Article pubs.acs.org/jced
Solubility and Solvation Thermodynamics of a Series of Homologous α‑Amino Acids in Nonaqueous Binary Mixtures of Ethylene Glycol and Dimethyl Sulfoxide Kalachand Mahali,† Sanjay Roy,‡ and Bijoy Krishna Dolui*,§ †
Department of Chemistry, University of Kalyani, Nadia, 741235, West Bengal, India Department of Chemistry, Shibpur Dinobundhoo Institution (college), Howrah, 711102, West Bengal, India § Department of Chemistry, Visva-Bharati, Santiniketan, Pin, 731235, West Bengal, India ‡
ABSTRACT: In this article the standard free energies (ΔG0t (i)) and entropies (ΔS0t (i)) of transfer of four homologous α-amino acids including glycine (Gly), DL-alanine (DL-Ala), DLα-amino butyric acid (DL-Aba.) and DL-nor-valine (DL-n-Val) from ethylene glycol (EG) to nonaqueous mixtures of ethylene glycol and dimethyl sulfoxide (DMSO) at 298.15 K are reported. The Gibbs energies of solutions have been determined from solubility measurements of each amino acid at different temperatures, that is, from 288.15 to 308.15 K by “formol titrimetry”. The chemical parts of free energies (ΔG0t,ch(i)) and entropies (TΔS0t,ch(i)) of transfer of the homologous α-amino acids have been computed by subtracting the cavity effects and dipole−dipole interaction effects from the total transfer energies. The characteristics of the solvation thermodynamics of α-amino acids in EG-DMF and EG-ACN mixed solvent systems studied earlier are also discussed here for comparison.
1. INTRODUCTION Proteins are essentially polypeptide macromolecules formed from α-amino acids linked by peptide (−CONH−) bonds. Most of the amino acids are involved in protein formation. Each amino acid contains at least two functional groups, that is, −NH2 and −CO2H. The amino acid remains predominantly as zwitterions, H3N+CH(R) CO2− in biological systems. Here side chains of these building units differ in size, shape, charge, hydrogen bonding capability, hydrophobicity (HbH), hydrophilicity (HIH), chemical reactivity, etc. Individually and collectively, these side chains contribute to the structural stability and functional activity of proteins. On the other hand, protein folding and unfolding processes are generally much more important in biological systems. The conformation of a protein in solution is generally a function of electrostatic, hydrogen bonding, van der Waals forces, acid− base interactions, hydrophobic, and hydrophilic interactions among the amino acid residues that overall leads to a folded state overcoming an entropic penalty.1−3 Denaturation or defolding of proteins is also an essential process for dissolution and purification during its extraction from natural sources. In this regard, the knowledge of the thermodynamic properties of proteins as well as amino acids in different solution is necessary. For a long time many researchers had drawn their attention4−12 to determine the solubilities as well as various thermodynamic properties of amino acids in aquaorganic and aqua-ionic solvent mixtures. The purposes of such studies were to gain a clear insight about the various aspects of protein folding and hydration5,6 with biological as well as industrial importance.9−12 In this context Tanford, Nozaki, and other authors13−25 reported Gibbs free energies and entropies of some amino acids from water to urea, glycerol, EG, © XXXX American Chemical Society
acetonitrile (ACN), 2-propanol, ethanol, DMF, and 1,2dimethoxyethane. Transfer free energies and entropies data of dipeptides, tripeptides, and other biomolecules in aqueous urea and glycerol are also available.15,35 Free energies of transfer of amino acid chains can help to predict the stability of different conformations of proteins. Some authors30−32 also believed that entropy of transfer of amino acids can be used as a structural probe to understand the structural changes taking place in various solvent systems in the presence of amino acids. All these experiments also tried to give an idea about the relative stabilization of these amino acids and other biomolecules in aqua-organic mixtures with respect to water and the complex solute−solvent and solvent−solvent interactions therein. In such situation we also have to first realize the transfer energetics of amino acids or other biomolecules in mixed nonaqueous binary solvent systems as a baseline “normal behavior” to get some important ideas about structural eccentricities of water and the role of highly complex aqueous chemistry in the context of stabilization of the same. In fact, the environment in which the different biological processes occur may be much more “amide-like” than “waterlike”. But the study on solvation thermodynamics of amino acids and other biomolecules in completely nonaqueous binary solvent mixtures is very scarce. In this regard to get broader insight we have published the results of two earlier experiments16,17 to determine various thermodynamic properties of a series of homologous α-amino Received: August 27, 2014 Accepted: March 26, 2015
