1D-RISM study of glycine zwitterion hydration and ion-molecular complex formation in aqueous NaCl solutions

Journal of Molecular Liquids 169 (2012) 1–7

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1D-RISM study of glycine zwitterion hydration and ion-molecular complex formation in aqueous NaCl solutions Marina V. Fedotova ⁎, Sergey E. Kruchinin Institute of Solution Chemistry, Russian Academy of Sciences, Akademicheskaya St., 1, 153045 Ivanovo, Russia

a r t i c l e

i n f o

Article history: Received 20 December 2011 Received in revised form 9 February 2012 Accepted 9 March 2012 Available online 23 March 2012 Keywords: Amino acid Hydration Complex formation 1D-RISM integral equation method

a b s t r a c t Structural aspects of the hydration of glycine zwitterion (Gly-ZW) in NaCl(aq) were studied over a wide concentration range of NaCl (c = 0–5 M) with the 1D-RISM integral equation method. Analysis of the structural data revealed that increasing salt concentration leads only to minor changes in hydration structure of Gly-ZW with the maximum effect occurring for the \NH3+ and \COO − groups where the number of H-bonds is decreased. On the other hand, increasing salt concentration stimulates the formation of ion-molecular complexes like (\NH3+:Cl −)aq and (\COO −:Na +)aq. On the basis of the obtained data a structural mechanism for this process is suggested. © 2012 Elsevier B.V. All rights reserved.

1. Introduction As most biological processes occur in an aqueous environment, the hydration of biomolecules like proteins is of interest for study in order to understand the mechanism of many biochemical processes such as the folding of proteins [1,2] and their stability [3], molecular recognition [4], or protein–protein interactions [5]. Knowledge of the structure of the hydration shells with solvent particles (including water molecules, cations, and anions) surrounding these systems can provide also important information necessary for designing enzymes with adjusted properties [6] and drugs, for instance, using molecular docking [7]. Aqueous environments may vary broadly in composition. Effects of solvents appear both on the conformation, dynamics, thermodynamics of biomolecules [8,9] and on their physicochemical properties [10]. For proteins it has been found [11–13] that the solvent controls chemical reactions, e.g., in enzyme catalysis, and modulates non-covalent interactions, thus governing the dynamics of molecular association/dissociation. Moreover, salts and cosolvents added to the solution can be a reason for significant changes in many biomolecular properties [14–20]. For instance, the addition of salts to the solution can change the protein solubility [21]. On the other hand, the investigation of the entire biomolecules in aqueous solution is often inconvenient because of the difficulties associated with separating the different effects originating from the many types of interactions present in such systems [22]. Therefore,

⁎ Corresponding author. Tel.: + 7 9432 336237. E-mail address: [email protected] (M.V. Fedotova). 0167-7322/$ – see front matter © 2012 Elsevier B.V. All rights reserved. doi:10.1016/j.molliq.2012.03.008

it is often more suitable to study simple model compounds, like amino acids, where a specific functional group typical for biological systems is isolated. Since amino acids are elemental building blocks of proteins, good understanding of their hydration should give important insights into corresponding interactions of biomolecules and on the role of the solvent for biological systems. Among the various amino acids, glycine (Gly) is often chosen for investigations as a biochemical model substance because of its simple molecular structure. In aqueous solutions at pH ~ 7 the Gly molecule adopts a zwitterionic (ZW) form [23–25], which consists of the charged hydrophilic \COO − and \NH 3+ groups, and the hydrophobic \CH2 group (Fig. 1). Note, that this amino acid performs some vitally essential functions. For example, the Gly-ZW can act as a neurotransmitter in the central nervous system [26] and prevents structural modifications of the intracellular chromatin which can be induced by changes in the ion concentration inside the cell [27–29]. The last decades saw a significant growth in the number of studies investigating glycine hydration in biologically relevant aqueous electrolyte solutions like NaCl(aq), KCl(aq), CaCl2(aq) and MgCl2(aq). However the structural features of this process and the effects of salt addition on it at molecular level are far from being fully understood, partly owing to the scarcity of experimental data. For instance, for the case of Gly in sodium salt solutions the data are few and discrepant. In particular, the IR-spectroscopic results of Max et al. [30] indicate that the total hydration number of Gly in 5.13 M NaCl(aq) is 3 with the author's assuming that all these water molecules belong to the \COO − group. On the other hand, neutron diffraction experiments carried out by Kameda Y. et al. [31,32] for Gly in NaOD-water system indicate that the first hydration shell of the amino acid contains 5 water molecules. Three of them are the H-bonded with the

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In addition to the PCFs solution the structure is also expressed in partial hydration numbers (HN), nαβ, which were calculated as: r min

uv

2

nαβ ¼ 4πρβ ∫ g αβ ðr Þr dr:

1

0

Fig. 1. Spatial configuration and schematic representation with atom labeling for the Gly-ZW. The rotation angles φ and θ indicate the rotation of the NH3 group and the rotation of the CO2 group correspondingly.

