Why Is Poly(oxyethylene) Soluble in Water? Evidence from the

Article pubs.acs.org/JPCB

Why Is Poly(oxyethylene) Soluble in Water? Evidence from the Thermodynamic Profile of the Conformational Equilibria of 1,2Dimethoxyethane and Dimethoxymethane Revealed by Raman Spectroscopy Ryoichi Wada,† Kazushi Fujimoto,‡ and Minoru Kato*,‡,§ †

Graduate School of Science and Engineering, ‡Department of Pharmacy, College of Pharmaceutical Sciences, and §Graduate School of Life Science, Ritsumeikan University, 1-1-1 Nojihigashi, Kusatsu, Shiga 525-8577, Japan S Supporting Information *

ABSTRACT: The origin of high solubility of poly(oxyethylene) in water has been an open question. Although it is thought that the high solubility of poly(oxyethylene) arises from an increase of the trans−gauche−trans (tgt) conformer in water, the relationship between the increase of the tgt conformer and the solubility is unclear. In this study, we have investigated the conformational equilibria of 1,2-dimethoxyethane, which is a model molecule for poly(oxyethylene), by using Raman spectroscopy, and determined the change in the population and the free energy of each conformer with the aid of density functional theory calculations. The free energy of transfer of the tgt conformer from the pure liquid to the water phase is −6.1 ± 0.2 kJ mol−1. Furthermore, the fraction of the tgt conformer increases from 0.37 to 0.78. Thus, the net contribution of the tgt conformer is −4.8 ± 0.2 kJ mol−1, which is 79% of the total free energy of transfer (−6.07 kJ mol−1). This demonstrates that the high solubility of 1,2-dimethoxyethane originates from the lowest free energy and the highest fraction of the tgt conformer in water. We also successfully explain the thermodynamic mechanism of the low solubility of dimethoxymethane, which is the model molecule for poly(oxymethylene).

1. INTRODUCTION Poly(oxyethylene) (POE) (OCH2CH2)n, also known as polyethylene glycol (PEG) and poly(ethylene oxide) (PEO), is an important material because of its many chemical, biological, medical, and industrial applications. PEO has a wide variety of uses that mainly stem from its flexible structure, nonreactivity, water solubility, and low toxicity. The chemical and biological uses of polymers in surfactant chemistry, osmotic stress techniques, and drug delivery systems are related to the infinitely water-soluble character of the polymers at moderate temperature.1−5 Conversely, poly(oxymethylene) (POM) (OCH2)n is insoluble in water,5 even though the ratio of oxygen to carbon atoms of the POM polymer unit is greater than that of the POE unit. This does not seem to make sense from a chemical point of view, and the molecular mechanism for the high solubility of PEO has long been an open question in solution chemistry. In 1957, a calorimetric study reported that the solvation enthalpy and entropy of POE (MW < 5 000) are negative.6 In 1958−9, the solubility and viscosity of high molecular weight POE (MW = ca. 7 000 000) in aqueous solutions were reported by Bailey et al.,7−9 and the negative solvation enthalpy and entropy of that POE were also estimated.9 This result indicates that the structure and strength of hydration around the POE polymer are important for understating of the solubility © 2014 American Chemical Society

behavior. In 1964, an X-ray study reported that the conformation of the C−O−C−C−O−C segment of crystalline POE is trans−gauche−trans (tgt).10 In 1965 and 1969, NMR11 and IR spectroscopic12 studies showed that the preferred conformations around the C−C and C−O bond of POE in aqueous solutions were gauche and trans, respectively. These results suggest that POE in aqueous solution preferentially adopts the tgt conformation, which is the same conformation observed in the crystalline state. In 1969, Blandamer et al.13 noted that water molecules around POE in aqueous solution form hydrogen bonding networks similar to that of bulk water on the basis of the distances between oxygen atoms in the tgt conformer of POE and suggested that good fitting of the tgt conformer into the hydrogen bonded networks in the aqueous solution is related to the high solubility of POE in water. Since the study by Blandamer et al., a large number of experimental14−37 and theoretical37−50 studies have been performed to elucidate the relationship between the solubility property and the conformation of POE. A Raman spectroscopic study14 indicated that the spectra of POE in aqueous solutions are similar to that of the crystal rather than that of the pure Received: May 19, 2014 Revised: September 1, 2014 Published: September 29, 2014 12223

dx.doi.org/10.1021/jp5048997 | J. Phys. Chem. B 2014, 118, 12223−12231

The Journal of Physical Chemistry B

Article

liquid, suggesting that POE in aqueous solution prefers to form a helical structure. Molecular dynamics (MD) studies38,41 also indicated that POE in aqueous solution forms a helical structure because of the tgt conformation in the C−O−C− C−O−C segments. Vibrational spectroscopic studies of shortchain POEs by Matsuura15−22 showed that the conformations around the C−C and C−O bonds of the short-chain POE in aqueous solution tend to take gauche and trans conformations, respectively. Matsuura et al.32 also suggested that the gauche form around the C−C bond could permit water molecules to form bridging hydrogen bonds between the oxygen atoms of POE and the water molecules. Furthermore, recent ultrafast IR,28 NMR,33 and MD38 studies have reported that the dynamics of hydrated water molecules are slower than bulk water. As discussed above, recent studies support that the tgt form is stabilized in aqueous solution. However, it has not been determined how the increase of the tgt segment influences the solubility of POE. That is, there are no studies to quantitatively estimate the contribution of the increase of the tgt segment to the solubility. The enormous number of possible conformations of POE makes it impossible to quantitatively study. However, the shortest POE, 1,2-dimetoxyethane (DME) (CH3O−CH2− CH2−OCH3), is worth considering as a model molecule because the conformation of DME completely corresponds to the conformational unit of POE. Indeed, there have been a large number of studies using DME as a model molecule.30,32,51−56 The conformers of DME can be quantitatively analyzed by vibrational spectroscopy. A Raman study by Matsuura et al.51 confirmed that the fraction of the tgt conformer of DME increases with increasing water concentration, while the fractions of the ttt and tgg′ conformers decrease. This is consistent with the nature of POE where the conformations around the C−C and C−O bonds prefer gauche and trans, respectively, in aqueous solution. Since the study by Matsuura et al.,51 a substantial amount of important information about the conformational preference53 in aqueous solution, the hydration structure,52,53 and the dynamics of hydrated water52−54 have been accumulated. However, the quantitative relationship between the increase of the proportion of the tgt conformer and the solubility has not yet been clarified. The goal of this study is to establish the relationship, that is, the free energy scheme, as shown in Figure 1. Previous studies by Matsuura et al. provided the data for the free energy differences between the conformers corresponding to the horizontal arrows in Figure 1. However, because the free energy of the transfer of each conformer from its molecular pure liquid to water (vertical arrows in Figure 1) is unknown, the relationship between the solubility (the gross free energy, ΔL→WG) and the change in the population of the conformers has not been established. In this paper, we experimentally determined these values in the pure liquid phase and in aqueous solution to establish the free energy scheme and clarify the thermodynamic origin of the high solubility of DME. In addition, we performed a similar investigation for dimethoxymethane (DMM) (CH3O−CH2−OCH3), which is a model molecule for POM. It is interesting to compare the results between DME and DMM. The solubility of DMM (ΔL→WG = −2.48 kJ mol−1)57,58 is much less than that of DME (ΔL→WG = −6.07 kJ mol−1),59 even though the DMM molecule has fewer hydrophobic methylene groups.60 This characteristic relationship of the solubility between DMM and DME is qualitatively consistent with that between POM and POE.

