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Complex Formation of Semifluorinated γ-Cyclodextrin and Surfactants in Liquid Carbon Dioxide Ha Soo Hwang,† Min Young Lee,† Yeon Tae Jeong,† Seong-Soo Hong,‡ Yeong-Soon Gal,§ and Kwon Taek Lim*,† DiVisions of Image and Information Engineering and Chemical Engineering, Pukyong National UniVersity, Pusan 608-739, Korea, and College of General Education, Kyung Il UniVersity, Gyeongsang buk-do 712-701, Korea
γ-Cyclodextrins functionalized at the 6-position with perfluoro butanoate groups were prepared from the esterification reaction between γ-cyclodextrin and perfluorobutanoic acid. The semifluorinated γ-cyclodextrin derivatives exhibited amphiphilic behavior and an apparent solubility in densified CO2. They can form soluble complexes with surfactants such as bis(2-ethylhexyl)sulfosuccinate sodium salt (AOT) and N-lauroylsarcosine sodium salt in liquid CO2. The complex with AOT was confirmed visually and by differential scaning calorimetry (DSC), which did not show the characteristic melting endotherm of AOT. The formation of complexes of the single-tail surfactant N-lauroylsarcosine sodium salt and γ-cyclodextrins was also investigated. 1. Introduction It is widely known that cyclodextrins (CDs) form inclusion complexes with a number of organic molecules without any covalent bonds. CDs are cyclic oligosaccharides that are classified as R-, β-, and γ-CD according to the number of (1,4)linked R-D-glucopyranose units (six, seven, and eight, respectively) and have a hydrophobic cavity into which a guest molecule of appropriate size and shape can be incorporated in aqueous media.1 Recently, supercritical CO2 was utilized as a nontoxic medium for inclusion of solid-state drugs into β-CD.2 For many years, modifications of CDs have provided interesting organic host molecules for the encapsulation, solubilization, and transport of drugs.3 However, their use in biological systems requires amphiphilic properties. To improve amphiphilic cyclodextrin, one of the two hydrophilic rims has to be modified by the introduction of liphophilic groups. Whereas a large variety of amphiphilic CDs based on long alkyl chains as hydrophobic substituents have been described in the literature,4-6 few works have been reported for fluorinated CDs.7 Recently, fluorine-containing organic compounds have attracted much attention owing to their high solubilities in the environmentally benign solvent CO2 and their potential importance in the biological field.8,9 On the other hand, compressed carbon dioxide (CO2) has emerged as a leading alternative to toxic organic solvents because it is abundant, nontoxic, nonflammable and its critical points are relatively mild: Tc ) 31 °C, Pc ) 73.8 bar.10-12 However, carbon dioxide has no permanent dipole moment and has a low polarizability per volume (i.e., weak van der Waals interactions), causing many nonvolatile compounds to be insoluble. To effectively use CO2 in a number of potential environmentally responsible processes, surfactants and polymers have to be developed to transport and stabilize insoluble dispersions. It has been found that polymers with low surface tension, and hence low cohesive energy densities, such as * To whom correspondence should be addressed. Fax: +82-51-6252229. E-mail:
[email protected]. † Division of Image and Information Engineering, Pukyong National University. ‡ Division of Chemical Engineering, Pukyong National University. § Kyung Il University.