\NH3+ group and two of them are located close to the methyl group. According to MD simulation performed by Campo [33], the total hydration number of the Gly-ZW in 1 M NaCl solution is 8.75 with partial hydration numbers for the functional groups of n(\COO −) = 4.86, n(\NH3+) = 2.66, and n(\CH2) = 1.23. Thus, at present there is no consensus on the hydration structure of the Gly-ZW in salt solutions in general, and in NaCl(aq) in particular. A possible ion-molecular complex of Gly-ZW with inorganic ions is of particular interest. It is well known [34] that in biological systems amino acids form salts and various complexes with alkali metals (Na +, K +) [33,35–38], copper (Cu +) [39,40], (Cu 2+) [39,40] or other ions [41] which stabilize the zwitterionic form. Ab initio calculations [42] show this stabilization with Na + and Cl −. This effect may be linked with the empirically established correlation between the tendency for contact ion-pair formation and the match between the hydration enthalpies of cation and anionic carboxylate group [43–45]. In particular, the hydration enthalpy of Na + matches those of major intracellular anions or anionic groups, such as carboxylate, better than K +. This conclusion has been confirmed by the recent XAS spectroscopy [37] and by a combined molecular dynamics and quantum chemical study [46] which revealed that sodium interacts more strongly with the COO − group than potassium and that this ionspecific interaction is mediated by weak ion pairs (COO −:X +)aq. Moreover, the pair (COO −:Na +)aq is more stable than the pair (COO −:K +)aq [37]. However, the details and consequences of such ion-molecular complex formation on the molecular level are far from being fully understood. In this paper we present a study of the salt effect on Gly-ZW hydration in NaCl(aq) covering a wide concentration range of NaCl (0–5 M) using one-dimensional RISM (1D RISM) theory. The RISM (Reference Interaction Site Model) approach [47] provides the detailed information about solute–solvent interactions in terms of statistically averaged site–site pair correlation functions (PCFs), which makes it a good method to investigate solvation phenomena. 2. Calculation method and computational details An introduction to the basic concepts of RISM theory can be found in Refs. [47–52], with a discussion of the problems associated with the treatment of ionic systems given in Refs. [53,54]. In particular, a description of the 1D RISM approach may be found in Refs. [48,49]; see also a set of points discussed in our early paper [55]. Thus, here only some practical computational details will be discussed for brevity. uv Calculation of the PCFs, gαβ (r), where α and β labels are the interaction sites (atoms) belonging to the solute (u) and solvent (v) molecules, was based on the solution of the site–site Ornstein–Zernike equation (SSOZ) [47] with the partially linearized hypernetted chain closure (PLHNC) [56,57]. It is important to emphasize that for the Gly-ZW–NaCl(aq) system the sodium chloride solution is playing the role of solvent.

The partial HN is the average number of solvent sites/atoms of kind β in a hydration sphere of radius rmin i around an α-type site/ atom of the solute molecule or ion. Our calculations were performed for one molecule of Gly-ZW in NaCl(aq) in the salt concentration range c = 0–5 M at ambient conditions. Fig. 1 shows the spatial configurations and schematic representations for Gly-ZW with the used atom numbering. Solute–atom coordinates were adapted from the PubChem Structure DataBase [58] showing the most stable conformation of Gly-ZW in aqueous solution [59] which is characterized by the dihedral angles φ = 0 and θ = 0 (Fig. 1). The geometric parameters of the Gly-ZW structure are summarized in Table 1. We used the modified SPC/E water model (MSPC/E) proposed by Lue and Blankshtein [60]. The partial charges and LJ parameters were taken from the General Amber Force Field (GAFF) [61]. The densities of NaCl(aq) were adopted from the data of Ref. [62]. The PCFs for the studied solutions are shown in Figs. 2–12. The structural parameters for Gly-ZW–NaCl(aq) system are presented in Table 2. 3. Results and discussion 3.1. Hydration of Gly-ZW 3.1.1. Hydration of the \NH3+ group At c = 0 M the main peak of gN1OW(r) (W denotes the water molecule) characterizing the first hydration shell of the \NH3+ group is located at a distance of 0.285 nm (Fig. 2). This distance is not changing with the salt concentration growth (Table 2) and coincides with the values for rN1OW obtained in neutron diffraction study of Kameda et al. [31]. According to our calculations for the Gly-ZW in neat water (0 M NaCl) the hydration number of the \NH3+ group is 5.1 (Table 2, nN1OW). Upon salt addition up to 5 M this value decreases to 4.5 (ΔnN1OW = − 11.4%, Table 2). The calculated HNs exceed the values from neutron diffraction [31] and MD simulations [33]. The PCF gN1HW(r) is indicative for H-bonding of the nitrogen atom with the hydrogen atoms on the water molecules. This function has its first peak at a distance of 0.360–0.355 nm depending on salt

Table 1 Geometry of glycine zwitterion molecule. Bond lengths (nm) C1\C2 C2\N1 C1\O1,2 N1\H1,2,3 C2\H4,5