A
DOI: 10.1021/je5007899 J. Chem. Eng. Data XXXX, XXX, XXX−XXX
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facilitate good mixing and shaken until and unless saturated solution of the amino acids were obtained. These solutions were then kept under a thermostat adjusted at the desired temperature and allowed to equilibrate for 2 to 3 days with occasional shaking and addition of solutes, if necessary. After 4 to 5 days a filtered and weighed mass of about 0.3 g to 0.4 g of aliquot from the supernatant phase of the saturated solutions was taken by a pipet in well stoppered conical flasks, and the solubility measurements of the four amino acids were made by the “formol titrimetric method”15 using freshly standardized (0.1 N) NaOH (GR, E Merck; > 99.0 %) solution and 1 % alcoholic phenolphthalein solution as indicator. Excess freshly neutralized formaldehyde (GR, E Merck; > 99 %) solution was used in the method to mask the α-amino group of amino acids. Standardized (0.1 N) NaOH solution from a buret was added to 5 mL of formaldehyde with one drop of indicator to get freshly neutralized formaldehyde. The end point was indicated by the appearance of pink color. The neutral formaldehyde solution was then added to the preneutralized amino acid solution followed by titration with NaOH until the color change to pale pink. A solution was considered to attain saturation when successive concentration measurements at five day intervals agreed within the experimental error of ± 1 %. Attainment of saturation usually took 6 to 8 days at each temperature. Fresh solvents were used at different temperatures to avoid the effect of change of composition of solvents. These measurements were made at five equidistant temperatures ranging from 288.15 K to 308.15 K. The thermostat used for all measurements is capable of registering temperatures with an accuracy of ± 0.1 K. Three sets of measurements were made for all the amino acids and the solubilities were found to be reproduced with uncertainties mostly to within 3 %. The gravimetrical method12 is also reliable in this regard. The same procedure should be adopted in both methods to get saturated solubility. The “formol titrimetric” method may be useful for the analysis of solubility of such simple amino acids as used here.
acids in nonaqueous mixtures of protic ethylene glycol and cationophilic dipolar aprotic (EG + DMF) and anionophobic dipolar aprotic acetonitrile (EG + ACN) at 298.15 K. The solvation character of these complete nonaqueous solvent mixtures undergoes gradual but material change compared to aqua-organic mixed solvent systems13−25 with respect to amino acid solvation. It is observed that N,Ndimethylformamide16 undergoes stronger stabilization for αamino acids than acetonitrile.17 Also both systems16,17 show their originality with respect to solute−solvent and solvent− solvent interactions. The relevant data in these two nonaqueous binary solvent systems are likely to be very useful in understanding the solvation mechanism of amino acid and the amino acid induced solvent−solvent interaction in nonaqueous as well as aqua-organic binary solvent mixtures. DMSO with immense biological importance25 is chosen here as cosolvent with EG to obtain further broader insight about nonaqueous chemistry for amino acid solvation. DMSO possesses two hydrophobic methyl groups with +I effect, and these hydrogen atoms of two CH3- groups are of acidic character. Also DMSO has increased basicity as well as protophilic dipolar aprotic character compared to EG. Therefore, study of amino acid solvation may be rewarding in EGDMSO mixtures. Considering these points-of-view and following our previous works,16,17 we are presenting the standard transfer free energy (ΔG t0 (i)) and entropies (ΔS0t (i)) of homologous series of α-amino acids such as glycine, DL-alanine, DL-α-amino butyric acid and DL-nor-valine from EG to a nonaqueous mixture of EG and DMSO at 298.15 K.
