J. Phys. Chem. 1992,96,9545-9550
Interactions between Cryptate 222 and Sodium Glycodeoxychoiate Micelles Bianca Sesta, Alessandro D'Aprano,* Antonio Princi, Catia Filippi, and Margberita Iammarino Department of Chemistry, University uLASAPIENZA". 00185 Rome, Italy (Received: June 10, 1992)
The electrical conductance of sodium glydeoxycholate in pure water and in water-cryptate 222 mixtures was measured at 25 O C to determine what counterion-specific effect controls the micellization process of bile salt. The complex trend of the conductometric curve with a minimum and a maximum has been interpreted in terms of anion dimerization and higher self-association of the surfactant molecules. The complexing agent, on one hand, reduces the ionic mobility of sodium ions and, on the other hand, stabilizes the glydeoxycholate micelles. Ion pairing, stabilized by hydrophobic interactions between the inclusion complexes of sodium ion and glydeoxycholate anion, has been postulated. The micellar properties of aqueous solutions of sodium glydeoxycholate with and without added cryptate have been determined at 10 and 25 OC by surface tension measurements. The mc's of the surfactant in pure water and in water-cryptate mixtures were assigned and the minimum areas per molecule at the air-water surface calculated. The tensiometric results, discussed on a thermodynamic basis, have shown that the favorable entropy change of the systems plays the main role in the micellization process.
Introdpction
Macrocyclic compounds such as cyclic polyethers and cryptate8 owing to their ability to complex metal ions of suitable sizes'-3 are largely used in membrane electrode preparation, catalysis, metal separation, protein extraction, and many other processes of technological interest. If used for pharmacological purposes, their interactions with biological components must be taken into account. In the last few years, our interest has been focused on monocyclic and bicyclic synthetic ligands for alkali metal These compounds are active in the ion transport across the membrane, and their use as antibiotics could be considered. Aqueous solutions containing bile salts, which are the usual components of liver products, have been also studied with different From the chemical point of view, bile salts are peculiar amphiphiles which, in aqueous environments, aggregate step by step, in molecular dimers, small micelles, elongated structures, and liquid ~rystals.~~-l~ The addition of an interacting compound influences both the thermodynamic process and the kinetic mechanism of aggregation.14J5 In this paper, the interactions between sodium glycodeoxycholate and 4,7,13,16,21,24-hexaoxa-1,lO-diazabicyclo[8.8.8]hexacosane have been investigated by conductometricand surface tension measurements. The study provides the opportunity to investigate how the bile salt self-aggregation responds to the perturbation induced by cryptate counterion complexation. The results show that the macrobicycle hosting the alkali metal ion is responsible for the increase of the cation hydrodynamic size and for the increase of area per molecule at the airwater M a c e . On the other hand, it reveals unexpected favorable effects on the stability of glydeoxycholate aggregates. The aurface'tension results, discussed on a thermodynamic basis, show that the selfassociation process of bile salt in water and in water-cryptate solution is an entropy-dominated process.
Experimental Section M.tahb sodkn Clycodeoxycaohte. This is a Sigma product, hereafter indicated as NaGDO, that has been purified according to the following procedure: a concentrated solution of NaGDO in bidistilled water was filtered through a fine fritted glass funnel to eliminate the macroscopic impurity; then acetone was added until a white, soft precipitate was obtained. After the solution stood overnight, the solvent was removed. The purified bile salt was dried for 24 h at 80 "C. The purification procedure was repeated twice. To test the purity of NaGDO, a small amount of the purified samples was recrystallized once more. The conductance of the aqueous solution of NaGDO recrystallized twice and 3 times gave identical results. 47,13,16,21,24-Hexaoxa1,l Odi.zabicyclo[8.8S]cos~e ((322). This was obtained from Merck-Suchard (>98% pure) and used as received.
