6114
Langmuir 1996, 12, 6114-6118
Monolayer Behavior of [6-Deoxy-6-S-phenyl]-r-, β-, and γ-cyclodextrins at the Air-Water Interface Kazimierz Chmurski,† Renata Bilewicz,*,‡ and Janusz Jurczak†,‡ Institute of Organic Chemistry, Polish Academy of Sciences, Kasprzaka 44/52, 01-224 Warsaw, Poland, and Department of Chemistry, Warsaw University, Pasteura 1, 02-093 Warsaw, Poland Received March 6, 1996. In Final Form: September 4, 1996X Characteristics of monolayers of 15 new amphiphilic R-, β-, and γ-cyclodextrins at the air-water interface are reported. The modification involves substitution at the positions C-6 of the cyclodextrin with S-phenyl, S-(4-bromophenyl), S-(4-n-butoxyphenyl), S-(4-n-pentylphenyl), and S-(4-nitrophenyl). Even simple thiophenol-substituted cyclodextrins exhibit good amphiphilic properties, and the sequence of increasing degree of organization and stability of the monolayers is given. Increasing hydrophobicity of the group attached to the position C-6 results in the increase of the stability of the monolayer. However, for highly substituted cyclodextrins agglomeration of the molecules at the air-water interface was observed. This problem displayed by mean molecular areas smaller than those obtained from the crystal structures can be overcome by using more diluted spreading solutions. The β-series was found to deviate from other cyclodextrins in that the collapse surface pressure is higher than and almost independent of the substituent. This was ascribed to the 7-fold symmetry of β-cyclodextrin molecules.
Introduction Cyclodextrins (CD’s), cyclic oligosaccharides finding various technological applications and well-known to form inclusion complexes, have been extensively studied.1 Amphiphilic CD’s are usually prepared by the introduction of alkyl chains into the CD molecule.2,3 In general, there are two ways of chemical modification leading to amphiphilic forms of these compounds. The lipophilic groups can be linked to glucose units of CD either at primary4,5 or at secondary positions.6-9 It was postulated that amphiphilic CD molecules should form stable monolayers when alkyl chains containing more than four carbon atoms at each glucose unit are present.2 In practice, however, CD’s with alkyl chains of more than eight carbon atoms were needed to form stable monolayers at the air-water interface.10 Formation of stable monolayers of amphiphilic CD’s at the air-water interface has been studied extensively since 1986.2 Various processes occur in CD monolayers: association with other amphiphile molecules in binary assemblies,11 molecular recognition,12 and photopoly†
Polish Academy of Sciences. Warsaw University. X Abstract published in Advance ACS Abstracts, November 15, 1996. ‡
(1) Szejtli, J. CD Technology; Kluwer Academic Publishers: Dordrecht, The Netherlands, 1988. (2) Kawabata,Y.; Matsumoto, M.; Tanaka, M.; Takahashi, H.; Irinatsu, Y.; Tamura, S.; Tagaki, W. Chem. Lett. 1986, 1933. (3) Tanaka, M.; Ishizuka, Y.; Matsumoto, M.; Nakamura, T.; Yabe, A.; Nakanishi, H.; Kawabata, Y. Chem. Lett. 1987, 1307. (4) E.g. refs 2 and 3 and Yabe, A.; Kawabata, Y.; Niino, H.; Tanaka, M.; Ouchi, A.; Takahashi, H.; Tamura, S.; Tagaki, W. Chem. Lett. 1988, 1. (5) Niino, H.; Yabe, A.; Ouchi, A.; Tanaka, M.; Kawabata,Y.; Tamura, S.; Miyasaka, T.; Tagaki, W.; Nakahara, H.; Fukuda, K. Chem. Lett. 1988, 1227. (6) Coleman, A. W.; Kasselouri, A. Supramol. Chem. 1993, 1, 155. (7) Zhang, P.; Ling, C.-C.; Coleman, A. W.; Parrot-Lopez, H.; Galons, H. Tetrahedron Lett. 1991, 32, 2769. (8) Parrot-Lopez, H.; Ling, C-C.; Zhang, P.; Baszkin, A.; Albrecht, G.; de Rango, C.; Coleman, A. W. J. Am. Chem. Soc. 1992, 114, 5479. (9) Tchoreloff, P. C.; Boissannade, M. M.; Coleman, A. W.; Baszkin, A. Langmuir 1995, 11, 191. (10) Kawabata, Y.; Matsumoto, M.; Nakamura, T.; Tanaka, M.; Manda, E.; Takahashi, H.; Tamura, S.; Tagaki, W.; Nakahara, H.; Fukuda, K. Thin Solid Films 1988, 159, 353. (11) Taneva, S.; Katsuhiko, A.; Tagaki, W.; Okahata, Y. J. Colloid Interface Sci. 1989, 131, 561.
