J. Phys. Chem. 1989, 93, 3721-3723
3721
Inclusion Process of Ionic Detergents with Cyclodextrins As Studied by the Conductance Stopped-Flow Method Tsuneo Okubo,* Yasushi Maeda, and Hiromi Kitano Department of Polymer Chemistry, Kyoto University, Kyoto, Japan (Received: August 25, 1988)
Inclusional association of ionic detergent molecules into the cavity of a-, 0-, and y-cyclodextrins is observed by using the conductance stopped-flowtechnique. Detergents used are sodium dodecyl sulfate and sodium I-alkanesulfonates (alkyl group: tetradecyl, dodecyl, decyl, octyl, heptyl, and hexyl). A clear relaxation curve is observed by mixing a solution of an ionic surfactant with that of an excess amount of cyclodextrin. The forward (kf) and backward (kb)rate constants and the association constant ( K ) are evaluated from the plots of pseudo-first-order rate constant versus initial concentration of the cyclodextrin. From the activation and thermodynamicparameters the driving forces of the inclusion process are van der Waals and hydrophobic interactions between an alkyl chain of the detergent and an inner wall of the cavity of the cyclodextrin. Effects of cavity size of the cyclodextrin, length of alkyl chain of the detergent, and ethanol added are also examined.
Introduction Cyclodextrins (abbreviated as CD's hereafter) are known to form so-called inclusion compounds by capturing a number of compounds into their cavities.1,2 Inclusion of organic compounds by C D s sometimes inhibits an oxidation or a biological digestion of the included compounds. The inclusion complexes have been, therefore, widely used in the fields of food industries and pharm a ~ o l o g y . CD's ~ also show catalytic activities in many kinds of reactions such as hydr~lysis,~ decarboxylation,s,6 hydrogenation of olefins,' site-specific substitution reactions of included compounds,* and so on. Previously we examined the formation of inclusion complexes of CD's with ionic detergents by the conductometric method and determined equivalent conductances and association constants of the inclusion c o m p l e ~ e s . ~ Kinetic studies of inclusion reactions of organic dyes with CD's have been extensively performed with the temperature jump As for detergent molecules, however, there has been only one kinetic report in which Hersey et al. examined inclusion reactions based on competition experiments.12 They adopted the spectrophotometric method using an azo dye as competitor. Considering the disturbing effect of the interaction between an added azo dye and a detergent on the equilibrium between a CD and a detergent, it is desirable to examine simpler systems in which only CD's and detergents are present. As described above, the inclusion of ionic detergents by CD's affects the conductance of the s o l ~ t i o n . The ~ conductometric method, therefore, seems to be useful for the kinetic estimation (1) Bender, M. L.; Komiyama, M. Cyclodextrin Chemistry; SpringerVerlag: Berlin, 1978. (2) (a) Crarner, F.; Hettler, H. Narurwissenschaften 1967, 54, 625. (b) Saenger, W. Angew. Chem., Inr. Ed. Engl. 1980, 19, 344. (c) Breslow, R. Acc. Chem. Res. 1980, 13, 170. (3) (a) Uekama, K. Pharm. Inr. 1985, 6 , 61. (b) Szejtli, J. The Cyclodextrins and Their Inclusion Complexes; Academiai Kiado: Budapest, Hungary, 1982. (4) . . (a) . , VanEtten. R. L.: Sebastian. J. F.: Clowes. G. A.: Bender. M. L. J . Am. Chem. SOC.1967, 89, 3242. (b) VanEtten, R. L.;'Clowes,'G.A,; Sebastian, J. F.; Bender, M. L. Ibid. 1967, 89, 3253. (c) Kitano, H.; Okubo, T. J . Chem. SOC.,Perkin Trans 2 1977, 432. (d) Ihara, Y . ;Nakanishi, E.; Nango, M.; Koga, J. Bull. Chem. SOC.Jpn. 1986, 59, 1901. (5) Straub, T. S.; Bender, M. L. J. Am. Chem. SOC.1972, 94, 8875. Ibid. 1972, 94, 888 1 . (6) Cramer, F.; Kampe, W. J . Am. Chem. SOC.1965.87, 1 1 15. (7) Komiyama, M.; Hirai, H. Bull. Chem. SOC.Jpn. 1983, 56, 2833. (8) Breslow, R.; Campbell, P.J . Am. Chem. SOC.1969, 91, 3085; Biorg. Chem. 1971, I , 140. (9) Okubo, T.; Kitano, H.; Ise, N . J . Phys. Chem. 1976, 80, 2661. (IO) Cramer, F.; Saenger, W.; Spatz, H. Ch-. J . Am. Chem. SOC.1967, 89, 14. (1 1) Hersey, A,; Robinson, B. H. J . Chem. SOC.,Faraday Trans. 1 1984, 80. - - ,2039.
