Thermophysical Properties of 1-Hexyl-3-methylimidazolium Salicylate

Article pubs.acs.org/jced

Cite This: J. Chem. Eng. Data XXXX, XXX, XXX−XXX

Thermophysical Properties of 1‑Hexyl-3-methylimidazolium Salicylate as an Active Pharmaceutical Ingredient Ionic Liquid (APIIL) in Aqueous Solutions of Glycine and L‑Alanine Hemayat Shekaari, Mohammed Taghi Zafarani-Moattar, Seyyedeh Narjes Mirheydari,* and Saeid Faraji Department of Physical Chemistry, University of Tabriz, Tabriz, Iran Downloaded via UNIV OF KANSAS on January 3, 2019 at 19:50:08 (UTC). See https://pubs.acs.org/sharingguidelines for options on how to legitimately share published articles.

S Supporting Information *

ABSTRACT: The effect of 1-hexyl-3-methylimidazolium salicylate, [HMIm][Sal] as an ionic liquid form of active pharmaceutical ingredient (API-IL) on the thermodynamic behavior of two simple amino acids, glycine and L-alanine have been investigated. The densities, speeds of sound, viscosities, and refractive indices of the amino acids in the mixtures of ([HMIm][Sal] + water) have been determined at T = 298.15 K. Moreover, the electrical conductivities of the studied API-IL in water and aqueous mixtures of the amino acids have been calculated using the measured specific conductivities. The measured data were utilized to compute the partial molar volume of transfer (ΔtraV0ϕ), partial molar isentropic compressibility of transfer (Δtraκ0ϕ), viscosity B-coefficient of transfer (ΔtraB), ion association constant (KA), and molar refraction (RD) quantities. The increase in the positive values of ΔtraV0ϕ, Δtraκ0ϕ and ΔtraB with an increase in the API-IL concentration indicates that the ion−polar and polar−polar interactions between the API-IL and amino acid are dominant. Besides, the decrease in the KA values of [HMIm][Sal] with the addition of amino acid concentration suggests that the formation of ion pair does not proceed spontaneously due to the ions solvated by the zwitterions of amino acid.

1. INTRODUCTION

In recent years, some references reported the thermodynamic properties of the mixtures containing amino acid and the first generation of ionic liquid in aqueous media at different temperatures.15−19 For the first time, Shekaari et al.20−22 have examined the effect of the active pharmaceutical ingredients in the ionic liquids form (API-ILs), 1-butyl-3-methylimidazolium salicylate and ibuprofenate on the thermodynamic properties of aqueous mixtures of amino acids, glycine, and L-alanine. Results show that the ion−polar and polar−polar interactions between the amino acid and API-IL are predominant. As a continuation of our systematic thermodynamic studies20−22 in this work, the measured density, speed of sound, viscosity, electrical conductivity, and refractive index data for glycine and L-alanine in the mixtures of (1-hexyl-3methylimidazolium salicylate ([HMm][Sal]) + water) were reported at T = 298.15 K and atmospheric pressure. The measured data were used to compute the partial molar volume of transfer ΔtraV0ϕ, partial molar isentropic compressibility of transfer Δtraκ0ϕ, viscosity B-coefficient, ion association constant (KA) and molar refraction RD.

Salicylic acid is one of the active pharmaceutical ingredients (APIs) with low water solubility (2 g/L at 20 °C) and many applications in the pharmaceutical, food, health, and cosmetic industries. The poor water solubility of this API limits its therapeutic applications.1 In the new approach for drug solubility improvement, the active pharmaceutical ingredient (API) is combined with the second generation of ionic liquid to create the third generation of ionic liquid namely API-IL.2,3 This form of API presents improved solubility, drug delivery, and bioavailability due to the hydrophobicity and hydrophilicity natures.4−7 In recent years, Viau and Pinto et al. introduced 1-butyl-3-methylimidazolium ibuprofenate and salicylate as new gels for drug delivery.8,9 To design and improve the biotechnological processes such as stability and solubility of the protein, information about the molecular mechanism interactions existing between pharmaceutically active ionic liquid form and protein is required.10−12 Proteins are complicated biomolecules which comprise amino acid units; therefore studying the amino acids is easier than studying the protein.13,14 In this respect, the thermophysical properties (i.e., the volumetric and transport properties) of amino acid in the presence of API-IL give us useful information about the possible interaction between solute and solvent as well as solute−solute interactions. © XXXX American Chemical Society

Received: July 24, 2018 Accepted: December 13, 2018

A

DOI: 10.1021/acs.jced.8b00644 J. Chem. Eng. Data XXXX, XXX, XXX−XXX

Journal of Chemical & Engineering Data

Article

Table 1. Description of the Chemicals Used chemical name

CASRN

source

glycine L-alanine [HMIm][Sal] N-methylimidazole 1-chlorohexane sodium salicylate ethyl acetate dichloromethane

56-40-6 56-41-7 this work 7-47-616 544-10-5 54-21-7 6-78-141 75-09-2

Loba Chemie Merck synthesized Merck Merck Merck Merck Fluka

initial mass fraction purity 0.99 >0.99 >0.99 ≥0.99 ≥0.995 >0.998 ≥0.999

purification method none none rotary/evaporator and vacuum none none none none none

2. EXPERIMENTAL SECTION 2.1. Materials. Table 1 gives the source, CAS number, mass fraction purity, and used method for analysis of the chemicals. The deionized water with specific conductivity lower than 1 μS cm−1 at T = 298.15 K was used for the electrical conductivity measurements. 2.2. Preparation of the Ionic Liquid. The ionic liquid, 1hexyl-3-methylimidazolium salicylate, [HMIm][Sal] was synthesized from sodium salicylate and 1-hexyl-3-methylimidazolium chloride [HMIm][Cl]. The preparation and purification of the 1-hexyl-3-methylimidazolium chloride were performed according to the method stated in the references.23−25 The moisture content of the prepared ionic liquid, [HMIm][Cl] using the Karl Fischer method was below 0.05% in mass fraction. Analysis of the ionic liquid by 1HNMR and IR spectroscopy showed good agreement compared with the literature and confirmed the absence of any significant impurity.26 The mass fraction purity of the prepared ionic liquid was 98%. Then the similar procedure utilized for the preparation of IL, 1-butyl-3-methylimidazolium dicyanamide,23 [BMIM][DCA], was applied for synthesis of the 1-hexyl-3methylimidazolium salicylate ionic liquid [HMIm][Sal]. For this purpose, (0.4 mol) sodium salicylate was dissolved in acetonitrile and added gradually to (0.4 mol) [HMIm][Cl] dissolved in a minimum amount of dry acetonitrile. The following mixture was agitated at T = 298.15 K overnight. The rotary evaporator at 350 K and reduced pressure was used to extract the water in the mixture. The resulting mixture was then dissolved in a large amount of dichloromethane to observe white precipitate containing sodium chloride. The filtration of precipitate was continued until no white solid formed with the addition of dichloromethane.27,28 The silver test confirmed the lack of sodium chloride. The obtained product (a yellowish liquid) was further evaporated at 343.15 K by rotary evaporator.23 A coulometric Karl Fischer titrator (Metrohm 756 KF) was used to determine the water content of the prepared [HMIm][Sal] and the value was nearly 0.1% in mass fraction. The 1H NMR (Bruker Av-400) and IR (Bruker, tensor27) spectroscopy were applied to characterize the prepared API-IL. Figure S1 in the Supporting Information shows the 1H NMR spectrum of [HMIm][Sal]. 2.3. Instrument and Procedure. Measurements of density d and speed of sound u of the mixtures were made by vibrating tube densimeter, Anton Paar, DSA 5000. Distilled deionized and degassed water as well as dry air at atmospheric pressure were applied to calibrate the instrument. The temperature was kept constant within ±10−3 K using the Peltier technique embedded in the densimeter. The standard uncertainty of the measurements of d and u were approximately 0.3 kg·m−3 and 0.5 m·s−1, respectively. The

final mass fraction purity

0.98

analysis method

1

HNMR and FT-IR

analytical balance (AND, GR202, Japan) with a precision of ±1 × 10−8 kg was used for the preparation of the samples. The Anton Paar Rolling-ball viscometer Lovis 2000 M/ME was applied to measure the viscosity η of desired solutions. Controlling the temperature of the instrument was made by a Peltier technique built in the thermostat. The standard uncertainty for the η measurements was nearly 0.015 mPa·s. Measurement of the electrical conductivities, κ, were performed by a conductivity meter (Metrohm model 712, Switzerland) with an accuracy of ±0.5%. The instrument was calibrated using the measurement specific electrical conductivities for KCl solutions. For measuring the κ values, the weighed drop of pure API-IL was added into the cell container of the conductivity meter which contains 60 mL of solvent. The magnetic stirrer was applied to agitate the solution. The temperature was fixed by circulation of water from the thermostatically adjusted bath around the cell with an uncertainty ±0.02 K. The molar conductivity (Λ) values of 1000κ the solutions were computed using the relation, Λ = c , where κ and c are the specific electrical conductance and the molarity of the mixtures, respectively. Refractive indices nD of the mixtures were measured by a digital refractometer (ATAGO-DRA1, Japan) with the standard uncertainty of ±0.002. The temperature was kept constant using a circulating thermostatic bath (Cooling Bath 490, Iran) with a thermal stability of ±0.01 K.