0.15210 0.14837 0.12370 0.10058 0.10913

Angles ∠C1C2N1 ∠C2C1O1,2 ∠C2N1H1,2,3 ∠C1C2H4,5 ∠H4C2H5 ∠H1N1H2, ∠H2N1H3, ∠H3N1H1

110.8° 116.9° 110.3° 108.9° 108.7° 108.2°

Dihedral angles H1N1C2C1 (φ) N1C2C1O1 (θ)

0° 0°

M.V. Fedotova, S.E. Kruchinin / Journal of Molecular Liquids 169 (2012) 1–7

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Fig. 2. Pair correlation functions gN1OW(r) and gN1HW(r) for the Gly-ZW–NaCl(aq). Atom labeling for the Gly-ZW corresponds to Fig. 1.As these PCFs for all salt concentrations are rather similar, only the curves for the lowest (0 M) and the highest (5 M) salt concentrations are shown.

Fig. 4. Pair correlation functions gC2OW(r) and gH4, 5OW(r) for the Gly-ZW–NaCl(aq). Atom labeling for the Gly-ZW corresponds to Fig. 1.As these PCFs for all salt concentrations are rather similar, only the curves for the lowest (0 M) and the highest (5 M) salt concentrations are shown. As an example, decomposition of the PCF gC2OW(r) into Gaussians (see Section 3.1.2) is presented for c = 0 M (inset).

concentration (Fig. 2, Table 2). However, gN1HW(r) does not show the typical H-bond peak in region of 0.170–0.180 nm which is present for neutral molecules with an amino (\NH2) group [63,64]. This lacking feature of gN1HW(r) is a clear evidence of the absence of H-bonding between the nitrogen atom of the \NH3+ group of Gly-ZW and water molecules. A similar behavior of the PCF gN1HW(r) has been reported previously for the \NH3+ group of methylammonium ion in water as a result of RISM calculations [65] and computer simulations [66]. It was shown that this is a result of the amino group protonation [65]. As can be seen from Fig. 3, the peak height of gH1OW(r) does not exceed unity. This feature clearly indicates the low probability for Hbond formation between the H1 atom of the \NH3+ group and water molecules and is in agreement with the results of Monte Carlo calculations by Alagona et al. [67]. For the H2 and H3 atoms the obtained PCFs coincide and are thus denoted further as gH2, 3OW(r) and gH2, 3HW(r), indicating that the H2 and H3 sites of the \NH3+ group (Fig. 1) are equivalent. The function gH2, 3OW(r) (Fig. 3), describing H-bonding of these hydrogen atoms with water molecules, has its first peak at r = 0.183 nm for all salt concentrations (Table 2). A comparison with available literature data shows that the obtained distance is close to the value (r ~ 0.180 nm) from the MD simulation of Ref. [68] and comparable with the results (r ~ 0.190 nm) of other simulations [33,67,69].

According to our calculations, on average ~ 1.15 H-bonds are formed at c = 0 M by each of the hydrogen atoms H2 and H3 of the \NH3+ group (Table 2, nH2, 3OW). Thus, the total number of H-bonds formed by this group is ~ 2.3. Computer simulations [33,59,67–69] indicated 0.93 to 1.07 H-bonds on one hydrogen atom. Note, that in the studies [33,59,68,69] all three hydrogen atoms of the protonated amino group are considered as equivalent. As a consequence, the estimated numbers of H-bonds between the \NH3+ group and water molecules reported from computer simulations scatter significantly (from ~ 2 up to 3.3). Salt addition has a rather small effect on the PCFs gH1OW(r) and gH2, 3OW(r) (Fig. 3). The corresponding peak distances are not changed. Only the number of H-bonds formed by the H2 and H3 atoms is decreased by 15.7% (Table 2). 3.1.2. Hydration of the \CH2 group For all salt concentrations the PCFs gC2OW(r) have their first peak at a distance of 0.323 nm (Fig. 4, Table 2). However for all investigated solutions this peak is not well resolved because of partly overlapping first and second hydration shells (Fig. 4). Since in this case straightforward application of Eq. (1) will give incorrect HNs of the \CH2 group, we decomposed gC2OW(r) in the region from 0 to 1.0 nm into Gaussians g αβ ðr Þ ¼ ∑i Gi ðr Þ with a least-squares fitting procedure. This approach allows extraction of the component corresponding to

Fig. 3. Pair correlation functions gH1OW(r) and gH2, 3OW(r) for the Gly-ZW–NaCl(aq). Atom labeling for the Gly-ZW corresponds to Fig. 1.As these PCFs for all salt concentrations are rather similar, only the curves for the lowest (0 M) and the highest (5 M) salt concentrations are shown.

Fig. 5. Pair correlation functions gO1, 2OW(r) and gO1, 2HW(r) for the Gly-ZW–NaCl(aq). Atom labeling for the Gly-ZW corresponds to Fig. 1.As these PCFs for all salt concentrations are rather similar, only the curves for the lowest (0 M) and the highest (5 M) salt concentrations are shown.