S0743-7463(96)00205-3 CCC: $12.00
merization.13 Charge-transfer interactions in LangmuirBlodgett films formed by these systems with other components were also studied.14 Self-assembly7,15-17 of these systems was described. Thin films of alkyl-chain CD derivatives found application in the construction of sensors.18,19 Synthesis of versatile materials, per(6-deoxy-6-bromo)CD’s described by Defaye and co-workers,20,21 helped us to elaborate a simple method of preparing amphiphilic CD’s. It is based on the nucleophilic displacement of the bromine moieties with strong nucleophile reagents such as various substituted thiophenols, having at least six carbon atoms.22 Application of simple alkylthiols as nucleophilic reagents was reported earlier.23 In this study our aim is to compare the properties of Langmuir monolayer films formed by the members of the newly synthesized group of compoundssderivatives of R-, β-, and γ-CD’s. Instead of a typical long alkyl chain, the group responsible for the amphiphilic nature of the molecules is the thiophenol substituent. This kind of substitution seemed especially attractive since it introduces chromophoric properties to the molecules and thus opens the possibilities of employing various spectroscopic methods in the studies of phenomena occurring in mono(12) Matsumoto, M.; Tanaka, M.; Azumi, R.; Tachibana, H.; Nakamura, T.; Kawabata, Y.; Miyasaka, T.; Tagaki, W.; Fukuda, K. Thin Solid Films 1992, 210/211, 803. (13) Fukuda, K.; Shibasaki, Y.; Nakahara, H.; Tagaki, W.; Takahashi, H.; Tamura, S.; Kawabata, Y. Thin Solid Films 1992, 210/211, 387. (14) Niino, H.; Miysayaka, H.; Ouchi, A.; Kawabata, Y.; Yabe, A.; Nakahara, H.; Fukuda, K.; Miyasaka, T.; Tagaki, W. Chem Lett. 1990, 1121. (15) Coleman, A. W.; Kasseulori, A. Supramol. Chem. 1993, 1, 155. (16) Zang, P.; Parrot-Lopez, H.; Tchoreloff, P.; Baszkin, A.; Ling, C.-C.; de Rango, C.; Coleman, A. W. J. Phys. Org. Chem. 1992, 5, 518. (17) Sommer, F.; Duc, T. M.; Coleman, A. W.; Skiba, M.; Wouessidjewe, D. Supramol. Chem. 1993, 3, 19. (18) Nagase, S.; Kataoka, M.; Naganawa, R.; Komatsu, R.; Odashima, K.; Umezawa, Y. Anal. Chem. 1990, 62, 1252. (19) Odashima, K.; Kotato, M.; Sugawara, M.; Umezawa, Y. Anal. Chem. 1993, 65, 927. (20) Gadelle, A.; Defaye, J. Angew. Chem. 1991, 103, 94; Angew. Chem., Int. Ed. Engl. 1991, 30, 78. (21) Baer, H. H.; Berenguel, A. V.; Shu, Y. Y.; Defaye, J.; Gadelle, A.; Gonzalez F.S. Carbohydr. Res. 1992, 228, 307. (22) Chmurski, K.; Coleman, A. W.; Jurczak, J. J. Carbohydr. Chem. 1996, 15, 787. (23) Ling, C.-C.; Darcy, R.; Risse, W. J. Chem. Soc., Chem. Commun. 1993, 438.
© 1996 American Chemical Society
[6-Deoxy-6-S-phenyl]-R-, β-, and γ-cyclodextrins
Langmuir, Vol. 12, No. 25, 1996 6115
Figure 2. Surface pressure-molecular area isotherms for R-, β-, and γ-CD’s (1-3) with the simplest S-phenyl substituents.
Figure 3. Surface pressure-molecular area isotherms for R-, β-, and γ-CD’s with S-(4-bromophenyl) substituent (compounds 4-6). Table 1. Comparison of Parameters of Isotherms for r-, β-, and γ-CD’s with Unsubstituted S-phenyl Groups compound
R
n
Πcoll (mN/m)
A0 (Å2)
calculateda (Å2)
1 2 3
H H H
6 7 8
25.6 34.1 25.0
172 228 238
158-177 177-196 229-252
a Calculated by Taneva et al.26 from the external diameter of unsubstituted CD’s.