water 10% 11.633 16.913 22.253 27.743 32.854 38.462 42.201 48.073 53.471 58.768 64.003 69.188 73.820 78.923 83.865
A 60.93 60.49 60.16 59.94 59.80 59.65 59.67 59.82 60.05 60.29 60.53 60.74 60.87 6 1.03 61.12
lo4c 26.421 34.856 40.399 45.790 53.847 61.759 69.459 79.738 92.348 96.117 99.915 104.60 113.89 127.80 153.72 178.11
A 59.97 59.66 59.60 59.69 59.99 60.36 60.69 60.99 61.17 61.20 61.23 61.21 61.17 61.05 60.64 60.20
wated222 10% A 9.2410 23.37 17.238 22.10 24.986 21.89 32.604 21.96 39.545 22.12 47.485 22.47 55.150 22.66 62.683 22.90 69.993 22.95 78.247 22.99 86.357 22.88 95.674 22.71 106.73 22.56 117.40 22.35 130.09 22.12 141.79 21.71
Water. This was laboratory supplied and further bidistilled over KMn04 and NaOH. The specific conductivity was xo = (1-2) x Q' cm-' at 25 "C. Methods. Master solutions of NaGDO and solvent mixtures were prepared by weight. The runs for the conductometric and tensiometric measurements were carried out by adding progressive amounts of concentrated master solutions from a weight buret into the solvent. For the ternary systems, the binary solvent was prepared, and then a weighed amount of this solvent mixture was used to prepare the master ternary solution, and another portion was put into the conductance cell or into the tensiometric cup in order to measure the conductance or the surface tension of the solvent. Appamtm. Conductance measurements were performed using a Shedlowsky bridge previously described.'6 After temperature equilibrium [Le& and Northrup oil thermatat (25 f 0.003 "C)], resistance with an accuracy of 0.01% was measured at 2,5, and 10 kHz and extrapolated to infinite frequency. The cell constant was 1.244 63 0.00002 cm-l, as determined by the Lind et al. method" using aqueous potassium chloride solutions. Surface tension measurements were carried out with a Lauda digital tensiometer equipped with a 13-mm-diameter platinum Du Nouy ring. The apparatus was provided with a device that allowed us to predetermine the raising velocity of the ring and the interval of time between two consecutive measurements. The accuracy of the measurements and the reproducibilityof the tests were within 0.05 dyn cm-'.The measurements were performed at loand 25 OC. The constancy of the temperature within 10.02 O C during the msssuramnts was assured by surmrwnding the v d containing the S O ~ U ~ ~ Owith M a jacket through which thennostated liquid was circulating.
*
0022-365419212096-9545$03.00/0 Q 1992 American Chemical Society
Sesta et al.
9546 The Journal of Physical Chemistry, Vol. 96, No. 23, 1992
6 6 4 A&d (222 0.02 M NaGDO
A
6ot
\
-
58
\
-
\
\ \
56 -
\ \
\
\ \ \
52L 0
I
I
5
10
15
100fi Figure 1. Experimental trend of A vs cl/* for NaGDO in pure water at 25 OC compared with Onsager's linear prediction (dashed line): (0)and ( 0 )refer to the duplicate rum reported in Table VII. 28 I
0.0 4.621 13.011 28.499 51.491 8 1.869 107.54 138.08 162.80 173.05 173.93 176.18 179.50 184.21 190.35 191.18 191.31 199.70 205.41 283.89 353.11 387.49
1169.2 1159.3 1124.4 1069.9 989.8 888.7 807.8 717.9 654.7 636.3 635.7 632.4 628.1 623.7 620.8 620.7 621.2 623.7 628.3 710.5 758.7 780.6
1\
'I
- 600
0
100
16
0
-9.9 -44.8 -99.3 -179.4 -280.5 -361.4 -45 1.3 -514.5 -532.9 -533.5 -536.8 -541.1 -545.5 -548.4 -548.5 -548.0 -545.5 -540.9 -458.7 410.5 -388.6
0.01 M NaGDO 10'M~ lex 0.0 546.5 1,899 543.7 -2.8 8.306 -22.1 524.3 16.943 498.4 -48.1 30.898 456.2 -90.3 49.959 402.1 -144.4 79.902 340.4 -206.1 103.61 350.4 -196.1 126.26 415.9 -130.6 151.52 424.0 -122.5 21 1.64 481.0 -65.5
200
300
-300
400
io3M~ 5
10
15
100 fi
for NaGDO in waterC222 Ftpn 2. Experimental trend of A VB at 25 OC compared with Onsagcr's linear prediction (dashed line).
