: its role in the

AC

protection of cell from freeze-induced stress, Amino Acids. 48 (2016) 1685-1694. [52] S. Bruzzone, M. Malvaldi and C. Chiappe, A RISM approach to the liquid structure and solvation properties of ionic liquids, Phys. Chem. Chem. Phys. 9 (2007) 5576–5581. [53] S. Bruzzone, M. Malvaldi and C. Chiappe, Solvation Thermodynamics of Alkali and Halide Ions in Ionic Liquids through Integral Equations, J. Chem. Phys. 129 (2008) 074509. [54] M. Malvaldi, S. Bruzzone, C. Chiappe, S. Gusarov and A. Kovalenko, Ab Initio Study of Ionic Liquids by KS-DFT/3D-RISM-KH Theory, J. Phys. Chem. B. 113 (2009) 3536–3542. [55] Y. Nishimura, D. Yokogawa and S. Irle, Theoretical study of cellobiose hydrolysis to glucose in ionic liquids, Chem. Phys. Lett. 603 (2014) 7–12.

21

ACCEPTED MANUSCRIPT [56] Arifin, M. Puripat, D. Yokogawa, V. Parasuk and S. Irle, Glucose Transformation to 5Hydroxymethylfurfural in Acidic Ionic Liquid: A Quantum Mechanical Study, J. Comput. Chem. 37 (2016) 327–335. [57] K. Kikui, S. Hayaki, K. Kido, D. Yokogawa, K. Kasahara, Y. Matsumura, H. Sato and S. Sakaki, Solvent structure of ionic liquid with carbon dioxide, J. Mol. Liq. 217 (2016) 12–16. [58] S. Hayaki, Y. Kimura and H. Sato, Ab Initio Study on an Excited-State Intramolecular Proton-Transfer Reaction in Ionic Liquid, J. Phys. Chem. B. 117 (2013) 6759−6767.

RI PT

[59] S. Hayaki, K. Kido, D. Yokogawa, H. Sato, S. Sakaki, A Theoretical Analysis of a DielsAlder Reaction in Ionic Liquids, J. Phys. Chem. B. 113 (2009) 8227−8230. [60] T. Yamaguchi, S. Koda, Mode-Coupling Theoretical Analysis of Transport and Relaxation Properties of Liquid Dimethylimidazolium Chloride, J. Chem. Phys. 132 (20100 114502.

SC

[61] H. Nakano, J. Noguchi, T. Mochida and H. Sato, Theoretical Studies on the Electronic States and Liquid Structures of Ferrocenium-Based Ionic Liquids, J. Phys. Chem. A. 119 (2015)

NU

5181−5188.

[62] D. Chandler and H. C. Andersen, Optimized Cluster Expansions for Classical Fluids. II.

MA

Theory of Molecular Liquids, J. Chem. Phys. 57 (1972) 1930-1937. [63] H. C. Andersen, D. Chandler and J. D. Weeks, Optimized cluster expansions for classical fluids. III. Applications to ionic solutions and simple liquids, J. Chem. Phys. 57 (1972) 2626-

D

2631.

PT E

[64] F. Hirata and P. J. Rossky, An extended RISM-equation for molecular polar fluids, Chem. Phys. Lett. 83 (1981) 329-334.

[65] F. Hirata, B. M. Pettitt and P. J. Rossky, Application of an extended RISM equation to

CE

dipolar and quadrupolar fluids, J. Chem. Phys. 77 (1982) 509-520. [66] Molecular Theory of Solvation, F. Hirata (ed.), Kluwer Academic Publishers, Dordrecht, 2003.