3. EXPERIMENTAL RESULTS AND DISCUSSION 3.1. Volumetric Properties. To study the hydration layer volume surrounding the amino acid as well as the interactions in the studied systems, calculating the apparent molar volume Vϕ using density is an appropriate approach. So, density d of glycine in the mixtures of ([HMIm][Sal] + water) with 0.0978, 0.1977, and 0.3011 molality and L-alanine in the mixtures of ([HMIm][Sal] + water) with 0.0999, 0.1989, and 0.2927 molality were measured and reported in Table S1. The measured densities increase with the amino acid and [HMIm][Sal] concentration. The measured densities were used to calculate the Vϕ values29 ÄÅ ÉÑ ÅÅÅ 1000(d − d0) ÑÑÑ M ÑÑ Vϕ = − ÅÅÅ ÑÑ ÅÅÇ d mdd0 (1) ÑÖ where m and M are the molality and molar weight of the amino acid, d0 and d are the densities of the solvent ([HMIm][Sal] + water) and ternary mixtures (amino acid + [HMIm][Sal] + water), respectively. Table 2 reports the values of Vϕ for the studied mixtures. Moreover, Figure S2 shows the Vϕ values of glycine in the mixture of ([HMIm][Sal] + water) with 0.3011 molality. This figure shows that the apparent molar volumes B



Article

Table 2. Apparent Molar Volume, Vϕ, Apparent Molar Isentropic Compressibility, κϕ, Hydration Number nH (eq 8) of Glycine and L-Alanine in the Aqueous Solutions of [HMIm][Sal] with Several Molalities (mAPI‑IL) Accompanied by the Viscosity and Refractive Index of Ternary Solutions of (Glycine + [HMIm][Sal] + Water) and (L-Alanine + [HMIm][Sal] + Water) at T = 298.15 K and 0.087 MPaa Glycine in mAPI‑IL([HMIm][Sal] + Water) mAPI‑IL = 0.0978 mol·kg−1 0.1496 0.1999 0.2497 0.3001 43.67 43.64 43.63 43.61 −2.4 −2.4 −2.39 −2.39 3.7 3.68 3.67 3.66 1.09 1.097 1.105 1.112 3.884 3.895 3.906 3.917 mAPI‑IL = 0.1977 mol·kg−1 0.1474 0.2005 0.2541 0.2964 43.95 43.95 43.94 43.94 −2.3 −2.28 −2.24 −2.22 2.82 2.8 2.77 2.75 1.255 1.264 1.275 1.285 4.037 4.047 4.059 4.071 mAPI‑IL = 0.3011 mol·kg−1 0.1484 0.1996 0.2463 0.2964 44.27 44.27 44.26 44.26 −2.16 −2.12 −2.09 −2.06 2.27 2.24 2.22 2.2 1.395 1.406 1.417 1.427 4.2 4.212 4.223 4.234 L-Alanine in mAPI‑IL([HMIm][Sal] + Water) b

a

−1

m/mol·kg 106Vφ/m3·mol−1 1014κφ/m3·mol−1·Pa−1 nH η /mPa·s 106RD/ m3·mol−1

0.0984 43.67 −2.41 3.71 1.075 3.848

m/mol·kg−1 106Vφ/m3·mol−1 1014κφ/m3·mol−1·Pa−1 nH η /mPa·s 106RD/m3·mol−1

0.0994 43.95 −2.33 2.85 1.237 4.002

m/mol·kg−1 106Vφ/m3·mol−1 1014κφ/m3·mol−1·Pa−1 nH η /mPa·s 106RD/ m3·mol−1

0.0968 44.28 −2.19 2.29 1.374 4.113


0.0997 60.72 −2.33 4.3 1.078 3.858

0.149 60.72 −2.31 4.27 1.104 3.891


0.1041 61.05 −2.14 3.37 1.238 4.002

0.1495 60.96 −2.14 3.22 1.272 4.047


0.099 61.12 −2.00 2.64 1.364 4.132

0.1547 61.06 −1.97 2.61 1.403 4.195

mAPI‑IL = 0.0999 mol·kg−1 0.1997 0.2484 60.72 60.72 −2.3 −2.28 4.25 4.22 1.117 1.132 3.905 3.92 mAPI‑IL= 0.1989 mol·kg−1 0.2287 0.2509 60.86 60.86 −2.12 −2.12 3.64 3.21 1.288 1.315 4.061 4.085 mAPI‑IL= 0.2927 mol·kg−1 0.1997 0.2557 61.02 60.98 −1.94 −1.91 2.59 2.56 1.425 1.443 4.213 4.227

0.3496 43.58 −2.38 3.64 1.12 3.928

0.3988 43.56 −2.37 3.63 1.128 3.94

0.4367 43.55 −2.37 3.62 1.136 3.951

0.3514 43.94 −2.2 2.73 1.293 4.08

0.3986 43.93 −2.2 2.72 1.304 4.092

0.4521 43.93 −2.16 2.69 1.314 4.102

0.3468 44.26 −2.03 2.18 1.438 4.246

0.3964 44.25 −2.01 2.17 1.449 4.258

0.442 44.25 −1.98 2.14 1.46 4.269

0.295 60.72 −2.26 4.19 1.146 3.935

0.3457 60.73 −2.24 4.16 1.159 3.948

0.3975 60.73 −2.21 4.13 1.174 3.964

0.449 60.73 −2.19 4.1 1.188 3.98

0.303 60.8 −2.11 3.24 1.323 4.092

0.3455 60.74 −2.1 3.14 1.341 4.108

0.3977 60.68 −2.1 3.13 1.355 4.12

0.432 60.66 −2.1 3.01 1.372 4.137

0.3 60.94 −1.91 2.55 1.466 4.245

0.3477 60.9 −1.89 2.53 1.483 4.259

0.3988 60.86 −1.87 2.51 1.501 4.274

0.447 60.83 −1.85 2.5 1.521 4.29

Standard uncertainties u are, u(T) = 0.01 K, u(η) = 0.015 mPa.s, and u(P) = 0.01 MPa. The estimated uncertainties are uc(Vϕ) = 0.05 × 10−6 m3· mol−1, uc (κϕ) = 0.02 × 10−14 m3 mol−1·Pa−1 and uc (RD) = 0.003. bRelative standard uncertainties ur for molalities of API-IL and amino acids are ur(mAPI‑IL) = 0.02 and ur (m) = 0.005, respectively, where mAPI‑IL is the molal concentration of API-IL in water and m is the molal concentration of amino acid in the ([HMIm][Sal] + water) solutions. a

Vϕ = V ϕ0 + Svm

increase with the [HMIm][Sal] concentration increment. Moreover, the Vϕ values decrease with amino acid molality increment which may be related to the release of the water molecules from the hydration layer surrounding the amino acid zwitterion and forming the new interaction between API-IL and amino acid. This phenomenon leads to lowering the molar volume of the amino acid in solutions with the addition of the API-IL. The following equation was used to correlate the obtained Vϕ values30