Result8 The conductometric results of NaGDO in pure water and in water42222 (0.04 M)at 25 OC are summanzed ' in Table I where A (rl cm2 mol-') is the molar conductance and c the molar concentration of NaGDO (mol L-I). The experimentaltrendsof the molar conductancevs the square root of the equivalent concentration of NaGDO in pure water and in waterC222 (0.04 M) are compared in Figures 1 and 2, respectively, with the theoretical linear behaviors of the Onsager limiting law'* A I& - sc'/2 (1) where A,, is the molar conductance at infinite dilution and S is a constant depending on the temperature and on the bulk macro8copic dielectric constant and viscosity of the solvent. As can be seen,the experimental conductance of NaGDO docs not conform with the theoretical prediction in both cases. Table I1 summarizes the relative changes of the specific conductance of aqueous solutions of NaGDO (0.02 and 0.01 M)by
Figure 3. Relative changca of specific conductance (Ax) for NaGDOwater solutions of 0.02 M (0)and 0.01 M ( 0 )at 25 OC as a function
of C222 concentration. addition of C222, as a function of the molar concentration (MK) of the added cryptate. The changes were calculated as Ax = x* - x where x* is the specific conductance of the aqueous NaGDO solution (at fued concentration) and x the specific conductance of the solution after the addition of cryptate. As shown in Figure 3, where Ax is plotted against the molar concentration of cryptate, the curves pass through a minimum when the concentration of added cryptate matches that of NaGDO. Ctiven the complexhg capability of C222 for sodium ion (log K, 3.9 in water at 25 0C),'9820such a feature indicates that 1:l C 2 2 2 4 i u m complexes are formed in both cases. Table I11 summarizes the surface tension results ( 7 ) as a function of the NaGDO molar concentrations (c) in pure water and in waterC222 (0.04 M) at 10 and 25 OC. The results are expressed graphically as a function of In c in Figure 4. The break points in the curves are indicative of the critical micelle concentration (cmc) of the surfactant. Figure 4 shows that the presence of C222 slightly decreases the cmc, whereas for each system the cmc demases significantly with increasing temperature.
-
The Journal of Physical Chemistry, Vol. 96, No. 23, 1992 9547
Cryptate 222 and Sodium Glycodeoxycholate Micelles TABLE I&
Surface Tensions of NaGDO la Pure Water and la WaterC222 (0.04 M) at 10 and 25 O C O water waterC222 (0.04 M) 10 O C 25 'C 10 oc 25 'C 10% 0.0 4.066 9.921 15.246 21.861 28.369 34.972 41.669 47.3 12 52.603 58.261 63.782 69.949 75.791 81.420 115.91 134.80 220.21 366.00