Figure 1. Free energy scheme of transfer of DME from the pure liquid phase to the water phase. Black and red arrows represent the conformational equilibria of DME and the transfer from the pure liquid to water. ΔL→Wμi is the free energy of transfer of each conformer.

Thus, investigating DMM is also of interest to demonstrate the validity of the present research approach.

2. MATERIALS AND METHOD Materials. 1,2-Dimethoxyethane (99.5%) and dimethoxymethane (98.0%) were purchased from Tokyo Kasei Kogyou Co. (Tokyo, Japan) and were used without further purification. Pure water was prepared by the milli-Q system. The concentration of samples was prepared to be 0.02 of the mole fraction of the solute (xsolute). Raman Measurements. Raman spectra were recorded on a JASCO NR-1800 Raman spectrometer (JASCO, Tokyo, Japan) equipped with an Andor Technology CCD detector. The 90° scatterings were excited by a Spectra Physics Stabilite 2017 argon ion laser (Spectra Physics, Santa Clara, CA) at 514.5 nm with power of 500−800 mW. The spectral resolution was 4.5 cm−1 in all spectra. The sample temperature was controlled at 25 ± 0.3 °C by circulating thermostated water around the cells. Each Raman spectrum of the solute was obtained after subtracting the solvent spectrum from the solution spectrum. All spectral lines were fitted with Gaussian− Lorentzian mixing functions using a curve analysis program (Grams/386, Galactic Industries Co, Salem, NH). The Raman intensities were corrected by a frequency dependent factor: (ν0 − ν)4

⎡ hcν ⎤ ν⎢1 − exp − k T ⎥ ⎣ ⎦ B

( )

where, ν0, ν, h, c, kB, and T are the wavenumber of incident light, Raman shift, Plank constant, speed of light, Boltzmann constant, and thermodynamic temperature, respectively. DFT Calculations. All density functional theory (DFT) calculations were carried out using the Gaussian 09 program.61 The DFT method used the Becke (B) exchange function and Becke’s three-parameter (B3) exchange function62,63 combined with the Lee−Yang−Parr correlation function (B3LYP).64 The geometric optimization, harmonic vibrational wavenumber, and Raman scattering activity calculations were performed for all the conformers of DME and DMM at the B3LYP/aug-ccpVTZ level of theory.65 Here, the Raman activity is defined as (45α′2 + 7γ′2), where α′ and γ′ are the mean polarizability derivative and anisotropy of polarizability tensor derivative, respectively. 12224



Article n

Determination Process of Free Energy of Transfer of Each Conformer from the Pure Liquid to the Water Phase. In this subsection, we derive the equation for calculating the free energy of transfer of each conformer from the pure liquid phase to the water phase (ΔL→Wμi, red arrows in Figure 1) from Raman spectral data with the aid of quantum chemical calculations. ΔL→WG is obtained by subtracting the chemical potential of the molecule in its pure liquid (μL) from that in water (μW) as follows: ΔL → W G = μ W − μL

∑ (yWi i=1

⇔ (yWj − yLj )μLj n

because

Σni=1yiL

=

Σni=1yiW

= 1. Therefore, eq 5 can be written as

n

n

∑

ΔL → W G =

i (yW − yLi )Δj → i μL +

i = 1, i ≠ j

i=1

where ΔL→Wμ and Δ μL in eq 7 correspond to the red and black arrows in Figure 1, respectively. According to the free energy scheme, ΔL→Wμj + Δj→iμW = Δj→iμL + ΔL→Wμi. This equation leads to ΔL→Wμi = ΔL→Wμj + ΔL→WΔj→iμ, where ΔL→WΔj→iμ = Δj→iμW − Δj→iμL. Therefore, eq 7 becomes

(2)

j→i

n

n

μW =

ΔL → W G =

∑ yWi μ Wi

=

μW = =

n

+

i=1 n

∑

n i yW ΔL → W μi

−

∑ yLi μLi

− yLi )μLi +

i=1

∑ yWi ΔL→ W μi i=1

(5)

Now, we consider the jth conformer. The first term on the second line of the right-hand side of eq 5 can be written as n

i=1

∑

i (yW − yLi )μLi + (yWj − yLj )μLj

i = 1, i ≠ j n

=

∑ i = 1, i ≠ j n

=

∑

n i (yW − yLi )μLi −

∑

i (yW − yLi )μLj

i = 1, i ≠ j i (yW − yLi )(μLi − μLj )

i = 1, i ≠ j n

=

∑ i = 1, i ≠ j

i (yW − yLi )Δj → i μL

(8)