(2)

where V0ϕ is the standard partial molar volume and Sv is an experimental parameter. Table 3 listed the values of V0ϕ and Sv accompanied by their standard deviation σ(Vϕ) derived by least-squares correlating of the Vϕ values to eq 2. The rise in the V0ϕ values with increase in the API-IL concentration shows that the volume of the amino acid molecules in the solutions C



Article

Table 3. Values of Standard Apparent Molar Volume, V°ϕ, Experimental Slope, Sv, Transfer Volume ΔtraV0ϕ, Hydration Number, ◦⧧ nH, Viscosity B-Coefficients, Free Energy of Activation per Mole of Solvent (Δμ◦⧧ 1 ) and the Solute (Δμ1 ), Viscosity BCoefficient of Transfer (ΔtraB), Pair (VAB and κAB) and Triplet (VABB and κABB) Interaction Coefficients of Glycine and LAlanine in Water and Aqueous Mixtures of [HMIm][Sal] at T = 298.15 K and 0.087 MPa Glycine in ([HMIm][Sal] + Water) mAPI‑IL/mol·kg−1 106 V0ϕ/m3·mol−1 106Sv/m3·mol−2·kg 106σ(Vϕ) 106ΔtraV0ϕ/m3·mol−1 nH (eq 3) 106VAB/m3·mol−2·kg 106VABB/m3·mol−3·kg2 1014κ0φ k/m3·mol−1·Pa−1 10 14Sk/m3·mol−2·kg·Pa−1 10 14σ(κϕ) 10 14Δtraκ0ϕ/ m3·mol−1·Pa−1 nH (eq 8) B/dm3·mol−1 Δμ°1 #/kJ·mol−1 Δμ2°#/kJ·mol−1 ΔtraB/dm3·mol−1 1014κAB/m3·mol−2·kg·Pa−1 1014κABB/m3·mol−3·kg2·Pa−1 a

0.0978 43.72 ± 0.01 −0.38 ± 0.02 0.01 0.49 2.35

−2.42 ± 0.00 0.11 ± 0.01 0.00 0.23 2.99 0.141 ± 0.001 9.70 31.97 0.006

L-Alanine

0.1977 43.96 ± 0.00 −0.08 ± 0.01 0.01 0.73 2.28 2.50 4.68 −2.37 ± 0.01 0.47 ± 0.03 0.01 0.28 2.92 0.154 ± 0.001 10.1 33.56 0.019 1.11 −1.00

0.3011 44.28 ± 0.00 −0.06 ± 0.01 0.00 1.05 2.18

0.0999 60.72 ± 0.00 0.02 ± 0.00 0.01 0.75 3.34

−2.24 ± 0.01 0.59 ± 0.03 0.01 0.41 2.77 0.157 ± 0.001 10.42 33.65 0.022

−2.37 ± 0.01 0.40 ± 0.02 0.00 0.28 2.93 0.256 ± 0.001 9.70 49.71 −0.002

in ([HMIm][Sal] + Water) 0.1989 61.14 ± 0.02 −1.16 ± 0.04 0.01 1.17 3.21 4.68 −5.90 −2.16 ± 0.01 0.14 ± 0.02 0.00 0.5 2.66 0.272 ± 0.001 10.11 51.22 0.014 1.62 −1.26

0.2927 61.19 ± 0.01 −0.82 ± 0.01 0.01 1.22 3.2

−2.03 ± 0.01 0.42 ± 0.04 0.01 0.62 2.51 0.287 ± 0.002 10.4 52.53 0.029

a

The molal concentration of [HMIm] in water.

Another suitable parameter to determine the interactions type is the partial molar volume of transfer calculated using the relation33

with higher amount of API-IL is largely due to the effective interaction between amino acid and API-IL. To evaluate the extent of solute hydration, hydration number nH can be computed using the following equation29 nH =

V ϕ0(elect) V E0 − V B0

Δtra V φ0 = V φ0([HMIm][Sal] + water) − Vφ 0(water)

The data for the binary systems, (glycine + water) and (Lalanine + water) used in the calculations were taken from earlier published data.21 The calculated values of ΔtraV0ϕ for the studied mixtures given in Table 3 and Figure 1 are positive and increase as the concentration of [HMIm][Sal] increases. The observed positive values of ΔtraV0ϕ indicating the strong ion− zwitterion interactions between [HMIm][Sal] and the amino acid. According to the cosphere overlap model, the contribution of solute−solute interactions is negligible, and

(3)

where V0ϕ(elect) is the molar volume of electrostrictive water and V0B is the molar volume of the bulk water. The value of (V0E − V0B) for electrolytes at 298.15 K is about 3.0 cm3 mol−1. The values were achieved by30 V ϕ0(elect) = V ϕ0 − V ϕ0(int)

(6)

(4)

where V0ϕ(int) is the inherent partial molar volume originating from the hydration of amino acid zwitterions. Combining the volume from van der Waals and packing effects can produce the V0ϕ(int) term which is obtained from31 V ϕ0(int) =

0.7 0 V ϕ(cryst) 0.634

in which V ϕ0(cryst) =

M is d(cryst)

(5)

the molar volume of the crystal

which can be computed using densities of the amino acids (crystal form) supposed by Berlin and Pallansch at 298.15 K.32 Table 2 gives the calculated nH values for the studied solutions. The nH values for the (amino acid + [HMIm][Sal] + water) mixture are less than the ([HMIm][Sal] + water)20,21 which is indicative of the stronger interactions between [HMIm][Sal] and zwitterion forms of amino acid than that in water. In the high concentration of [HMIm][Sal], the water molecular structure around the amino acids is disrupted, and water molecules are released to the bulk and hydration number decreases.

Figure 1. Partial molar volume of transfer for glycine (●) and Lalanine (■) in the solutions of ([HMIm][Sal] + water) with several molalities at T = 298.15 K. D



Article

hence the information about the solute−solvent interactions can be obtained. The different types of possible interactions in these systems are the ion−polar, polar−polar, ion−nonpolar and nonpolar−nonpolar interaction occurred between the amino acid and API-IL. The positive ΔtraV0ϕ values indicate that the ion−polar and polar−polar interactions are predominant, while negative values of ΔtraV0ϕ originate from the ion− nonpolar and nonpolar−nonpolar interactions. The obtained ΔtraV0ϕ values presented in Table 3 for L-alanine are greater than glycine and increase with an increase in the [HMIm][Sal] concentration. This phenomenon suggests the stronger interactions between the zwitterionic center of glycine and [HMIm][Sal] which result in the decrease of the solvation layer volume.34 The comparison of V0ϕ and ΔtraV0ϕ with data presented in the literature21 indicates that these values increase with an increase in the alkyl chain length of the cation. For example, the ΔtraV0ϕ values for glycine in aqueous solution of [BMIm][Sal] and [HMIm][Sal] with 0.3 molality are 0.80 and 1.05, respectively. In the API-ILs with the longer alkyl chain, the electrostatic forces between cation and anion are weaker, and the more free API-IL ions tend to have stronger interactions with the zwitterions of the amino acids. 3.2. Ultrasonic Properties. Table S1 reports the measured speed of sound values for the studied mixtures of (glycine, Lalanine + [HMIm][Sal] + water). The isentropic compressibility κs(Pa−1) was calculated using the Laplace−Newton’s equation as follows20 κs =

1 du 2

κϕ =

nsolvent ijj κ yz jj1 − s zzz j nsolute k κs0 z{

(9)

where κs0 and κs are isentropic compressibility of the solvent ([HMIm][Sal] + water) and ternary (amino acid + [HMIm][Sal] + water) mixtures, respectively. The obtained κϕ values for the studied mixtures presented in Table 2 indicate that the κϕ values increase with an increase in the [HMIm][Sal] concentration. This trend originates from the release of some water molecules into the bulk and the presence of [HMIm][Sal] around the amino acid is intensified at the higher concentrations of API-IL. Extrapolating the κϕ value to the infinite dilution using the next relation obtains the partial apparent molar isentropic compressibility κ0ϕ values21 κϕ = κϕ0 + Skm