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Fig. 6. Pair correlation functions gH1Cl−(r) for the Gly-ZW–NaCl(aq) with different NaCl concentrations. Atom labeling for the Gly-ZW corresponds to Fig. 1.

Fig. 8. Pair correlation functions gH2, 3Cl−(r) for the Gly-ZW–NaCl(aq) with different NaCl concentrations. Atom labeling for the Gly-ZW corresponds to Fig. 1.

the first hydration shell. Seven Gaussians were assumed for this decomposition. Three of them approximate the first peak of gC2OW(r) and the others represent the second peak and some background contributed by further water layers (Fig. 4, Gaussians are presented only for c = 0 M as an example). As a result of this approach, at c = 0 M an average number of ~ 4.4 water molecules was found in the first hydration shell of the \CH2 group. When the salt concentration is increased up to 5 M this value slightly decreases by 7% (Table 2). Similar to the PCFs gH2W(r) and gH3W(r) for the \NH3+ group, the functions gH4W(r) and gH5W(r)gO2W(r), W = O or H, coincide and are denoted further as gH4, 5OW(r) and gH4, 5HW(r), respectively. Thus, the H4 and H5 sites of the \CH2 group are equivalent (Fig. 1). The first peaks of gH4, 5OW(r) and gH4, 5HW(r) (Fig. 4) are located at the distances of 0.238 nm and 0.320 nm, respectively. These positions do not change with salt concentration (Table 2). Since the distance rH4, 5HW is considerably longer than rH4, 5OW this means that the solvent molecules are directed in such a way by the hydrogen atoms that their hydrogen atoms point away from the hydrophobic group of the Gly-ZW. According to our calculations, the value of nH4, 5OW is ~ 2.4 at c = 0 M and decreases slightly to ~ 2.22 when the salt concentration increases to 5 M (Table 2). In any case, these values suggest some kind of H-bond formation between the hydrophobic \CH3 group and the surrounding water molecules.

3.1.3. Hydration of the \COO − group In this case as the outcome of our calculations we have again obtained very similar behavior of gO1W(r) and gO2W(r), W = O or H.

These PCFs have very similar characteristic distances (Table 2) and the heights of the first peaks differ only marginally (not more than 4.5–5% between gO1OW(r) and gO2OW(r) as well as 2.6–3.8% between gO1HW(r) and gO2HW(r) for all salt concentrations). The small difference in peak heights is possibly a consequence of the intramolecular H-bond between O1 (O δ −) and H1 (H δ +) atoms as this bond also stabilizes the prevailing Gly-ZW conformation (Fig. 1). The PCF gO1, 2OW(r) has its first peak at an average distance of 0.290–0.292 nm (Table 2, see also Fig. 5, with the PCF gO1OW(r) shown as an example). The first peak of gO1, 2HW(r), characterizing H-bonding of these oxygen atoms with water molecules, is located at a distance of 0.160 nm (Table 2, see also Fig. 5, with the PCF gO1HW(r) shown as an example). The distances rO1, 2OW and rO1, 2HW do not change practically with salt concentration (Table 2). Note that rO1, 2HW is much shorter than rO1, 2OW. This fact indicates that the water molecules are directed with their protons toward the oxygen atoms of the \COO − group by protons acting as H-bond donors. According to our calculations for the partial coordination number nO1, 2HW, at c = 0 M the \COO − group forms in total ~6.8 H-bonds to surrounding water molecules, with 3.3 of them directed to O1 and 3.5 bonds for O2 (Table 2). Increasing salt concentration leads to a decrease of nO1, 2HW. At 5 M NaCl(aq) carboxylate forms only ~5.8 Hbonds in total, with 2.8 bonds belonging to O1 and 3.0 to O2 (Table 2). Thus, the change in the number of carboxylate hydrogen bonds, ΔnO1, 2HW, is −15%. The integration of gO1, 2OW(r) up to the first minimum gives on average ~6.3 water molecules around each oxygen in the first hydration shell at c = 0 M (Table 2, nO1OW = 6.1 and nO2OW = 6.5). Consistent with the finding gO1, 2HW(r) this value

Fig. 7. The dependence of nH1Cl−(c) on salt concentration.

Fig. 9. Pair correlation functions gH4, 5Cl−(r) for the Gly-ZW–NaCl(aq) with different NaCl concentrations. Atom labeling for the Gly-ZW corresponds to Fig. 1.

M.V. Fedotova, S.E. Kruchinin / Journal of Molecular Liquids 169 (2012) 1–7

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Fig. 10. Pair correlation functions gO1Na+(r) for the Gly-ZW–NaCl(aq) with different NaCl concentrations. Atom labeling for the Gly-ZW corresponds to Fig. 1.