3. RESULTS AND DISCUSSION Raman Spectra. In theory, DME can have ten conformers: ttt, tgt, tgg′, tgg, ttg, gtg, gtg′, ggg, gg′g, and ggg′. However, it is impossible for DME to take the gg′g conformer because of steric repulsion between terminal methyl groups. Figure 2 shows the Raman spectra of the pure liquid and an aqueous solution of DME. The mole fraction of DME (xDME) in the aqueous solution was 0.02, to ensure that the DME molecules were fully hydrated. The Raman bands were assigned by comparing with DFT calculations of Raman peak shifts and activities. All of the results are summarized in Table S1 (Supporting Information). Next, we discuss the conformational analyses. The band at 400 cm−1 in Figure 2a is assigned to the O−C−C bending mode of the ttt conformer. The three bands at 545, 555, and 572 cm−1 are assigned to the O−C−C deformation modes of the tgg′, tgg, and tgt conformers, respectively. The bands at 917 and 820 cm−1 are assigned to the C−O stretching vibration modes of the ttg and tgg′ conformers, respectively. These bands are well-resolved and have sufficient intensity to determine the conformer fractions. Although the strong peak at about 840 cm−1 is well-fitted by the three components shown in Figure 2b, four bands are

i=1 n

− yLi )μLi =

i (yW − yLi )Δj → i μL

where ΔL→Wμj is the free energy of transfer of the individual conformer from its molecular pure liquid to water. This is the target parameter in the present study, which corresponds to a red arrow in Figure 1. The values of yiW, yiL, and Δj→iμL are determined both from observed Raman intensities and calculated Raman activities. The values of ΔL→WΔj→iμ are determined from the observed Raman intensities. The details of these determinations are described below.

(4)

i=1

n

∑

∑ yWi ΔL→ W Δj → iμ i=1

n

∑ (yWi

i=1

i = 1, i ≠ j

where ΔL→Wμi indicates the chemical potential of transfer of conformer i from the pure liquid phase to the water phase. Hence, ΔL→WG is given by

=

∑ yWi ΔL→ W Δj → iμ + ΔL→W μ j

n

−

i=1

∑


ΔL → W μ j = ΔL → W G −

− μLi )

∑ yWi μLi + ∑ yWi ΔL→ W μi

ΔL → W G =

i=1 n

Then,

i=1 n

i yW μLi

∑ yWi (ΔL→ W μ j + ΔL→ W Δj → iμ)

n

∑ yWi μLi + ∑ yWi (μ Wi i=1

∑ (yWi

∑

n

i=1 n


i = 1, i ≠ j

where yiL and yiW are the fraction of conformer i of the solute molecule in its pure liquid and in water, respectively, and Σni=1yiL = Σni=1yiW = 1. μiL and μiW are the chemical potentials of conformer i in its pure liquid and in water, respectively. Equation 3 can also be written as n

n

∑ i = 1, i ≠ j n

(3)

i=1

∑ yWi ΔL→ W μi (7)

i

n i=1

i (yW − yLi )μLj

i = 1, i ≠ j

(1)

∑ yLi μLi

∑

=−

When the solute molecule could form n conformers, μL and μW are written as

μL =

− yLi )μLj = 0

(6)

where Δj→iμL = μiL − μjL. To derive the second line from the first line on the right-hand side of eq 6, the following relationships were used: 12225



Article

conformation because of stereorepulsion between the terminal methyl groups. Figure 3 shows the Raman spectra of the DMM

Figure 3. Raman spectra of DMM (a) in the pure liquid and (b) in aqueous solution (xDMM = 0.02). The red, black, blue, and green lines represent the observed spectra, Gaussian−Lorentzian fitted component bands, the sum of the fitted bands, and the difference between the observed and calculated spectra, respectively. The bottom line in each figure is the green line magnified five times.

Figure 2. Raman spectra (230−1010 cm−1) of the DME (a) in the pure liquid and (b) in aqueous solution (xDME = 0.02). The red, black, blue, and green lines represent observed spectra, calculated Gaussian− Lorentzian component bands, the sum of the component bands, and the difference between the observed and calculated spectra, respectively. The bottom line in each figure is the green line magnified 5 times.

liquid and the DMM aqueous solution (xDMM = 0.02) in the region of the C−O−C deformation modes. The other regions of the Raman spectra are unsuitable for conformational analysis because of significant band overlap (data not shown). The bands at 555 and 601 cm−1 are from the tg and gg conformers, respectively. It is well-known that the gauche forms are stabilized by the interaction between the electron lone pairs on the oxygen atoms (anomeric effect).66 However, no bands for the tt conformer were observed in any region, suggesting that the tt conformer has significantly higher energy than the other conformers. Indeed, it has been confirmed by quantum chemical calculations that the energy of the tt conformer is significantly higher than the energies of the gg and tg conformers (Δgg→ttE = 23.3 kJ mol−1 and Δtg→ttE = 12.3 kJ mol−1).67 Figure 3b shows that the relative intensity of the tg conformer is stronger in DMM aqueous solution than in the DMM pure liquid. Conformer Fractions and the Free Energy Difference between the Conformers. The conformer fraction ratios (yi/ yj) between conformers i and j can be calculated using the results of the Raman spectra according to the following equation:

expected from the DFT calculation (Table S1, Supporting Information). Thus, this band overlapping indicates that these bands are unsuitable for the conformational analyses. The weak band at about 935 cm−1 is also interpreted as overlapping bands of the gtg and gtg′ conformers on the basis of the results of DFT calculations (Table S1, Supporting Information). The energies of the gtg, gtg′, ggg, and ggg′ conformers are significantly larger than the other conformers (Table S2, Supporting Information). Consequently, the fractions of those conformers are at most 0.6%. However, because the Raman activities of the H3C−O stretching modes of gtg and gtg′ are very strong, a very weak overlapping band of these conformers was observed at around 935 cm−1. Thus, only the five conformers ttt, tgt, tgg, tgg′, and ttg should be considered. As shown in Figure 2b, the relative intensities of the tgt conformer at 572 cm−1 and the tgg′ conformer at 545 cm−1 become stronger and weaker, respectively, upon changing from the pure liquid to water. The bands of the ttt conformer at 400 cm−1 and the ttg conformer at 917 cm−1 disappear in aqueous solution. Thus, the fraction of the tgt conformer increases and the fractions of the ttt, ttg, and tgg′ conformers significantly decrease upon changing from the pure liquid to the aqueous solution. These results are in agreement with a previous report by Matsuura et al.48 In theory, DMM can have four conformers: tt, tg, gg, and gg′. In fact, it is practically impossible for DMM to form the gg′

yi I is j = yj I jsi

(9)

where I and s are the integrated intensity and Raman activity of each conformer, respectively. The values of I were determined from the observed Raman bands. The values of s were 12226