(10)

where Sk is indicative of the solute−solvent interaction and m is the molality of amino acid in the mixtures. The obtained κ0ϕ and Sk values for the studied solutions along with the standard deviation σ(κϕ0 ) are given in Table 3. Owing to the insignificance of interactions between the solute (amino acid) at infinite dilution, solute−solvent interactions in the solutions are prevailing. The hydration of amino acids is reduced at the higher concentrations of [HMIm][Sal] due to the attractive [HMIm][Sal]-amino acid interactions. Therefore, at a higher amount of [HMIm][Sal], the hydration shells surrounding the amino acids have more compressibility compared to the lower concentrations of [HMIm][Sal].35,36 The negative values of Sk in almost all cases show that the interactions between amino acid molecules are weaker than their interactions with water or API-IL. The partial molar isentropic compressibility of transfer Δtraκ0ϕ from water to the ([HMIm][Sal] + water) mixture was calculated by the following relation

(7)

The following equation was used to obtain the hydration number nH of amino acids20−22 nH =

(κsd0 − κs0d) M + κs mdd0 d

(8)

Δtra κφ0 = κφ0([HMIm][Sal] + water) − κφ0(water )

where nsolvent and nsolute are the mole number of ([HMIm][Sal] + water) and solute (amino acids) κs, κs0 are the isentropic compressibility of the mixtures and the solvent ([HMIm][Sal] + water), respectively. Tables 2 and 3 present the obtained nH values and their average for the mixtures of (glycine, L-alanine + [HMIm][Sal] + water) with several molalities of the ([HMIm][Sal] + water) mixtures. The calculated values of the nH using eqs 3 and 8 are relatively close to each other and have similar trends (decrease with the addition of API-IL to the mixtures) with an increase in the [HMIm][Sal] molality. Moreover, Figure S3 presents the obtained nH values (eq 8) for glycine and L-alanine in the mixtures of ([HMIm][Sal] + water) with 0.1977 and 0.1989 molalities. The higher amount of the nH values for L-alanine in the aqueous solutions of [HMIm][Sal] compared to glycine is indicative of the stronger hydration of this amino acid rather than glycine. Moreover, it can be seen in Figure S3 that the nH values of amino acids decrease with an increase in the concentration of [HMIm][Sal]. The results indicate that the addition of [HMIm][Sal] to the aqueous mixtures of amino acid leads the disruption of the water molecules structure around the amino acid and formation of the new interaction between API-IL and amino acid. To understand the solvent structure around the amino acid as well as in the bulk, the following equation was used to calculate the apparent molar isentropic compressibility κϕ20

(11)

represents the obtained Δ tra κ ϕ0 values for mixtures. Moreover, the Δtraκ0ϕ of glycine and L-

Table 3 investigated alanine in the mixtures of ([HMIm][Sal] + water) with several molalities were plotted in Figure 2. The positive values of Δtraκ0ϕ declare the dominance the interactions between the

Figure 2. Partial molar isentropic compressibility of transfer for glycine (●) and L-alanine (■) in the mixtures of ([HMIm][Sal] + water) with several molalities at T = 298.15 K. E



Article

where η and η0 are the viscosity of the ternary mixtures (amino acid + [HMIm][Sal] + water) and solvent ([HMIm][Sal] + water), respectively, and c is the molarity of amino acid in the studied mixtures. The slope of the linear plot of (ηr − 1) vs c by the least-square method was used to calculate the viscosity B-coefficients. Table 3 listed the calculated viscosity Bcoefficients and σ(η) for the studied solutions. The size, shape, structure, and solute molecules charge induced by solute−solvent interactions affect the viscosity B-coefficient.40 The high positive values of the viscosity B-coefficients of (glycine + [HMIm][Sal] + water) compared to (L-alanine + [HMIm][Sal] + water) mixtures is illustrative of the greater kosmotropic effect of this amino acid in the mixtures of ([HMIm][Sal] + water) (see Figure 3).40

head polar moieties of the amino acid and the ions of [HMIm][Sal] which these values become more favorable with an increase in the [HMIm][Sal] concentration. As a result, the hydration layer around the amino acid is much more compressible than the water in bulk with an increase in [HMIm][Sal] concentration.36 In the following, the κ0ϕ and Δtraκ0ϕ values for the amino acid in the mixtures of ([HMIm][Sal] + water) were compared with those data in the literature for [BMIm][Sal]21 which show that these values became more positive with an increase in the alkyl chain length of the cation. In fact in the longer alkyl chain of the API-IL cation, the systems are more compressible due to the stronger interaction between API-IL and amino acid and disruption of the water molecules structure around the amino acid. 3.3. Pair and Triplet Interaction Coefficients. The McMillan and Mayer theory36 developed by Friedman and Krishnan,37 offered a simple method to calculate interaction coefficients which separate the interactions between two or more solute molecules. Therefore, the subsequent relations were applied to evaluate the values of Δtraκ0ϕ and Δtraκ0ϕ36,37 2 Δtra V ϕ0 = 2VABmAPI − IL + 3VABBmAPI − IL

(12)

2 Δtra κϕ0 = 2κABmAPI − IL + 3κABBmAPI − IL

(13)

where A and B denote the amino acid and [HMIm][Sal], respectively, and mAPI-IL is the molality of [HMIm][Sal] in the mixtures of ([HMIm][Sal] + water). The pair and triplet interaction coefficients express the corresponding parameters VAB, VABB, for volume and, κAB, κABB for compressibility. These parameters were calculated by correlating the values of ΔtraV0ϕ and Δtraκ0ϕ to the above equations (see Table 3). This table shows that the pair interaction coefficients VAB and κAB are positive, whereas triplet interaction coefficients VABB and κABB are negative for the systems. The positive values of VAB and κAB predict that frequent interactions between API-IL and amino acids in solutions are mostly pairwise.38 3.4. Viscometric Properties. The viscosity B-coefficient is one of the other parameters used to survey the solute−solvent interactions. In this respect, the experimental viscosities η of the mixtures of (glycine + [HMIm][Sal] + water) and (Lalanine + [HMIm][Sal] + water) with several modalities were measured and presented in Table S1. The η values of the ternary mixtures of (glycine, L-alanine + [HMIm][Sal] + water) with 0.1977 and 0.1989 molalities of ([HMIm][Sal] + water) were presented in Figure S4, respectively. This figure shows that the η values increase with an increase in the amino acid and [HMIm][Sal] concentrations. The Jones−Dole equation represents the variation of relative η viscosity ηr = η of the amino acid in the aqueous mixtures of

Figure 3. B-coefficient viscosity of the mixtures of (glycine (•) + [HMIm][Sal] + water) and (L-alanine (■) + [HMIm][Sal] + water) with several molalities of the ([HMIm][Sal] + water) solutions at T = 298.15 K.

The following relation presents the variation of Bcoefficients ΔtraB from water to the ([HMIm][Sal] + water) mixtures21,29 Δtra B = B‐coefficient ([HMIm][Sal] + water) − B‐coefficient (water)

For the studied ternary mixtures (amino acids + [HMIm][Sal] + water), the viscosity B-coefficients are higher than those in water; as a result, the ΔtraB values are positive. The values of viscosity B-coefficients decrease as a function of [HMIm][Sal] in the mixtures. The magnitude of the ΔtraB values for glycine is greater than those for L-alanine which suggests the greater dehydration effect of glycine by adding the API-IL to the mixture. The values of viscosity, B-coefficients, and B-coefficients of transfer of the studied systems were also compared with those previously presented for [BMIm][Sal]21 which show that these values have a similar trend with those concluded from volumetric and compressibility properties. This phenomenon verifies the stronger amino acid-API-IL interactions for the API-IL with longer alkyl chain of the cation. Feakins and co-worker proposed the analysis based on the calculation of transition state using the viscosity B-coefficient. The following relation gives the viscosity B-coefficient regarding this theory40,41

0

[HMIm][Sal]39

ηr = 1 + Ac1/2 + Bc

(14)

The A-coefficient (also named Falkenhagen coefficient, indicative of the solute−solute interactions) can be theoretically calculated, but this coefficient is usually insignificant for nonelectrolytes. Viscosity B-coefficients essentially illustrate the interactions between solute and solvent. In fact, by neglecting A-coefficient in eq 14, it is simplified to the following viscosity equation29 ηr = 1 + Bc