AC

[67] A. Kovalenko and F. Hirata, First-principles realization of a van der Waals–Maxwell theory for water, Chem. Phys. Lett. 349 (2001) 496-502. [68] A. Kovalenko and F. Hirata, Potential of Mean Force between Two Molecular Ions in a Polar Molecular Solvent: A Study by the Three-Dimensional Reference Interaction Site Model, J. Phys. Chem. B. 103 (1999) 7942-7957. [69] D. Beglov and B. Roux, Solvation of complex molecules in a polar liquid: An integral equation theory, J. Chem. Phys. 104 (1996) 8678-8689. [70] D. Beglov and B. Roux, An Integral Equation To Describe the Solvation of Polar Molecules in Liquid Water, J. Phys. Chem. B. 101 (1997) 7821-7826.

22

ACCEPTED MANUSCRIPT [71] A. Kovalenko and F. Hirata, Three-dimensional Density Profiles of Water in Contact with a Solute of Arbitrary Shape: a RISM Approach, Chem. Phys. Lett. 290 (1998) 237-244. [72] A. Kovalenko and F. Hirata, Self-consistent description of a metal–water interface by the Kohn– Sham density functional theory and the three-dimensional reference interaction site model, J. Chem. Phys. 110 (1999) 10095-10112. [73] L. Lue and D. Blankschtein, Liquid-state theory of hydrocarbon-water systems: application to methane, ethane, and propane, J. Phys. Chem. 92 (1992) 8582-8594.

RI PT

[74] M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria, M. A. Robb, J. R. Cheeseman, G. Scalmani, V. Barone, B. Mennucci, G. A. Petersson, H. Nakatsuji, M. Caricato, X. Li, H. P. Hratchian, A. F. Izmaylov, J. Bloino, G. Zheng, J. L. Sonnenberg, M. Hada, M. Ehara, K. Toyota, R. Fukuda, J. Hasegawa, M. Ishida, T. Nakajima, Y. Honda, O. Kitao, H. Nakai, T.

SC

Vreven, J. A. Montgomery, Jr., , J. E. Peralta, F. Ogliaro, M. Bearpark, J. J. Heyd, E. Brothers, K. N. Kudin, V. N. Staroverov, T. Keith, R. Kobayashi, J. Normand, K. Raghavachari, A.

NU

Rendell, J. C. Burant, S. S. Iyengar, J. Tomasi, M. Cossi, N. Rega, J. M. Millam, M. Klene, J. E. Knox, J. B. Cross, V. Bakken, C. Adamo, J. Jaramillo, R. Gomperts, R. E. Stratmann, O.

MA

Yazyev, A. J. Austin, R. Cammi, C. Pomelli, J. W. Ochterski, R. L. Martin, K. Morokuma, V. G. Zakrzewski, G. A. Voth, P. Salvador, J. J. Dannenberg, S. Dapprich, A. D. Daniels, O. Farkas, J. B. Foresman, J. V. Ortiz, J. Cioslowski and D. J. Fox, Gaussian 09, revision B.01, Gaussian,

D

Inc., Wallingford CT, 2010.

PT E

[75] P. Yee, J. K. Shah and E. J. Maginn, State of Hydrophobic and Hydrophilic Ionic Liquids in Aqueous Solutions: Are the Ions Fully Dissociated?, J. Phys. Chem. B. 117 (2013) 12556-12566. [76] G. Zhou, X. Liu, S. Zhang, G. Yu and H. He, A Force Field for Molecular Simulation of

CE

Tetrabutylphosphonium Amino Acid Ionic Liquids, J. Phys. Chem. B. 111 (2007) 7078-7084. [77] D. A. Case, V. Babin, J. T. Berryman, R. M. Betz, Q. Cai, D. S. Cerutti, T. E. Cheatham, III, T. A. Darden, R. E. Duke, H. Gohlke, A. W. Goetz, S. Gusarov, N. Homeyer, P. Janowski, J.