Article

Table 1. Free Energy Difference (kJ mol−1) between the tgt Conformer and Conformer i (Δtgt→iμL), the Fraction of Conformer i (yi), and ΔL→WΔtgt→iμ of the DME Molecule in Its Pure Liquid and in Water (xDME = 0.02) at 298.2 K Δtgt→iμL

conformer i tgt tgg′ ttt tgg ttg

0 1.8 0.4 5.5 8.3

± ± ± ±

0.4 0.2 0.4 0.4

Δtgt→iμW

yiW

ΔL→WΔtgt→iμ

0 6.0 ± 0.4 8.3 ± 0.4b 8.0 ± 0.4 >15

0.78 ± 0.02 0.14 ± 0.03 0.014 ± 0.003b 0.06 ± 0.01 7

yiL 0.37 0.36 0.16 0.08 0.03

± ± ± ± ±

0.02 0.03 0.01 0.01 0.02

a The errors of ΔL→WΔtgt→iμL are due to the Raman integrated intensity. The errors of the other parameters include errors of the Raman integrated intensity and Raman activities (see Supporting Information for details). bThis value was estimated from the linear extrapolation of the concentration dependence of ΔL→WΔtgt→iμL. cThis value was estimated from S/N of the Raman spectrum

Table 2. Free Energy Difference (kJ mol−1) between the gg Conformer and Conformer i (Δgg→iμ), the Fraction of Conformer i (yi), and ΔL→WΔgg→iμ of the DMM Molecule in Its Pure Liquid and in Water (xDMM = 0.02) at 298.2 Ka conformer i

Δgg→iμL

yiL

Δgg→iμW

yiW

ΔL→WΔgg→iμ

gg tg

0 8.0 ± 0.2

0.93 ± 0.01 0.07 ± 0.01

0 5.1 ± 0.2

0.80 ± 0.01 0.20 ± 0.01

0 −2.89 ± 0.05a

a The error of ΔL→WΔgg→iμ is due to the Raman integrated intensity. The errors of the other parameters include errors of the Raman integrated intensity and Raman activities (see Supporting Information for details)

estimated from the Raman intensities. The value of ΔL→WΔtgt→tttμ at 0.02 was estimated to be 7.9 ± 0.4 kJ mol−1 by linear extrapolation using the data for mole fractions >0.1, as shown in Figure 4. The value of Δtgt→tttμW was determined to

estimated by B3LYP/aug-cc-pVTZ DFT calculations. The values of I and s for DME and DMM are shown in Tables S3−S5 (Supporting Information). The fractions of the conformers of DME and DMM calculated in this way are summarized in Tables 1 and 2, respectively. It is known that the quantum calculation of s has a significant error. We estimated the errors according to the error evaluation method of Zvereva et al.68 (see the Supporting Information for details). The chemical potential difference between conformers j and i (Δj→iμ) is given by the following equation: Δj → i μ = −RT ln i

d jy i d js jI i i j = − RT ln i i j dy dsI

(10)

j

where d and d are the degeneracy of conformers i and j, respectively (e.g., dttt = 1 and dtgt = 2 for DME). R and T are the gas constant and the thermodynamic temperature, respectively. From the calculated values of si and the observed values Ii for the conformers summarized in Tables S3−S5 (Supporting Information), we determined the values of Δj→iμLin eq 8. The values are summarized in Table 1. Furthermore, ΔL→WΔj→iμ is given by the following equation:

Figure 4. Concentration dependence of ΔL→WΔttt→tgtμ of DME in aqueous solution. The solid line represents the linear fit to the data.

be 8.3 ± 0.4 kJ mol−1 from this data, and Δtgt→tttμL = 0.4 ± 0.2 kJ mol−1 in Table 1. From these values, the mole fraction of the ttt conformer in aqueous solution is expected to be 2.8 × 10−4, which is too small to observe the Raman band. Free Energy of Transfer of Each Conformer from the Pure Liquid to the Water Phase. Here, we discuss the thermodynamic mechanism of the high solubility of DME in water on the basis of the conformational thermodynamic data obtained above. The free energy of transfer of each conformer of DME and DMM from the pure liquid to the water phase, which is given by eq 8, can be calculated using the data in Tables 1 and 2. The free energy values calculated in this way are summarized in Table 3. These values correspond to the changes in chemical potential indicated by the red arrows in Figure 1. For the quantitative comparison, we also give the thermodynamic profiles among these values, as shown in Figure 5. Except for the ttt and ttg conformers, the free energy was negative. Because the fractions of the ttt and ttg conformers are very small, the net contributions of these conformers are negligible. For DME, the notable points are that the negative

ΔL → W Δj → i μ = Δj → i μ W − Δj → i μL ⎛ ⎛ d js jI i ⎞ d js jI i ⎞ = ⎜ −RT ln i i j ⎟ − ⎜ −RT ln i i j ⎟ ⎝ d s I ⎠W ⎝ d s I ⎠L (11)

Assuming that the Raman activity ratio of conformer i to j does not depend on the solvent, eq 11 can be rewritten as ⎛ ⎛ Ii ⎞ Ii ⎞ ΔL → W Δj → i μ = ⎜ −RT ln j ⎟ − ⎜ −RT ln j ⎟ ⎝ I ⎠W ⎝ I ⎠L