(16)

(15) F



Article

Table 4. Molar Electrical Conductivities (Λ) of the API-IL, [HMIm][Sal] in Water and Aqueous Mixtures of Glycine and LAlanine as a Function of API-IL Molality (mAPI‑IL) at T = 298.15 K and 0.087 MPaa b,c

104Λ/S·m2· mol−1

103 mAPI‑IL/ mol·kg−1


104Λ/S·m2· mol−1


104Λ/S·m2· mol−1

b,c mGly = 0.0 mol·kg−1 0.0370 77.51 0.0839 76.41 0.1477 75.09 0.2155 74.23 0.2694 73.77 0.3205 73.33 0.4082 72.67 0.4728 72.31 0.5305 71.74 0.6157 71.13 0.6979 70.58 0.7632 70.12 0.8165 69.79

mGly = 0.1 mol·kg−1 0.0564 72.18 0.1197 71.77 0.1826 71.35 0.2480 70.93 0.3106 70.56 0.3697 70.17 0.4239 69.82 0.4837 69.37 0.5481 69.04 0.6156 68.63 0.6831 68.29 0.7376 68.03 0.7914 67.72

mGly = 0.3 mol·kg−1 0.0644 66.95 0.1025 66.71 0.1534 66.50 0.2100 66.29 0.2752 66.07 0.3279 65.89 0.3819 65.69 0.4384 65.52 0.4951 65.30 0.5554 65.14 0.6172 64.94 0.7348 64.67

mAla= 0.0 mol·kg−1 0.0370 77.51 0.0839 76.41 0.1477 75.09 0.2155 74.23 0.2694 73.77 0.3205 73.33 0.4082 72.67 0.4728 72.31 0.5305 71.74 0.6157 71.13 0.6979 70.58 0.7632 70.12 0.8165 69.79

mAla= 0.1 mol·kg−1 0.0843 72.99 0.2043 72.47 0.2529 72.22 0.3087 71.93 0.3610 71.76 0.4300 71.42 0.5115 71.08 0.5554 70.87 0.6479 70.44 0.7157 70.12 0.8119 69.8

mAla = 0.3 mol·kg−1 0.0335 71.01 0.0751 70.62 0.1129 70.24 0.2102 69.31 0.2657 68.82 0.3038 68.52 0.3590 68.12 0.4204 67.52 0.4792 67.07 0.5339 66.69 0.6087 66.00 0.6747 65.53 0.7996 64.70

b,c


104Λ/S·m2· mol−1

mGly = 0.5 mol·kg−1 0.0516 63.19 0.1253 62.94 0.1860 62.79 0.2470 62.60 0.3193 62.47 0.3829 62.30 0.4427 62.10 0.5092 62.00 0.5913 61.82 0.6718 61.64 0.7417 61.54 0.7993 61.39 0.8916 61.16 0.9313 61.10 1.0203 60.94 mAla= 0.5 mol·kg−1 0.0442 65.87 0.0830 65.42 0.1252 65.15 0.1642 64.90 0.2217 64.62 0.2817 64.39 0.3462 64.20 0.3946 64.08 0.4694 63.82 0.5151 63.72 0.5828 63.56 0.6322 63.48 0.6922 63.27

Standard uncertainties u are u(Λ) = 1.5 × 10 −4S m2 mol−1, u(T) = 0.01 K and pressure u(P) = 0.01 MPa. bmAPI‑IL is the molality of API-IL in water and aqueous solutions of amino acid, mGly and mAla are the molalities of glycine and L-alanine in water, respectively. cRelative standard uncertainties ur are ur (mAPI‑IL) = 0.007 and ur (mGly, mAla) = 0.005. a

◦⧧ ◦⧧ ji Δμ − Δμ1 zyz zz B = (V1̅ 0 − V2̅ 0) + V1̅ 0jjjj 2 zz j RT k {

(

where V1̅ 0 = ∑ (v̅02

V0ϕ)

xiMi ρ

the ground state compared to the transition state. The values of Δμ2◦⧧ increase with an increase in the molality of [HMIm][Sal] up to 0.3 mol·kg−1. The higher values of Δμ◦⧧ 2 for L-alanine suggest that this amino acid requires more energy to transfer from the ground state solvent to transition state solvent compared to the glycine.40−42 3.5. Conductometric Properties. Another appropriate way to interpret the possible ions interactions is determination of the molar conductivity and ion association of API-IL and their changes in the amino acid mixtures. In this respect, specific conductivities (see Table S2) were measured to calculate the molar conductivity Λ for [HMIm][Sal] in water and aqueous mixtures of amino acid. The Λ values were correlated by the LcCM conductance model. The Onsager model was used to evaluate the initial values of limiting molar conductivity Λ0 and ion association constant KA. The low concentration Chemical Model (lcCM) conductivity equation assesses the real values of the Λ0 for the [HMIm][Sal] in water and the aqueous amino acid solutions using the following set of equations43

(17)

) is the mean volume of the solvent and

= is the standard partial molar volume of the pure solute. The terms v̅01, xi, Mi, and d are the molar volume of the pure solvent, mole fraction, molar masses, and density of solvent ([HMIm][Sal] + water), respectively. Eyring’s simple model was used to calculate the free energy of activation per 22,29 ◦⧧ mole of the solvent Δμ◦⧧ 1 and solute Δμ2 as follows Δμ1◦⧧ = ΔG1◦⧧ = RT ln Δμ2◦⧧ = Δμ1◦⧧ +

η1V10 hNA

RT [B − (V1̅ 0 − V2̅ 0)] V10

(18)

(19)

where h is the Planck constant, NA is the Avogadro number and η0 is the viscosity of the solvent. Table 3 presents the ◦⧧ calculated values of Δμ◦⧧ 1 and Δμ2 . It is clear that the values ◦⧧ of Δμ2 are positive and more significant than Δμ◦⧧ 1 for both amino acids which indicate the stronger interactions between solute (amino acids) and solvent ([HMIm][Sal] + water) in

Λ = α[Λ 0 − S(cα)1/2 + Ecα ln(cα) + J1cα + J2 (cα)3/2 ] (20) G



Article

Table 5. Limiting Molar Conductivities (Λ0), Walden Products (Λ0η), Ion Association Constants (KA), Standard Free Gibbs Energies of Ion Pair Formation (ΔG°A), Distance Parameters (R), and Standard Deviations (σ (Λ)) of [HMIm][[Sal] in Water and Aqueous Solutions of Glycine and L-Alanine at T = 298.15 K and 0.087 MPaa mAAb/ mol·kg−1

KA/dm3·mol−1

0.0 0.1 0.3 0.5

54.75 49.13 34.23 23.51

0.1 0.3 0.5

48.84 33.27 21.22

a

104Λ0/S·cm2·mol−1

1010 R/m

σ(Λ)

[HMIm][Sal] in (Glycine + Water) 0.27 48.11 0.42 0.03 40.57 0.04 0.02 33.41 0.04 0.02 31.91 0.02 [HMIm][Sal] in (L-Alanine + Water) 73.58 ± 0.03 33.42 0.05 71.41 ± 0.03 50.21 0.04 65.76 ± 0.10 38.95 0.16

77.09 72.70 67.18 63.34

± ± ± ±

104Λ0η/S·cm2·mPa·s·mol−1

ΔG°A/kJ·mol−1

68.98 67.17 63.82 62.35

−9.92 −9.65 −8.76 −7.83

66.96 68.19 65.82

−9.64 −8.6 −7.57

The estimated uncertainties for u(KA) = 0.2 dm3 mol−1, u(104 Λ0) = 0.04 S m2 mol−1 and u(T) = 0.01. bmAA is the molality of amino acid in water.

a

KA =

1−α α 2cγ±2

ln γ± = κ2 =

q=

κq 1 + κR

16000NAz 2e 2αc ε0εKBT

z+z −e 2 8πε0εkT

(21)

(22)

(23)

(24)

