Solvation Structure of 1,3-Butanediol in Aqueous Binary Solvents with

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Solvation Structure of 1,3-Butanediol in Aqueous Binary Solvents with Acetonitrile, 1,4-Dioxane, and Dimethyl Sulfoxide Studied by IR, NMR, and Molecular Dynamics Simulation Toshiyuki Takamuku, Yasuhito Higuma, Masaru Matsugami, Takahiro To, and Tatsuya Umecky J. Phys. Chem. B, Just Accepted Manuscript • DOI: 10.1021/acs.jpcb.7b02202 • Publication Date (Web): 20 Apr 2017 Downloaded from http://pubs.acs.org on April 24, 2017

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The Journal of Physical Chemistry

Solvation Structure of 1,3-Butanediol in Aqueous Binary Solvents with Acetonitrile, 1,4-Dioxane, and Dimethyl Sulfoxide Studied by IR, NMR, and Molecular Dynamics Simulation

Toshiyuki Takamukua,*, Yasuhito Higumaa, Masaru Matsugamib, Takahiro Toa, and Tatsuya Umeckya a

Department of Chemistry and Applied Chemistry, Graduate School of Science and

Engineering, Saga University, Honjo-machi, Saga 840-8502, Japan b

Faculty of Liberal Studies, National Institute of Technology, Kumamoto College, 2659-2

Suya, Koshi, Kumamoto 861-1102, Japan

Corresponding Author Tel: +81-952-28-8554 *E-mail: [email protected]

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ABSTRACT

The solvation structure of 1,3-butanediol (1,3-BD) in aqueous binary solvents of acetonitrile (AN), 1,4-dioxane (DIO), and dimethyl sulfoxide (DMSO) at various mole fractions of organic solvent xOS has been clarified by means of infrared (IR) and 1H and

13

C NMR. The

change in the wavenumber of O−H stretching vibration of 1,3-BD in the three systems suggested that water molecules which are initially hydrogen-bonded with the 1,3-BD hydroxyl groups in the water solvent (xOS = 0) are more significantly replaced by organic solvent molecules in the order of DMSO >> DIO > AN. This agrees with the order of the electron donicities of the organic solvents. The 1H and

13

C chemical shifts of 1,3-BD also

revealed the most remarkable replacement of water molecules on the hydroxyl groups by DMSO. In contrast to the DMSO system, the O−H vibration band of 1,3-BD in the AN and DIO systems suggested the formation of the intramolecular hydrogen bond between the two hydroxyl groups of 1,3-BD above xOS = ∼0.9. To further evaluate the intramolecular hydrogen bonding of 1,3-BD in AN−water binary solvents, molecular dynamics (MD) simulations and NMR experiments for spin-lattice relaxation times T1 and 1H−1H nuclear Overhauser effect (NOE) were conducted on 1,3-BD in the AN system. These results showed the intramolecular hydrogen bond within 1,3-BD in the AN−water binary solvents in the high AN mole fraction range of xAN > 0.9. Especially, the pair correlation functions g(r) of the OH−O interactions of 1,3-BD obtained from the MD simulations indicated that the intramolecular hydrogen bond remarkably increases in the AN solvent as the xAN rises to the unity.


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1. INTRODUCTION Various diols like ethylene glycol, which have two hydroxyl groups within the hydrocarbon chain, are often used for cryobiology. Biological cells and organs may be prevented from damaging in their aqueous solutions during cryopreservation on adding diols.1,2 This is because diol molecules inhibit the crystallization of water, which may injury cells and organs. By adding diol water may be unfrozen or vitrified even below the freezing point of water.3,4 The hydration structure of diols is the key to prevent the formation of regular ice Ih. The hydrogen bonding of the two hydroxyl groups of diol with water molecules may mainly govern the thermal properties of the aqueous mixtures of diols.5-7 Additionally, the conformation of the hydrophobic hydrocarbon chain of diols may contribute to the properties. The hydrophobic chain may be folded to reduce the surface area against water.8,9 The intramolecular hydrogen bond between the two hydroxyl groups within a diol molecule plays the key to the determination of conformation if the geometry of the hydroxyl groups is able to form the hydrogen bond. Butanediols (BDs) with the linear hydrocarbon chain involve four isomers depending on the positons of the hydroxyl groups, except for their optical isomers. Many researches have been conducted on the conformation of BDs using several techniques, such as microwave spectroscopy10,11 and NMR.12 The majority of the researches are the theoretical calculations, such as density functional theory (DFT).11-15 The DFT calculations have suggested that all of the four isomers may form the intramolecular hydrogen bond between the two hydroxyl groups. In the gas state, the hydrogen bond of BDs is more stable in the order of 1,4-BD > 1,3-BD > 1,2-BD ≈ 2,3-BD.14 The intramolecular hydrogen bond has also been experimentally evaluated in carbon tetrachloride (CCl4) solutions by infrared (IR) spectroscopy.14 The strength of the hydrogen bond of BDs in CCl4 is stronger in the same 3 ACS Paragon Plus Environment


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order as that of the gas state. One can expect that the intramolecular hydrogen bonding of BDs should be governed by two factors in their solutions; one is the solvation for the two hydroxyl groups of BDs by solvent molecules, and the other is the electrostatic environment for BDs generated by polarities of solvents. However, the dependence of the intramolecular hydrogen bonding of BDs on solvent properties has not yet been elucidated in various solvents on the molecular scale. In the present study, we have clarified the solvation structure of 1,3-BD in aqueous binary solvents of three aprotic solvents, acetonitrile (AN), 1,4-dioxane (DIO), and dimethyl sulfoxide (DMSO) with varying mole fraction of organic solvent xOS. One of the reasons why we chose 1,3-BD is the stronger intramolecular hydrogen bonding in the gas state and CCl4 solutions than 1,2-BD and 2,3-BD as described above. In addition, although the intramolecular hydrogen bond within 1,4-BD molecule is the strongest among the BDs, 1,3-BD is more suitable to observe 1H and

13

C NMR peaks for each atom within 1,3-BD

compared to 1,4-BD due to the asymmetry of 1,3-BD. On the other hand, the aprotic solvents play a role as the hydrogen bonding acceptor for the 1,3-BD hydroxyl groups depending on their electron donicities, but not as the hydrogen bonding donor. Thus, the hydrogen bonding ability of the binary solvents may change with varying their mole fraction xOS. This paper is organized as follows. In the next section details of the experimental techniques and molecular dynamics (MD) simulation are described. The mixture of 1,3-BD enantiomers was used in the present experiments, while only the (S)-form of 1,3-BD was modeled in the MD simulations. The structure of (S)-1,3-BD is depicted in Figure 1 with the notation of the atoms. The third section constitutes the core of this paper. First, the solvation structure and the intramolecular hydrogen bonding of 1,3-BD in the three aqueous binary solvents are discussed according to the results of IR spectroscopy and 1H and 13C NMR. Then,


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we targeted 1,3-BD molecule in the AN−water solvents. The intermolecular hydrogen bonds of the two hydroxyl groups of 1,3-BD with water and AN and the intramolecular hydrogen bond are evaluated by the pair correlation functions g(r) obtained from the MD simulations. The MD results are confirmed by the 1H NMR measurements of spin relaxation time T1. Based on the intensities of 1H−1H nuclear Overhauser effect (NOE) for 1,3-BD, the conformational change of 1,3-BD molecule with increasing AN concentration is discussed to relate the intramolecular hydrogen bond. Finally, the solvation structure of 1,3-BD in the three aqueous binary solvents is concluded from all of the results.