2. EXPERIMENTAL SECTION 2.1. Materials and Their Purifications. Homologous αamino acids such as glycine (> 99.0 % E Merck) and DL-alanine (> 99.0 %, E-Merck), DL-α-amino butyric acid (> 99.0 %, EMerck) and DL-nor-valine (> 99.0 %, E-Merck) were used after being dried in a vacuum desiccator without further purification.27 Ethylene glycol (> 99.0 %, LR, BDH) was purified26,29,31 by refluxing with 2 % to 3 % NaOH (> 97.0 % EMerck) for 3 h to 4 h followed by distillation. The distilled ethylene glycol was then dried over freshly baked anhydrous Na2SO4 (> 98.0 %, E-Merck) for 4 to 5 days then decanted off and fractionally distilled through a 2/3 m long vigreux column, rejecting the head and tail portions. Dimethyl sulfoxide (DMSO)28 (> 99.8 %, Sigma-Aldrich) was first dried over fused CaCl2 for 3 to 4 days, decanted, and then distilled under reduced pressure. The distilled sample was preserved in a well stoppered Jena bottle in desiccators and redistilled before use. The water content of the solvents was determined by Karl Fischer titration29 and found to be less than 0.02-mol dm−3 in each case. 2.2. Method. Nonaqueous solvent mixtures of EG (1) and DMSO (2) that have been used were (0, 16.60, 34.60, 54.40, 76.10, and 100) mol % of DMSO. The mixed solvents were prepared by mixing freshly distilled EG (1) and DMSO (2) in mass fractions by weight using a Mettler balance having a precision of ± 0.01 mg. Pure solvents and solvent mixtures were preserved in well stoppered glass bottles and protected by being stored in desiccators when not in use. Small quantities of each amino acid, whose solubilities are to be measured, were added with shaking to about 25 mL of each of the solvent mixtures from 0 to 100 mol % EG, taken in standard-joint test tubes. Test tubes were incompletely filled to
3. THEORETICAL 3.1. Calculations of Thermodynamic Parameters. The Gibbs energy of solution (ΔG0s (i)) on the molal scale is computed at five different temperatures for each solvent mixture using eq 1 as stated below, following previous studies of Nozaki and Tanford,13 Datta and Kundu,31,32 Lahiri and coworkers,33,34 and Basumallick and co-workers.6 ΔGs0(i) = −RT ln Sγ ≈ −RT ln S
(1)
where γ is the molal activity coefficient and “S” is the experimental saturated solubility of the solute in mol·kg−1. Amino acids are likely to be zwitterions in solutions.15 So they are expected to have large dipole−dipole interaction among themselves. Therefore, the activity coefficient factor −RT ln γ may contribute to ΔG0s (i). In this regard Held and coworkers12 had concentrated their efforts to measure the activity coefficients of some amino acids like glycine, proline, hydroxyproline, L-leucine, L-methionine, etc., in aqueous systems. They had computed values of the activity coefficient (γ) to near unity for such amino acids in lower concentrations. It is to be noted here that the mole fractions of amino acids present in different compositions of the EG-DMSO solvent system here, as calculated from experimental solubility values (shown in Table2) are negligibly small (i.e., 0.004 to 0.01). B
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Table 1. Specification of Chemical Samples
a
Declared by the supplier. bGas−liquid chromatography.
The ΔG0s values are fitted to eq 2 by the method of leastsquares to test the reliability of it and to quantify the effect of temperature on it.
In such context also due to unavailability of relevant literature data useful for our EG-DMSO system, the activity coefficient γ has been taken as unity for the present experimental solvent system as is usually done for nonelectrolytes30−32 in calculating of ΔG0s (i). This assumption is possible because the factor containing the ratio of activity coefficient, −RT ln γs/γR (“s” for EG-DMSO and “R” for reference solvent, EG), in determining transfer free energies, ΔG0t (i) (ΔG0t (i) = ΔG0s (i) − ΔG0R(i)), which is our main concern, is likely to be negligibly small.
ΔGs0 = a + bT + cT ln T
(2)
where T is the temperature in Kelvin. The values of the coefficients a, b, c are found to reproduce the experimental data mostly to within ± 0.04 unit (a in kJ·mol−1, b and c in kJ·mol−1· K−1). Transfer Gibbs energies, ΔG0t (i) and entropies ΔS0t (i) of the amino acids from EG to DMSO mixtures are calculated at C
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Table 2. Solubilities (mol·kg−1) of Glycine, DL-Alanine, DL-α-Amino Butyric Acid and DL-nor-Valine in Binary Nonaqueous Solvent Mixtures of EG(1) + DMSO(2) at Five Equidistant Temperatures (i.e. 288.15, 293.15, 298.15, 303.15 and 308.15 K) at Experimental Pressure, p = 0.1 MPaa solubility (S) mass fractions of DMSO(x2) 0.00
0.20
0.40
0.60
0.80
1.00
54.40
76.10
100
0.0590 0.0637 0.0709 0.0764 0.0825
0.0506 0.0561 0.0609 0.0651 0.0705
0.0330 0.0359 0.0420 0.0451 0.0504
0.0607 0.0659 0.0707 0.0752 0.0791
0.0508 0.0545 0.0597 0.0642 0.0702
0.0338 0.0389 0.0458 0.0503 0.0571
0.0891 0.0945 0.1054 0.1111 0.1179
0.0643 0.0721 0.0784 0.0887 0.0945
0.0483 0.0541 0.0617 0.0675 0.0712
0.0613 0.0662 0.0723 0.0793 0.0931
0.0518 0.0570 0.0607 0.0666 0.0727
0.0345 0.0378 0.0424 0.0491 0.0549
mole % of DMSO(2) T/K
a
0.0
16.60
288.15 293.15 298.15 303.15 308.15
0.1453 (0.1430)b 0.1580 0.1754 (0.1700)b 0.1832 0.1900 (0.1860)b
0.1061 0.1117 0.1331 0.1462 0.1550
288.15 293.15 298.15 303.15 308.15
0.1353 (0.1260)b 0.1432 0.1536 (0.1400)b 0.1590 0.1661 (0.1600)b
0.0953 0.1010 0.1106 0.1176 0.1241
288.15 293.15 298.15 303.15 308.15
0.2037 (0.1900)b 0.2122 0.2234 (0.2200)b 0.2389 0.2568 (0.2550)b
0.1538 0.1607 0.1690 0.1813 0.1957
288.15 293.15 298.15 303.15 308.15
0.1191 (0.1220)b 0.1301 0.1394 (0.1300)b 0.1569 0.1752 (0.1380)b
0.0908 0.0989 0.1084 0.1167 0.1265
34.60 Glycine 0.0775 0.0837 0.0919 0.1055 0.1168 DL-Alanine 0.0759 0.0876 0.0934 0.1022 0.1082 DL-α-Amino Butyric Acid 0.1135 0.1221 0.1325 0.1453 0.1523 DL-nor-Valine 0.0761 0.0813 0.0888 0.0991 0.1143
u(T) = ± 0.1; u(x2) = ± 0.01; u(S) = ± 0.001. bValues in the parentheses are taken from ref 16.