10% 0.0 4.574 11.261 18.136 24.374 30.942 36.922 43.331 49.502 55.382 61.632 83.930 106.52 165.53 213.84 293.93
Y
74.2 67.1 61.7 59.0 57.9 56.4 55.2 53.3 52.5 51.6 50.8 49.9 49.5 49.7 49.7 49.9 49.9 49.5 49.7
Y
72.0 64.0 59.6 57.0 54.4 52.6 51.1 50.1 49.2 49.2 49.2 49.1 49.1 49.1 48.0 49.0
10% 0.0 4.358 9.952 22.421 28.762 35.189 41.391 47.68 1 53.922 60.03 1 65.972 72.012 77.620 83.171 106.40 142.79 212.60
10% 0.0 3.448 5.291 9.07 1 11.781 16.692 23.284 23.482 30.114 36.973 43.284 49.862 56.584 63.404 103.91 179.74 389.12
Y
63.9 57.7 54.5 51.0 50.0 48.9 48.1 47.2 46.4 45.8 45.2 45.4 45.4 44.1 45.8 46.2 46.6
Y
58.6 54.0 51.9 49.6 47.8 45.9 44.4 43.8 43.4 42.7 42.3 42.6 42.5 43.6 43.7 43.6 44.0
'Units: c, mol L-I; y, dyn cm-I. TABLE Iv: Surface Teadons of NaGDO la Water-C222 (0.05 M) and la Watclcc222 (0.08 M)at 25 OCQ water-C222 water42222 (0.05 M) (0.08 M) 104~ Y 10% Y 57.3 55.2 0.0 0.0 6.538 50.6 6.842 50.4 13.262 47.4 48.1 13.600 20.28 1 19.990 45.6 45.6 27.3 12 44.5 44.1 27.050 40.361 43.5 42.6 33.810 47.662 40.03 1 42.8 43.1 54.271 46.412 43.7 43.4 60.884 52.799 43.7 44.5 67.552 44.7 58.950 43.9 74.192 44.8 65.269 43.9 115.62 71.510 44.1 45.1 191.71 94.869 44.3 45.1 152.00 382.43 44.1 44.7 44.5 246.77 287.90 44.5 E
20.
fi
10
0 -8
-6
-7
-5
-4
-3
In c
Units: c, mol L-I; y, dyn cm-'.
Figure 5. Plots of surface pressure (T = yo - y) against the logarithm of surfactant molarity (In c) for NaGDO in water: (0)water4222 (0.04M)(A),waterC222 (0.05 M)(U), and waterC222 (0.08 M)(w) at 25 O C . TABLE V Surface Tension Data for C222 in Pure Water at 25 OCQ 10% 199.3 259.7 314.8 371.8 424.8
Y
65.8 63.3 61.6 60.6 59.6
10% 473.6 566.9 737.7 911.0 939.7
Y
58.3 57.1 55.6 54.1 53.5
'Units: c, mol L-I; y, dyn cm-'.
I
40 -8
I
-7
I
-6
I
-5
I
-4
-3
In c Figure 4. Plots of surface tension (y)against the logarithm of surfactant molarity (In c) for NaGDO in water at 10 OC (0)and at 25 "C (a),and in water4222 (0.04 M) at 10 "C (A)and at 25 OC (A).
In order to investigate the effect of the concentration of cryptate on the cmc, additional surface tension measurements of NaGDO in water42222 (0.05 M) and in w a M 2 2 2 (0.08 M) were carried out at 25 OC. The results are summarized in Table IV. The results are compared in Figure 5 in terms of the surface pressure x = yo- y to account for the differences of the surface tension of the solvent (yo). The figure shows that the cmc values do not depend significantly on the concentration of C222 added to the solution. At high concentration, the y and x values (Figures 4 and 5 ) depend sightly on the concentration. The phenomenon has been
9548 The Journal of Physical Chemistry, Vol. 96, No. 23, 1992
Sesta et al.