2. EXPERIMENTAL SECTION 2.1. Reagents and Sample Solutions. AN (Wako Pure Chemicals, grade for high performance liquid chromatography) was dried using 3 Å molecular sieves. 1,3-BD (Wako Pure Chemicals, extra grade), DIO (Wako Pure Chemicals, grade of Infinity Pure), and DMSO (Wako Pure Chemicals, grade of Infinity Pure) were dried on 4 Å molecular sieves for several days. After drying, the water contents of the liquids were estimated to be less than 100 ppm using a Karl Fischer titration equipment (Mettler Toledo, DL32). Deuterium oxide (D2O) (Cambridge Isotope Laboratories, D atom content of 99.9%) was used for IR and 1

H−1H NOE experiments, while double distilled water was employed into 1H and 13C NMR

and T1 measurements. Deuterated AN (AN-d3) (Cambridge Isotope Laboratories, D atom content of 99.8%) and deuterated DIO (DIO-d8) (Cambridge Isotope Laboratories, D atom content of 99%) were used for 1H−1H NOE measurements of 1,3-BD−AN−water solutions and a part of chemical shift measurements for 1,3-BD−DIO−water solutions, respectively. The deuterated organic liquids were also dried on molecular sieves before the use, as well as the undeuterated ones. 5 ACS Paragon Plus Environment


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Binary solvents were first prepared by weighing organic solvent and water to reach the desired mole fractions xOS. Then, 1,3-BD was dissolved into the binary solvent in a measuring flask at the concentration of 100 mmol dm−3. All of the deuterated solvents were handled under dry nitrogen atmosphere in a glove box. 2.2. IR Spectra. At 25.0 °C IR spectra of 100 mmol dm−3 1,3-BD in the AN−D2O, DIO−D2O, and DMSO−D2O solutions at various xOS were recorded on an FT-IR spectrometer (JASCO, FT/IR-6100). The spectra of the organic liquid−D2O solvents at the corresponding xOS were also measured as a background. During measurements the sample solution was kept in a sample cell with two CaF2 windows separated with Teflon spacer of 0.5 mm in the thickness. The temperature of sample solution was controlled within ±0.1 °C by circulation of thermostated water in a cell holder (Specac). Spectrum of each solution was accumulated for 32 times with the resolution of 4.0 cm−1. 2.3. 1H and 13C NMR Chemical Shifts. 1H and 13C NMR spectra for 1,3-BD at 100 mmol dm−3 in the AN−H2O, DIO−H2O, and DMSO−H2O solvents were measured at 25.0 °C as a function of xOS using a 400 MHz FT-NMR spectrometer (Agilent, 400 MHz NMR System). For the DIO system, 1,3-BD−DIO-d8−D2O solutions at xOS = 0.5 and 1 were also examined to prevent from overlapping the peaks of 1,3-BD with those of the solvents. The sample solution was kept in a sample tube with 5 mm in the outer diameter (Shigemi, PS-001-7). The sample temperature was controlled within ±0.1 °C by a heater and dry cold air from a sample cooler (FTS Systems, Air-Jet XR401, TC-84) during measurements. Hexamethyldisiloxiane (HMDS) (Wako Pure Chemicals, first grade) sealed into an external double reference tube (Shigemi) was used as reference substance for both nuclei. The double reference tube was inserted into the sample tube including the sample solution. The observed 1H and

13

C


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chemical shifts were corrected for the volume magnetic susceptibility of the sample solutions by an external double reference method according to the literature.16-18 2.4. MD Simulations. MD simulations were conducted on (S)-1,3-BD−AN−water systems at acetonitrile mole fractions of xAN = 0, 0.25, 0.5, 0.75, and 1 with an NTP ensemble in a cubic cell under a periodic boundary condition at 25 °C and 1 atm using the GROMACS 4.5.6 program package.19 In Table 1 the compositions of the five systems are outlined. In the MD simulations, bending and torsion terms for the intramolecular interactions and Lennard−Jones and Coulomb terms for the intermolecular interactions were taken into account by the potential function: V V V  E = ∑ K (θ − θ ) 2 + ∑  1 {1 + cos(φ + φ )} + 2 {1 − cos( 2φ + φ )} + 3 {1 + cos(3φ + φ )} 0 0 0 0  2 2 angle θ torsion  2   σ σ qq  1 ij 12 ij 6 i j  + ∑ 4ε {( ) − ( ) }+ ,  ij R R 4πε R  i< j ij ij 0 ij   (1) where the subscript ‘0’ indicates the equilibrium values for bond angles and torsion angles, σij and εij are 6–12 Lennard−Jones parameters for the nonbonding atom pair i-j with the distance of Rij, and qi is an atomic point charge. The bond stretching terms of 1,3-BD and AN molecules were constrained using the LINCS algorithm.20 The Lennard−Jones parameters between two different atoms were calculated as geometric means of the corresponding parameters for both atoms: σij = (σiσj)1/2 and εij = (εiεj)1/2. The Lennard−Jones and Coulomb potentials between atoms within the same molecule separated by at least three bonds (1–4 interactions) were reduced by scale factors of 0.5 and 0.5, respectively. The electrostatic interactions were computed using the smooth particle mesh Ewald (PME) method with a real-space cut off of 13.5 Å, a spline order of 6, and a reciprocal space mesh size of 32 for



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each of the x, y, and z direction.21 The van der Waals interactions were cut off beyond 12.0 Å, with switching range of 10.0−12.0 Å. Table S1 in the Supporting Information (S.I.) shows all atom-atom bond lengths, potential parameters, and atomic point charges for the model of each molecule. The constrained bond lengths,22 the angles,22 and the torsion parameters23 for the 1,3-BD molecule were built using the AMBER parameter set. The Lennard−Jones parameters and atomic point charges for 1,3-BD were employed from the OPLS force field.23 All of the intra and intermolecular parameters for AN molecule were cited from the literature.24 For the model of water molecule the rigid body TIP5P was employed.25 Firstly, the centers of mass for all molecules were randomly set in a cubic MD cell. The total simulation time was 22 ns with a time step of 2 fs, corresponding to the total steps of 11×106. In the first 2 ns, the molecules were stirred in the cell at 527 °C and 1000 atm. The temperature and pressure were then changed to 25 °C and 1 atm. The system was equilibrated from 2 to 12 ns. The data obtained from 12 to 22 ns (1 million snap shots) were used for analyses. The equation of motion was integrated with the leap-flog algorithm.26 The temperature and pressure were controlled by the Nose-Hoover thermostat27,28 and Parrinello-Rahman barostat,29,30 respectively. The present results were evaluated by comparing the densities obtained by the MD simulations with those experimentally determined using an electronic densimeter (ANTON Paar K.G., DMA60 and DMA602). As shown in Table 1, the densities obtained from the MD simulations satisfactorily agree with those experimentally determined within the deviation of 10%.

