J. Phys. Chem. 1984, 88, 1243-1248
1243
Volumetric Study of Solubilization of Hydrophobic Liquids in Nonionic Micelles Noriaki Funasaki,* Sakae Hada, and Saburo Neya Kyoto Pharmaceutical University, Yamashina-ku, Kyoto 607, Japan (Received: May 6, 1983; In Final Form: July 28, 1983)
Excess molar volumes AVof mixed micelles of heptaethylene glycol moncdcdecyl ether (DE7) and a hydrophobic solubilizate are measured systematically for 10 solubilizates whose solubility parameters range from 5.9 to 11.8. Furthermore, partial excess molar volumes Ab2 of the solubilizates at high dilution in the DE7 micelle are evaluated. These values of AVand Abz are compared with those in related solvents and predictions by solubility parameter theory. Solubility parameter theory is shown to be useful for mixed micelles as well as for liquid mixtures; the solubility parameter and the internal pressure at the solubilizationsite are estimated. From these results, one can obtain information about the activity coefficients,molecular orientation, and location of the solubilizates in the micelle. The Ab2 values are larger for the micelle than for related liquids. This difference is not explicable by the Laplace pressure effect and the deep penetration of water into the micelle but it may be explained by the more ordered structure of the micelle over the liquids. The molar volumes of pentaethylene and hexaethylene glycol monododecyl ethers in the micellar state are smaller by about 13 mL/mol than those in the liquid state. This difference is ascribed to the “demixing” of the dodecyl group from the polyethylene glycol group on micellization, in addition to the hydration of polyethylene glycol group at the micellar surface. Some implications of the present work to general anesthetic action are discussed.
Introduction Lipid aggregates, such as micelles, are different from bulk liquids in orientation and structure formation. The solvent properties of these lipid aggregates are important for understanding solubilization of water-insoluble substances as well as the structure and function of biological membranes. In most of these systems, mixing of lipids with solubilized species (solubilizates) is highly nonideal from the thermodynamic viewpoint. Although ideality of mixing in micelles has been established experimentally and theoretically, there are few studies on nonideal systems.’ We found that some fluorocarbon and hydrocarbon surfactants demix in their micelles as the result of severe nonideality of mixingZ and that the volume change AVon mixing of micelles can be a measure of nonideality of m i ~ i n g . ~The excess free energy G,, of mixing and the activity coefficient in the micelle would be more useful measures of nonideality than AV and the partial excess volume. The former quantities cannot be easily determined because of the difficulties in the determination of the composition of mixed micelles. We have shown for some mixed micelles that G,, is roughly proportional to AV and that the proporti?onality constant is close to those in liquid^.^ Since AVfor mixed micelles is an easily determinable quantity, we can use AV as t6o1 for characterizing the intermolecular interaction in the micelles. The solubility parameter 6 for liquids is a quantiti easily available and convenient for predicting nonideality of mixing.46 Therefore, this parameter is widely used for a variety of solut i o n ~ . ~Furthermore, -~ simple equations are developed for the relation between AVand 6.4-7 However, there is little use of 6 and these equations for micelles and other lipid aggregates. In this work, we investigate the volume changes on mixing of heptaethylene glycol monododecyl ether (DE7) micelles with liquid hydrophobic substances ranging from 5.9 to 11.8 of 6 . The measurements are made at high dilution of the solubilizates in the DE7 micelle, because of solubility limits of solubilizates and for comparison with theory. For comparison, A’Vfor binary liquid systems is also determined. Ionic surfactants and solubilizates (1) Mukerjee, P.; Mysels, K. J. ACS Symp. Ser. 1975, No. 9, 239. Shinoda, K.; Nomura, T. J . Phys. Chem. 1980, 84, 365. Funasaki, N.; Hada, S. Ibid. 1979, 83, 2471 and references cited therein. (2) Funasaki, N.; Hada, S. J . Phys. Chem. 1983,87, 342 and references cited therein. (3) Funasaki, N.; Hada, S.J . Phys. Chem. 1982, 86, 2504. (4) Hildebrand, J. H.; Prausnitz, J. M.; Scott, R. L. “Regular and Related Solutions”; Van Nostrand-Reinhold: New York, 1970. ( 5 ) Barton, A. F. Chem. Reu. 1975, 75, 731. (6) Burrell, H. In “Polymer Handbook”; Brandrup, J., Immergut, E. H., Eds.; Wiley-Interscience: New York, 1975; pp IV-337. (7) Hildebrand, J. H.; Dymond, J. J . Chem. Pbys. 1967, 46, 624.