Fig. 12. The dependence of nO1, 2Na+(c) on salt concentration.

decreases to 5.8 when the salt concentration is reaching 5 M (Table 2, nO1OW = 5.7 and nO2OW = 5.9). However, the spatial configuration of the Gly-ZW (Fig. 1) suggests that solvent molecules should be partly “collectivized” by the oxygen atoms of the carboxylate group, i.e. solvent molecules will be shared by O1 and O2. Such a feature of the \COO − hydration shell is also discussed in Refs. [53,70]. Thus, the number of water molecules in the nearest environment of the \COO − group will be not the sum of hydration numbers of nO1OW and nO2OW. It is possible to assume that all water molecules in the hydration shell (or at least most of them) will be H-bonded with oxygen atoms of the \COO − group. This assumption is confirmed by computer simulations yielding an average number of 5.1–5.4 solvent molecules around \COO − [33,67,71,72] but numbers of 3.8–5.8 H-bonds formed by \COO − with water molecules [33,59,67–69]. Increasing salt concentration leads to a decrease of nO1, 2OW and nO1, 2HW (Table 2). In 5 M NaCl(aq) on average ~ 5.8 water molecules were found around each oxygen in the first hydration shell of the \COO − group of Gly-ZW. As mentioned above, this group forms 5.8 H-bonds in total, with on average ~ 2.9 bonds (ΔnO1, 2HW ~ −15%) for each oxygen atom (Table 2).

the peak height, to a shift of its position down to r = 0.378 nm and to the transformation of the shoulder into a small peak at r ~ 0.252 nm (Fig. 6). Our calculation of the coordination number nH1Cl− indicates a low probability for H-bond formation between the Cl − ion and the H1 atom of the \NH3+ group (nH1Cl− = 0.06) in 0.154 M NaCl(aq). This value increases to 1.24 when the salt concentration grows up to 5 M (Fig. 7). This dependence of nH1Cl−(c) on salt concentration indicates that the inorganic anion Cl − ion can form approximately one H-bond with the H1 atom of the \NH3+ group when c > 3 M. As this H1 atom does not form an H-bond with the solvent (see Section 3.1.1), it is possible to suppose that Cl − ion can occupy “vacant” position of oxygen atom of water molecule. The PCF gH2, 3Cl−(r) at the lowest salt concentration is characterized by a doublet of peaks at r = 0.243 nm and r = 0.398 nm respectively (Fig. 8). With increasing salt concentration the peaks heights decrease, the position of the first peak shifts to r = 0.238 nm and the second to r = 0.400 nm (Fig. 8). Comparison of rH2, 3Cl− with rH2, 3OW (0.183 nm, Table 2) indicates that atoms H2 and H3 of the \NH3+

3.2. Ion-molecular complex formation of Gly-ZW with inorganic ions 3.2.1. \NH3+ group At the lowest salt concentration (c = 0.154 M) the PCF gH1Cl−(r) has its first peak at r = 0.395 nm and a shoulder on the left side at r ~ 0.240 nm (Fig. 6). Increasing salt content leads to a decrease of

Fig. 11. Pair correlation functions gO2Na+(r) for the Gly-ZW–NaCl(aq) with different NaCl concentrations. Atom labeling for the Gly-ZW corresponds to Fig. 1.

Table 2 Structural parameters of Gly-ZW hydration at different NaCl concentrations. Subscript W denotes water molecule. Atom labeling for the Gly-ZW corresponds to Fig. 1. Structural parameters

NaCl concentration (mol/l) 0

0.154

0.5

1.0

1.5

2.0

3.0

4.0

5.0

\NH3+ group nN1OW rN1OW (nm) nH2, 3OW rH2, 3OW (nm)

5.09 0.285 1.15 0.183

5.07 0.285 1.14 0.183

5.00 0.285 1.12 0.183

4.93 0.285 1.10 0.183

4.86 0.285 1.08 0.183

4.80 0.285 1.07 0.183

4.69 0.285 1.00 0.183

4.58 0.285 0.99 0.183

4.51 0.285 0.97 0.185

\CH2 group nC2OW rC2OW (nm) nH4, 5OW rH4, 5OW (nm) rH4, 5HW (nm)

4.41 0.323 2.36 0.238 0.320

4.39 0.323 2.36 0.238 0.320

4.33 0.323 2.34 0.238 0.320

4.40 0.323 2.31 0.238 0.320

4.32 0.323 2.29 0.238 0.320

4.25 0.323 2.27 0.238 0.320

4.09 0.323 2.24 0.238 0.320

4.06 0.323 2.24 0.238 0.318

4.10 0.323 2.22 0.238 0.318

\COO− group nO1OW rO1OW (nm) nO2OW rO2OW (nm) nO1HW rO1HW (nm) nO2HW rO2HW (nm)