system and ΔX0t,d−d(i) represents the dipole−dipole interaction effect involving interaction between dipolar-zwitter-ionic amino acids and the solvent molecules. On the other hand, ΔX0t,ch(i) includes that for all other effects such as those arising from acid−base or short-range dispersion interaction, solvophilic or solvophobic solvation and structural effects, etc. Here ΔX0t,cav(i) values are computed by scaled particle theory (SPT),17 assuming the solutes and solvent molecules as equivalent to hard-sphere models as dictated by their respective diameter (Table 4). The Keesom-orientation expression36 is used to calculate ΔG0d−d(i) and sΔS0d−d(i) as
298.15 K on the mole fraction scale by using the following eqs 3, 4, and 5: ΔGt0(i) = sΔGs0(i) − RΔG R0 (i)
(3)
that is, ΔGt0(i) = (as − aR ) + (bs − bR )T + (cs − c R )T ln T − RT ln(Ms /MR )
(4)
and ΔSt0(i) = (bR − bs) + (c R − cS)(1 + ln T ) + R ln(Ms /MR )
0 0 0 ΔGt,d −d (i) = ( sΔGd−d (i) − RΔGd−d (i))
(5)
here the subscript “s” denotes EG/DMSO mixtures, “R” denotes reference solvent EG, and Ms and MR are the molar mass of the mixed and pure reference solvent, EG respectively. The calculated values show uncertainties in ΔG0t (i) and ΔS0t (i) of about ± 0.05 kJ·mol−1 and 2 kJ·mol−1, respectively. Now ΔX0t (i) (where X = G or S) may be ascribed as the sum of the following terms (assuming the dipole-induced dipole term to be negligibly small). 0 0 0 ΔX t0(i) = ΔX t,cav (i) + ΔX t,d −d(i) + ΔX t,ch(i)
(7)
and 0 0 0 ΔSt,d −d(i) = ( sΔSd−d(i) − RΔSd−d(i))
(8)
For sΔG0d−d(i) in a solvent “S”, as given below: 0 sΔGd−d (i)
= −(8Π/9)N 2μs2 μx2 σs−−3x(kT )−1V s−1 = A /TVs (9)
(6)
−1 −(8Π/9)N2μ2s μ2xσ−3 s−x(k)
where A = and Π = 22/7, Vs = Ms/ds = molar volume of solvent, Ms = molar mass of solvent, ds = density of solvent, k is the Boltzmann constant. Here ΔS0d−d(i) can be written as follows:
Here, ΔX0t,cav(i) means for the transfer energy contribution of the cavity effect which is involved due to creation of cavities for the species (amino acids) in EG and EG+DMSO mixed solvent D
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= −{δ sΔGd0−d(i)/δT }p
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Table 3. Coefficients a, b, and c in Glycine, DL-alanine, DL-αAmino Butyric Acid, and DL-nor-Valine and Gibbs Energies ΔG0t (i) and Entropies TΔS0t (i) of Transfer of the Amino Acids (on Mole Fraction Scale) in kJ·mol−1 from Ethylene Glycol to Nonaqueous Mixtures of EG(1) +DMSO(2) at 298.15 Ka
(10)
that is, T sΔSd0−d(i) = sΔGd0−d(i)[1 + Tα]
(11)
where N stands for Avogadro’s number, μs and μx are the dipole moment of solvents and amino acid molecules, respectively (Table 4). σs−x represents the distance at which the attractive and repulsive interactions between the solvent and solute molecules are equal and is generally equal to 1/2(σs + σx) where σs and σx are the hard sphere diameters of cosolvent and solute molecules respectively (Table 4) and α is the isothermal expansibility30 of the mixed solvent and represented by eq 12 as α = (δ ln Vs/δ T)P = −(δ ln ds/δT ) 36
mass fractions of DMSO
X s1 =
b kJ·mol ·K
0.000 0.200 0.400 0.600 0.800 1.000
174.23 134.75 −132.71 28.32 65.81 25.52
−3.7052 −2.7357 3.2994 −0.3738 −1.2264 −0.2435
0.000 0.200 0.400 0.600 0.800 1.000
69.55 38.99 74.56 80.84 −35.25 103.56
0.000 0.200 0.400 0.600 0.800 1.000
−104.10 −116.06 42.23 60.43 64.69 189.90