Results and Discussion
Figure 1. Structures of the compounds studied.
layer assemblies of CD’s. The size of the CD ring was found to be an important parameter for the surface behavior of the studied amphiphiles. The monolayer properties of the CD’s can also be changed in a controlled way by appropriate modification of the group R in the aromatic moiety (Figure 1). Experimental Section The synthesis and characteristics of the compounds 1-15 (Figure 1) are described elsewhere.22 All solutions were prepared by dissolving the compounds in DMSO (Ubichem) and diluting the solutions using chloroform. For solutions more diluted than 0.2 mg/mL, pure chloroform could be used as solvent. All solutions were prepared daily. The solvents were distilled before use, and water for the subphase was distilled and passed through a Milli-Q water purification system. The final resistivity of water was 18.3 MΩ cm. Surface-pressure vs mean molecular area isotherms were recorded using the KSV-Minitrough with a Wilhelmy plate type microbalance. Software version KSV-5000 was used to control the experiments. The experimental setup was placed in the laminar flow hood. The procedures of cleaning the trough and monolayer spreading have been described earlier.24 (24) Bilewicz, R.; Majda, M. Langmuir 1991, 7, 2794.
Π-A Isotherms for r-, β-, and γ-CD’s with S-phenyl Substituent at the Position C-6. The isotherms recorded for compounds 1-3 are exhibited in Figure 2. Incorporation of the simple S-phenyl substituent is sufficient to obtain molecules with good amphiphilic properties. This means that six carbon atoms forming an aromatic unit per each glucose unit allow one to organize the molecules into a stable monolayer at the air-water interface. The characteristics of the isotherms of compounds 1-3 are given in Table 1. The mean molecular areas A0 increase with an increase of the CD ring. The A0 values agree well with those determined by Saenger from the X-ray structures of the unsubstituted CD’s.25 The values calculated from the external diameter of unsubstituted CD’s26 are included in Table 1 for comparison. The interesting feature of this series of compounds is that the collapse pressure is highest for the β-CD (Figure 2, compound 2). Similar behavior is found for the S-(4bromophenyl) derivatives (Figure 3, compounds 4-6). Usually the order of decreasing collapse pressure is R-, β-, and γ-CD, as described by Kawabata et al.10 for S-C-18 n-alkyl derivatives. On the other hand, Nicolis et al.29 postulated that the stability of the monolayer of per(6deoxy-6-bromo)-CD’s increased with larger number of (25) Saenger, W. Angew. Chem. 1980, 92, 343; Angew. Chem., Int. Ed. Engl. 1980, 19, 344. (26) Taneva, S.; Ariga, K.; Okahata, Y. Langmuir 1989, 5, 111.
6116 Langmuir, Vol. 12, No. 25, 1996
Chmurski et al.
Figure 5. Influence of the aryl substituent on the surface pressure-molecular area isotherms of R-CD. Substituent: S-phenyl (1); S-(4-bromophenyl) (4); S-(4-n-butoxyphenyl) (7); S-(4-nitrophenyl) (13). Table 3. Parameters of Isotherms of r-, β-, and γ-CD’s with R Groups Equal to O-n-C4H9 or n-C5H11
Figure 4. Surface pressure-molecular area isotherms for R-, β-, and γ-CD’s with the S-phenyl group containing an additional n-alkyl chain at the para-position: (A) -O-n-C4H9 derivatives (7-9); (B) n-C5H11 derivatives (10-12). Table 2. Isotherm Parameters of S-(4-bromophenyl) Derivatives of r-, β-, and γ-CD’s compound
R
n
Πcoll (mN/m)
A0 (Å2)
calculateda (Å2)
4 5 6
Br Br Br
6 7 8
29.8 34.6 29.8
134 228 268
158-177 177-196 229-252
a Calculated by Taneva et al.26 from the external diameter of unsubstituted CD’s.