0022-3654/84/2088-1243$01.50/0
are not used, since the electrostatic interaction at the micellar surface complicates data interpretation. These results are analyzed on the basis of the organized structure of the micelle, the intermolecular interaction of DE7 and the solubilizates in the micelle, and location and orientation of the solubilizates in the micelle. Further, the molar volumes of pentaethylene (DE5) and hexaethylene (DE6) glycol dodecyl ethers are measured in the micellar and liquid states and are discussed on the basis of the structure of the micelles. Some implications of the present work to general anesthetic action are also discussed.
Experimental Section Materials. n-Perfluorohexane from PCR Research Chemicals was once distilled before use. Perfluoromethylcyclohexane (cC7FI4), 1,2-dichlorohexafluorocyclobutane(c-C4C12F6),and 2,2,3-trichloroheptafluorobutane(C4C1,F,) from PCR are used without purification. These substances are gas-chromatographically pure. 1-Chloropentane, n-dodecane, and triethylene glycol from Tokyo Kasei Organic Chemicals were shown to be at least 99% pure by gas chromatography. Triethylene glycol monomethyl ether from Tokyo Kasei Organic Chemicals is used as received. Bromoform is passed through an alumina column after distillation. Methylene diiodide is twice passed through an alumina column. DE5 (lot no. 71116), DE6 (lot no. 71112), and DE7 (lot no. 800525) were purchased from Nikko Chemicals. These nonionic surfactants were placed in a desiccator, which was stored in a refrigerator. The deionized water is twice distilled before use. Method. The densities d of all micellar solutions are measured with a 20-mL Ostwald pycnometer. The densities d of liquid mixtures are measured with 5- and 10-mL Ostwald pycnometers. The temperature of a thermostat was kept constant at 25.00 0.005 “C. The apparent molar volume 4 of mixed micelles is calculated from eq 1, where do and d a r e the densities of water and aqueous
*
Q, = l O O O ( ~ o- d ) / ( m d o d ) + (Mixi + M 2 ~ 2 ) / d (1) solution, m is the total molality of DE7 ( m , ) and a solubilizate (mz),and MIand xi are the molecular weight and the mole fraction of component i (equal to m , / m ) ,respectively. The total molality used ranges from 0.03 to 0.05 mol/kg. So that the precision of our volume data was checked, we measured Q, of sodium dodecyl sulfate in water under similar conditions and the Q, determined was in agreement with the literature6 within 0.1 mL/mol. The partial molar volume u of mixed micelles is calculated from eq (8) Musbally, G. M.; Perron, G.; Desnoyers, J. E. J . Colloid Interface Sei. 1974, 48, 494.
0 1984 American Chemical Society
1244
The Journal of Physical Chemistry, Vol. 88, No. 6, 1984
Funasaki et al.