0.000 0.200 0.400 0.600 0.800 1.000
−131.54 21.88 −234.35 −232.25 −30.34 −107.82
kJ·mol
−1
ΔG0t (i)
c
−1
x2
−1
−1
−1
TΔS0t (i)
kJ·mol
kJ·mol−1
0.55030 0 0.40378 0.573 −0.49748 1.365 0.05282 1.932 0.18059 2.148 0.03237 2.998 DL-Alanine −1.4019 0.20785 0 −0.6657 0.09711 0.715 −1.4341 0.21126 0.990 −1.6081 0.23852 1.586 1.0445 −0.15845 1.901 −1.9330 0.28282 2.447 DL-α-Amino Butyric Acid 2.5166 −0.37822 0 2.7918 −0.41911 0.585 −0.7170 0.10393 1.067 −1.1351 0.16696 1.568 −1.1569 0.16867 2.114 −3.9627 0.58778 2.608 DL-nor-Valine 3.2434 −0.48897 0 −0.2391 0.03237 0.629 5.5723 −0.83652 0.943 5.5282 −0.82971 2.349 0.9404 −0.14311 1.641 2.7855 −0.42082 2.396
0 3.632 4.091 0.481 −0.339 2.713
kJ·mol ·K
−1
Glycine
(12)
37
Following Marcus and Kim et al. in order to get this ΔX0t,d−d(i) term on mole fraction scale the quantities are again multiplied by the term Xs1. X s(μs /σs3)/(μR /σR3)
a
(13)
Xs1 is the real mole fraction contribution due to dipole−dipole interaction.37 Subtraction of ΔX0t,cav(i) and ΔX0t,d−d(i) from the total we can get ΔX0t,ch(i) of amino acids.
4. RESULTS AND DISCUSSION 4.1. Solvation of α-Amino Acids. The specifications of chemical samples used in the experiment are given in Table 1. The experimental solubility (mol·kg−1) of the four amino acids (glycine, DL-alanine, DL-α-amino butyric acid and DL-nor valine) are measured on molal scale and are listed in Table 2. Standard uncertainties of solubilities in all compositions at the five equidistant temperatures are found to be ±0.001 and cited in Table 2. The computed values of a, b, c and ΔG0t (i) are shown in Table 3. The variations of ΔG0t (i) values of the involved four amino acids with mol % DMSO at 298.15 K are also presented by Figure 1. The positive increment of ΔG0t (i) values of αamino acids with increased concentration (mol %) of DMSO in EG-DMSO mixed solvent system indicates destabilization of all the four α-amino acids. It is observed here (Tables 3 and 4) that except for DL-nor-valine the increments of ΔG0t (i) values of other three amino acids are mainly regular. The total transfer free energies, ΔG0t (i) of amino acid are mainly the sum of ΔG0t,cav(i), ΔG0t,d−d(i) and ΔG0t,ch(i) (Table 4). The more or less gradual increase of components of ΔG0t (i) due to dipole− dipole interaction, ΔG0t,d−d(i) and cavity effect, ΔG0t,cav(i) are seemingly responsible for this trend. Therefore, the discussion on chemical transfer free energies, ΔG0t,ch(i) of amino acids rather than total transfer free energies ΔG0t (i) shall be more informative. The ΔG0t,ch(i) values of all the four α-amino acids at 298.15 K for EG-DMSO binary solvent mixtures are presented in Table 4. Here, ΔG0t,ch(i) values are obtained after subtraction of ΔG0t,cav(i) and ΔG0t,d−d(i) from ΔG0t (i) of each amino acid (Table 4). All α-amino acids become stabilized due to accommodation in the cavity created by the mixed solvent of EG-DMSO mixtures. Dipole−dipole interactions between solute (α-amino acids) and mixed solvents (EG-DMSO) also become favorable for the stabilization of amino acids. The order of stabilization of α-amino acids in term of ΔG0t,d−d(i) (Table 4) is Gly > DL-Ala > DL-α-Aba > DL-n-Val. ΔG0t,ch(i) represents the
a
0 1.742 3.003 0.560 2.512 9.211 0 −0.294 1.510 0.417 3.621 3.379 0 −2.646 −0.131 −0.467 −3.559 1.005
u(T) = ± 0.1; u(x2) = ± 0.01.