2.5. NMR T1 Measurements. To discuss the intramolecular hydrogen bonding within 1,3-BD in terms of the dynamics of each position of the molecule, 1H NMR spin-lattice relaxation times T1 for the 1,3-BD−AN−H2O solutions at 25.0±0.1 °C and various xAN were 8 ACS Paragon Plus Environment

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determined by an inversion recovery method using the same NMR spectrometer as the above. The sample solutions were kept into the same tubes as those for the chemical shift measurements. The magnetic relaxation of the protons within 1,3-BD occurs through the intra and intermolecular dipole−dipole processes.31,32 Hence, the T1 values give us the information on the sum of the rotational and translational motions for each position of the molecule.

2.6. 1H−1H NMR NOE. The magnetic interaction between the hydrogen atoms at the positions 1 and 4 (H1 and H4) of 1,3-BD in the AN-d3−D2O solutions at xAN = 0, 0.5, and 1 was observed using a 1H−1H NMR NOE technique. The same NMR spectrometer and temperature control system as the above were used in the NOE measurements. The sample solutions were kept in the same NMR tube as the above. The NOE intensities of the H4 atoms of 1,3-BD were measured after the H1 atoms were magnetically excited. In a series of measurements, a mixing time between the excitation and probe pulses was varied from 0 to 3000 ms. On the basis of the NOE intensities for the solutions, the conformational change of the alkyl chain of 1,3-BD against the increase in the xAN can be discussed because the intensities correlate with the distance between the hydrogen atoms at the two positions as explained by33

ߪ௜௝ =

ଵ ఊ ర ℏమ ଵ଴

ల ௥೔ೕ

(

଺ఛౙ ଵାସఠ మ ఛౙమ

− ߬ୡ ).

(2)

Here, ߪ௜௝ represents the cross-relaxation rate between protons i and j, and rij is the distance between two protons. γ, τc, and ω are the gyromagnetic ratio, the correlation time of the i−j interproton vector, and angular velocity of a proton, respectively. Thus, the ߪ௜௝ value is inversely proportional to the distance rij to the power of six. The initial slope of NOE



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intensities against the mixing times between the excited and probe pulses gives us information on the distance rij.

3. RESULTS AND DISCUSSION 3.1. IR Spectra. Figure 2 shows the O−H stretching vibration band of 1,3-BD in the three organic liquid−water solvents at various xOS. The spectra for each system show the interesting change against the increase in the xOS depending on the organic solvents. The O−H stretching vibration band of 1,3-BD molecules may involve various modes. The deconvolution of the dull band is not easy using any functions. Hence, the peak positon and full width at half maximum (FWHM) of the whole band for each system are plotted against the xOS in the panels a and b of Figure 3, respectively. For all of the three systems, the O−H stretching vibration band blue-shifts as the xOS increases from 0 to ∼0.9. The blue-shift of the O−H vibration means that the O−H bonds of 1,3-BD are gradually strengthened with increasing xOS to ∼0.9. This is because the disruption of the hydrogen bonds between the 1,3-BD hydroxyl hydrogen atoms with water due to the increase in the organic solvent content. The magnitude of the blue-shift is larger in the sequence of the AN > DIO >> DMSO systems. This is opposite to the sequence of the electron donicities of organic solvents, that is, the donor numbers DN are larger in the order of DMSO (29.8) >> DIO (14.8) > AN (14.1).34 On the other hand, the higher the electron donicity of the organic solvent, the stronger the hydrogen bonds of the organic solvent molecules with the 1,3-BD hydroxyl hydrogen atoms are formed after the elimination of the water molecules from the hydroxyl groups. It results in the weakening of O−H bonds. Thus, the two opposing factors decide the magnitude of the blue-shift of the O−H vibration with increasing xOS to ∼0.9. Namely, the replacement of the


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water molecules by the organic solvent molecules on the hydroxyl hydrogen atoms is more easily taken place in the order of DMSO >> DIO > AN. Above xOS = ∼0.9, the O−H vibration red-shifts in all the systems. In the DMSO system above the mole fraction, the water molecules that are hydrogen-bonded with the 1,3-BD hydroxyl groups may be fully replaced by DMSO. Thus, the red-shift for the DMSO system is the most significant among the three systems. Particularly, the wavenumber (3380 cm−1) of the O−H vibration band in the DMSO solution (xOS = 1) becomes lower beyond that (3400 cm−1) in the D2O solution (xOS = 0). This suggests that the O−H bonds in the DMSO solvent more weakens than in the water solvent because of the strong hydrogen bonds with the higher electron donicity of DMSO than that (DN = 18.0) of water.34 In contrast to the DMSO system, the red-shift of the O−H vibration of 1,3-BD in the AN and DIO systems above xOS = 0.9 is smaller. The wavenumbers (3530 and 3490 cm−1, respectively) of the vibration for the AN and DIO systems at xOS = 1 are not lower than that (3400 cm−1) at xOS = 0. This is attributed to that AN and DIO molecules do not strongly hydrogen-bonded with the 1,3-BD hydroxyl hydrogen atoms even in the organic solvents (xOS = 1) due to their lower electron donicities by a factor of 50% than that of DMSO. The more plausible reason for the red-shift of the O−H vibration is the intramolecular hydrogen bond between the two hydroxyl groups of 1,3-BD in the AN and DIO solvents above xOS = ∼0.9. In fact, the wavenumber (3530 cm−1) of the 1,3-BD O−H vibration band in the AN solvent (xOS = 1) is close to that (3549 cm−1) of the band for the intramolecular hydrogen bonding of 1,3-BD in CCl4 solutions.14,35 The lower wavenumber (3490 cm−1) for the DIO solvent than that of the AN solvent means the weaker intramolecular hydrogen bond of 1,3-BD in the former.



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These different features of the 1,3-BD O−H vibration band between the DMSO system and the AN and DIO systems are also observed for the FWHM values (Figure 3 b). The FWHM of the O−H vibration band for all of the systems decreases with increasing xOS to 0.9, although the value for the AN system once increases with the increase in xOS to ∼0.4. At xOS = 0.99 the FWHM of the AN and DIO systems does not markedly change from that at xOS = 0.9. The band shape at xOS = 0.99 is asymmetry because the component of the nonbonding hydroxyl groups of 1,3-BD appears at the higer wavenumber together with that of the intermolecular hydrogen-bonded groups with organic solvent or water molecule at the lower wavenumber. The significant difference between the DMSO system and the AN and DIO systems is found at xOS = 1. The FWHM of the AN and DIO systems dips at xOS = 1 (both values are overlapped with each other at ∼100 cm−1). The narrowing of the band at xOS = 1 suggests the significant increase in the intramolecular hydrogen bond of 1,3-BD and the decrease in the intermolecular hydrogen bond. In fact, the O−H vibration band for the intramolecular hydrogen bond of 1,3-BD in CCl4 solutions is much sharper than the band for the intermolecular hydrogen bond.14,35 On the contrary, the FWHM of the DMSO system rises at xOS = 1. This may arise from the various O−H vibration modes due to the hydrogen bonding of the hydroxyl groups with DMSO. The increase in the FWHM for the AN system with increasing from xOS = 0 to ∼0.4 may be attributed to the various modes, such as the hydrogen bonding and nonbonding hydroxyl groups. These features of the FWHM of the O−H vibration band suggest the formation of the intramolecular hydrogen bond of 1,3-BD in the AN and DIO systems in the range of xOS > 0.9, as well as the wavenumber.