hydroxyls adhering to the water surface. Collapse pressures were reported to be 6, 16, and 19 mN/m for the R-, β-, and γ-CD, respectively. However, neither of these trends is present for the series of 1-3 and 4-6 derivatives of CD’s, described in this study, and this point will be returned to below. Introduction of the Br group at the para-position of the S-phenyl substituent results in an increase of the collapse pressures for all compounds and thus to an increase of the stability in this series compared to the unsubstituted S-phenyl-CD’s (Table 2). The molecular area increases in the order 4, 5, and 6 and hence with an increase of the ring size. Comparison of the mean molecular areas in this series with the X-ray values gives good agreement only in case of β- and γ-CD while too small experimental molecular area is obtained for R-CD (compound 4). As will be seen below, this feature of the isotherms will be met for all CD’s with the substituted S-phenyl groups. Π-A Isotherms for r-, β-, and γ-CD’s with Hydrophobic Chains at the S-Phenyl Substituents. The isotherms for CD’s with substituents more lipophilic than S-Phe-Br (compounds 7-9 and 10-12) are shown in parts A and B of Figure 4 and in Table 3. In the case of these compounds gain in stability of the monolayers is clearly exhibited by higher collapse pressures and is related to the presence of the hydrophobic chain. The surface pressure is similarly high for all of the CD’s, and hence the monolayer properties seem to improve upon this substitution.
compound
R
n
Πcoll (mN/m)
A0 (Å2)
calculateda (Å2)
7 8 9 10 11 12
O-n-C4H9 O-n-C4H9 O-n-C4H9 n-C5H11 n-C5H11 n-C5H11
6 7 8 6 7 8
35.3 37.3 35.7 35.7 36.2 36.2
130 163 206 148 180 228
158-177 177-196 229-252 158-177 177-196 229-252
a Calculated by Taneva et al.26 from the external diameter of unsubstituted CD’s.
Isotherms for the series of R-CD’s 1, 4, 7, and 13 (Figure 5) show that substitution of the hydrogen atom at the para-position of the aromatic group leads to a more condensed monolayer. Exceptions are the compounds containing the nitro group at the para-position [compounds 13-15], which have much lower slopes than other CD’s studied in this work. This indicates more fluid character of the layer. This feature has been noted earlier27 for the para-isomer of the β-CD derivative (compound 14) in the contrary to its ortho- and meta-isomers. It was interpreted in the mentioned study as due to fluid folding of the p-nitrothiophenol group. This reveals the crucial role of the para-position substituent on the packing of the molecules in the monolayer. On the other hand, the feature previously noted for the S-(4-bromophenyl) derivative of R-CD, namely, the unexpected decrease of the area occupied by the molecule, is observed for most of the chain-substituted derivatives (Table 3, compounds 7-10). The mean molecular area smaller than that obtained from the crystal structure may be explained in several ways: (1) incomplete dissolution of the sample in the spreading solvent; (2) loss of the compound due to partial dissolution in the subphase; (3) loss of the compound from the air-water interface due to the presence of DMSO in the molecules; (4) agglomeration of the molecules at the air-water interface or formation of multilayered structures during compression of the molecules. Increased substitution of the phenyl ring should improve the solubility of the compound in the spreading solvent (chloroform). However, the areas tend to become smaller when the chain is incorporated into the S-phenyl group. Although no precipitates can be detected in the solutions prepared from R-CD’s with simple S-phenyl and S-(4-nbutoxyphenyl), the molecular area for the latter case is much smaller (Figure 5). This excludes the insufficient (27) Chmurski, K.; Jurczak, J.; Kasselouri, A.; Coleman, A. W. Supramol. Chem. 1994, 3, 171.
[6-Deoxy-6-S-phenyl]-R-, β-, and γ-cyclodextrins
Langmuir, Vol. 12, No. 25, 1996 6117 Table 4. Isothermal Parameters of Selected CD’s Chemically Modified at the Position C-6
Figure 6. Influence of the concentration of spreading solutions of S-(4-n-pentylphenyl)-R-CD (10) on the surface pressuremolecular area isotherms. Concentrations (mg/mL) of R-CD: (a) 1.0; (b) 0.33; (c) 0.17.