6.10 0.292 6.50 0.290 3.30 0.160 3.50 0.160

6.07 0.292 6.38 0.290 3.26 0.160 3.52 0.160

6.05 0.292 6.36 0.290 3.21 0.160 3.47 0.160

6.01 0.292 6.24 0.290 3.15 0.160 3.40 0.160

5.97 0.292 6.20 0.290 3.10 0.160 3.33 0.160

5.93 0.292 6.16 0.290 3.05 0.160 3.28 0.160

5.84 0.290 6.06 0.290 2.96 0.160 3.17 0.160

5.81 0.290 6.04 0.290 2.87 0.160 3.09 0.160

5.70 0.290 5.90 0.290 2.80 0.160 3.00 0.160

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group can form “direct” H-bonds only with water molecules. This conclusion is also confirmed by the value for nH2, 3OW (Table 2). Since the distance rH2, 3Cl− is much larger than rH2, 3OW, it is possible to assume that H-bonds between the atoms H2, H3 of the \NH3+ group and Cl − ions are formed through a bridging water molecule, i.e. as – H2,3 … Ow Hw … Cl −. However, the bad resolution of the peak doublet on gH2, 3Cl−(r) does not allow a correct estimate of the fraction of such bonds. 3.2.2. \CH2 group The PCF gH4, 5Cl−(r) characterizing possible H-bonding between the inorganic anion and the atoms H4 and H5 of the \CH2 group has its first peak at r = 0.280 nm (Fig. 9). When the salt concentration grows this peak decreases without changing its position (Fig. 9). According to our calculations, the value of the coordination number nH4, 5Cl− increases from 0.02 for 0.154 M NaCl(aq) to 0.5 for 5 M NaCl(aq). A comparison of rH4, 5Cl− and nH4, 5Cl− with rH4, 5Ow (0.238 nm, Table 2) and nH4, 5Ow (2.2–2.4, Table 2) indicates preferred H-bond formation between water molecules and atoms H4 and H5 of the \CH2 group than between water molecules and Cl − ion. 3.2.3. \COO − group The PCFs gO1Na+(r) and gO2Na+(r) have their first peaks at r = 230 nm (Figs. 10 and 11). With growing salt concentration these peaks decrease without changing position (Figs. 10 and 11). Our calculation of the values nO1, 2Na+ reveals for 0.154 M NaCl(aq) a low probability for the presence of Na + ions in the nearest environment of the \COO − group (nO1Na+ = 0.03, nO2Na+ = 0.04). This probability increases considerably when the salt concentration grows (Fig. 12). In 5 M NaCl(aq) the values for nO1Na+ and nO2Na+ are 0.61 and 0.73, respectively. Taking into account a closeness of these values, equivalence of atoms O1 and O2, and also the fact that the distances rO1, 2Na+ = 0.230 nm is less than distances rO1, 2OW = 0.292 nm, it is possible to assume, that at high salt concentration (3–5 M) the Na + ion is entering into the first hydration shell of the \COO − group between atoms O1 and O2. 4. Conclusions We have presented the results of a 1D-RISM study of the hydration structure of the glycine zwitterion in aqueous NaCl solutions covering a wide concentration range of NaCl (c = 0–5 M). It has been found that at c = 0 M the average number of water molecules in the hydrophilic hydration shells of the \NH3+ and \COO − groups is ~ 5 and ~6 respectively, in the hydrophobic hydration shell of \CH2 group ~ 4 water molecules are located. The average number of Hbonds formed by the \NH3+ group with water molecules is ~ 2, whereas that of \COO − is ~3. Analysis of the structural data revealed that increasing salt concentration only insignificantly decreases the hydration numbers of the functional groups of Gly-ZW (not more than −11.4%). The maximum effect of salt addition on the number of H-bonds formed by the \NH3+ and \COO − groups is − 15%. We suppose that these minor changes in the hydration structure of GlyZW due to the salt effect are connected with an increasing dehydration of the inorganic ions as the salt concentration is growing. Such a dehydration of inorganic ions was frequently observed by dielectric relaxation spectroscopy [73] and diffraction studies [74–76]. In the present study it was established that in Gly-ZW–water and GlyZW–NaCl(aq) systems the probability for H-bond formation between the H1 atom of \NH3+ and water molecules is low. Also H-bonding between the nitrogen atom of \NH3+ and water molecules is absent. It was found that in the Gly-ZW–NaCl(aq) system increasing salt content stimulates the formation of ion-molecular complexes like (\NH3+:Cl −)aq and (\COO −:Na +)aq. We have ascertained the structural mechanism of this process. Namely, the Cl − ion is capable to form a complex with the \NH3+ group through atom H1 of \NH3+