TABLE I: Molar Volumes of Polyethylene Glycol Monododecyl Ethers (DEn) in the Liquid and Micellar States at 25.0 “C Uobsd,
DEn
liquid
DE5 DE6
424.27a 462.96a
mL/mol micelle
Ucalcd, mL/mol
liquid
micelle
412.1’
417.6
408.9
445.7‘
456.6
446.0
447.1d 45 l e
DEI
485.4’
495.1
483.1
DE8
486.9a 524.2f
534.8
520.2
’
This work. Taken from ref 3. ‘Taken from ref 9. Taken from ref 10. Taken from ref 11. Taken from ref
a
@
Z I
12
Figure 2. Excess molar volumes of mixed micelles of DE7 and a solute
(dashed lines) and liquid mixtures (solid line) plotted against the mole fraction of the solute in the micelles and the liquids at 25.0 “C. The number attached to the lines denotes the solute shown in Table 11: (a) in the following solvents: (0 and A) DES; ( 0 )triethylene glycol; (0 and 0)n-dodecane; (b) benzene in the following solvents: (0) n-hexane,13 (0) n-heptane,I4(A) n-dodecane,I5 (A) n-hexadecane.’) 0
01
02
1.0
03
XZ
Figure 1. Excess molar vdumes of mixed micelles of DE7 and a solubilizate plotted against the mole fraction of the solubilizate in the micelles at 25.0 “C. The number attached to the lines denotes the solute shown in Table 11.
-3
N
-
c
I>”
0.5
a
Y
2 by using a number of 4’s for aqueous solutions with a constant molar ratio of DE7 to solubilizate. u =
4 + m(d4/WT,P,x
(2)
For each ratio, about five u values are determined and the standard deviation is below 0.15 mL/mol for most cases. The mean molar volume of a liquid mixture of components 1 and 2 is calculated from eq 3. The maximum deviation of u values u = (Mix,
+ Mzx2)/d
(3)
from the average is below 0.02 mL/mol for all mixtures. The excess molar volume (volume change on mixing) AV is calculated from eq 4. Here ul0 is the molar volume of DE7
(4) micelles or pure liquid 1 and uZois that of pure solute 2.
Results Excess Molar Volumes of Mixed Micelles and Liquid Mixtures. The 4 value of DE7 in water increased with increasing concentration above the critical micellization concentration and leveled off at very high concentration. By applying eq 2 to this result, we obtained a constant molar volume of 486.9 f 0.08 mL/mol (standard deviation) for DE7 in the micellar state. This value is significantly larger than the value that we have r e p ~ r t e d . ~ Similar differences in the micellar molar volume data of DE6 are observed in the literature, as shown in Table All dodecyl ethers shown in this table were obtained from Nikko Chemicals. These discrepancies are larger than experimental errors and consequently could be ascribed to the difference of purity in the different lots used. In Table I, the molar volumes of liquid DE5 and DE6 are compared with those in the micellar state. Since DE7 is a solid at 25 “C, we could not determine its molar volume in the liquid state. (9) Tanford, C.; Reynolds, J. A. Biochim. Biophys. Acta 1976, 457, 133. (10) Harada, S.;Nakajima, T.; Komatsu, T.;Nakagawa, T. Chem. Lett. 1975 -_. _ ) I74 (11) Nishikido, N.; Imura, Y.; Kobayashi, H.; Tanaka, M. J . Colloid Interface Sci. 1983, 91, 125. (12) Tanford, C.; Nozaki, Y.; Rohde, M. F. J. Phys. Chem. 1977, 81, 1555.
I
O‘
6
10 sZ (cal/rnL)”’
8
12
Figure 3. Square roots of relative partial excess volume of solutes at high dilution plotted against the solubility parameters of the solutes (Table 11) in the DE7 micelle.