(12)

Finally, ΔL→WΔ μ can be determined only from the observed Raman intensities. The errors due to the above assumption would be as small as the experimental errors (Supporting Information). The values determined for j = tgt (DME) and j = tg (DMM) are also summarized in Tables 1 and 2, respectively. As mentioned above, the band of the ttt conformer was not observed at a mole fraction of 0.02 in aqueous solution. Thus, ΔL→WΔtgt→tttμ at a mole fraction of 0.02 cannot be directly j→i

12227



Article

Nevertheless, it is important to discuss the effect of the DME concentration on the present thermodynamic picture, given that the structure of longer POE polymers is analogous to the locally crowded state of the unit. It is known that the fraction of the tgt conformer decreases while those of the other conformers increase as the DME concentration increases.51 In this work, we also measured the concentration dependence of the Raman spectra to obtain the concentration effect on the relative free energies of the transfer of the tgt conformer from the pure liquid to aqueous solution (ΔL→WΔi→tgtμ) given by eq 11, as shown in Figure S1 (Supporting Information). The figure shows that all these values are negative over the whole concentration range and are greatly negative at concentrations below 40 wt %. Thus, the present thermodynamic picture could hold at a modest concentration of DME and in the case of the POE polymer in aqueous solution. The above approach used in the analysis of DME would be useful for other similar systems. Therefore, we discuss the molecular mechanism for the relatively low solubility of DMM in water in a similar way. The values of ΔL→Wμgg and ΔL→Wμtg are −2.9 ± 0.1 and −5.8 ± 0.2 kJ mol−1, respectively. The latter value is comparable with ΔL→Wμtgt of DME. If the tg conformer was the main conformer in water, the solubility of DMM would be high, as is the case for DME. However, the fraction of the tg conformer of DMM in water is only 0.20, which is small compared with the tgt conformer of DME. Thus, the net contribution (ytgWΔL→Wμtg) becomes −1.2 ± 0.2 kJ mol−1 (−5.8 ± 0.2 kJ mol−1 × 0.20), which accounts for 48% of the total free energy of transfer of DMM from its pure liquid to water (−2.48 kJ mol−1).57,58 Unlike the case of DME, the conformer tg contributing to the decrease of the free energy is minor in the conformer population. This is the reason why the solubility of DMM in water is lower than that of DME. In the case of DMM, the tg conformer is significantly stabilized in water, as is the case of the tgt conformer of DME. Nevertheless, the tg conformer in water does not significantly contribute to increase of the solubility of DMM. Although the contrasting behavior of DME and DMM seems not to make sense, it is easily understood if we consider the chemical potential profile in Figure 5. In aqueous solution, the tgt conformer of DME is the energetically most favorable conformer, whereas the tg conformer of DMM is the energetically least favorable conformer. Even though the solvation energies of both conformers are similar, the tg conformer is still the least energetically favorable conformer of DMM in aqueous solution. As a result, the solvation energy of the tg conformer does not significantly contribute to the solubility.

Table 3. Free Energy of Transfer of Conformer i of the DME and DMM Molecules from the Pure Liquid to Water at 298.2 Ka solute

conformer i

DME

tgt tgg′ ttt tgg ttg gg tg

DMM

ΔL→Wμi/kJ mol−1 −6.1 +1.8 −1.9 −3.6 >+1 −2.9 −5.8

± ± ± ±

0.2 0.2 0.4 0.2

± 0.1 ± 0.2

a

The errors of the parameters include errors of the Raman integrated intensity and Raman activities (see Supporting Information for details).

Figure 5. Chemical potential profiles of the conformers of DME and DMM in the pure liquid (black bar) and water (blue bar). Red arrows indicate the free energies of the transfer of the conformers of DME and DMM, which correspond to the red arrows in Figure 1. The values above and below the lines of the energy levels represent the fractions of each conformer.

value of the tgt conformer (ΔL→Wμtgt) is markedly larger (−6.1 ± 0.2 kJ mol−1) than those of the other conformers, which are between 1.8 ± 0.4 and −3.6 ± 0.2 kJ mol−1. Furthermore, the fraction of the tgt conformer drastically increases from 0.37 to 0.78 when going from the pure liquid to the aqueous phase tgt (Table 1). Hence, the net contribution of ytgt W ΔL→Wμ is −4.8 ± −1 −1 0.2 kJ mol (−6.1 ± 0.2 kJ mol × 0.78), which accounts for 79% of the total free energy (−6.07 kJ mol−1) obtained from a vapor pressure measurement by Cabani et al.59 The remaining contribution of −1.2 ± 0.2 kJ mol−1 (21%) comes from the ttt, tgg′, and tgg conformers. Therefore, the high solubility of DME in water mainly originates from the increase in the fraction of the tgt conformer, which has the lowest free energy of transfer among the conformers. The present approach based on the free energy scheme provides definitive evidence for the mechanism of the high solubility of DME in water. In the above discussion, we focused on the dilute aqueous solution because the infinitely dilute solution is supposed to be the thermodynamic standard state. Thus, we can use the standard free energy quantity calculated from Cabani’s solubility data59 to obtain the present free energy scheme.

4. CONCLUDING REMARKS To understand the mechanism of high solubility of poly(oxyethylene) (POE), we have investigated the solvent (water) effect on the conformational equilibria of 1,2-dimethoxyethane (DME) by Raman spectroscopy with the aid of DFT calculations. We determined the change in the population and the free energy of transfer of each conformer from the pure liquid phase to the water phase. From the results, we established the free energy scheme of conformational equilibria of DME in its pure liquid and in water (Figure 1), which quantitatively explains the high solubility of DME in water. This approach was also successful for explaining the low solubility of DMM in water. 12228