TABLE VI: !kface Tearim R d b for NaCDCkH& dNaCDOC222-€I& sobdior at 10 d25 OC medium T,OC 1o3cmc,mol L-' ioL0r,, mol cm-l I ~ A ~nm2 , , water 10 7.6 1.60 104 water4222 (0.04 M) 10 6.6 1.06 156 25 4.7 1.47 water 113 water4222 (0.04 M) 25 4.3 0.89 187 water42222 (0.05 M) 25 4.0 0.88 189 0.9 1 water4222 (0.08 M) 25 3.8 183
,,II
dyn cm-l 24.2 18.0 21.7 14.2 12.0 10.4
For NaGDO in water4222 mixtures, the surface tension functions exhibit a minimum (see Figure 4) due to the cryptate presence and its interaction with the bile salt. It reveals that NaGDO micelles adsorb part of macrobicycle molecules. A p proximately, the cmc of the ternary system falls around the minimum in the y vs In c plots. These values and the related Properties are reported in Table VI and could give semiquantitative information. The A h obtained for NaGDO in pure water at 25 OC is of the same order of magnitude as those reported for other bile salts,12723whereas the cmc values are between that found by mol L-') and that Kratohvil and Delli Colli" (cmc = 2.1 X reported by Roda et al.25(cmc = 6.0 X lo-' mol L-'), Mselprsion
-4
- 3.5
- 2.5
-3 In
-2
c
Figure 6. Surface tension ( 7 ) as a function of the logarithm of molar concentration (In c) of C222 in pure water at 25 OC.
generally correlated with the completeness of the surface monofilm of surfactant. The surface tensions of solution of C222 in pure water at 25 OC are summarized in Table V and plotted against the logarithm of the molar concentration of cryptate in Figure 6. The surface tension reduction, comparable to that observed with short-chain alcohols, indicates a small hydrophobic character of the C222 molecules. The experimental surface tension data were used to derive additional information on the micellar parameters. According to the Gibbs equation2' dy = -2rRT d(ln c I n n (2)
+
where R is the gas constant and T the absolute temperature. The factor of 2 in the above equation arises because both surfactant ion and counterion must be adsorbed to maintain neutrality.22 The surface tension data can be used to evaluate the surface excess concentration (I') of surfactants at the airwater interface. Approaching the cmc, the y vs In c plots are practically linear, and from their slopes, the maximum surface excess concentration per unity of area, r-, can be calculated as rmax = dy/2RT d In c (3) The minimum area per molecule of surfactant, Amin,required by a surfactant headgroup at the air-water interface can be estimated through the excess surface concentration, rmx, by A,,,~,,= 1014/m,,,
where N is Avogadro's number. The efficiency of surface tension reduction, calculated from
(4)
nmX, has been
%ax = YO - ~ m c (5) where yoand ymcare the surface tensions of the solvent and of the solution at cmc, respectively. The surface tension properties of NaGDO in pure water obtained as described above are summarized in Table VI.
Examination of the conductance curve for NaGDO-water solutim (Figure1) reveals that the change of A with amcentration is quite complex. The curve passes through a minimum (& = 59.6) at a concentration of about c = 3.8 X lV3(mol L-I), through a maximum (A- = 61.2) at a concentration of c = 10 X l e mol L-I, and thereafter decreases relatively rapidly. Such a trend, similar to that found for sodium deoxycholate,8.2628 sodium taurodeoxycholate26aqueous solutions, and paraffin-chain salts in water and aqueous propanol solution^,^ is neither that of nonnal uni-univalent electrolytap nor that of the classical micellar systems (Le., sodium dodecyl sulfate). Previous~tudies~JOJ~ have suggested that in aqueous solutions bile salts are associated by hydrophobic forces. Bile salt aggregation differs from that of typical ionic detergent in that it occurs over a relatively broad concentration range. The aggregation, at least in its early stage, is stepwise: initially small aggregates (dimers and tetramers) are formed, whereas at higher concentrations larger aggregates have been postulated. In contrast, typical ionic surfactants aggregate abruptly over a narrow concentration range (cmc), and the micelles usually contain a large number of monomers (Le, 20-100 monomers). To account for the difference in the self-association of bile salts, the term "noncritical multimer concentration" rather than the conventional cmc term has been In view of the above features, bile salts, in aqueous solution, can be considered to be formed by transient structures (i.e., monomers, dimers,tetramers, and higher oligomers) in dynamical equilibrium. The relative population of these structures is determined by the concentration of the system and by the temperature. Before we examine the complex trend of the conductance d e picted in Figure 1 in light of the above framework, let us consider briefly the interionic effects that determine the conductance of electrolytic solutions at finite concentration. As is well-known, ionic motions have a 'group" effect essentially related to the interactions of each ion with its environment of solvent molecules and other ions. Ion-ion interactions result from the overlapping of the Coulombic field of each ion; thus, the mutual location of the ions in solutions plays an important role in the electrostatic coupling between ions. This coupling, described in the Debye-Hiickel by the relaxation and electrophoretic effect, results in a decrease of the conductance with electrolyte concentration expressed for unassociated electrolytes by eq 1. If the system undergoes self-association, the extent of selfassociation and the shape of the aggregates can modify the primitive DebyeHQckel c l d , thus, a dependence of conductance with concentration more complex than the simple Onsager dependence can be expected.