3.2. 1H and

13

C NMR Chemical Shifts. NMR spectra for the 1H and

13

C atoms within

1,3-BD in the three organic solvent−water systems at various xOS are depicted with the assignments of peaks in Figures S1−S7 (S.I.). For the DIO system, 1H NMR spectra of the 12 ACS Paragon Plus Environment

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1,3-BD−DIO-d8−D2O solutions at xOS = 0.5 and 1 were also measured to avoid the overlapping of the peaks of 1,3-BD with those of DIO and H2O (Figure S4). As shown in the 1

H NMR spectrum of 1,3-BD in the AN solution at xOS = 1 (Figure S1), two peaks of the

hydroxyl hydrogen atoms are separately found at 2.91 and 3.02 ppm. It is difficult to assign each peak to either OH1 or OH3 atom. Here, the peaks at 2.91 and 3.02 ppm are tentatively assigned to the OH1 and OH3 atoms, respectively. The reasons for the assignments will be discussed in the MD simulation section. With decreasing xOS from 1 to 0.7 the peaks still individually appear in the spectra, whereas below xOS = 0.6 the two peaks overlap with each other as a singlet. For the DIO solution at xOS = 1 (Figures S3 and S4), two peaks for the OH1 and OH3 atoms can also be found at 3.18 and 3.28 ppm, respectively. Unfortunately, the peaks cannot be observed in the spectra for the DIO system at the other xOS because they are hidden by the peak of DIO. Figure S6 indicates that both OH1 and OH3 signals are found as a single peak in the spectrum of the DMSO solution at xOS = 1. The peak for the two hydroxyl groups appears at the much lower magnetic field of 4.44 ppm than those for the AN and DIO systems. In Figure 4, the chemical shifts of the OH1 and OH3 atoms for the three systems are plotted against the xOS. For the AN and DMSO systems, the hydroxyl hydrogen atoms of 1,3-BD are gradually shielded (shifted toward the high magnetic field) as the xOS increases. The shielding of the hydroxyl hydrogen atoms for the AN system with increasing xOS is much larger compared to that of the DMSO system. Additionally, the shielding of the hydrogen atoms in the AN system is remarkable above xOS = 0.7, whereas that in the DMSO system becomes moderate above the mole fraction. As mentioned above, the chemical shifts of the OH1 and OH3 atoms for the AN system can be individually plotted in the range of xOS > 0.7. These features reveal the different states of the 1,3-BD hydroxyl hydrogen atoms between the AN and DMSO systems. First, the shielding of the hydroxyl hydrogen atoms in both AN and 13 ACS Paragon Plus Environment


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DMSO systems arises from the disruption of the hydrogen bonds between the hydroxyl hydrogen atoms and water. Second, the milder shielding of the 1,3-BD hydroxyl hydrogen atoms in the DMSO−water solutions results from the replacement of water molecules hydrogen-bonded with the hydroxyl hydrogen atoms by DMSO because the formation of the hydrogen bonds may cause the deshielding of the hydrogen atoms.18 The contribution of the replacement of the hydrogen bonds by AN is smaller than DMSO. Third, in the AN−water solutions in the range from xOS = 0.7 to 1, the electron densities of the OH1 and OH3 atoms differ from each other. This feature shows the formation of the intramolecular hydrogen bond between the two hydroxyl groups of 1,3-BD. The more deshielded hydroxyl hydrogen atom with 3.02 ppm in the solution at xOS = 1 may be assigned to the OH atom for the intramolecular hydrogen bonding donor, while the other with 2.91 ppm may be attributed to the OH atom within the hydroxyl group of the hydrogen bonding acceptor. This is also valid for the intramolecular hydrogen bonding in the DIO−water solutions, where the peaks of the OH1 and OH3 atoms individually appear at 3.18 and 3.28 ppm in the DIO solvent (Figure 4). The strong hydrogen bonding between the hydroxyl hydrogen atoms and DMSO may cancel the different electron densities between the OH1 and OH3 atoms, resulting in the single peak of the two hydrogen atoms in the spectra at the lower magnetic field (Figure S6). In the S.I., the variations of the 1H and

13

C NMR chemical shifts for the 1,3-BD

hydrocarbons against the xOS are discussed. The chemical shifts are mainly governed by the hydrogen bonding of the hydroxyl groups with the organic solvent molecules; that is, the changes in the chemical shifts with increasing xOS are more significant in the sequence of DMSO > DIO > AN. In contrast, the changes in the chemical shifts of the hydroxyl hydrogen atoms of 1,3-BD with increasing xOS are more remarkable in the sequence of AN > DIO >> DMSO (Figure 4). The 1H NMR chemical shifts for the hydroxyl groups together with the IR


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spectra reveal that the intramolecular hydrogen bond between the 1,3-BD hydroxyl groups is formed in the AN and DIO systems at the high xOS.

3.3. MD Simulations on the AN System. In Figure 5 the coordination numbers of the O1,3−OW interactions between the 1,3-BD hydroxyl oxygen and water oxygen atoms, which were estimated from the first peak at 2.65 Å in the g(r) (Figure S10 (S.I.)) by integration up to the first minimum of 3.40 Å, are depicted as a function of xAN. At xAN = 0 (in the water solvent) ∼2.9 molecules of water may be hydrogen-bonded with one hydroxyl group of 1,3-BD. Hence, the three sites of the hydroxyl group, one hydroxyl hydrogen atom and two lone pairs, may be fully hydrogen-bonded with water molecules. With increasing xAN, the coordination number gradually decreases. However, ∼1.6 of water molecules may still be hydrogen-bonded with the hydroxyl group in the solution at xAN = 0.75. The coordination numbers of the OH1−N and OH3−N interactions between the hydroxyl hydrogen atoms of 1,3-BD and the nitrogen atom of AN, which were estimated from the first peak at 2.00 Å by integration of the g(r) (Figure S11 (S.I.)) up to r = 2.90 Å, are plotted against the xAN in Figure 5. The numbers of both OH1−N and OH3−N interactions overlap with each other. The hydrogen bonds are not easily formed between the 1,3-BD hydroxyl hydrogen and AN nitrogen atoms in the solutions below xAN = 0.75. However, the coordination number near the unity at xAN = 1 suggests that the two hydroxyl hydrogen atoms of 1,3-BD are almost fully hydrogen-bonded with the AN nitrogen atom in the AN solvent. Consequently, the MD simulations reveal that the two hydroxyl groups of 1,3-BD favor to form the hydrogen bonds with water molecules rather than AN molecules in the solutions even at the high xAN. As the AN content is close to xAN = 1, AN molecules may be finally hydrogen-bonded with the 1,3-BD hydroxyl hydrogen atoms.