Article

(6) Malcolm, G. N.; Rowlinson, J. S. The Thermodynamic Properties of Aqueous Solutions of Polyethylene Glycol, Polypropylene Glycol and Dioxane. Trans. Faraday Soc. 1957, 53, 921−931. (7) Bailey, F. E., Jr.; Powell, G. M.; Smith, K. L. Solution Property. Ind. Eng. Chem. 1958, 50, 8−11. (8) Bailey, F. E., Jr.; Callard, R. W. Properties of Poly(ethylene oxide) in Aqueous Solution. J. Appl. Polym. Sci. 1959, 1, 56−62. (9) Bailey, F. E., Jr.; Callard, R. W. Thermodynamic Parameters of Poly(ethylene oxide) in Aqueous Solution. J. Appl. Polym. Sci. 1959, 1, 373−374. (10) Tadokoro, H.; Chatani, Y.; Yoshihara, T.; Murahashi, S. Structural Studies on Polyethers, [-(CH2)m-O-]n II. Molecular Structure of Polyethylene Oxide. Makromol. Chem. 1964, 73, 109− 127. (11) Connor, T. M.; McLauchlan, K. A. High Resolution Nuclear Resonance Studies of the Chain Conformation of Polyethylene Oxide. J. Phys. Chem. 1965, 69, 1888−1893. (12) Liu, K.; Parsons, J. L. Solvent Effects on the Preferred Conformation of Poly(ethylene glycols). Macromolecules 1969, 2, 529−533. (13) Blandamer, M. J.; Fox, M. F.; Powell, E.; Stafford, J. W. A Viscometric Study of Poly(ethylene oxide) in t-Butyl Alcohol/Water Mixtures. Makromol. Chem. 1969, 124, 222−231. (14) Koenig, J. L.; Angood, A. C. J. Raman Spectra of Poly(ethylene glycols) in Solution. Polym. Sci. Part A-2 1970, 8, 1787−1796. (15) Matsuura, H.; Fukuhara, K. Conformational Analysis of Poly(oxyethylene) Chain in Aqueous Solution as a Hydrophilic Moiety of Nonionic Surfactants. J. Mol. Struct. 1985, 126, 251. (16) Masatoki, S.; Takamura, M.; Matsuura, H.; Kamogawa, K.; Kitagawa, T. Raman Spectroscopic Observations of Anomalous Conformational Behavior of Short Poly(oxyethylene) Chains in Water. Chem. Lett. 1995, 24, 991−992. (17) Matsuura, H.; Sagawa, T. Anomalous Conformational Behavior of Short Poly(oxyethylene) Chains in Water: An FT-IR Spectroscopic Study. J. Mol. Liq. 1995, 65−66, 313−316. (18) Begum, R.; Matsuura, H. Conformational properties of short poly(oxyethylene) chains in water studied by IR spectroscopy. J. Chem. Soc., Faraday Trans. 1997, 93, 3839−3848. (19) Wahab, S. A.; Matsuura, H. IR Spectroscopic Study of Conformational Properties of a Short-chain Poly(oxyethylene) (C1E3C1) in Binary Mixtures with Liquids of Different Hydrogenbonding Abilities. Phys. Chem. Chem. Phys. 2001, 3, 4689−4695. (20) Wahab, S. A.; Matsuura, H. Temperature Dependence of the Anomalous Conformational Behavior of a Short-Chain Poly(oxyethylene) in Water Studied by Raman Spectroscopy. Chem. Lett. 2001, 30, 198−199. (21) Marinov, V. S.; Matsuura, H. Raman Spectroscopic Study of Temperature Dependence of Water Structure in Aqueous Solutions of a Poly(oxyethylene) Surfactant. J. Mol. Struct. 2002, 610, 105−112. (22) Wahab, S. A.; Matsuura, H. Raman Spectroscopic Study of Conformational Properties of a Short-Chain Poly(oxyethylene) (C1E3C1) in Polar Solvents at Different Temperatures. J. Mol. Struct. 2002, 606, 35−43. (23) Ide, M.; Yoshikawa, D.; Maeda, Y.; Kitano, H. State of Water Inside and at the Surface of Poly(ethylene glycol) Films Examined by FT-IR. Langmuir 1999, 15, 926−929. (24) Maeda, Y.; Ide, M.; Kitano, H. Vibrational Spectroscopic Study on the Structure of Water in Polymer Systems. J. Mol. Liq. 1999, 80, 149−163. (25) Ohno, K.; Takao, H.; Katsumoto, Y. Geometrical Behavior of Hydrogen Bonding Patterns in the α-Dodecyl-ω-hydroxy-tris(oxyethylene)−water System Monitored by Near Infrared Spectroscopy. Spectrochimica Acta Part A 2006, 63, 690−693. (26) Matin, M. R.; Wahab, S. A.; Katsumoto, Y.; Matsuura, H.; Ohno, K. Thermal Stability of the Hydration Structure of Short-Chain Poly(oxyethylene) in Carbon Tetrachloride: An Infrared Spectroscopic Observation of the Breakdown of Hydrogen Bonds. Chem. Lett. 2005, 34, 502−503.

The contrasting features of DME and DMM are interesting from the viewpoint of the solution property of the chain polymer. In general, the solution property of a molecule depends on the properties of the functional groups composing the molecule, that is, whether the functional groups are hydrophilic, hydrophobic, or ionic. However, the solubilities of DME and DMM do not obey the general rule. In the present study, we explain the seemingly conflicting results from the different conformational behavior of DME and DMM: the conformer tgt contributing to greatly increase the solubility in water for DME whereas the corresponding conformer tg only modestly increasing the solubility of DMM in water. This reveals that the conformational behavior of the chain molecule significantly influences the solution property of the molecules. Application of this feature of the chain molecule to develop functional molecules would be attractive from the viewpoint of molecular design.

■

ASSOCIATED CONTENT

S Supporting Information *

Explanation of the assignment of Raman spectra of DME energy of conformers, estimation of the accuracy of the calculated Raman scattering cross-section, calculation of ΔL→WG from the experimental data of Cabani et al., and the solvent dependence on Raman scattering activity ratios. Tables of Raman peack frequencies and activities, conformer energies, Raman activity ratios, integrated intensity ratios, and Raman scattering activity ratios. Figure showing the concentration dependence of ΔL→WΔi→tgtμ. This material is available free of charge via the Internet at http://pubs.acs.org.