AC

Kaus, I. Kolossváry, A. Kovalenko, T. S. Lee, S. LeGrand, T. Luchko, R. Luo, B. Madej, K. M. Merz, F. Paesani, D. R. Roe, A. Roitberg, C. Sagui, R. Salomon-Ferrer, G. Seabra, C. L. Simmerling, W. Smith, J. Swails, R. C. Walker, J. Wang, R. M. Wolf, X. Wu and P. A. Kollman, AMBER 14, University of California, San Francisko, 2014. [78] A. Kovalenko, S. Ten-no and F. Hirata, Solution of three-dimensional reference interaction site model and hypernetted chain equations for simple point charge water by modified method of direct inversion in iterative subspace, J. Comput. Chem. 20 (1999) 928-936. [79] B. Fazio, A. Triolo and G. Di Marco, Local organization of water and its effect on the structural heterogeneities in room-temperature ionic liquid/H2O mixtures, J. Raman Spectrosc. 39 (2008) 233-237. 23

ACCEPTED MANUSCRIPT [80] M. Moreno, F. Castiglione, A. Mele, C. Pasqui and G. Raos, Interaction of Water with the Model Ionic Liquid [bmim][BF4]: Molecular Dynamics Simulations and Comparison with NMR Data, J. Phys. Chem. B. 112 (2008) 7826-7836. [81] B. Wu, Y. Liu, Y. Zhang and H. Wang, Probing Intermolecular Interactions in Ionic Liquid–Water Mixtures by Near-Infrared Spectroscopy, Chem. Eur. J. 15 (2009) 6889-6893. [82] Y. Danten, M. I. Cabaço and M. Besnard, Interaction of Water Highly Diluted in 1-Alkyl-3methyl Imidazolium Ionic Liquids with the PF6− and BF4− Anions, J. Phys. Chem. A. 113

RI PT

(2009) 2873-2889. [83] A. Mele, C. D. Tran and S. H. De Paoli Lacerda, The Structure of a Room-Temperature Ionic Liquid with and without Trace Amounts of Water: The Role of C–H···O and C–H···F

SC

Interactions in 1-n-Butyl-3-Methylimidazolium Tetrafluoroborate, Angew. Chem. Int. Ed. 42 (2003) 4364-4366.

[84] H. V. R. Annapureddy and L. X. Dang, Pairing Mechanism among Ionic Liquid Ions in

NU

Aqueous Solutions: A Molecular Dynamics Study, J. Phys. Chem. B. 117 (2013) 8555-8560. [85] Q.-G. Zhang, N.-N. Wang and Z.-W. Yu, The Hydrogen Bonding Interactions between the

MA

Ionic Liquid 1-Ethyl-3-Methylimidazolium Ethyl Sulfate and Water, J. Phys. Chem. B. 114 (2010) 4747-4754.

[86] T. Köddermann, C. Wertz, A. Heintz and R. Ludwig, The Association of Water in Ionic

D

Liquids: A Reliable Measure of Polarity, Angew. Chem. Int. Ed. 45 (2006) 3697-3702.

PT E

[87] T. Takamuku, Y. Kyoshoin, T. Shimomura, S. Kittaka and T. Yamaguchi, Effect of Water on Structure of Hydrophilic Imidazolium-Based Ionic Liquid, J. Phys. Chem. B. 113 (2009) 10817-10824.

CE

[88] A. Downard, M. J. Earle, C. Hardacre, S. E. J. McMath, M. Nieuwenhuyzen and S. J. Teat, Structural Studies of Crystalline 1-Alkyl-3-Methylimidazolium Chloride Salts, Chem. Mater. 16

AC

(2004) 43-48.

[89] Y. Wang, H. Li and S. Han, A Theoretical Investigation of the Interactions between Water Molecules and Ionic Liquids, J. Phys. Chem. B. 110 (2006) 24646-24651. [90] L. Cammarata, S. G. Kazarian, P. A. Salter and T. Welton, Molecular states of water in room temperature ionic liquids, Phys. Chem. Chem. Phys. 3 (2001) 5192-5200. [91] W. Jiang, Y. Wang and G. A. Voth, Molecular Dynamics Simulation of Nanostructural Organization in Ionic Liquid/Water Mixtures, J. Phys. Chem. B. 111 (2007) 4812-4818. [92] T. Singh and A. Kumar, Aggregation Behavior of Ionic Liquids in Aqueous Solutions: Effect of Alkyl Chain Length, Cations, and Anions, J. Phys. Chem. B. 111 (2007) 7843-7851.