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Figure 6 shows the g(r) of the total OH1−O3 and OH3−O1 interactions between the hydroxyl hydrogen and oxygen atoms of 1,3-BD in the solutions over the entire xAN range by the black line. Several peaks gather in the r-range from 4.0 to 5.5 Å in all of the g(r). Thus, the hydrogen and the oxygen atoms of the two hydroxyl groups are far from each other in the r-range and cannot form the intramolecular hydrogen bonds between them. This may be caused by the strong hydrogen bonds of the hydroxyl groups with water molecules. However, a tiny peak appears at 1.90 Å in the g(r) of the OH1−O3 interaction above xAN = 0.5. The peak can be found in the g(r) of the OH3−O1 interaction even at xAN = 0.25. At xAN = 1 the peak significantly grows, especially in the g(r) for OH3−O1. In Figure 6, the intermolecular OH1−O3 and OH3−O1 interactions below 4 Å are depicted by the red lines. The intermolecular interactions appear at xAN = 0.75 and increase with increasing xAN from 0.75. However, the contribution of the intermolecular interactions to the total interactions is not dominant, particularly for the OH3−O1 interaction. Hence, the peak at 1.90 Å mainly shows the intramolecular hydrogen bond between the two hydroxyl groups of 1,3-BD in the AN system. The coordination numbers of the intramolecular hydrogen bonds of OH1−O3 and OH3−O1 were estimated to be much less than the unity. Although the MD results reveal that the hydroxyl hydrogen atoms of 1,3-BD are almost fully hydrogen-bonded with AN in the AN solvent (xAN = 1) (Figure 5), the free sites, which are not the hydrogen-bonded with water or AN molecules, may be generated to form the intramolecular hydrogen bond in the solutions at the high xAN. Because the electron donicity of the 1,3-BD hydroxyl oxygen atoms may be higher than that of AN as well as most of the monohydroxyl alcohols such as ethanol (DN = 20).34 Figure 6 suggests that the intramolecular OH3−O1 hydrogen bond is more frequently formed in the solution than the OH1−O3 bond. This is the opposite of the DFT calculations in 16 ACS Paragon Plus Environment

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the gas state; the OH1−O3 hydrogen bond is slightly stable rather than the OH3−O1 bond.14 This may be because in the AN−water solutions the OH1 atom projected from the hydrocarbon chain is more easily hydrogen-bonded with water or AN compared to the OH3 atom. The consideration is also consistent with the larger contribution of the intermolecular OH1−O3 interaction than the OH3−O1 one (Figure 6). In the section of NMR chemical shifts, we assigned the peaks of the hydroxyl hydrogen atoms at 2.91 and 3.02 ppm in the AN solvent (xOS = 1) to the OH1 and OH3 atoms, respectively. According to the MD results, the OH3 atom would be more deshielded than the OH1 atom because of the more frequent intramolecular hydrogen bond of OH3−O1. On the contrary, the OH1 atom would be less deshielded even if the atom may form the intermolecular hydrogen bond with AN due to the lower electron donicity of the AN nitrogen atom than the 1,3-BD hydroxyl oxygen atom.

3.4. 1H NMR Spin-Lattice Relaxation Times T1. In Figure 7 a the 1H NMR spin-lattice relaxation times T1 determined for all of the hydrogen atoms within 1,3-BD in the AN−H2O solutions are depicted against the xAN. The values for each hydroxyl hydrogen atom below xAN = 0.6 could not be individually determined because of the overlapping of both peaks, as described in the above section. Moreover, those for the alkyl hydrogen atoms in the range from 0.1 to 0.5 could not be exactly estimated because of the influence of the peaks of the solvent. The T1 values for the OH1 and OH3 atoms drastically decrease as the xAN rises from 0.7 to 1. The values of the OH1 and OH3 atoms at xAN = 1 overlap with each other at T1 ≈ 7.0 s. The decrease in the T1 values suggests that the translational and rotational motions of both hydroxyl groups of 1,3-BD are vigorously restricted with increasing xAN.31,32 Especially, the motions of the atoms are remarkably retarded with the increase in the xAN from 0.9 to 1. In Figure 7 b, the vertical axis of Figure 7 a is expanded for clarity of the change in the T1 17 ACS Paragon Plus Environment


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values of the alkyl hydrogen atoms against the xAN. The T1 values of all of the alkyl hydrogen atoms gradually increase with increasing xAN to 0.9. This may arise from the conformational change of the skeletal hydrocarbon chain of 1,3-BD as described in the next section. However, the T1 values of the H1 and H3 atoms dip at xAN = 1. Thus, the motions of the H1 and H3 atoms are retarded at xAN =1 again. The variations of the T1 values of both atoms with increasing xAN bear resemblance to that of the O−H stretching vibration band (Figure 3 a). The T1 values of the OH1, OH3, H1, and H3 atoms suggest that the hydrogen bonds of the hydroxyl hydrogen atoms remarkably change as the xAN increases from 0.9 to 1. One of the reasons is the hydrogen bond of the hydroxyl hydrogen atoms with AN molecules in the AN solvent (xAN =1). The other one is the intramolecular hydrogen bonds between the hydroxyl groups of 1,3-BD as discussed on the IR and MD results.

3.5. 1H−1H NMR NOE. To clarify the conformational change of the 1,3-BD molecules in the AN−water solutions with increasing xAN, the distance between the H1 and H4 atoms was relatively evaluated by 1H−1H NMR NOE. The average conformation of 1,3-BD may be influenced by the intermolecular hydrogen bonding of the 1,3-BD hydroxyl groups with water or AN molecules, especially by the intramolecular one between the groups. The NOE spectra of 100 mmol dm−3 1,3-BD−AN-d3−D2O solutions at xAN = 0, 0.5, and 1 are depicted as a function of the mixing time in Figures S12−S14 (S.I.). In Figure 8 the NOE intensities of the H4 atoms, which correspond to the magnetic response after the excitation of the H1 atoms, for the 1,3-BD−AN-d3−D2O solutions at xAN = 0, 0.5, and 1 are plotted against the mixing time. The initial slop for the plots of the intensities is in inverse proportion to the distance between the H1 and H4 atoms, as explained by eq 2. The slope is decreased with increasing xAN. In particular, the decrease in the slope is significant as the xAN increases from 0.5 to 1. Hence, the distance between the H1 and H4 18 ACS Paragon Plus Environment