The Journal of Physical Chemistry, Vol. 96, No. 23, 1992 9549
Cryptate 222 and Sodium Glycodeoxycholate Micelles
of cation cryptate 00mplexes~~ have established, in fact, that the nitrogen and oxygen atoms are oriented toward the inside of the molecular cavity hosting the cation. Consequently, the ethylene groups face out toward the aqueous phase and the complex acquires hydrophobic nature that allows it to interact with the hydrophobic environment of the GDO- anions. In the dilute region, ion pairing, hydrophobically stabilized, accounts for the decrease of conductance, which is greater than that required by the Onsager equation (1). It accounts also for the stability of primary micelles evidenced by the location of the minimum in the conductance curve, occurring far water4222 solution at lower bile salt concentration than that observed in pure water. Extrapolation of A 4 / * plots (Figures 1 and 2) at infinite dilution giva & = 64.3 C1cm2mol-' and & = 27.6 E'cm2mol-' for NaGDO in pure water and in water4222 mixtures, respectively. From these values and from the limiting values of sodium ion in water, &+ , = 50.1 C' cm2mol-', obtained combining the Kunze and F u w conductance data for NaCl in ~ a t e with 9~ Longsworth's transference data,40 we obtain the limiting ionic conductance summarized in Table VII. In the table, the Stokes radii calculated as
TABLE M: Uniting Ionic Cooductaocerad Stokes Radii for NffiDO in Rc Water ud in Wa-22 at 25 O C solvent 4 b+ b&+ &1.8 6.5 50.1 14.2 64.3 water ~
water4222 a Units:
27.6
13.4
A, A, iT1cm2 mol-'; R,*,
14.2
6.9
6.5
A.
ks can be seen in F i i 1, differtnt regionscanbedistinguished in the curve. In the fmt region, between infiite dilution and the minimum, the bile salt can be considered to be entirely in the monomeric fully dissociated form; thus, the trend of the conductance with the concentration, depending wentially on the long-range interionic effects between sodium cations and glycodaoxycholate anions, approaches the theoretical behavior predicted by eq 1. The second region, between minimum and maximum values, is in the range of concentrations where the cmc was ob served by tensiometric measurements. Lindenbaum and Vadned3 have calculated the aggregate species distribution of bile salts in aqueous solution as a function of total molar concentration of bile salts. In particular for sodium cholate, they found that the population of monomers and dimers is relatively high in the concentration range between 0.004 and 0.01 mol L-' and that the population of dimers increases from 27 to 45% in the same concentration range. Assuming that the behavior of the self-association of NaGDO does not differ substantially from that of sodium cholate, we can reasonably assume that in the second regionof concentration the overall self-asaociation process is mainly triggered by the equilibrium between monomers and dimers. Mukerjee et a1.34*35 have shown that dimers of sodium lauryl sulfate act as divalent ions at infinite dilution. With increasing concentration, the thickness of the ionic atmospheres decreases and the extent of their overlap is reduced. As soon as the ionic cloud becomes small compared with the separation of the headgroups, the dimers act like two monovalent ions with a consequent increase in the conductance. Assuming that bile salt dimers behave in the same way, the rise in molar conductance observed in our experiment can be explained considering the overcoming of such an effect on the interionic short-range retardation ones. As the concentration of NaGDO increases above 0.01 mol L-', the conductance decreases. This trend can be attributed to the evolution of the self-associations of dimers toward higher agg r e g a t e ~ .Micellar ~~ aggregation increases the viscosity of the system and the counterion binding. Under these circumstances, the friction of the growing micelles