compound
group at position C-6
Πcoll (mN/m)
A0 (Å2)
6-Br-R-CD 6-Br-β-CD 6-Br-γ-CD 6-azido-R-CD 6-azido-β-CD 6-azido-γ-CD 1 2 3 4 5 6 7 8 9 10 11 12 6-SO-C12-β-CD 6-SO-C8-β-CD 6-SO-C4-β-CD 6-S-C18-R-CD 6-S-C18-β-CD 6-S-C18-γ-CD
Br Br Br N3 N3 N3 S-phenyl S-phenyl S-phenyl S-(4-bromophenyl) S-(4-bromophenyl) S-(4-bromophenyl) S-(4-n-butoxyphenyl) S-(4-n-butoxyphenyl) S-(4-n-butoxyphenyl) S-(4-n-pentylphenyl) S-(4-n-pentylphenyl) S-(4-n-pentylphenyl) SO-n-C12H25 SO-n-C8H17 SO-n-C4H9 S-n-C18H37 S-n-C18H37 S-n-C18H37
6 16 19 6 13 17 26 34 25 30 35 30 47 45 42 42 40 38 60 55 unstable 60 55 50
180 220 260 160 208 238 172 228 238 134 228 268 213 225 348 200 224 264 217 223
a
173 210 281
ref 29 29 29 30 30 30 a a a a a a a a a a a a 2 2 2 10 10 10
Results from this study.
(compounds 7-9) and S-(4-n-pentylphenyl) groups (compounds 10-12). Figure 7. Surface pressure-molecular area isotherms for the S-(4-n-pentylphenyl) series (derivatives 10-12). Spreading solutions: 0.17 mg/mL CD in a chloroform-DMSO (9:1) mixture.
solubility in the spreading solvent as the reason for the observed deviations of the molecular areas compared to X-ray data. Loss due to dissolution in the subphase can be excluded as well, since dilution of the sample leads to an increase of the area per molecule in the layer. Figure 6 demonstrates that, for decreasing concentration (1.0, 0.33, 0.17 mg/mL) of compound 10, the mean molecular area increases; hence, dissolution in the subphase is not the reason for the deviations. When the concentrations are low, the DMSO content was found not to affect the molecular area. As seen in Figure 7, good agreement with the X-ray data is obtained for all types of S-(4-npentylphenyl) (compare with Figure 4Bswhere too concentrated solutions were spread) although 10% of DMSO is present in both series of experiments. All the results discussed above point to agglomeration or multilayer formation during compression. The latter is less probable since the reverse isotherms retrace the curve obtained during compression, provided that change in direction is done below the collapse pressure value. This suggests that below the collapse pressure we have a well-organized monolayer at the air-water interface. For concentrations typically suggested to be employed for the monolayer formation (1 mg/mL), the reason for too low molecular areas observed for our most substituted CD’s is that some aggregates are present together with the monolayer at the air-water interface. We remove this agglomeration by using more diluted samples (Figures 6 and 7). The molecular area data obtained under these conditions for all of the CD’s studied are depicted in Table 4. The strongest tendency to aggregate is exhibited by the highly substituted CD’s: with S-(4-n-butoxyphenyl)
Conclusions When R- and γ-CD’s are compared in a series of the same number of glucose units but with different R groups, the sequence of increasing degree of organization and stability of the monolayer (increasing isotherm slope and collapse pressure and decreasing molecular area) is the following:
S-phenyl < S-(4-bromophenyl) 25 mN/m) than the compounds described by Nicolis et al.29 As one could expect, the Π collapse values collected in Table 4 are increasing with exchange of the group attached at the position C-6 of the CD for one of higher hydrophobicity. As Kawabata reported,2 SO-C4H9-β-CD derivative does not form stable monolayer, due to insufficient alkyl chain length. However, we could show that only a small modification of the substituentsinsertion of a phenyl group between S and O atomssallows to one employ this CD as the building block of a stable and well-organized chromophoric monolayer. For CD’s with substituents of low hydrophobicity, e.g., per(6-Br) and per(6-azido),30 the
monolayers exhibit low collapse-pressure values. Higher stability of all of our S-phenyl-CD’s points to the utility of our approach in introducing amphiphilicity to the macrocycle. As proven, further gain of monolayer stability can be obtained upon appropriate substitution of H atom in the aryl moiety. The agglomeration problem has to be overcome by dilution of the sample studied. Another solution currently under study is to use mixtures with a standard amphiphile-like arachidic acid to produce the monolayer on the air-water interface. This approach should be especially useful if CD is used to construct molecular assemblies that mimic biological membranes and for new types of sensing devices.31
(30) Kaselouri, A.; Munoz, M.; Parrot-Lopez, H.; Coleman, A. W. Pol. J. Chem. 1993, 67, 1981.
(31) Greenhall, M. H.; Lukes, P.; Kataky, R.; Agbor, N. E.; Badyal, J. P. S.; Yarwood, J.; Parker, D. Langmuir 1995, 11, 3997.
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