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atoms of 1,3-BD is the shortest in the water solvent (xAN = 0), whereas that is the longest in the AN solvent (xAN = 1). Figure 9 a and b show two plausible conformations of 1,3-BD in the solutions at the low and high xAN, respectively, according to the results of 1H−1H NMR NOE. At the low xAN the dihedral angle of C1C2−C3C4 may be around 60° or −60° to form the gauche conformation (Figure 9 a). In the conformation the distance between the H1 and H4 atoms is short. The hydrophobic alkyl chain is folded to reduce the interaction with water. The two hydroxyl groups may be easily hydrogen-bonded with water molecules because the groups project from the skeletal hydrocarbon chain. The shorter T1 values for the H1, H2, H3, and H4 atoms at the low xAN (Figure 7 b) suggest that the rotational motion of the skeletal chain may be retarded in the solution due to the folded conformation. On the other hand, the dihedral angle may be near 180° to form the trans conformation in the solutions at the high xAN (Figure 9 b). In the conformation the H1 and H4 atoms are far from each other. The two hydroxyl groups can form the intramolecular hydrogen bond. Indeed, the previous investigations showed that the trans form of the C1C2−C3C4 dihedral angle is the most stable to form the intramolecular hydrogen bond between the hydroxyl groups in the lower dielectric constant media, such as the gas state and CCl4 solutions.11,14,15

3.6. Solvation Structure of 1,3-BD. On the basis of all of the results, the solvation structure of 1,3-BD in the three organic liquid−water solvents can be concluded as follows. Here, it should be kept mind that the results obtained from IR, NMR, and MD techniques indicate the average structure of all of 1,3-BD molecules in the environment given by the binary solvents, but not a discrete structure. In the DMSO solutions, water molecules that are initially hydrogen-bonded with the two hydroxyl groups of 1,3-BD are gradually eliminated with increasing DMSO content. Due to the higher electron donicity of DMSO than water, the 19 ACS Paragon Plus Environment


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hydrogen bonding of the hydroxyl groups with DMSO is mainly taken place in the range of xDMSO from ∼0.9 to 1. In the DMSO solvent (xDMSO = 1), the two hydroxyl hydrogen atoms of 1,3-BD may be fully hydrogen-bonded with DMSO. DIO has the lower electron donicity by a factor of 50% compared to DMSO. Thus, the elimination of water molecules from the 1,3-BD hydroxyl groups more progresses with increasing DIO mole fraction xDIO than the replacement of the water molecules by DIO. The electron donicity of AN is the lowest among the three organic solvents. As seen in the most remarkable blue-shift of the O−H vibration (Figure 3 a), the elimination of water molecules from the 1,3-BD hydroxyl hydrogen atoms most significantly occurs in the AN system as the xAN increases to ∼0.9 among the three systems. The O−H vibration of 1,3-BD in both AN and DIO systems red-shifts above xOS = 0.9. One of the reasons for the red-shift is that AN and DIO molecules may frequently form the hydrogen-bonds with the 1,3-BD hydroxyl hydrogen atoms in the organic solvents due to no water molecules. However, the more plausible reason is the intramolecular hydrogen bond between the two hydroxyl groups of 1,3-BD. Actually, the MD g(r) shows that the intramolecular hydrogen bond between the hydroxyl groups is formed in the AN−water solutions above xAN = 0.25. Especially, the intramolecular hydrogen bond significantly increases in the AN solvent. Nevertheless, the number of the intramolecular hydrogen bond is much less than the unity. Probably, the negative point charge for the nitrogen atom of the present AN model is too high to exactly simulate the intramolecular hydrogen bond. However, the following experimental results maintain the intramolecular hydrogen bond of 1,3-BD. The wavenumber of the O−H stretching vibration band for the AN solvent (xOS = 1) is comparable with that for the intramolecular hydrogen bond in CCl4 solutions.14,35 Furthermore, the O−H stretching band for the AN solvent becomes sharper as well as that in 20 ACS Paragon Plus Environment

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CCl4 solutions. The sharp O−H band for the DIO solvent also suggests the intramolecular hydrogen bond of 1,3-BD in the DIO system. The individual peaks of the 1,3-BD hydroxyl hydrogen atoms in the 1H NMR spectra for the AN and DIO solutions at the high xOS reveal the different states of the two hydroxyl groups due to the intramolecular hydrogen bond. The marked dip of the T1 values for the OH1, OH3, H1, and H3 atoms within 1,3-BD in the AN system at xAN = 1 may be caused by the intramolecular hydrogen bonds between the hydroxyl groups. When the hydroxyl groups form the intramolecular hydrogen bonds, the skeletal hydrocarbon chain should be in the trans conformation to keep the suitable distance between the two groups. Indeed, the 1H−1H NOE intensities between the H1 and H4 atoms shows the longest distance between the H1 and H4 atoms in the solution at xAN = 1 over the entire xAN range.

4. CONCLUSIONS The water molecules that are hydrogen-bonded with the 1,3-BD hydroxyl groups are most significantly replaced by DMSO molecules with the highest electron donicity (hydrogen bonding acceptability) among the three organic solvents and water. At xOS = 1, the two hydroxyl hydrogen atoms of 1,3-BD may be fully hydrogen-bonded with DMSO molecules. On the contrary, the red-shift of the O−H stretching vibration of 1,3-BD in the AN−water and DIO−water solutions suggests the intramolecular hydrogen bonding between the two hydroxyl groups of 1,3-BD. All of the other results reveal the formation of the intramolecular hydrogen bond within 1,3-BD in the AN and DIO solutions. This is caused by the weaker electron donicity of AN and DIO compared to those of water and DMSO. Thus, the present results show that the hydrogen bonding abilities of the water and organic solvents mainly decide the intramolecular hydrogen bonding of 1,3-BD rather than the electrostatic 21 ACS Paragon Plus Environment


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environment provided by the polarities of the aqueous binary solvents with the organic liquids. Actually, the sequence of the strength of the intramolecular hydrogen bond, AN > DIO >> DMSO ≈ 0, determined by the IR spectroscopy does not agree with that of the relative dielectric constants εr, DMSO (46.6) > AN (35.95) >> DIO (2.2).

ASSOCIATED CONTENT Supporting Information The Supporting Information is available free of charge via the ACS Publication website at DOI: XXXXXXX. The intramolecular atom−atom bond lengths and potential parameters for (S)-1,3-BD, AN, and water molecules employed for the MD simulations, 1H and 13C NMR spectra, discussion on the NMR chemical shifts on the 1,3-BD hydrocarbons, g(r) for O1,3−OW, OH1−N, and OH3−N interactions, and 1H−1H NOE spectra.

AUTHOR INFORMATION Corresponding Author Tel: +81-952-28-8554 Email: [email protected]

ACKNOWLEGEMENTS This work was supported partly by JSPS KAKENHI Grant Numbers 26410018 and Dean’s Grant for Progressive Research Projects from Saga University. The NMR measurements of the sample solutions were conducted at the Analytical Research Center for Experimental Sciences of Saga University.