24

ACCEPTED MANUSCRIPT [93] E. Chi, S. Krishnan, T. Randolph and J. Carpenter, Physical stability of proteins in aqueous solution: mechanism and driving forces in nonnative protein aggregation, Pharm. Res. 20 (2003) 1325–1336. [94] H. Zhao, Are ionic liquids kosmotropic or chaotropic? An evaluation of available thermodynamic parameters for quantifying the ion kosmotropicity of ionic liquids, J. Chem.

AC

CE

PT E

D

MA

NU

SC

RI PT

Technol. Biotechnol. 81 (2006) 877–891.

25

ACCEPTED MANUSCRIPT Figure Captions Figure 1. Schematic representation with atom labeling for [EMIM]+ (a), [EtSO4]– (b), and [Gly]– (c). Figure 2. Cation-water RDFs g C1Ow (r ) & g H1Ow (r ) (a), g C2Ow (r ) & g H2Ow (r ) (b), g C3Ow (r ) & g H3Ow (r ) (c) at the lowest and highest concentrations of [EMIM][EtSO4]. Atom labeling corresponds to Figure 1a.

RI PT

Figure 3. Cation-water RDFs g C4Ow (r ) & g H4,5,6Ow (r ) (a), g C5Ow (r ) & gH7,8Ow (r ) (b), g C6Ow (r ) & g H9,10,11Ow (r ) (c) at the lowest and highest concentrations of [EMIM][EtSO4]. Atom labeling corresponds to Figure 1a.

SC

Figure 4. Anion-water RDFs gO1,2,3W (r ) (a), g C1Ow (r ) & gH4,5Ow (r ) (b), g C2Ow (r ) & g H1,2,3Ow (r ) (c) at the lowest and highest concentrations of [EMIM][EtSO4]. Atom labeling is corresponding to Figure 1b. Figure 5. Spatial distribution functions of the oxygen (red) and hydrogen (white) atoms of water

NU

around: a. EMIM+ (the isodensity surfaces correspond to SDF values of g EMIM-Ow ( r ) = 3.0 &

MA

g EMIM-Hw ( r ) = 1.7); b. Cl– (the isodensity surfaces correspond to SDF values of g Cl-Ow ( r ) = 1.9 & g Cl-Hw ( r ) = 2.1); c. EtSO4– (the isodensity surfaces correspond to SDF values of g EtSO -Ow ( r ) = 3.2 & g EtSO -Hw ( r ) = 2.7); d. Gly– (the isodensity surfaces correspond to SDF values of g Gly-Ow ( r ) = 3.3 & g Gly-Hw ( r ) = 4.1). 4

D

4

PT E

Figure 6. Ion-water potentials of mean force for systems under study. Figure 7. Cl–-water RDFs gCl− -W ( r ) for aqueous [EMIM][Cl] solution.

CE

Figure 8. Gly–-water RDFs gO1,2W ( r ) (a) and g N1W ( r ) & g H1,2W ( r ) (b) for aqueous [Emim][Gly] solution. Atom labeling corresponds to Figure 1c.

AC

Figure 9. Cation-water RDFs g H1Ow (r ) (a), g C4Ow (r ) (b), and g C6Ow (r ) (c) of [EMIM]+ in imidazolium-based ILs with various anions.

26

ACCEPTED MANUSCRIPT Highlights

AC

CE

PT E

D

MA

NU

SC

RI PT

• Ion hydration structure of aqueous imidazolium-based ionic liquids (ILs) was studied. • The effects of concentration and anion nature were considered. • Concentration effect is in significant dehydration of both the cation and the anion. • At low IL content ions are well hydrated with stronger anion-water interactions. • The dependence of strength of anion-water interactions on anion nature is discussed.

27