In the above equations, Λ0 is molar conductivities at molarity at infinite dilution, (1 − α) is the fraction of formed ion pairs, γ± is the mean activity coefficient of the separated ions, κ is the Debye parameter, e is the electronic charge, z is the ionic charge, ε0 is the vacuum permittivity and ε is the dielectric constant of the solvent. The required coefficients E, J1, and J2 for calculations were taken from the literature.43 The parameter R represents the distance between the centers of the ions in the ion pairs. The values of molar conductivities, Λ for ([HMIm][Sal] + water) and ([HMIm][Sal] + amino acid + 1000κ water) were computed using Λ = C (see Table 4). Figure S5 displays the dependency of the molar conductivities Λ on the [HMIm][Sal] concentration in the (amino acid + water) mixtures. This trend shows that the values of Λ decrease with increase in the [HMIm][Sal] concentration due to ionic atmosphere effects, and in more concentrated mixtures, the ion pairing is responsible for the observed lowering of the molar conductivities. The lcCM model was used to analyze the molar conductivity (Λ) and the Λ0, KA, and distance parameter (R) were obtained for [HMIm][Sal] in water and the aqueous amino acid solutions (see Table 5). From Table 5, the values of Λ0 decrease with an increase in the amino acid concentration. These reduced values indicate the low mobility of the ions solvated by the zwitterionic centers of amino acid as well as viscous medium as the amino acid is added to the solution. The lower values of Λ and Λ0 in the mixtures of glycine show that the zwitterions centers of glycine with less hydrophobicity can solvate the API-IL ions more easily than L-alanine.21 Moreover, Figure 4 compares the obtained KA values of [HMIm][Sal] in several molalities of glycine and L-alanine. It is clear that the KA values of [HMIm][Sal] reduce with the amino acid concentration. The strong interaction of ions with zwitterions reduce the ion-pair formation in the concentrated

Figure 4. Ionic association constant of [HMIm][Sal] in the mixtures of (glycine (■) + water) and (L-alanine (●) + water) with several molalities at T = 298.15 K.

solutions. The lower values of KA in the (L-alanine + water) mixtures compared to the (glycine + water) mixtures suggest the stronger interactions between (COO − /NH 3+ ) of zwitterions and ions of [HMIm][Sal] in this amino acid. The evaluated values of the distance parameter (R) have no meaningful trend. 43,44 The Walden product has been calculated to eliminate the effect of η on the ionic mobility. The conductivity of the ions at infinite dilution only depends on their mobility. Therefore, the product of the viscosity of solvent by the ion conductivity is not dependent to the nature of the solvent.45 Table 5 represents the calculated Walden product (Λ0η0) of [HMIm][Sal] in the studied solutions. The smaller amount of Λ0η0 of [HMIm][Sal] in the amino acid mixtures compared to pure water may be related to the preferential solvation of the ions of API-IL by amino acid zwitterions and large effective radius with low mobility. The standard deviations of the experimental molar conductivities (Λ) and the calculated ones (Λcal) were computed as follows: ÄÅ É ÅÅ ∑ (Λ − Λ )2 ÑÑÑ1/2 cal Ñ Å Å ÑÑ σ(Λ) = ÅÅ ÑÑ ÅÅÅ n p − ÑÑÖ (25) Ç in which n and p represent the number of data point and parameters, respectively. Table 5 shows the calculated standard deviations of electrical conductivity using the lcCM model. 3.6. Diffusion Coefficient and Walden Product of Ions. The diffusion coefficients for API-IL at infinite dilution H



Article

Table 6. Values of Ionic Limiting Molar Conductivity (λ0), Walden Product (λ0ionη), Stoke’s Radius (rs), Diffusion Coefficient (D0AB), and Transport Number (t+) of [HMIm]+ and [Sal]− in Water at T = 298.15 K and 0.087 MPa ions

104λ0/S·m2·mol−1

104λ0ionη/S·cm2·mPa·s·mol−1

[HMIm]+ [Sal]−

35.4a 41.69

31.68 37.30

1010rs m

1010D0AB/m2·s−1

[HMIm][Sal] in Water 2.59 10.19 2.20

1010D0ion/m2·s−1

t

ΔG°A/kJ·mol−1

9.43 11.10

0.459 0.541

−9.92

The λ0 values of the cations were taken directly from ref 45.

a

water and aqueous solutions of amino acid were presented in Table 5. By looking at this table, it is understood that the Λ0η values decrease with an increase in the amount of [HMIm][Sal] which confirms the low mobility of the solvated ions by amino acid. Ion transport number or transference number is the fraction of molar conductivity for the ions to the total molar conductivity of the solution including that ion. The ion transport number can be determined as follows22

can be calculated using the Nernst−Haskell equation as follows46 + − RT |z+||z −| λ 0 λ 0 + 2 F |z+z −| λ 0 + λ 0−

0 = DAB

(26)

D0AB

where is the diffusion coefficient of API-IL (A) in water (B), F is the Faraday’s constant, z+ and z− are the charge numbers of the cation and anion, λ+0 and λ−0 are the limiting molar conductivities of the cation and anion, respectively. Table 6 presents the calculated D0AB value of [HMIm][Sal] in water. The following relation determines the ionic limiting molar conductivity values of the individual ions22 Λ 0 = z+λ 0+ + z −λ 0−

t± =

RTλ 0 |z ion|F 2

(28)

Table 6 listed the obtained values of the diffusion coefficient D0ion and mobility of the ions λ0. The more significant values of D0ion for anion rather than cation indicate the feasibility of the anions diffusion through the solvent. On the other hand, the ionic mobility of the anion is higher than that of the cation which means a more significant contribution of the limiting molar conductivity by this ion. The Stoke’s radius (rs) or practical hydrodynamic radius of the ions can be calculated using the D0ion values and viscosity η of pure water through the following equation22 rs =

kT 0 6πηDion

(29)

where xi, Mi, and d are the mole fraction, molar mass of components and the density of solutions, respectively. Table 2 reports the calculated RD values of the investigated solutions. Moreover, the RD values of ternary mixtures of (glycine, Lalanine + [HMIm][Sal] + water) with 0.3011 and 0.2927 molality of (HMIM][Sal] + water) are depicted in Figure 5, respectively. The RD value is directly proportional to molecular polarizability. As can be seen in Table 2, the RD values increase with the [HMIm][Sal] concentration. When the molecule structure is more complicated, its electron cloud becomes more disturbed, and the polarizability of the molecule intensifies. The comparison of the RD values for the studied amino acid in [HMIm][Sal] solution with those reported for [BMIm][Sal]21 show that these values increase with the alkyl chain length of cations. This means that the molecular polarizability

The rs values are closely related to the mobility of the solute and affected by not only size but also the solvent. The calculated values of rs for [HMIm]+ and [Sal]− collected in Table 6 show that the rs for the cation is larger than that for anion. The combination of eq 28 and eq 29 and its rearrangement will result in the following relation49,22 λ 0η =

k|z ion|F 2 6πRrs

(31)

The symbols t+ and t− are usually used to express the transport numbers of cation and anion, respectively. Table 6 gives the calculated values of t+ and t−. These values show that the contribution of the anion to the overall molar conductivity is higher than the cation due to the smaller stock radius and higher mobility. The standard Gibbs energy (ΔG◦A) of the ion-association process was obtained using the ion association constants. Tables 5 and 6 present the calculated values of ΔG◦A for the ion association process of ([HMIm][Sal] + water) and (amino acid + [HMIm][Sal] + water) mixtures. As can be observed in these tables, the ion-association process of [HMIm][Sal] in water and aqueous mixtures of the amino acid is not spontaneous and as a result, the values of ΔG◦A are negative. The more negative values of the ΔG◦A for API-IL in the glycine mixtures indicate a more spontaneous and feasible ion pair formation process in this amino acid. 3.7. Refractometric Properties. The measured refractive index data nD for (glycine, L-alanine + [HMIm][Sal] + water) with several molalitities of ([HMIm][Sal] + water) are listed in Table S1. The molar refraction RD is computed using the Lorentz−Lorenz equation46 ÄÅ ÉÑ 3 x M zy ÅÅÅ nD − 1 ÑÑÑjij ÑÑjj∑ i i zzz RD = ÅÅÅ 2 Ñ j z ÅÅ nD + 2 ÑÑj (32) Ç Ök i = 1 d z{

(27)

The ionic limiting molar conductivity of the [HMIm]+, λ+0 , in water was obtained from the literature.48 Subsequently, the evaluated values of λ−0 using eq 27 as well as λ+0 value were presented in Table 6. As can be observed in this table, the obtained λ−0 is larger than λ+0 which means that the conductivity and mobility of the anion are higher than the cation. The diffusion coefficients of the separate ions can be determined by the subsequent relation45,47 ◦ = Dion

λ0 Λ0

(30)

This equation reveals an inverse relationship between the effective hydrodynamic radius of an ion and its Walden product (Λ0η). In the above equation, all parameters except rs are constant, and the Walden product varies only if the rs changes. The calculated values of Λ0η for [HMIm][Sal] in I



Article

■

Figure 5. Molar refraction of ternary mixtures of (glycine (●) + [HMIm][Sal] + water) and (L-alanine (■) + [HMIm][Sal] + water) with 0.3011 and 0.2927 molalities of ([HMIm][Sal] + water), respectively, at T = 298.15 K.