Figure 1. Variation of total transfer free energies, ΔG0t (i) in kJ·mol−1 of glycine, DL-alanine, DL-α-amino butyric acid and DL-nor-valine in nonaqueous mixtures of EG (1) + DMSO (2) at 298.15 K.
chemical interaction, that is, H-bonding, acid−base, dispersion, solvophilic, solvophobic, and hard−soft interactions. Gradual destabilizations of α-amino acids are observed (Table 4) in term of chemical interactions. All the α-amino acids become relatively destabilized as the concentration of DMSO gradually become richer in EG-DMSO mixtures.Initially in the ethylene glycol-rich region protic ethylene glycol stabilizes all the αE
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Table 4. Total Transfer Free Energies [ΔG0t (i)] and Entropies [TΔS0t (i)]; Transfer Free Energies [ΔG0t,cav(i)], Enthalpies [ΔH0t,cav(i)] and Entropies [TΔS0t,cav(i)] for Cavity Formation; Transfer Free Energy [ΔG0t,d−d(i)] and Entropy [TΔS0t,d−d(i)] for Dipole−Dipole Interaction and Transfer Free Energies [ΔG0t,ch(i)] and Entropies [TΔS0t,ch(i)] for Chemical Interaction of Glycine, DL-Alanine, DL-α-amino Butyric Acid and DL-nor-Valine from Ethylene Glycol to EG(1) + DMSO(2) at 298.15 K* (on Mole Fraction Scale in kJ·mol−1) mass fractions of DMSO
ΔG0t (i) −1
ΔG0t,cav(i)
ΔG0t,d−d(i)
−1
(x2)
kJ·mol
0.000 0.200 0.400 0.600 0.800 1.000
0 0.573 1.365 1.932 2.148 2.998
0 −0.359 −0.660 −0.913 −1.114 −1.139
0.000 0.200 0.400 0.600 0.800 1.000
0 0.715 0.990 1.586 1.901 2.447
0 −0.379 −0.691 −0.947 −1.141 −1.140
0.000 0.200 0.400 0.600 0.800 1.000
0 0.585 1.067 1.568 2.114 2.608
0 −0.369 −0.691 −0.950 −1.138 −1.115
0.000 0.200 0.400 0.600 0.800 1.000
0 0.629 0.943 2.349 1.641 2.396
0 −0.460 −0.790 −1.052 −1.235 −1.193
kJ·mol
−1
kJ·mol
ΔG0t,ch(i)
TΔS0t (i)
ΔH0t,cav(i)
−1
−1
−1
kJ·mol
kJ·mol
Glycine 0 2.252 7.866 17.845 32.862 56.137 DL-Alanine 0 0 −1.170 2.264 −5.210 6.891 −13.40 15.933 −26.40 29.442 −46.50 50.087 DL-α-Amino Butyric 0 0 −1.06 2.014 −4.73 6.488 −12.20 14.718 −24.00 27.252 −42.40 46.123 DL-nor-Valine 0 0 −0.973 2.062 −4.34 6.073 −11.20 14.601 −22.10 24.976 −39.00 42.589 0 −1.32 −5.85 −15.00 −29.60 −52.00
kJ·mol
TΔS0t,cav(i) −1
kJ·mol
TΔS0t,d−d(i) kJ·mol
−1
TΔS0t,ch(i) kJ·mol−1
0 3.632 4.091 0.481 −0.339 2.713
0 −0.057 0.411 1.482 3.595 8.090
0 0.302 1.071 2.395 4.709 9.229
0 −1.73 −7.79 −20.30 −40.80 −73.10
0 5.060 10.81 18.386 35.752 66.584
0 1.742 3.003 0.560 2.512 9.211 Acid 0 −0.294 1.510 0.417 3.621 3.379
0 −0.069 0.467 1.696 4.124 9.293
0 0.310 1.158 2.643 5.265 10.433
0 −1.53 −6.930 −18.10 −36.40 −65.30
0 2.962 8.775 16.017 33.647 64.078
0 −0.080 0.514 1.880 4.578 10.325
0 0.289 1.205 2.830 5.716 11.44
0 −1.39 −6.28 −16.40 −33.10 −59.40
0 0.807 6.585 13.987 31.005 51.339
0 −2.646 −0.131 −0.467 −3.559 1.005
0 −0.089 0.554 2.036 4.964 11.200
0 0.371 1.344 3.088 6.199 12.393
0 −1.27 −5.76 −15.10 −30.40 −54.60
0 −1.747 4.285 11.545 20.642 43.212
*
u(T) = ± 0.1; u(x2) = ± 0.01. Here σEG = 4.37 Å, σDMSO = 4.91 Å, μEG = 2.28 D, and μDMSO = 3.90 D are taken from ref 36. The required hard sphere diameter of glycine, DL-alanine, DL-α-amino butyric acid, and DL-nor-valine are 5.64, 6.16, 6.58, and 6.92 Å, respectively, as given in ref 30. Dipole-moment values of α-amino acids are 15.7 D for glycine, 15.9 D for alanine, and 16 D for amino butyric acid and nor-valine.30,39
amino acids through H-bonding, acids-base, and solvophilic interactions. The Hydrogen bonding between the H3N+ and COO− groups of α- amino acid and −OH groups of EG becomes gradually weaker with the increased concentration of DMSO in that mixed solvent system. Dimethyl sulfoxide is a dipolar aprotic solvent, with weaker capacity of H-bonding, cation/ anionophilic and acid−base interaction than protic EG. Alternately, the association between EG and DMSO (Scheme 2)25 in a 1:2 ratio may occur26,38 resulting in comparatively larger associated mixed-solvent molecules as the concentration of DMSO is increased. The self-association (dimerization) of DMSO (Scheme 3)38 also occurs in higher concentrations of DMSO in the mixed EG-DMSO systems.