(12) Hersey, A.; Robinson, B. H.; Kelly, H . C. J . Chem. Soc., Faraday
Trans. I 1986, 82, 1271.
0022-3654/89/2093-3721$01.50/0
of the inclusion process. A conductance stopped-flow (CSF) method is advantageous to investigate fast ionic reactions without any changes in the absorbance of the solution. We have examined association equilibria of ionic detergents,') an association of alkaline-earth-metal ions with cryptand,14an association of a hapten with an antibody,15 and others by using the conductance stopped-flow method.I6 In this report we examine the kinetic studies of an inclusion process of various kinds of ionic surfactants with CD's using the C S F technique.
Experimental Section Materials. Sodium dodecyl sulfate (SDS, protein research grade) was obtained from Wako Pure Chemicals, Osaka, Japan. Sodium tetradecanesulfonate, sodium dodecanesulfonate, sodium decanesulfonate, sodium octanesulfonate, sodium heptanesulfonate, and sodium hexanesulfonate were obtained from Tokyo Kasei Co., Tokyo, and purified by recrystallization from H20. Cyclohexaamylose (a-CD), cycloheptaamylose (p-CD), and cyclooctaamylose (7-CD) were purchased from Nakarai Chemicals Co., Kyoto. For preparation of solutions, Milli-Q grade water was used. Conductometric Measurements. A Wayne-Kerr autobalance precision bridge (B 311, mark 11) was used for conductometric measurements. The cell constant of the thermostated conductance cell was 4.74 cm-' at 25 "C. Kinetic Measurements. The inclusion reaction of detergents with CD's was followed by using a conductance stopped-flow apparatus. The details of the apparatus are described elsew h e r e . ' ) ~ The ~ ~ solution of the cyclodextrin was rapidly mixed with an equal volume of the detergent solution. The initial concentration of the CD ([CD],) was much in excess compared to that of the detergent solution ([SI,). To avoid the disturbing effect of the association equilibria of the detergent molecules themselves,') the initial concentration of the detergent was always far below the critical micellar concentration (cmc) of the detergent (for example, [SDS], = 2 mM. The cmc of SDS was reported to be 8.2 mM at 25 O C ) . " Results and Discussion A . Relaxation Curve Corresponding to Inclusion Process. When the solution of the cyclodextrin was mixed with that of the detergent, a single-exponential curve was observed, as exemplified (13) Okubo, T.; Kitano, H.; Ishiwatari, T.; Ise, N. Proc. R. SOC.London A 1979, A366, 81.
(14) Kitano, H.; Hasegawa, J.; Iwai, S.; Okubo, T. J. Phys. Chem. 1986, 90, 6281. (15) Kitano, H.; Hasegawa, J.; Iwai, S.; Okubo, T. Polym. Bull. 1986, 16, 89. (16) Okubo, T. Makromol. Chem. Suppl. 1985, 14, 161. (17) Rosen, H. J. Surfactants and Interfacial Phenomena; Wiley-Interscience: New York, 1978.
0 1989 American Chemical Society
Okubo et al.