group, whereas the Na + ion forms a complex with the \COO − group by means of chelate formation, i.e. its embedding between the oxygen atoms of \COO −. Acknowledgments This work was supported by funds from the European Union's Seventh Framework Program (FP7-PEOPLE-2009-IRSES, Marie Curie Project) under grant agreement no. 247500 and by the Russian Foundation for Basic Research (grant no. 12-03-97508-r_centre_a). References [1] T.M. Raschke, Current Opinion in Structural Biology 16 (2006) 152–159. [2] G.A. Papoian, J. Ulander, M.P. Eastwood, Z. Luthey-Schulten, R.G. Wolynes, Proceedings of the National Academy of Sciences of the United States of America 101 (2004) 3352–3357. [3] R. Guerois, J.E. Neilsen, L. Serrano, Journal of Molecular Biology 320 (2002) 369–387. [4] S.K. Pal, A.H. Zewail, Chemical Reviews 104 (2004) 2099–2123. [5] L. Jiang, B. Kuhlman, T. Kortemme, D. Baker, Proteins 58 (2005) 893–904. [6] M.A. Dwyer, L.L. Looger, H.W. Hellinga, Science 304 (2004) 1967–1968. [7] G.G. Chilov, O.V. Stroganov, V.K. Svedas, Biochemistry (Moscow) 73 (2008) 56–64. [8] G.I. Makhatadze, P.L. Privalov, Journal of Molecular Biology 232 (1993) 639–659. [9] P.L. Privalov, G.I. Makhatadze, Journal of Molecular Biology 232 (1993) 660–679. [10] C. Reichardt, Solvents and Solvent Effects in Organic Chemistry, Third ed. WileyVCH, Weinheim, Germany, 2002. [11] A. Ben-Naim, K.L. Ting, R.L. Jernigan, Biopolymers 29 (1990) 901–919. [12] A. Ben-Naim, Biopolymers 29 (1990) 567–596. [13] C.J. Camacho, Z.P. Weng, S. Vajda, C. DeLisi, Biophysical Journal 76 (1999) 1166–1178. [14] C.L. Brooks, L. Nilsson, Journal of the American Chemical Society 115 (1993) 11034–11035. [15] R. Carta, G. Tola, Journal of Chemical and Engineering Data 41 (1996) 414–417. [16] W.D. Kohn, C.M. Kay, R.S. Hodges, Journal of Molecular Biology 267 (1997) 1039–1052. [17] A. Kumar, Chemical Reviews 101 (2001) 1–20. [18] S. Dixit, J. Crain, W.C.K. Poon, J.L. Finney, A.K. Soper, Nature 416 (2002) 829–832. [19] K.K. Lee, C.A. Fitch, J.T.J. Lecomte, E.B. Garcia-Moreno, Biochemistry 41 (2002) 5656–5667. [20] J.M. Hamelink, E.S.J. Rudolph, L.A.M. van der Wielen, J.H. Vera, Biophysical Chemistry 95 (2002) 97–108. [21] D.R. Robinson, W.P. Jencks, Journal of the American Chemical Society 87 (1965) 2470–2479. [22] Y. Maréchal, The Hydrogen Bond and the Water Molecule: the Physics and Chemistry of Water, Aqueous and Bio Media, Elsiever, Amsterdam, 2007. [23] S. Takagi, H. Chihara, S. Seki, Bulletin of the Chemical Society of Japan 32 (1959) 84–88. [24] J.S. Gaffney, R.C. Pierce, L. Friedman, Journal of the American Chemical Society 99 (1977) 4293–4298. [25] R. Bonaccorsi, P. Palla, J. Tomasi, Journal of the American Chemical Society 106 (1984) 1945–1950. [26] M. Wolff, In Burger's Medicinal Chemistry, Fourth ed. Wiley, New York, 1979. [27] S. Flock, R. Labarbe, C. Houssier, Journal of Biomolecular Structure & Dynamics 13 (1995) 87–102. [28] S. Flock, R. Labarbe, C. Houssier, Biophysical Journal 71 (1996) 1519–1529. [29] S. Flock, R. Labarbe, C. Houssier, Biophysical Journal 70 (1996) 1456–1465. [30] J.-J. Max, C. Chapados, The Journal of Physical Chemistry. A 108 (2004) 3324–3337. [31] Y. Kameda, H. Ebata, T. Usuki, O. Uemura, M. Misawa, Bulletin of the Chemical Society of Japan 67 (1994) 3159–3164. [32] K. Sugawara, Y. Kameda, T. Usuki, O. Uemura, T. Fukunaga, Bulletin of the Chemical Society of Japan 73 (2000) 1967–1972. [33] M.G. Campo, The Journal of Chemical Physics 125 (114511) (2006) 1–8. [34] L. Stryer, Biochemistry, W. H. Freeman and Comp, San Francisco, 1981. [35] T. Wyttenbach, J. Bushnell, M.T. Bowers, Journal of the American Chemical Society 120 (1998) 5098–5103. [36] B.A. Cerda, S. Hoyau, G. Ohanessian, C. Wesdemiotis, Journal of the American Chemical Society 120 (1998) 2437–2448. [37] E.F. Aziz, N. Ottosson, S. Eisebitt, W. Eberhardt, B. Jagoda-Cwiklik, R. Vacha, P. Jungwirth, B. Winter, The Journal of Physical Chemistry. B 112 (2008) 12567–12570. [38] A. Soto, A. Arce, M.K. Khoskbarchi, Biophysical Chemistry 74 (1998) 165–173. [39] S. Hoyau, G. Ohanessian, Journal of the American Chemical Society 119 (1997) 2016–2024. [40] J. Bertran, L. Rodriguez-Santiago, M. Sodupe, The Journal of Physical Chemistry. B 103 (1999) 2310–2317. [41] S. Hoyau, G. Ohanessian, Chemistry A European Journal 4 (1998) 1561–1569. [42] R.M. Minyaev, A.G. Starikov, V.I. Minkin, Mendeleev Communications 10 (2000) 43–44. [43] K.D. Collins, Biophysical Journal 72 (1997) 65–76.