Scheme 2. H-Bonded Associated Form between EG and DMSO
Scheme 1. Dimerized Form of Ethylene Glycol
Now the associated or self-associated larger size molecule of mixed solvent takes part in the dispersion interaction between α-amino acids. Valine (6.92 Å)15,30 being the largest among the four amino acids becomes comparatively more stabilized. The order of stabilization is DL-n-Val > DL-α-Aba > DL-Ala > Gly. F
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It is worth noting that in all the three solvent systems the largest α-amino acids, DL-nor-valine, is the most stabilized among the four acids because of such size-dependent dispersion interaction. 4.2. Role of α-Amino Acids for Controlling Solvent− Solvent Interaction in Protic and Dipolar Aprotic Binary Solvent Mixtures. The variations of TΔS0t (i) values of the amino acids with the increased concentration of DMSO in this EG-DMSO mixed solvent system are presented in Tables 3 and 4. Like ΔG0t (i), TΔS0t (i) is also composed of cavity, dipole− dipole, and chemical interaction effect; that is,
Scheme 3. Dimerized form of Dimethylsuphoxide
A comparative study of amino acid solvation in term of 0 chemical interactions [ΔGt,ch (i)] in three protic−dipolar aprotic mixed solvent systems, that is, EG + DMF, EG + ACN, and EG + DMSO is presented in Figure 2. The observed stability order of the four α-amino acids in these three mixed solvent system is EG + DMF16 > EG + DMSO > EG + ACN.17
0 0 0 T ΔSt0(i) = T ΔSt,cav (i) + T ΔSt,d −d(i) + T ΔSt,ch(i)
(14)
TΔS0t,cav(i), TΔS0t,d−d(i) and TΔS0t,ch(i) values are presented in Table 4. Here the first two energy terms stand for the difference in the entropy change involved in creating appropriate cavities for accommodating the amino acids and in dipole−dipole interaction of the amino acid dipole with the solvent dipole, respectively. These two effects in combination, being superimposed on other effects, may play a main role for the up-anddown trends of TΔS0t (i) composition profiles. TΔS0t,ch(i), the chemical transfer entropy change, stands for the combined effects of chemical interactions between solvent molecules induced by α-amino acids. Here it is observed that, all four αamino acids induce a regular increase of respective TΔS0t,ch(i) values in the order DL-n-Val < DL-α-Aba < DL-Ala < Gly. Here the intermolecular hydrogen bonding between EG molecules becomes weaker with the increment of the concentration of DMSO in the mixed solvent system. On the other hand due to poorer H-bonding capacity of DMSO, EGDMSO association (Scheme 2) will not be as strong as EG-EG association (Scheme 1).29 Therefore, gradual increments of TΔS0t,ch(i) values with the mole % DMSO are reflected for all α-amino acids. The size of α-amino acids vary in the order DL-n-Val > DL-α-Aba > DL-Ala > Gly. The hydrophobic parts of these amino acids induce dispersion interaction. With the increment of the concentration of DMSO in this mixed solvent system dimerization of DMSO (Scheme 3) occurs gradually. Such a dimerized self-associated form of DMSO will be more easily formed by the induction of the largest amino acids, that is, n-valine, and it will be less easily formed by the induction of the smallest amino acid, that is, glycine. Larger self-associated dimerized, (DMSO)2 imparts the strongest dispersion interaction toward the largest amino acid, DL-n-valine, and the weakest dispersion interaction toward the smallest amino acid, glycine. The dispersion interaction plays a dominant role over the gradually reduced hydrogen bonding, solvophilic and solvophobic interactions with the increased concentration of DMSO in the mixed solvent system. Therefore, in term of TΔS0t,ch(i) values the reflected order is DL-n-Val < DL-α-Aba < DL-Ala < Gly (Table 4). Figure 3 represents a comparative variation of α-amino acid induced TΔS0t,ch(i) values in three protic−dipolar aprotic binary nonaqueous mixed solvent systems. The α-amino acids induced disorderness of mixed solvents is gradually increased for the three mixed solvent systems. The order of α-amino acids induced disorderness of solvent molecules in such mixed binary solvent mixtures behaves in this way due to involvement of gradually increased dispersion interaction and reduced hydrogen bonding, solvophilic, solvophobic, and acid−base interactions with the increased concentration of cosolvent in the
Figure 2. Variation of transfer free energies [ΔG0t,ch(i)] for chemical interactions in kJ·mol−1 of glycine, DL-alanine, DL-α-amino butyric acid, and DL-nor-valine in nonaqueous mixtures of EG (1) + DMSO (2) (solid line), EG + ACN (dash line), and EG + DMF (dotted line) at 298.15 K.
