J. Phys. Chem. 1994, 98, 8594-8595
8594
Direct Measure of Hydrophilic Interaction Jacob Wilf and A. Ben-Naim’ Department of Physical Chemistry, The Hebrew University of Jerusalem, Jerusalem 91 904, Israel Received: January 5, 1994; In Final Form: June 11, 1994”
W e have measured the distribution coefficients of different isomers of hydroxybenzyl alcohols between water and hexane and between water and cyclohexane. The solvation Gibbs energies of transferring these solutes from water to the organic phase were calculated. From these quantities we have obtained some information on the solvent-induced interaction between the two hydrophilic groups.
1. Introduction
About 15 years ago, a measure of the intramolecular hydrophobic interaction was suggested, and some relevant experimental quantities were Recently, in analyzing the driving forces for protein folding we found that solvent-induced interactions between hydrophilic groups might be more important than the corresponding solvent-induced interactions between hydrophobic groups.” We referred to the former as hydrophilic (H4I) interactions. This paper reports some relevant experimental data on H4I interactions. Similar data were published by Haberfield et al.7 Consider reaction I, depicted in Figure 1, where a H4I group is transferred from position 4 to position 2 with respect to a H 4 I group at position 1. To obtain the solvent-induced contribution to the Gibbs energy change for this reaction, it is sufficient to consider a single solute at a fixed position and orientation in the liquid. The AG for this reaction can be written as
BA P (12) B Figure 1. Two “reactions” used for estimating the H@Iinteraction. In I a H4I group is transferred from position 4 to position 2 relative to an hydroxyl group at position 1. In I1 a H@Igroup is transferred from one carrier (benzyl ring) to phenol, to form 2-(hydroxylmethy1)phenol and benzene.
TABLE 1 ~~
AG(4-2)
= AU(4-2)
+ 6G(4-2)
(1.1)
where AU(4-2) is the energy change for the reaction had it been carried out in vacuum. The solvent induced contribution to AG is denoted by 6G. It can be shown that the later quantity may be related to the solvation Gibbs energies of the two isomers as follows:6
solute benzene benzyl alcohol
phenol 2-hydroxybenzyl alcohol
Since the solvation Gibbs energies of the two isomers may be obtained from the distribution coefficient of each of the solutes between the gaseous and the liquid phase, relation 2 provides an experimental way of calculating the quantity 661(4+2). If we further assume that in the 1.4 isomer, the distance between the two H 4 I groups is far enough, then 661(4+2) is also a measure of the H+I interaction between the two H4I groups at positions 1 and 2. Since we cannot be sure that in the 1.4 isomer there is no H 4 I interaction, we have also examined reaction I1 in Figure 1. Here we have two molecules at fixed position and orientations and at infinite separation from each other. Each of the solutes contain one H4I group. We now transfer one H 4 I group from one solute to the second to form one of the isomers of the hydroxybenzyl alcohol and benzene. The solvent-induced interaction between the two H4I groups at say positions (1,2) is now obtained from the relation
where the right-handsideofeqs 1-3 we havemeasurablequantities Abstract published in Advance ACS Abstracts, July 15, 1994.
0022-3654/94/2098-8594$04.50/0
3-hydroxybenzyl alcohol
solvents water n- hexane cyclohexane water n- hexane cyclohexane water n-hexane cyclohexane water n-hexane cyclohexane water n-hexane
cyclohexane 4-hydroxybenzyl alcohol
water
n-hexane cyclohexane
(nm)
254 254
254 270
270 270 270
270 270 270
270 270 270 270 270 270 270 270
c
180 250 250 190
190 190 1470 1530 1546 1600 1750 1750
1450 1670 1700 1744 2180
1895
for benzene (B), the 1,2-isomer, the phenol (P), and the benzyl alcohol (BA). Since now the two Hq5I groups are strictly at infinite separation in the initial state of the reaction, the quantity 6Gl1(1,2) is a measure of the H 4 I interaction at positions 1 and 2. 2. Experimental Section
The measurements of the solubilities and partition coefficients of phenol, benzene, benzyl alcohol, 2-hydroxybenzyl alcohol, 3-hydroxybenzyl alcohol, 4-hydroxybenzyl alcohol were carried out spectroscopically, in water, in n-hexane, and in cyclohexane. Doubly distilled water and spectrograde n-hexane and cyclohexane were used as solvents. All the materials were purchased from Janseen Chimica, 4-hydroxybenzyl alcohol was recrystallized from water mp 123-124 OC (lit. 124 “C). 2-Hydroxybenzyl 0 1994 American Chemical Society
The Journal of Physical Chemistry, Vol. 98, No. 34, 1994 8595
Direct Measure of Hydrophilic Interaction
TABLE 2 Partition Coefficients and Solvation Gibbs Energies (kcal/mol) of the Solutes between the Two Solvents at 25 OC (w = water, h = hexane, ch = cyclohexane)
-
solute
Pw/Ph
benzene benzyl alcohol phenol 2-hydroxybenzyl alcohol 3-hydroxybenzyl alcohol 4-hydroxybenzyl alcohol
8.6 X lO-' 4.37 7.58 23 1 10 934 1253
AG * = -RT In P w / P h hexane water 2.806 -0.87 -1.195 -3.21 1 -5.487 -4.209