as well as the partial neutralization of the surface charges causes the observed decrease of the molar conductance. As shown in Figure 2, the general trend of the conductometric curve of NaGDO in water4222 mixtures is similar to that of NaGDO in pure water (Figure 1). However, some differences can be observed. In particular, in the low concentration range, the experimental curve of NaGDO in water4222 is far below the Onsager theoretical plot and the minimum in conductance is located at lower concentration than that observed for NaGDO in pure water. These features can be rationalized taking into account the perturbation induced by the cryptate counterion complexation (Figure 3) on the self-association process of the bile salt. As shown in a previous work? ion pairing of the C222 inclusion complex occurs in water owing to the molecular details of the cryptate ion that allow for short-range intera~tion.'~For NaGDO in C222-water solutions, the ion pairing can be further enhand by hydrophobic interactions." Crystallographic analysa
&* = Fe/1800m&* = 0.819 X
(6)
are also reported. Table VI1 data show that, in agreement with the complexation process, the hydrodynamic size of the encapsulate sodium ion approaches the actual size of the ligand, estimated to be approximately 5 A from space-filling molecular models and X-ray diffraction measurements." In waterX222 mixtures, the complexed cation is practically the same size as the anion. This similarity, increasing the probability of anion-cation contact, supports the occurrence of hydrophobic interactions in the ionpairing proass as postulated above. We consider next the surface tension results. Standard free energies of adsorption (AGO&) were calculated from the AGO& = RT In ( X ) - 0.602311Adn
(7)
where X is the molar fraction of NaGDO. Standard entropies (Soa&) and enthalpies (AH",&)in the range 10-25 OC were evaluated from the relationships d(AGoa&)/dT = -Soa&
(8)
(9) The thermodynamic parameters of adsorption obtained from the above equations for NaGDO in pure water and in water4222 (0.04 M) are summarized in Table VIII. As can be seen, the thermodynamic stability of the surface monofilm is assured by the entropic and enthalpic favorable contributions. In comparison with other surfactants of similar cmc, the free energies of adsorption for NaGDO either in pure water or in the wate~C222mixture are appreciably higher. This peculiarity is obviously due to the higher Ami,, values characterizing the bile salts. Carey and Small'2describe the cholesteric molecules lying flat on the watcr-air surface with the hydrophilic side toward the aqueous environment and the hydrophobic backbone toward the air. The Ah values at 10 OC in pure water and in water4222 mixtures (see Table VI) are smaller than those calculated for the corresponding systems at 25 OC. Such results can be explained
TABLE MI: Thermodynamic Parmeters of Aduorpth of NaGDC&H20 rad NaGDO-C222-Hz0 Solutiom medium
T,O C
AGO&,
W mol-'
H20
10
-36.1
H20 H 2 W 2 2 2 (0.04 M)
25 10
-31.9 -38.7
HZ042222 (0.04 M)
25
-39.3
10 10
-
so&,
AGO&, W mol-'
kJ mol-' deg-l
W &W , mol-'
25
-37.0
0.12
-2.1
25
-39.0
0.04
-27.4
T,O C
9550
The Journal of Physical Chemistry, Vol. 96, No. 23, 1992
taking into account the reduced molecular motion correlated to the decrease of temperature. The minimum area per molecules in pure water at 25 "C (A- = 113 Az)is in good a cement with the area occupied by the anion (a = rR; = 132 2, calculated as the central section of the Stokes hydrodynamic sphere representing the ion in solution. On the contrary, the Aminvalue in the wateS222 mixtura (A& = 187 A2)is larger than the above values. Since in all the water4222 mixtures examined the cryptate is in excess with respect to the bile salt concentration, we can explain such a result considering the cooperative effects derived from the free hydrophobic C222 molecules and from the hydrophobic complexed cation that can contribute to the structure of the monofilm at the air-water interface. The phenomenon is in agreement with the ion-pairing process and the hydrophobic interactions between cryptate and anion postulated above. In spite of the complex mechanism of self-association of bile salts in an aqueous environment (see above), the micellization of these compounds has often been treatedI2 in terms of the mass action Accordingly for NaGDO, the equilibrium between single ions, GDO-, and micelles (GDO-), can be indicated by