3722 The Journal of Physical Chemistry, Vol. 93, No. 9, 1989
TABLE I: Thermodynamic and Activation Parameters for the Association of a-CD with SDS at 25 O C
h z
AG*, kcal mol-'
AH*, kcal mol-'
kf
14.7 f 0.5
kb
17.7 f 0.5
13.5 f 0.5 15.2 f 0.5
.-
AS', eu -4 f 1 -8 f 1
c
>
-G, kcal mol-'
v2
K
u 0
I
I
I
0
1
Time
08
06
04
02
(5)
Figure 1. Typical traces for the association of y-CD with SDS at 25 OC: [SDSl0 = 2.5 mM; (1) [y-CDIo= 23.3 mM; (2) [y-CD],, = 11.7 mM.
-3.0 f 0.5
A H , kcal mol-' -1.7 f 0.5
AS, eu
4fl
in good agreement with that evaluated by the static conductometric method (110 M-I), which was obtained by taking account of a change in cmc of the surfactant solution by the addition of CD, denote the concentrations of the using eq 2: where m , and massoc m* - m , massoc K=-(2) mrn[CDIf mrn([CDIo - m* + mrn) monomeric- and the associated-state detergents, and m* is given by mm + massoc. Association and dissociation rate constants for an inclusion process of CD with various kinds of molecules have been extensively studied, and in many cases both processes were very rapid. For example, the kf and kb values for the reactions C1- + a-CD a-CD have been reported to be 5.4 X lo7 M-I s-l and C10,and 2.1 X lo7 s-l, and 2.0 X lo9 M-' s-l and 7.4 X lo7 SKI, respectively.18 These guest molecules are compact, and it is easy for them to go out from and penetrate into the cavity of the CD molecule rapidly. In the case of bulky molecules, however, the rate of the association process might be much lower than those of rigid small molecules. Cramer et al. estimated the association constant of azo dyes with CD.'O They showed that some kinds of azo dyes had very small kf and kb values (2.8 M-' s-l and 0.01 s-' for a no. 10 compound in Table I1 of ref 10) because of the steric hindrance. The monomeric detergent molecule in the solution might shrink to reduce the contacting area with surrounding water molecules. In order to penetrate into the cavity of the CD molecule, the detergent molecule has to stretch itself. Therefore we consider that the slow association process observed here is understandable. Satake et al. carried out the conductometric and potentiometric studies of a - C D with ionic detergents.19 They reported that a 1:1 association scheme proposed by us9 is valid, but the association constant estimated by them was larger than the value evaluated here. They assumed two kinds of parameters without any basis for the evaluation of the association constant using a nonlinear least-squares method, and we consider that their evaluation method contained quite large uncertainties. We tried to evaluate the association constant for an a-CD-SDS system at 25 "C by using their method, but the K value obtained (100 M-l) was quite similar to the value observed in this work (the kinetic result by us, 160 M-l; the static result by Satake et al., 1120 M-I). B. Effect of Temperature on the Inclusion Process. From the Arrhenius plots of kf and kb and the van't Hoff plots of K , the activation and thermodynamic parameters of the a-CD-SDS system were evaluated and are listed in Table I. The AH value was negative and the A S value was positive, which is consistent with the data from the static methods9 There are several kinds of interactions between CD and guest molecules as given by eq 3,2°*21where AGhp,AGphr, AG,,,,, AGhb, AG = AGhp + AGpoIar + Acster + AGhb + + AGrel (3) Acto,, and AGrelare the free energy changes attributable to the hydrophobic interaction, the polar interaction (dipole-dipole, dipole-induced dipole), the steric interaction (London dispersion), hydrogen bonding, the torsional energy of the CD ring, and the release of water molecules with high energies, respectively. Among
+
0
20
60
40
CC D1, (mM 1
Figure 2. Plots of 1 / i against [a-CDIofor the association of a-CD with SDS at 15 OC (Q), 25 "C (0),and 35 OC ( 0 ) .