■

AUTHOR INFORMATION

Corresponding Author

*M. Kato. E-mail: [email protected]. Author Contributions

The manuscript was written through contributions of all authors. Notes

The authors declare no competing financial interest.

■

ACKNOWLEDGMENTS This work was supported by grants from the Ritsumeikan Global Innovation Research Organization (R-GIRO) and Institute for Chemical Fibers, Japan.

■ ■

ABBREVIATIONS POE, poly(oxyethylene); POM, poly(oxymethylene); DME, 1,2-dimethoxyethane; DMM, dimethoxymethane REFERENCES

(1) Elbert, D. L.; Hubbell, J. A. Surface Treatments of Polymers for Biocompatibility. Annu. Rev. Mater. Sci. 1996, 26, 365−394. (2) Harris, M., Jr.; Zalipsky, S. Poly(ethylene glycol): Chemistry and Biological Applications; American Chemical Society: Washington, DC, 1997. (3) Dhawan, S.; Varma, M.; Sinha, V. R. High Molecular Weight Poly(ethylene oxide)-based Drug Delivery Systems. Part I: Hydrogels and Hydrophilic Matrix Systems. Pharm. Technol. 2005, 29, 72−80. (4) Dhawan, S.; Dhawan, K.; Varma, M.; Sinha, V. R. Applications of Poly(ethylene oxide) in Drug Delivery Systems. Part II. Pharm. Technol. 2005, 29, 82−96. (5) Bailey, F. E., Jr.; Koleske, J. V. Poly(Ethylene Oxide); Academic Press, New York, 1976. 12229



Article

(27) Matin, M. R.; Katsumoto, Y.; Matsuura, H.; Ohno, K. Hydration of Short-Chain Poly(oxyethylene) in Carbon Tetrachloride: An Infrared Spectroscopic Study. J. Phys. Chem. B 2005, 109, 19704− 19710. (28) Fenn, E. E.; Moilanen, D. E.; Levinger, N. E.; Fayer, M. D. Water Dynamics and Interactions in Water-Polyether Binary Mixtures. J. Am. Chem. Soc. 2009, 131, 5530−5539. (29) Crupi, V.; Jannelli, M. P.; Magazu, S.; Maisano, G.; Ma-jolino, D.; Migliardo, P.; Ponterio, R. Raman Spectroscopic Study of Water in the Poly(ethylene glycol) Hydration Shell. J. Mol. Struct. 1996, 381, 207−212. (30) Georgiev, M.; Popova, T.; Nickolov, Z. S.; Goutev, N.; Georgiev, G.; Matsuura, H. Raman Spectroscopic Study of the Hydration of Short-chain Poly(oxyethylene)s C1EnC1 (n = 1−4). Cent. Eur. J. Chem. 2004, 4, 617−626. (31) Marinov, V. S.; Nickolov, Z. S.; Matsuura, H. Raman Spectroscopic Study of Water Structure in Aqueous Nonionic Surfactant Solutions. J. Phys. Chem. B 2001, 105, 9953−9959. (32) Matsuura, H.; Fukuhara, K. Hydration of the Oxyethylene Chain. Hypersonic Velocities in Aqueous Solutions of α-Methyl-ωmethoxyoligo(oxyethylene)s and α-Methyl-ω-hydroxyoligo(oxyethylene)s as Studied by Brillouin Scattering. Bull. Chem. Soc. Jpn. 1986, 59, 763−768. (33) Sturlaugson, A. L.; Fruchey, K. S.; Lynch; Aragón, S. R.; Fayer, M. D. Orientational and Translational Dynamics of Polyether/Water Solutions. J. Phys. Chem. B 2010, 114, 5350−5358. (34) Rogers, J. A.; Tam, T. Solution Behavior of Polyethylene Glycols in Water using Vapor Pressure Osmometry. Can. J. Pharm. Sci. 1977, 12, 65−70. (35) Maron, S. H.; Filisko, F. E. Heats of Solution and Dilution for Polyethylene Oxide in Several Solvents. J. Macromol. Sci. Phys. 1972, 6, 79−90. (36) Douheret, G.; Davis, M. I.; Fjellangerc, I. J.; Hoilandc, H. Ultrasonic Speeds and Volumetric Properties of Binary Mixtures of Water with Poly(ethylene glycol)s at 298.15 K. J. Chem. Soc., Faraday Trans. 1997, 93, 1943−1949. (37) Borodin, O.; Trouw, F.; Bedrov, D.; Smith, G. D. Temperature Dependence of Water Dynamics in Poly(Ethylene Oxide)/Water Solutions from Molecular Dynamics Simulations and Quasielastic Neutron Scattering Experiments. J. Phys. Chem. B 2002, 106, 5184− 5193. (38) Tasaki, K. Poly(oxyethylene)-Water Interactions: A Molecular Dynamics Study. J. Am. Chem. Soc. 1996, 118, 8459−8469. (39) Smith, G. D.; Bedrov, D.; Borodin, O. Molecular Dynamics Simulation Study of Hydrogen Bonding in Aqueous Poly(Ethylene Oxide) Solutions. Phys. Rev. Lett. 2000, 85, 5583−5587. (40) Bedrov, D.; Smith, G. D. A Molecular Dynamics Simulation Study of the Influence of Hydrogen-Bonding and Polar Interactions on Hydration and Conformations of a Poly(ethylene oxide) Oligomer in Dilute Aqueous Solution. Macromolecules 2002, 35, 5712−5719. (41) Lee, H.; Venable, R. M.; MacKerell, A. D., Jr.; Pastor, R. W. Molecular Dynamics Studies of Polyethylene Oxide and Polyethylene Glycol: Hydrodynamic Radius and Shape Anisotropy. Biophys. J. 2008, 95, 1590−1599. (42) Fischer, J.; Paschek, D.; Geiger, A.; Sadowski, G. Modeling of Aqueous Poly(oxyethylene) Solutions. 1. Atomistic Simulations. J. Phys. Chem. B 2008, 112, 2388−2398. (43) Fischer, J.; Paschek, D.; Geiger, A.; Sadowski, G. Modeling of Aqueous Poly(oxyethylene) Solutions. 2. Mesoscale Simulations. J. Phys. Chem. B 2008, 112, 13561−13571. (44) Hezaveh, S.; Samanta, S.; Milano, G.; Roccatano, D. Molecular Dynamics Simulation Study of Solvent Effects on Conformation and Dynamics of Polyethylene Oxide and Polypropylene Oxide Chains in Water and in Common Organic Solvents. J. Chem. Phys. 2012, 136, 124901. (45) Aray, Y.; Marquez, M.; Rodriguez, J.; Vega, D.; Simon-Manso, Y.; Coll, S.; Gonzalez, C.; Weitz, D. A. Electrostatics for Exploring the Nature of the Hydrogen Bonding in Polyethylene Oxide Hydration. J. Phys. Chem. B 2004, 108, 2418−2424.