AUTHOR INFORMATION

Corresponding Author

*Tel.: +98-41-33393094. Fax: +98-41-33340191. E-mail: [email protected]. ORCID

Hemayat Shekaari: 0000-0002-5134-6330 Mohammed Taghi Zafarani-Moattar: 0000-0002-2174-1639 Seyyedeh Narjes Mirheydari: 0000-0002-7666-4976

of the amino acid in the aqueous mixtures of [HMIm][Sal] is higher than that in [BMIm][Sal].

Funding

4. CONCLUSIONS The effect of an active pharmaceutical ingredient-based ionic liquid (API-IL), 1-hexyl-3-methylimidazolium salicylate ([HMIm][Sal]) on the volumetric, compressibility, viscometric, electrical conductivity, and refractometric properties of two amino acids, glycine and L-alanine have been studied at T = 298.15 K. The positive values of partial molar volumes of transfer ΔtraV0ϕ, partial molar isentropic compressibilities of transfer Δtraκ0ϕ and viscosity B-coefficients of transfer ΔtraB indicate that the ion−polar and polar−polar interactions between amino acid and [HMIm][Sal] are dominant. The VAB and κAB values confirm the superiority of the pairwise interactions between the amino acid and [HMIm][Sal]. The more significant amounts of Δμ◦⧧ 2 for L-alanine compared to the glycine show the more effectively of the structure making ability for this amino acid which strengthens with API-IL concentration. The low concentration Chemical Model (lcCM) was used to evaluate the ion association constant (KA), limiting molar conductivity (Λ0), and distance parameter (R). The lower values of Λ0 with the addition of amino acid to the [HMIm][Sal] solutions indicate the low mobility of the solvated ions by (COO−/NH+3 ) zwitterionic centers with large radii and increase in the viscosity of the medium. From the thermodynamic data analysis, the more negative values of ΔG◦A for [HMIm][Sal] in glycine solutions relative to L-alanine is indicative of the more spontaneous ion association process in this amino acid.

■

water) with 0.1977 and 0.1989 molalities (Figure S3); plot of viscosity of the solutions of (glycine + [HMIm][Sal] + water) and (L-alanine + [HMIm][Sal] + water) with 0.1977 and 0.1989 molalities of ([HMIm][Sal] + water) (Figure S4); plot of molar conductivity of [HMIm][Sal] in water and aqueous solutions of glycine and L-alanine with 0.5 molality (Figure S5); values of density (d) and speed of sound (u), for glycine and L-alanine in the aqueous solutions of [HMIm][Sal] and the viscosity (η) and refractive index (nD) values of ternary solutions of (glycine + [HMIm][Sal] + water), (L-alanine + [HMIm][Sal] + water) at T = 298.15 K and 0.0868 MPa (Table S1) (PDF)

The authors are greatful for the financial support from the graduate council of the University of Tabriz. Notes

The authors declare no competing financial interest.

■

REFERENCES

(1) Favre, H. A.; Powell, W. H. Nomenclature of organic chemistry: IUPAC recommendations and preferred names; Royal Society of Chemistry: Cambridge, UK, 2014. (2) Shamshina, J. L.; Barber, P. S.; Rogers, R. D. Ionic liquids in drug delivery. Expert Opin. Drug Delivery 2013, 10, 1367−1381. (3) Ferraz, R.; Branco, L. C.; Prudêncio, C.; Noronha, J. P.; Petrovski, Ž . Ionic Liquids as Active Pharmaceutical Ingredients. ChemMedChem 2011, 6, 975−985. (4) Moniruzzaman, M.; Goto, M. Ionic Liquids: Future Solvents and Reagents for Pharmaceuticals. J. Chem. Eng. Jpn. 2011, 44, 370−381. (5) Geppi, M.; Guccione, S.; Mollica, G.; Pignatello, R.; Veracini, C. A. Molecular Properties of Ibuprofen and Its Solid Dispersions with Eudragit RL100 Studied by Solid-State Nuclear Magnetic Resonance. Pharm. Res. 2005, 22, 1544−1555. (6) Bittner, B.; Mountfield, R. J. Intravenous administration of poorly soluble new drug entities in early drug discovery: the potential impact of formulation on pharmacokinetic parameters. Curr. Opin. Drug Discovery Devel. 2002, 5, 59−71. (7) Bittner, B.; Mountfield, R. J. Formulations and related activities for the oral administration of poorly water-soluble compounds in early discovery animal studies: An overview of frequently applied approaches. Part 1. Drugs made in Germany 2002, 45, 18−24. (8) Pinto, P. C.; Ribeiro, D. M.; Azevedo, A. M.; Justina, V. D.; Cunha, E.; Bica, K.; Vasiloiu, M.; Reis, S.; Saraiva, M. L. M. Active pharmaceutical ingredients based on salicylate ionic liquids: insights into the evaluation of pharmaceutical profiles. New J. Chem. 2013, 37, 4095−4102. (9) Viau, L.; Tourné-Péteilh, C.; Devoisselle, J.-M.; Vioux, A. Ionogels as drug delivery system: one-step sol−gel synthesis using imidazolium ibuprofenate ionic liquid. Chem. Commun. 2010, 46, 228−230. (10) Jencks, W. P. Catalysis in chemistry and enzymology; Courier Corporation: New York: Dover, 1987. (11) Von Hippel, P. H.; Schleich, T. Ion effects on the solution structure of biological macromolecules. Acc. Chem. Res. 1969, 2, 257− 265.

ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications Web site. . The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.jced.8b00644. 1 H NMR spectrum of [HMIm][Sal]) (Figure S1); plot of apparent molar volumes of glycine in the solutions of ([HMIm][Sal] + water) with several molalities (Figure S2); plot of hydration number calculated from eq 8 for glycine and L-alanine in the solution of ([HMIm][Sal] + J