in Figure 1. Any relaxation curves were imperceptible upon mixing the detergent solution or the CD solution with an equal volume of H 2 0 , which means that the relaxation curve observed here solely corresponds to the association of the detergent with the CD. The plots of 1 / (T, ~ relaxation time) versus [CD], at various temperatures are shown in Figure 2. The plots show linear relationships. To intepret the results in the figure we assume that the inclusion reaction proceeds via a single step (Scheme I), where SCHEME I
CD
+ s 2CD.S kb
CD, S, C D 6 , kf, and kb are the cyclodextrin, the detergent, the cyclodextrin-detergent complex, the forward reaction rate constant, and the backward reaction rate constant, respectively. Under the condition [CD], >> [SI,,the reciprocal of the relaxation time ( l / ~ is ) given as eq 1, where [CDIf and [S]fdenote the concen1 / = ~ kf([CD]f + [S]f) + kb
li.
kf[CD]o + kb
(1)
trations of free cyclodextrin and detergent in the solution, respectively. Under the condition [CD], >> [SI,, [CDIf + [SI, is nearly equal to [CD],. There is another possibility that the inclusion proceeds via a two-step mechanism and that these two steps could not be clearly separated. The two-step inclusion reaction was proposed by Hersey and Robinson for the inclusion of azo dyes with CD." Because of the experimental difficulties (solubilities of CD's are not so high) we could not examine a complexation reaction at high CD concentration. At the moment, therefore, we analyze the inclusion reaction as a single-step process, though the possibility of the two-step mechanism could not be completely excluded. From the slopes and the intercepts of the plots in Figure 2, the values of kf and kb were evaluated and the association constant, K, was given by kf/kb (Table I). At 25 OC, kf, kb, and K values for an a-CD-SDS system were estimated to be 110 M-' s-I, 0.7 s-l, and 160 M-l, respectively. The association constant ( K ) was
(18) Rohrbach, R. P.;Rodriguez, L. J.; Eyring, E. M.; Wojcik, J. F. J . Phys. Chem. 1911, 81, 944. (19) Satake, I.; Ikenoue, T.; Takeshita, T.; Hayakawa, K.; Maeda, T. Bull. Chem. SOC.Jpn. 1985, 58, 2146. (20) Tabushi, I.; Kiyosuke, Y.; Sugimoto, T.; Yamamura, K. J . Am. Chem. SOC.1918, 100, 916. (21) Tabushi, I.; Kuroda, Y . ;Mizutani, T. fbid. 1986, 108, 4514.
The Journal of Physical Chemistry, Vol. 93, No. 9, 1989 3123
Inclusion of Ionic Detergents with Cyclodextrins
-I
10000
- 5000
50
-
- 1000 5 VI
100)
-
500
I:
TABLE I 1 Rate and Equilibrium Constants for the Association of CD's with Sodium Decanesulfonate at 25 "C
kf, M-' a-CD P-CD y-CD
S-'
1800 f 150 3300 f 300 4400 f 400
kb, s-'
K,M-'
14f 1 18f2 21 2
130 f 15 180 f 20 210 f 2s
*
P TABLE 111: Rate and Equilibrium Constants for the Association of a-CD with Sodium Decanesulfonate at 25 OC solvent
I 6
8
IO n
12
14
Figure 3. Effect of the chain length of the detergent on the values of K (0), kf (O), and kf ( 0 )in the association with a-CD at 25 "C.