M.V. Fedotova, S.E. Kruchinin / Journal of Molecular Liquids 169 (2012) 1–7 [44] K.D. Collins, Methods 34 (2004) 300–311. [45] K.D. Collins, Biophysical Chemistry 119 (2006) 271–281. [46] L. Vrbka, J. Vondrasek, B. Jagoda-Cwiklik, R. Vacha, P. Jungwirth, Proceedings of the National Academy of Sciences of the United States of America 103 (2006) 15440–15444. [47] D. Chandler, H.C. Andersen, The Journal of Chemical Physics 57 (1972) 1930–1937. [48] M.V. Fedotova, M.F. Holovko, Theoretical and Experimental Methods of Solution Chemistry (Monograph in Russian), Prospect, Moscow, 2011, pp. 68–152. [49] F. Hirata (Ed.), Molecular Theory of Solvation, Kluwer Academic Publishers, Dordrecht, 2003. [50] C.G. Gray, K.E. Gubbins, Theory of Molecular Fluids, Clarendon Press, Oxford, 1985. [51] J.P. Hansen, I.R. McDonald, Theory of Simple Liquids, third ed. Academic Press, New York, 2006. [52] P.A. Monson, G.P. Morris, in: I. Prigogine, S.A. Rice (Eds.), Adv. Chem. Phys., Wiley, New York, 1990, pp. 451–550. [53] F. Hirata, P.J. Rossky, Chemical Physics Letters 83 (1981) 329–334. [54] J.S. Perkyns, B.M. Pettitt, Chemical Physics Letters 190 (1992) 626–630. [55] M.V. Fedotova, S.E. Kruchinin, Journal of Molecular Liquids 164 (2011) 201–206. [56] A. Kovalenko, F. Hirata, The Journal of Chemical Physics 110 (1999) 10095–10112. [57] A. Kovalenko, F. Hirata, The Journal of Chemical Physics 113 (2000) 2793–2805. [58] E. Bolton, Y. Wang, P.A. Thiessen, S.H. Bryant, Annu. Rep. Comp. Chem., Washington DC, 2008, pp. 217–241. [59] T. Watanabe, K. Hashimoto, H. Takase, O. Kikuchi, Journal of Molecular Structure (THEOCHEM) 397 (1997) 113–119. [60] L. Lue, D. Blankschtein, The Journal of Physical Chemistry 92 (1992) 8582–8594.

7

[61] J. Wang, R.M. Wolf, J.W. Caldwell, P.A. Kollman, D.A. Case, Journal of Computational Chemistry 25 (2004) 1157–1174. [62] M.K. Fedorov, V.I. Zarembo, Volumetric Properties of Aqueous Alkali Halides Solutions at Different Parameters of State (Book in Russian), Izdatelstvo Standartov, Moscow, 1983. [63] W.J. Dunn III, P.I. Nagy, The Journal of Physical Chemistry 94 (1990) 2099–2105. [64] P.G. Kusalik, D. Bergman, A. Laaksonen, The Journal of Chemical Physics 113 (2000) 8036–8046. [65] M.V. Fedotova, S.E. Kruchinin, The Russian Chemical Bulletin (in press). [66] H. Hesske, K. Gloe, The Journal of Physical Chemistry. A 111 (2007) 9848–9853. [67] G. Alagona, C. Ghio, P.A. Kollman, Journal of Molecular Structure (THEOCHEM) 166 (1988) 385–392. [68] K. Leung, S.B. Rempe, The Journal of Chemical Physics 122 (184506) (2005) 1–12. [69] J. Chang, A.M. Lenhoff, S.I. Sandler, The Journal of Physical Chemistry. B 111 (2007) 2098–2106. [70] E.C. Meng, P.A. Kollman, The Journal of Physical Chemistry 100 (1996) 11460–11470. [71] M. Mezei, P.K. Mehrotra, D.L. Beveridge, Journal of Biomolecular Structure & Dynamics 2 (1984) 1–27. [72] S. Gnanasambandam, Z. Hu, J. Jiang, R. Rajagopalan, The Journal of Physical Chemistry. B 113 (2009) 752–758. [73] R. Buchner, Pure and Applied Chemistry 80 (2008) 1239–1252. [74] T. Megyes, S. Bálint, T. Grόsz, T. Radnai, I. Bakό, P. Sipos, The Journal of Chemical Physics 128 (2008) 044501–044512. [75] T. Megyes, S. Bálint, E. Peter, T. Grόsz, I. Bakό, H. Krienke, M.C. Bellissent-Funel, The Journal of Physical Chemistry. B 113 (2009) 4054–4064. [76] A.K. Soper, K. Weckström, Biophysical Chemistry 124 (2006) 181–191.