f
n(GDO-)
+ (n - p)Na+
-
(GDO-)R
(10)
where n is the aggregation number and p is the charge of micelle that accounts for the counteriom adsorbed on the surface and those bound in the Stern layer. The equilibrium constant, K,, can be expressed by where C, and C, are the micellar and the surfactant concentrations, respectively. In eq 11, the activity coefficients are neglected.44 Assuming, for NaGDO in aqueous solution, p = 9 and n = 26, as previously reported,24K,, according to Phyllip~,4~ may be calculated by
K,-' = {[n(2n- p)(4n - p - 1)]/(2n - p - 2))([(2n - p ) X (4n - 2p - l)(cmc)]/[(2n - p - 1)(4n - 2p + l)])z"pl from which the change of free energy, AGOmic, per molecule associated with the micelle formation can be computed as -AGOmic = (RT/n) In K, (12) In eq 11, it is convenient to express the concentrations in mole fraction; thus, AGOmicis referred to a state of mole fraction unity. For NaGDO in pure water, we obtain AGOmic= -34.5 kJ mol-' at 10 OC and AGOmic= -38.3 kJ mol-' at 25 OC. The increase of negative AGOmicvalues with the increase of temperature is a feature common to other surfactants that can be justified, according to Sheraga,* by a reinforcement of the hydrophobic interactions at higher temperature. From the AGOmicvalues obtained at 10 and 25 OC, average values of AGOmic = -36.4, ASomic= -d(AGo,,,jc)/dT= 0.25 kJ mol-' deg-', and AHomic= TMomic= 37.3 kJ mol-' were calculated. In this temperature range, the micellization of NaGDO in pure water is an entropy-controlled process. The increase of entropy can be related to the loss of water molecules, assembled in clathratic structures, surrounding the hydrophobic situ of surfactant molecules. Within the limits of reliability of cmc's reported for NaGDO in C222-HzO systems, the lowering of the critical micellar concentration, due to the cryptate, indicates an enforcing of the intermolecular interactions. The effect, although moderate, depends on the macrocycle concentration, as mentioned above, and on the temperature. The entropic contribution to the micellar stability in water-C222 is less pronounced than in pure water. As may be noted, differences between the thermodynamic parameters of adsorption and micellization exist. As pointed out by Mukerjee and Handa,47there are fundamental discrepancies in the hydrophobic interactions leading to micellar assembly and those responsible for the interface monolayer.
+
Sesta et al. Conclllslone Small amounts of C222 added to NaGDO aqueous solutions have appreciable effects on the transport properties and on the stability of primary micelles of sodium glydeoxycholate. Such an influence is related to the C2224Do- hydrophobic interactions and to the sodium complexation rather than to the appreciable change of the physical properties of the solvent. The conductometric d t s show that besides of the macraxopic effects of C222 on the hydrodynamic behavior of NaGDO, the mambicyclic compound is responsible for the stabilization of ion pairs through hydrophobic interactions. Surface tension results show that the presence of C222 in the system, reducing the NaGDO dominion in the monolayer at the water-air interface, causes an appreciable reduction of the effectiveness of surfactant properties of bile salts.
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