(46) Wahab, S. A.; Harada, T.; Matsubara, T.; Aida, M. Quantum Chemical Study of the Interaction of the Short-Chain Poly(oxyethylene)s CH3(OCH2CH2)mOCH3 (C1EmC1; m = 1 and 2) with a Water Molecule in the Gas Phase and in Solutions. J. Phys. Chem. A 2006, 110, 1052−1059. (47) Kjellander, R.; Florin, E. Water Structure and Changes in Thermal Stability of the System Poly(ethylene oxide)-Water. J. Chem. Faraday Trans. 1981, 77, 2053−2077. (48) Goldstein, R. E. On the Theory of Lower Critical Solution Points in Hydrogen-Bonded Mixtures. J. Chem. Phys. 1984, 80, 5340− 5341. (49) Karlström, G. A New Model for Upper and Lower Critical Solution Temperatures in Poly(ethylene oxide) Solution. J. Phys. Chem. 1985, 89, 4962−4964. (50) Dormidontova, E. E. Role of Competitive PEO-Water and Water-Water Hydrogen Bonding in Aqueous Solution PEO Behavior. Macromolecules 2002, 35, 987−1001. (51) Goutev, N.; Ohno, K.; Matsuura, H. Raman Spectroscopic Study on the Conformation of 1,2-Dimethoxyethane in the Liquid Phase and in Aqueous Solutions. J. Phys. Chem. A 2000, 104, 9226− 9232. (52) Kriz, J.; Dybal, J. Hydration Modes of an Amphiphilic Molecule 2: NMR, FTIR and Theoretical Study of the Interactions in the System Water−1,2-dimethoxyethane. Chem. Phys. 2011, 382, 104− 112. (53) Goutev, N.; Nickolov, Z. S.; Matsuura, H. 1,2-Dimethoxyethane (C1E1C1): O-H Raman Band Studies. J. Mol. Liq. 1998, 76, 117−126. (54) Bedrov, D.; Pekny, M.; Smith, G. D. Quantum-Chemistry-Based Force Field for 1,2-Dimethoxyethane and Poly(ethylene oxide) in Aqueous Solution. J. Phys. Chem. B 1998, 102, 996−1001. (55) Bedrov, D.; Borodin, O.; Smith, G. D. Molecular Dynamics Simulation of 1,2-Dimethoxyethane/Water Solutions. 2. Dynamical Properties. J. Phys. Chem. B 1998, 102, 5683. (56) Hezaveh, S.; Samanta, S.; Milano, G.; Roccatano, D. Structure and Dynamics of 1,2-Dimethoxyethane and 1,2-Dimethoxypropane in Aqueous and Non-aqueous Solutions: A Molecular Dynamics Study. J. Chem. Phys. 2011, 135, 164501. (57) Cabani, S.; Gianni, P.; Mollica, V.; Lepori, L. Group Contributions to the Thermodynamic Properties of Non-ionic Organic Solutes in Dilute Aqueous Solution. J. Sol. Chem. 1981, 10, 563−595. (58) Pan, J.; Wu, J.; Liu, Z. Vapor Pressure of Dimethoxymethane and 1,1,1,3,3-Pentafluoropropane. J. Chem. Eng. Data 2006, 51, 186− 189. (59) Cabani, S.; Mollica, V.; Lepori, L. Thermodynamic Study of Dilute Aqueous Solutions of Organic Compounds. Part 5.Open-chain Saturated Bifunctional Compounds. J. Chem. Soc. Faraday Trans. 1978, I 74, 2667−2671. (60) The values of ΔL→WG were calculated from the experimental data of Cabani et al.57,58. See the Supporting Information for more detail. (61) Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman, J. R.; Scalmani, G.; Barone, V.; Mennucci, B. et al. Gaussian 09, Revision A.1; Gaussian, Inc.: Wallingford, CT, 2009. (62) Beche, A. D. Density Functional Thermochemistry. III. The Role of Exact Exchange. J. Chem. Phys. 1993, 98, 5648. (63) Beche, A. D. Density-functional Exchange-energy Approximation with Correct Asymptotic Behavior. Phys. Rev. A 1988, 38, 3098− 3101. (64) Lee, C.; Yang, W.; Parr, R. G. Development of the Colle-Salvetti correlation-energy formula into a functional of the electron density. Phys. Rev. B 1988, 37, 785−790. (65) Woon, D. E.; Dunning, T. H. Calculation of the Electron Affinities of the Second Row Atoms: Al−Cl. J. Chem. Phys. 1993, 99, 3730. (66) Edward, J. T. Stability of Glycosides to Acid Hydrolysis. Chem. Ind. (London) 1955, 36, 1102−1104. 12230



Article

(67) Vila, A.; Mosquera, R. A. Atoms in Molecules Interpretation of the Anomeric Effect in the O-C-O Unit. J. Comput. Chem. 2007, 28, 1516−1530. (68) Zvereva, E. E.; Shagidullin, A. R.; Katyuba, S. A. Ab Initio and DFT Predictions of Infrared Intensities and Raman Activities. J. Phys. Chem. A 2011, 115, 63−69.

12231


Why Is Poly(oxyethylene) Soluble in Water? Evidence from the

Recommend Documents