The 4 value of a mixed micelle of DE7 and a solubilizate (solubilized species) is measured and the partial molar volume u is calculated from eq 2. As already r e p ~ r t e deven , ~ if the molar ratio of DE7 and a solubilizate in the whole system is kept constant, the ratio of these substances in the mixed micelle changes with increasing total concentration. As the total concentration is high, these ratios become closer. Thus, we can determine the molar volume of the mixed micelle as a function of the micellar comp~sition.~ In Figure 1, AV on mixing of DE7 micelles with a liquid solubilizate is plotted against the mole fraction x2 of the solubilizate in the mixed micelle. Such data are included for seven liquids in Figure 1 and for four liquids in Figure 2. These solubilizates are not micellized by themselves and are not freely soluble in the DE7 micellar solution. On mixing, the volume increased for all liquids except n-dodecane. For comparison, we measured the densities of liquid-liquid mixtures and determined AV, as shown in Figure 2. In Figure 2a, three solutes and three solvents related with DE7 are included. In Figure 2b, AVvalues of mixtures of benzene with four n-alkanes are compared with those for mixed DE7-benzene micelle^.'^-'^ Partial Excess Molar Volumes of Solutes at High Dilution. Using AVdata for a binary*system, we can determine the partial excess molar volume Ad2 of solute 2 at infinite dilution, from the slope of a AVvs. x2 curve at x2 = 0, by eq 5 . However, since Ad2 = 02
- v ~ O= ( ~ A V / ~ X ~ ) ~ ~ = O
(5)
it is not easy to evaluate the slope at small x2, instead we obtained Ad2 by using the AVdata at the highest dilution in Figures 1 and (13) Heric, F. L.; Brewer, J. G. J . Chem. Eng. Data 1967, ZZ, 574. (14) Mathieson, A. R.; Thynne, J. C. J. J . Chem. SOC.1956, 3708. (15) Schmidt, R. L.; Randall, J. C.; Clever, H. L. J . Phys. Chem. 1966, 70, 3912.
The Journal of Physical Chemistry, Vol. 88, No. 6, 1984 1245
Solubilization of Hydrophobic Liquids in Micelles
TABLE 11: Solubility Parameters and Molar Volumes of Solutes and Partial Excess Volumes a t High Dilution in Liquids and the DE7 Micelle
1
Cf.FI.4
2
a
solvent (stat e)
solute
no.
I4
C,Cl,F,
5 .9a
201.4
6.1a
196.0
3 4
C4C1’2F6
6.9O 7.1a
165.2 142.7
5 6 7 8
CIZHZfi C,H,lCl C6H6
7.45b 7.9c 8.3C 9.15b
147Sb 228.6 121.6d 89-36
9 10
CHCI, CHBr,
9.2a 10.Sa
80.7d 87.gb
11
W I ,
1 1 P
81.0d
12
CH iO K z HqO) 3 H
Taken from ref 4.
N
O6I
Taken from ref 16.
157.2 Taken from ref 6.
DE7 (m) C I J 2 6 (1) HO(C,H,O),H (1) DE5 (1) DE7 (in) C,Hic, (1) DE7 (m) DE7 ( i n ) (l) C,H,, (1)
139 69 104 115 156 22.5b 50 53 8.3 11.16
0.83 0.59 0.72 0.76 0.89 0.34 0.55 0.6 1 0.24 0.28
-3.1 1.3 2.7 2.3e 1.7b 4.5 11.5 4.36 21 0.8 5.6
0.10 0.17 0.16 0.14 0.24 0.36 0.2 1 0.5 1 0.10 0.19
DE7 (m) DE7 (m) DE7 (m) Cl2H*6 (1) C,H,, (1) DE7 (m) DE7 (m) C,HIfi ( 0 DE7 (m) DE5 (I) Cl2H26 (1)
Taken from ref 17. e Taken from ref 15. TABLE 111: Internal Pressures (cal/mL) in the Liquid and Micellar States a t 25.0 “C
i
calcd by eq 6 at compd (state)
Figure 4. Square roots of relative partial excess volumes of solutes in n-heptane (0)and in n-dodecane ( 0 )a t high dilution plotted against the solubility parameters of the solutes. The data in heptane are taken from ref 16.
C1ZHZ6 (l) C,Fi, (1) HOCH,CH,OH (1) . * DE7 (m) MP DE8 (m) STS + NF (m)
+
at
theor*
b,> 6,
75.6 (23 ‘C).cse 51.3b 116.4d9f
61
12
74 112g 67h
2.8 112g 67h
6,