Here in all the three systems stability of α-amino acids decreases as DL-n-Val > DL-α-Aba > DL-Ala > Gly. The heaviest α-amino acids become more stabilized with the increased concentration of dipolar aprotic solvents. From Figure 2 it is also observed that the α-amino acids become less stable as the dipolar aprotic solvents are introduced in the protic solvent (EG). In all these three cases this phenomenon arises because of decreased H-bonding, and acid−base, solvophobic, and solvophilic interactions with the increased concentration of dipolar aprotic cosolvents. The order of size of cosolvents is 0.498 nm (DMF)27 > 0.491 nm (DMSO)36 > 0.412 nm (ACN).28 All the three dipolar aprotic cosolvents may participate in self-association (i.e., dimerization, Schemes 3,38 4a17, and 4b16,29) at a higher concentration. Therefore, strength of dispersion interaction toward solute (α-amino acids) by cosolvents will be in the order of DMF > DMSO > ACN. Scheme 4. (a). Dimerized Form of Acetonitrile; (b) Dimerized Form of Dimethylformamide
G
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REFERENCES
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Figure 3. Variation of transfer entropies, TΔS0t,ch(i) in kJ·mol−1 of glycine, DL-alanine, DL-α-amino butyric acid and DL-nor-valine in nonaqueous mixtures of EG (1) +DMSO (2) (solid line), EG+ACN (dash line), and EG+DMF (dotted line) at 298.15 K.
mixed solvent systems as reflected in Figure 3. The order of disorderness is as EG-ACN > EG-DMSO > EG-DMF. Also in all three mixed solvent systems here the heaviest α-amino acid (i.e., n-valine) encourages lesser disorderness (i.e., greater extent of association of solvent molecules), and the lightest amino acid (i.e., glycine) encourages greater disorderness (i.e., lesser extent of association of solvent molecules). The amino acids induced association (i.e., dimerization) due to intermolecular hydrogen bonding between protic solvents (EG) becomes gradually weaker due to the addition of dipolar aprotic solvent (i.e., ACN, DMSO, and DMF) to EG. The amino acids-induced dimerization due to the dispersion interaction between dipolar aprotic solvents at its higher concentration also becomes more significant here. Among the dimeric forms, (DMF)2 (Scheme 4b)16 is the most stable because of its six-member ring. Also (DMSO)2 (Scheme 3) is more stable than (ACN)2 (Scheme 4a)17 due to size of DMSO (0.491 nm) being larger than that of ACN (0.412 nm). Therefore, α-amino acids-induced solvent−solvent interactions as reflected by TΔS0t,ch(i) values (Figure 3) for the three mixed solvent systems are guided by gradually increased dispersion interactions as well as reduced hydrogen bonding, and solvophilic, solvophobic, and acid−base interactions.
5. CONCLUSION From the observation it may be concluded that amino acids with larger hydrophobic side chains are more stabilized than smaller ones with the increased proportion of dipolar aprotic solvent. The dispersion interaction plays dominant role in the control of solvation of amino acids as well as biomolecules. This type of interaction is also significant for amino acid-induced solvent−solvent interactions.
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AUTHOR INFORMATION
Corresponding Author
*E-mail:
[email protected]. Notes
The authors declare no competing financial interest.
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ACKNOWLEDGMENTS The authors record their kind thanks to DST-SAP, UGC, Government of India and Department of Chemistry, VisvaBharati and DST-PURSE Kalyani University for their financial assistance and computational facilities. The authors are also pleased to acknowledge the Shibpur Dinobundhoo Institution (college) for encouragement in this work. H
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