alcohol was recrystallized from benzene mp 86-87 O C (lit. 87 OC). 3-Hydroxybenzyl alcohol was recrystallized from benzene mp 67-69 O C (lit. 7 1 "C). All other materials were used without further purification. All spectrophotometric measurements were carried out on a Hewlett-Packard, diode-array, spectrophotometer. Model 8452A, in the UV region of 200-400 nm, in quartz cells of lengths between 0.1 and 10 cm. The optical densities (OD) were adjusted to fall in the region 0.006-2.2. The temperature was controlled by thermostat to within f 0 . 2 O C . The molar extinction coefficients t of the various solutes in the solvents were used as follows: In pure water, solutions with known concentration were prepared by direct dissolution of the solutes in the solvent. Furthermore, we also prepared concentrated solutions of the solutes in ethanol. These were then diluted in a known volume of water, where the concentration of the ethanol was about 0.3% of the total volume. In all of these solutions the values of t were reproducible within 0.5%. All measurements were carried out at pH 5.5-6 (to avoid the existence of the ion phenolate, 40-)
$OH
+ H,O s 40-+ H 3 0 +
K , = IO-''
In Table 1 we present the revelant spectroscopical data obtained in this work. For all the solutes we have determined the validity of Beer's law, by repeated measurements of the OD of a series of solutions from saturation to about 5% of the saturation value. The partition coefficients of all the solutes between n-hexane and water, and cyclohexane and water, were determined by measuring the OD of the solutions at equilibrium. The two phases were kept in the thermostat for 24 h, and samples of each phase were taken to measure the concentration of the solute. The ratio of the molar concentrations of the solute S in the two solvents, say water and hexane, was found to be constant in each series of solution, indicating that we are well within the region of dilute ideal solutions. Table 2 presents the measured partition coefficients between n-hexane and water, and between cyclohexane and water at 25 O C . 3. Results on Hydrophilic Interactions Table 3 summarizes the results for 6G1 and 6G11as defined in eqs 1.2 and 1.3. Actually these values are differences between 6G in water and 6G in the organic liquid. For instance the value of 661(4-3) in the first row in Table 3 is 6G1(4+3) = 6GI(in water) - GG,(in hexane)
(3.1)
The quantity needed for measuring the H 4 I interaction is 6G1 (in water). This is defined in eq 1.2 and in principle should be computed from the distribution coefficients between the gaseous phase and the aqueous phase. Unfortunately, because of the very low vapor pressure of all the solutes used in this work it is not possible to obtain 6G1 (in water). Assuming that neither hexane nor cyclohexane have significant solvent effect on the reactions I and I1 in Figure 1, we can
-
AG * = -RT In P w l P & cyclohexane water
Pw/Pch
802 X le3 3.702 5.66 191 13 921 905
2.847 -0.772 -1.022 -3.099 -5.630 -4.017
TABLE 3: Values of 6G and 6 6 Calculated from 4 s 1.2 and 1.3, Respectively (Values in kcal/mol at 25 " C ) hexane
-
water
cyclohexane
-
water
-1.613 +0.918 -2.531 +I ,542 -0.989 +0.624
tentatively assume that thevalues in Table 3 reflect predominately the solvation effects of water. We see that transferring from either position 4 or from 2 to position 3 involves large negative values of 6G1. We have previously argued that this large solvent effect is due to the possibility of water molecule forming a hydrogen-bonded bridge between the two H4I groups.4-6 The results for hexane water and cyclohexane water are not very different. Similarly for reaction I1 in Figure 1 we obtain negative values for ~ G I I1,3) ( but positive values for ~ G I I1.4) ( and 6G11(1,2). The relative magnitude of these quantities is as expected. However we feel that the absolute magnitude of 6G11(1.3) is much smaller than the value expected from theoretical calc~lations.~ We do not know the reason for these values whether this is because of the organic solvent, error in the measurement of the distribution coefficients, or from the effect of the benzyl ring on the H 4 I interactions. In proteins, H4I groups are found in the environment of the polypeptide backbone. This environment is quite different from the environment provided by the benzyl ring. We hope that in the future one would be able to measure distribution coefficients of compounds having two H4I groups attached to a backbone similar to that of a protein. Furthermore effort should be exercised to obtain the distribution coefficient between water and the gaseous phase as required in eqs 1.2 and 1.3. Another possible way of estimating the strength of the H 4 I interactions, is by calculating the solvation Gibbs energies of all the solutes on the right hand sides of eqs 1.2 and 1.3. This can be done today by one of the simulation techniques to obtain the required quantities.
-
-
Acknowledgment. We thank Miss Hadass Behar for carrying most of the measurements. This work was supported, in part, by the Basic research foundation administered by the Israel Academy of Sciences and Humanities. References and Notes (1) Ben-Naim, A.; Wilf, J. J . Chem. Phys. 1979, 70, 771. (2) Wilf, J.; Ben-Naim, A. J . Chem. Phys. 1979, 70, 3079. (3) Ben-Naim, A. Soluation Thermodynamics;PlenumPrtss: New York, 1987. (4) Ben-Naim, A. J . Chem. Phys. 1989, 90, 7412. (5) Ben-Naim, A. Biopolymers 1990, 29, 567. (6) Ben-Naim, A. Statistical Thermodyanmics for Chemists and Biochemists; Plenum Press: New York, 1992. (7) Haberfield, P.; Kivulus, J.; Haddad, M.;Rizzo, T. J . Phys. Chem. 1984, 88, 1913.