Article

(12) Northrop, D. B.; Simpson, F. B. New concepts in bioorganic chemistry beyond enzyme kinetics: Direct determination of mechanisms by stopped-flow mass spectrometry. Bioorg. Med. Chem. 1997, 5, 641−644. (13) Hvidt, A.; Westh, P. Different Views on the Stability of Protein Conformations and Hydrophobic Effects. J. Solution Chem. 1998, 27, 395−402. (14) Lavrich, R. J.; Torok, C. R.; Tubergen, M. J. Effect of the bulky side chain on the backbone structure of the amino acid derivative valinamide. J. Phys. Chem. A 2002, 106, 8013−8018. (15) Gaba, R.; Pal, A.; Sharma, D.; Sharma, K. Solvation behavior of glycine and diglycine in aqueous 1-butyl-3-methylimidazolium chloride ionic liquid solutions at different temperatures. J. Mol. Liq. 2016, 220, 954−960. (16) Shekaari, H.; Jebali, F. Densities and electrical conductances of amino acids+ iónic liquid ([Hmim] Br) + H2O mixtures at 298.15 K. Fluid Phase Equilib. 2010, 295, 68−75. (17) Shekaari, H.; Jebali, F. Volumetric and conductometric studies of some amino acids in aqueous ionic liquid, 1-hexyl-3-methylimidazolium chloride solutions at 298.15 K. Phys. Chem. Liq. 2011, 49, 572−587. (18) Kumar, H.; Chadha, C.; Verma, A.; Singla, M. Synthesis and study of interactions of ionic liquid 1-methyl-3-pentylimidazolium bromide with amino acids at different temperatures. J. Mol. Liq. 2017, 242, 560−570. (19) Sharma, S. K.; Singh, G.; Kataria, R.; Kumar, H.; Sharma, S. Investigations on molecular interaction of some amino acids with the drug levofloxacin in aqueous solution by volumetric and acoustic methods at different temperatures. J. Chem. Thermodyn. 2017, 105, 94−104. (20) Shekaari, H.; Zafarani-Moattar, M. T.; Mirheydari, S. N. Effect of 1-Butyl-3-methylimidazolium Ibuprofenate as an Active Pharmaceutical Ingredient Ionic Liquid (API-IL) on the Thermodynamic Properties of Glycine and l-Alanine in Aqueous Solutions at Different Temperatures. J. Solution Chem. 2016, 45, 624−663. (21) Shekaari, H.; Zafarani-Moattar, M. T.; Mirheydari, S. N. Thermodynamic properties of 1-butyl-3-methylimidazolium salicylate as an active pharmaceutical ingredient ionic liquid (API-IL) in aqueous solutions of glycine and L-alanine at T=(288.15−318.15) K. Thermochim. Acta 2016, 637, 51−68. (22) Shekaari, H.; Zafarani-Moattar, M. T.; Mirheydari, S. N. Conductometric analysis of 1-butyl-3-methylimidazolium ibuprofenate as an active pharmaceutical ingredient ionic liquid (API-IL) in the aqueous amino acids solutions. J. Chem. Thermodyn. 2016, 103, 165− 175. (23) Vraneš, M.; Armaković, S.; Tot, A.; Papović, S.; Zec, N.; Armaković, S.; Banić, N.; Abramović, B.; Gadžurić, S. Structuring of water in the new generation ionic liquid−Comparative experimental and theoretical study. J. Chem. Thermodyn. 2016, 93, 164−171. (24) Bonhôte, P.; Dias, A.-P.; Papageorgiou, N.; Kalyanasundaram, K.; Grätzel, M. Hydrophobic, Highly Conductive Ambient-Temperature Molten Salts. Inorg. Chem. 1996, 35, 1168−1178. (25) Chen, P.-Y.; Chang, Y.-T. Voltammetric study and electrodeposition of copper in 1-butyl-3-methylimidazolium salicylate ionic liquid. Electrochim. Acta 2012, 75, 339−346. (26) Welton, T. Room-temperature ionic liquids. Solvents for synthesis and catalysis. Chem. Rev. 1999, 99, 2071−2084. (27) Egorova, K. S.; Seitkalieva, M. M.; Posvyatenko, A. V.; Khrustalev, V. N.; Ananikov, V. P. Cytotoxic activity of salicylic acidcontaining drug models with ionic and covalent binding. ACS Med. Chem. Lett. 2015, 6, 1099. (28) Fortin, T. J.; Laesecke, A.; Freund, M.; Outcalt, S. Advanced calibration, adjustment, and operation of a density and sound speed analyzer. J. Chem. Thermodyn. 2013, 57, 276−285. (29) Sharma, S. K.; Singh, G.; Kumar, H.; Kataria, R. Densities, Sound Speed, and Viscosities of Some Amino Acids with Aqueous Tetra-Butyl Ammonium Iodide Solutions at Different Temperatures. J. Chem. Eng. Data 2015, 60, 2600−2611.

(30) Berlin, E.; Pallansch, M. Densities of several proteins and Lamino acids in the dry state. J. Phys. Chem. 1968, 72, 1887−1889. (31) Pal, A.; Kumar, H.; Maan, R.; Sharma, H. K. Solute−solvent interactions of glycine, l-alanine, and l-valine in aqueous 1-methyl-3octylimidazolium chloride ionic liquid solutions in the temperature interval (288.15−308.15) K. Thermochim. Acta 2014, 590, 127−137. (32) Hertz, H.; Franks, F. Water: A comprehensive treatise; Plenum Press: New York, 1973; p 3. (33) Mishra, A. K.; Ahluwalia, J. C. Apparent molal volumes of amino acids, N-acetylamino acids, and peptides in aqueous solutions. J. Phys. Chem. 1984, 88, 86−92. (34) Kumar, H.; Kaur, K. Volumetric, Compressibility and UV Spectral Studies on Interactions of Amino Acids with Aqueous Solutions of Potassium Dihydrogen Phosphate at Different Temperatures. J. Solution Chem. 2013, 42, 592−614. (35) McMillan, W. G., Jr; Mayer, J. E. The statistical thermodynamics of multicomponent systems. J. Chem. Phys. 1945, 13, 276− 305. (36) Shekaari, H.; Zafarani-Moattar, M. T.; Mirheydari, S. N. Volumetric, ultrasonic and viscometric studies of aspirin in the presence of 1-octyl-3-Methylimidazolium bromide ionic liquid in acetonitrile solutions at T= (288.15−318.15) K. Z. Phys. Chem. 2016, 230, 1773−1799. (37) Kumar, H.; Singla, M.; Jindal, R. Viscometric measurements of dipeptides of alanine in aqueous solutions of antibacterial drug ampicillin at different temperatures. J. Mol. Liq. 2014, 191, 183−188. (38) Boruń, A.; Bald, A. Ionic association and conductance of [emim][BF4] and [bmim][BF4] in 1-butanol in a wide range of temperature. J. Chem. Thermodyn. 2016, 96, 175−180. (39) Iqbal, M. J.; Chaudhry, M. A. Volumetric and Viscometric Studies of Antidepressant Drugs in Aqueous Medium at Different Temperatures. J. Chem. Eng. Data 2009, 54, 2772−2776. (40) Shedlovsky, T. The computation of ionization constants and limiting conductance values from conductivity measurements. J. Franklin Inst. 1938, 225, 739−743. (41) Barthel, J. M.; Krienke, H.; Kunz, W. Physical chemistry of electrolyte solutions: modern aspects; Springer Science & Business Media: Darmstadt: Steinkopff, 1998. (42) Pitzer, K. S. Electrolyte theory: improvements since Debye and Hückel. Acc. Chem. Res. 1977, 10, 371. (43) Shekaari, H.; Zafarani-Moattar, M. T.; Mirheydari, S. N. Conductometric analysis of some ionic liquids, 1-alkyl-3-methylimidazolium bromide with aspirin in acetonitrile solutions. Z. Phys. Chem. 2016, 230, 355−368. (44) Wang, H.; Wang, J.; Zhang, S.; Pei, Y.; Zhuo, K. Ionic association of the ionic liquids [C4 mim][BF4],[C4 mim][PF6], and [Cn mim] Br in molecular solvents. ChemPhysChem 2009, 10, 2516− 2523. (45) Soriano, A. N.; Agapito, A. M.; Lagumbay, L. J. L. I.; Caparanga, A. R.; Li, M.-H. Diffusion coefficients of aqueous ionic liquid solutions at infinite dilution determined from electrolytic conductivity measurements. J. Taiwan Inst. Chem. Eng. 2011, 42, 258−264. (46) Tjahjono, M.; Garland, M. On the Determination of Partial Molar Volumes, Partial Molar Refractions, Mean Electronic Polarizabilities and Effective Molecular Radii from Dilute Multi-component Data alone using Response Surface Models. J. Solution Chem. 2007, 36, 221−236. (47) Robinson, R.; Stokes, R. Solutions of electrolytes and diffusion in liquids. Annu. Rev. Phys. Chem. 1957, 8, 37−54. (48) Su, W. C.; Chou, C. H.; Wong, D. S. H.; Li, M. H. Diffusion coefficients and conductivities of alkylimidazolium tetrafluoroborates and hexafluorophosphates. Fluid Phase Equilib. 2007, 252, 74−78. (49) Voroshylova, I. V.; Smaga, S. R.; Lukinova, E. V.; Chaban, V. V.; Kalugin, O. N. Conductivity and association of imidazolium and pyridinium based ionic liquids in methanol. J. Mol. Liq. 2015, 203, 7− 15.

K


Thermophysical Properties of 1-Hexyl-3-methylimidazolium Salicylate

Recommend Documents