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REFERENCES (1) Boutron, P. Cryoprotection of Red Blood Cells by a 2,3-Butanediol Containing Mainly the Levo and Dextro Isomers. Cryobiology 1992, 29, 347-358. (2) Mehl, P.; Boutron, P. Cryoprotection of Red Blood Cells by 1,3-Butanediol and 2,3-Butanediol. Cryobiology 1988, 25, 44-54. (3) Boutron, P. Levo- and Dextro-2,3-Butanediol and Their Racemic Mixture: Very Efficient Solutes for Vitrification. Cryobiology 1990, 27, 55-69. (4) Boutron, P.; Mehl, P.; Kaufmann, A.; Angibaud, P. Glass-Forming Tendency and Stability of the Amorphous State in the Aqueous Solutions of Linear Polyalcohols with Four Carbons. I. Binary Systems Water-Polyalcohol. Cryobiology 1986, 23, 453-469. (5) Eusébio, M. E.; Jesus, A. J. L.; Cruz, M. S. C.; Leitão, M. L. P.; Redinha, J. S. Enthalpy of Vaporisation of Butanediol Isomers. J. Chem. Thermodyn. 2003, 35, 123-129. (6) Hawrylak, B.; Gracie, K.; Palepu, R. Thermodynamic Properties of Binary Mixtures of Butanediols with Water. J. Solution Chem. 1998, 27, 17-31. (7) Romero, C. M.; Paez, M. S. Volumetric Properties of Aqueous Binary Mixtures of 1-Butanol, Butanediols, 1,2,4-Butanetriol and Butanetetrol at 298.15 K. J. Solution Chem. 2007, 36, 237-245. (8) Matsugami, M.; Takamuku, T.; Otomo, T.; Yamaguchi, T. Thermal Properties and Mixing State of Ethylene Glycol-Water Binary Solutions by Calorimetry, Large-Angle X-Ray Scattering, and Small-Angle Neutron Scattering. J. Phys. Chem. B 2006, 110, 12372-12379. (9) Takamuku, T.; Tsutsumi, Y.; Matsugami, M.; Yamaguchi, T. Thermal Properties and Mixing State of Diol-Water Mixtures Studied by Calorimetry, Large-Angle X-Ray Scattering, and NMR Relaxation. J. Phys. Chem. B 2008, 112, 13300-13309. (10) Caminati, W.; Corbelli, G. The Six-Membered Ring Chair Conformation of Butane-1,3-Diol in the Gas Phase. J. Mol. Struct. 1982, 78, 197-202. (11) Velino, B.; Favero, L. B.; Maris, A.; Caminati, W. Conformational Equilibria in Diols: The Rotational Spectrum of Chiral 1,3-Butandiol. J. Phys. Chem. A 2011, 115, 9585-9589. (12) Lomas, J. S.; Maurel, F.; Adenier, A. 1H NMR Study of the Hetero-Association of Non-Symmetrical Diols with Pyridine; GIAO/DFT Calculations on Diols. J. Phys. Org. Chem. 2011, 24, 798-808. (13) Hasanein, A. A.; Kovac, S. CNDO/2 Study of the Intramolecular Hydrogen Bond in 1,2-, 1,3- and 1,4-Butanediols. J. Mol. Struct. 1974, 22, 457-462. (14) Jesus, A. J. L.; Rosado, M. T. S.; Leitão, M. L. P.; Redinha, J. S. Molecular Structure of Butanediol Isomers in Gas and Liquid States: Combination of DFT Calculations and Infrared Spectroscopy Studies. J. Phys. Chem. A 2003, 107, 3891-3897. (15) Rosado, M. T.; Jesus, A. J. L.; Reva, I. D.; Fausto, R.; Redinha, J. S. Conformational Cooling Dynamics in Matrix-Isolated 1,3-Butanediol. J. Phys. Chem. A 2009, 113, 7499-7507. (16) Momoki, K.; Fukazawa, Y. Bulbed Capillary External Referencing Method for Proton Nuclear Magnetic Resonance Spectroscopy. Anal. Chem. 1990, 62, 1665-1671. (17) Momoki, K.; Fukazawa, Y. Bulbed Capillary External Referencing Method Using a Superconducting Magnet NMR Instrument. Anal. Sci. 1994, 10, 53-58. (18) Mizuno, K.; Tamiya, Y.; Mekata, M. External Double Reference Method to Study Concentration and Temperature Dependences of Chemical Shifts Determined on a Unified Scale. Pure Appl. Chem. 2004, 76, 105-114. 23 ACS Paragon Plus Environment


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(19) Hess, B.; Kutzner, C.; van der Spoel, D.; Lindahl, E. GROMACS 4: Algorithms for Highly Efficient, Load-Balanced, and Scalable Molecular Simulation. J. Chem. Theory Comput. 2008, 4, 435-447. (20) Hess, B.; Bekker, H.; Berendsen, H. J. C.; Fraaije, J. G. E. M. LINCS: A Linear Constraint Solver for Molecular Simulations. J. Comput. Chem. 1997, 18, 1463-1472. (21) Essmann, U.; Perera, L.; Berkowitz, M. L.; Darden, T.; Lee, H.; Pedersen, L. G. A Smooth Particle Mesh Ewald Method. J. Chem. Phys. 1995, 103, 8577-8593. (22) Cornell, W. D.; Cieplak, P.; Bayly, C. I.; Gould, I. R.; Merz, K. M.; Ferguson, D. M.; Spellmeyer, D. C.; Fox, T.; Caldwell, J. W.; Kollman, P. A. A Second Generation Force Field for the Simulation of Proteins, Nucleic Acids, and Organic Molecules. J. Am. Chem. Soc. 1995, 117, 5179-5197. (23) Jorgensen, W. L.; Maxwell, D. S.; Tirado-Rives, J. Development and Testing of the OPLS All-Atom Force Field on Conformational Energetics and Properties of Organic Liquids. J. Am. Chem. Soc. 1996, 118, 11225-11236. (24) Nikitin, A. M.; Lyubartsev, A. P. New Six-Site Acetonitrile Model for Simulations of Liquid Acetonitrile and Its Aqueous Mixtures. J. Comput. Chem. 2007, 28, 2020-2026. (25) Mahoney, M. W.; Jorgensen, W. L. A Five-Site Model for Liquid Water and the Reproduction of the Density Anomaly by Rigid, Nonpolarizable Potential Functions. J. Chem. Phys. 2000, 112, 8910-8922. (26) Hockney, R. W.; Goel, S. P.; Eastwood, J. W. Quiet High-Resolution Computer Models of a Plasma. J. Comput. Phys. 1974, 14, 148-158. (27) Nosé, S. A Molecular Dynamics Method for Simulations in the Canonical Ensemble. Mol. Phys. 1984, 52, 255-268. (28) Hoover, W. G. Canonical Dynamics: Equilibrium Phase-Space Distributions. Phys. Rev. A 1985, 31, 1695-1697. (29) Parrinello, M.; Rahman, A. Polymorphic Transitions in Single Crystals: A New Molecular Dynamics Method. J. Appl. Phys. 1981, 52, 7182-7190. (30) Nosé, S.; Klein, M. L. Constant Pressure Molecular Dynamics for Molecular Systems. Mol. Phys. 1983, 50, 1055-1076. (31) Lang, E. W.; Lüdemann, H.-D. NMR Basic Principles and Progress. Springer: Berlin, 1991; Vol. 24. (32) Takamuku, T.; Hirano, T.; Yamaguchi, T.; Wakita, H. NMR Study on Dynamics of Water Molecules in Concentrated Aqueous Zinc(Ii) Bromide Solutions at Various Temperatures. J. Phys. Chem. 1992, 96, 9487-9492. (33) Clore, G. M.; Gronenborn, A. M. Assessment of Errors Involved in the Determination of Interproton Distance Ratios and Distances by Means of One- and Two-Dimensional NOE Measurements. J. Magn. Reson. 1985, 61, 158-164. (34) Gutmann, V. The Donor–Acceptor Approach to Molecular Interactions. Plenum Press: New York, 1978. (35) Ni, Y.; Dou, X.; Zhao, H.; Yin, G.; Yamaguchi, Y.; Ozaki, Y. Study on Multimers and Their Structures in Molecular Association Mixture. Sci. China Ser. B 2007, 50, 23-31.