these interactions, the hydrophobic interactions ( A H L 0, A S L 0) and the van der Waals interaction (AGpia,+ AG,,,,) ( A H < 0 , AS < 0) might be mainly attributable to the thermodynamic
parameter^.^^^^^ The negative AH observed here could be attributed to the van der Waals interaction between the inner wall of CD molecule and the hydrocarbon chain of the detergent. The positive AS value could be mainly attributed to the hydrophobic interaction between the alkyl chain and the inner wall of the CD molecule and partly to the release of water molecules from the alkyl chain of the detergent and the cavity of the CD during the penetration process into the cavity. AH* values of both k f and kb were much larger than those of a diffusion-controlled binary association process (the theoretical values for a binary association process: kf,4.1 f 0.3 kcal mol-'; 24 kb, 3.6 kcal mol-'), which means that the inclusion and release of the detergent into and from the CD cavity demands a large amount of energy. The energy to expand the shrunken alkyl chain of the detergent to be included into the cavity, that to repel water molecules from the cavity of the C D and around the alkyl chain of the surfactant, and that to change the conformation of the CD to receive the surfactant into its cavity can be attributed to the large AH* value of kf. Similarly, a friction energy between the inner wall of the CD and the alkyl chain of the detergent for the release of the surfactant from the cavity of the CD might be very large, which results in a large AH* value of k b . C. Effect of Chain Length of Detergents. Figure 3 shows the kf, k b , and K values for various kinds of sodium 1-alkanesulfonate (C,H2,+,S03Na, n = 6, 7, 8, 10, 12, 14). Both kf and kb values decreased with the increase in n value, and the degree of reduction for kb was slightly larger than that for kp The reduction of kf and kb could be attributed to the steric hindrance for the detergent molecule to enter and go out from the cavity of the CD molecule. The increase in K was attributed to the stabilization of inclusion compounds by the increase of contact area between the alkyl chain of the detergent and the inner wall of the C D molecule. It should be noted here that an increase in chain length of the surfactant is unexpectedly not so effective for the association with CD, especially for detergents of n > 8. Similar tendencies were (22) (a)-Gill,S. J.; Downing, M.; Sheats, G. F. Biochemistry 1967, 6, 272. (b) Gill, S. J.; Nichols, N. F.; Wadso, I. J . Chem. Thermodyn. 1976, 8, 445. (23) Ross, P. D.; Subramanian, S. Biochemistry 1981, 20, 3096. (24) Longsworth, L. E. J. Phys. Chem. 1954, 58, 770.
HZO 10% EtOH-HZO 20% EtOH-HZO
k f , M-'
S-'
1800 f 150 2000 f 200 2100 f 200
kb, S-'
K, M-'
14 f 1 21 f 2 25 2
130 f 15 95 f 10 83 f 10
*
observed previously by the static method.lg From the CoreyPauling-Koltun (CPK) model six methylene groups could be included in the cavity. The other methylene groups might attach to the exterior surface of the CD molecule, though the exterior surface is less hydrophobic than the cavity. There have been some reports suggesting the formation of a ternary complex such as (CD)2S in the case of detergents with a long alkyl chain.12,25 From the conductometric measurements, however, we could not observe the formation of a ternary complex but of a binary one. This is because, by the insertion of the alkyl chain into the cavity, the interaction between the free ends of the alkyl chain of the included detergent with other CD molecules might be very small because of steric hindrance. D. Effect of Cavity Size of the CD Molecule. We also examined the effect of cavity size of the CD molecule on the inclusion reaction. Table I1 shows the kinetic results. By the increase in the cavity size, kf, kb, and K increased, but the degree of increase in kb was slightiy smaller than those in k f and K . The increases in kf, kb, and K with the cavity size could be attributed to the reduction of steric hindrance. The reason for the smaller increase in the kb value is that the area of the detergent in contact with the inner wall of the CD is not so greatly changed by the increase in the cavity size. E. Effect ofEthano1. We examined the effect of ethyl alcohol on the association process of the detergent with CD (Table 111). By the addition of ethanol, both kfand kb values were increased and the K value was decreased. The decrease in K values could be attributed to the decrease of nonpolar interaction between the alkyl chain of the detergent and the nonpolar cavity of the CD. By the addition of ethanol, the number of water molecules around the detergent molecule might be decreased. In addition the detergent molecule might stretch its alkyl chain relatively more widely than in water, which is more advantageous for the detergent to penetrate into the cavity. These factors may enhance the rate of the penetration and releasing process of the detergent into and from the CD cavity to a larger extent than in H20. Acknowledgment. We thank Professor Norio Ise for his encouragement throughout the work. Registry No. a-CD, 10016-20-3; SDS, 151-21-3; 8-CD, 7585-39-9; y-CD, 17465-86-0; Cl,Hz9SO3Na,6994-45-2; C12H25S03Na, 2386-53-0; CloHZlSO3Na,13419-61-9; C8HI7SO3Na,5324-84-5; C7HI5SO3Na, 22767-50-6; C6HI3SO3Na,2832-45-3; ethanol, 64-17-5. ~~~~~
(25) Schlenk, H.; Sand, D. M. J. Am. Chem. Soc. 1961, 83, 2312.