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TABLE 1. Compositions of (S)-1.3-BD–Water and (S)-1,3-BD–AN–Water Systems Examined by MD Simulations and the Densities, dMD and dexp (g cm−3), Derived from the Simulations and Experimentally Determined, Respectively. dexp Numbers of molecules in a MD Cell dMD xAN (S)-1,3-BD AN Water 0 6 0 1692 0.98163 0.99744 0.25 6 423 1269 0.84794 0.90894 0.5 6 846 846 0.77866 0.84690 0.75 6 1269 423 0.73841 0.80600 1 6 1692 0 0.71585 0.77832



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Figure Captions Figure 1. Structure of (S)-1,3-BD with the notation of atoms.

Figure 2. The O−H stretching vibration band of 1,3-BD in aqueous binary solvents with AN, DIO, and DMSO at various xOS.

Figure 3. Wavenumbers and FWHM of the O−H stretching vibration band of 1,3-BD in aqueous binary solvents with AN, DIO, and DMSO as a function of xOS in panels a and b, respectively. The errors of both values are less than 4 cm−1.

Figure 4. Variations of 1H chemical shifts for the OH1 and OH3 atoms of 1,3-BD in aqueous binary solvents with AN, DIO, and DMSO against xOS.

Figure 5. Coordination numbers of the O1,3−OW interactions between the 1,3-BD hydroxyl oxygen and water oxygen atoms and the OH1−N and OH3−N interactions between the 1,3-BD hydroxyl hydrogen and the AN nitrogen atoms as a function of xAN. These values were estimated from MD g(r) displayed in Figures S10 and S11 (S.I.), respectively.

Figure 6. Total atom−atom pair correlation functions g(r) (black lines) for OH1−O3 (left panel) and OH3−O1 (right panel) between the 1,3-BD hydroxyl hydrogen and oxygen atoms in 1,3-BD−AN−water system at various xAN obtained from MD simulations. The contributions of the intermolecular OH1−O3 and OH3−O1 interactions below 4 Å are depicted by the red lines.

Figure 7. Spin-lattice relaxation times T1 for all of the 1,3-BD hydrogen atoms in AN−water solutions as a function of xAN. In panel b the vertical axis of panel a is expanded for clarity of the change in T1 of the 1,3-BD alkyl hydrogen atoms against xAN.

Figure 8. Experimental intramolecular 1H−1H NOE enhancements between the H1 and H4 atoms of 1,3-BD molecule in AN-d3−D2O solutions as a function of mixing time.


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Figure 9. Plausible conformations of (S)-1,3-BD in AN−water solutions at (a) low and (b) high xAN. White, black, and red spheres represent the hydrogen, carbon, and oxygen atoms with in 1,3-BD, respectively.



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O3 H4

OH3

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O1

OH1

C3 C1

C4

H3

C2

H1

H2 Figure 1. Structure of (S)-1,3-BD with the notation of atoms.


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AN

Absorbance

1.0

0.5

0.0 Absorbance

DIO

xOS 0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 0.99 1

1.0 0.5 0.0 1.5

Absorbance

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DMSO

1.0 0.5 0.0 3700 3600 3500 3400 3300 3200 Wavenumber / cm-1

Figure 2. The O−H stretching vibration band of 1,3-BD in aqueous binary solvents with AN, DIO, and DMSO at various xOS.



3700 Wavenumber / cm

-1

a 3600 3500 3400 AN DIO DMSO

3300 3200

0

0.2

0.4

0.6

0.8

1

300 b FWHM / cm

-1

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200

100

0

0

0.2

0.4 0.6 xOS

0.8

1

Figure 3. Wavenumbers and FWHM of the O−H stretching vibration band of 1,3-BD in aqueous binary solvents with AN, DIO, and DMSO as a function of xOS in panels a and b, respectively. The errors of both values are less than 4 cm−1.


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Chemical Shift / ppm

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OH

5.0 4.0

AN OH1 AN OH3 DIO OH1 DIO OH3 DMSO

3.0 0

0.2 0.4 0.6 0.8 xOS

1

Figure 4. Variations of 1H chemical shifts for the OH1 and OH3 atoms of 1,3-BD in aqueous binary solvents with AN, DIO, and DMSO against xOS.



3.0 Coordination Number

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

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2.0 O1,3-OW OH1-N OH3-N

1.0

0.0

0

0.2 0.4 0.6 0.8 xAN

1

Figure 5. Coordination numbers of the O1,3−OW interactions between the 1,3-BD hydroxyl oxygen and water oxygen atoms and the OH1−N and OH3−N interactions between the 1,3-BD hydroxyl hydrogen and the AN nitrogen atoms as a function of xAN. These values were estimated from MD g(r) displayed in Figures S10 and S11 (S.I.), respectively.


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OH3-O1

OH1-O3 300

300 xAN =1

250

xAN =1

250

200

200 0.75

g(r)

g(r)

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


150

0.75 150 0.50

0.50 100

100 0.25

50 0 0

0.25

50 0 2

4 6 r/Å

8

0 0

0 2

4 6 r/Å

8

Figure 6. Total atom−atom pair correlation functions g(r) (black lines) for OH1−O3 (left panel) and OH3−O1 (right panel) between the 1,3-BD hydroxyl hydrogen and oxygen atoms in 1,3-BD−AN−water system at various xAN obtained from MD simulations. The contributions of the intermolecular OH1−O3 and OH3−O1 interactions below 4 Å are depicted by the red lines.



a

H1 H2 H3 H4 OH1 OH3

30 T1 / s

20 10 0

0

0.2

0.4

0.6 xAN

0.8

1

8 b 6 T1 / s

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

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4 2 0

0.2

0.4 0.6 xAN

0.8

1

Figure 7. Spin-lattice relaxation times T1 for all of the 1,3-BD hydrogen atoms in AN−water solutions as a function of xAN. In panel b the vertical axis of panel a is expanded for clarity of the change in T1 of the 1,3-BD alkyl hydrogen atoms against xAN.


1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


Intensity / a.u.

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xAN 0 0.5 1

1.0

0.5

0.0

0

1000 2000 Mixing time / ms

3000

Figure 8. Experimental intramolecular 1H−1H NOE enhancements between the H1 and H4 atoms of 1,3-BD molecule in AN-d3−D2O solutions as a function of mixing time.



1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

a

ACS Paragon Plus Environment

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b

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1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 ACS Paragon Plus Environment

Solvation Structure of 1,3-Butanediol in Aqueous Binary Solvents with

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