fluorocarbons, fluoroethers, and siloxanes are most effective as CO2 stabilizers at low to moderate pressures.13,14 Herein, we describe the preparation of a novel semifluorinated CD (CD-F) and its solubility in CO2. We have investigated the complex formation of γ-CD-F and a common double-tail surfactant, sodium di-2-ethylhexylsulfosuccinate (AOT) (Figure 1), in liquid CO2. AOT has a melting point of ca. 170 °C and is not soluble in pure CO2; thus, it is relatively easy to identify complex formation either by differential scaning calorimetry (DSC) analysis or by visual inspection through a high-pressure view-cell window. This observation suggests that γ-CD-F can be utilized as a host molecule to solubilize CO2-insoluble AOT by forming an inclusion complex in CO2, which has very poor solvent character. Another type of surfactant, single-tail Nlauroylsarcosine sodium salt (Figure 1), was also examined to form a complex with γ-CD-F in CO2. 2. Experimental Section 2.1. Materials. γ-CD (Junsei Chemical Co., Osaka, Japan) was dried for 24 h at 60 °C before use. Heptafluorobutyric acid (Aldrich, Milwaukee, WI), AOT (Aldrich, Milwaukee, WI), and N-lauroylsarcosine sodium salt (Aldrich, Milwaukee, WI) were used as received. Semifluorinated γ-CD (γ-CD-F) was prepared by reacting γ-CD with a 6-fold molar excess of heptafluorobutyric acid at 110 °C for 9 h. After the reaction was completed, unreacted heptafluorobutylic acid was removed by vacuum evaporation. The resulting product was washed with benzene and water several times to remove trace heptafluorobutylic acid and unreacted γ-CD, respectively, and dried in a vacuum. 2.2. Complex Formation of γ-CD-F and AOT in Liquid CO2. For the preparation of a complex between γ-CD-F and AOT in CO2, 73.5 mg (0.026 mmol) of γ-CD-F powder and 5 mg (0.011 mmol) of AOT were placed in a 3.5-mL highpressure view cell equipped with a magnetic stir bar and sapphire windows. Carbon dioxide (Daeyoung Co., 99.99%, Pusan, Korea) was charged into the cell using an automated syringe pump (ISCO 260D, ISCO Inc., Lincoln, NE) until the pressure reached 345 bar at room temperature (ca. 21 °C). After 18 h of stirring, the CO2 was slowly vented off, and the powders were collected. The complex between γ-CD-F and N-lauroylsarcosine sodium salt was prepared in a similar manner.
10.1021/ie050719l CCC: $33.50 © 2006 American Chemical Society Published on Web 02/01/2006
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Figure 1. Molecular structures of AOT and N-lauroylsarcosine sodium salt.
Figure 2. Synthesis of semifluorinated γ-cyclodextrin.
Figure 3.
1H
NMR specta of (a) γ-CD-F and (b) γ-CD.
Table 1. Solubilities of γ-CD and γ-CD-F in Various Solventsa
γ-CD γ-CD-F a
water
DMSO
methanol
trifluorotoluene
CO2
O X
O O
X O
X O
X O
O, soluble; ∆, slightly soluble; X, insoluble.
2.3. Characterization. 1H NMR spectra were recorded using a JNM-ECP 400 spectrometer (JEOL, Tokyo, Japan). The structure of γ-CD-F was confirmed by 1H NMR spectroscopy in DMSO-d6 solution. Differential scanning calorimetry (DSC) data were obtained with a DSC-60 thermal analysis system (Shimadzu Corporation, Kyoto, Japan). The cloud point was determined by simple visual inspection using a 28-mL stainless steel variable-volume view cell equipped with a sapphire window that permitted visual observation of phase behavior.15 The cell was immersed in a water bath in which the temperature was controlled by a thermostatic head (LABTECH, ISCO Inc., Lincoln, NE). A piston inside the view cell was used to vary the volume of sample at constant weight fraction and to vary the pressure independently of the temperature. 3. Results and Discussion γ-CD-F was successfully synthesized by the selective esterification of the 6-position of γ-CD by reacting it with excess of heptafluorobutyric acid (Figure 2). Selectivity can be attained by the fact that the primary alcohol of the 6-position has higher reactivity toward fluorinated acids than secondary alcohols of the 2- and 3-positions of the R-D-glucopyranose unit. Almost quantitative conversion at the 6-position was confirmed by 1H NMR analysis (Figure 3). The hydroxyl proton of the 6-position at 4.5 ppm disappeared, and the H-6 protons shifted upfield with two separate peaks upon esterification. Table 1 summarizes the solubility behaviors of γ-CD and γ-CD-F in various solvents.
Figure 4. Cloud-point profiles of γ-CD-F in CO2.
Whereas γ-CD is soluble in water and DMSO, γ-CD-F is not soluble in water, but is soluble in common organic solvents as well as fluorinated solvents. Upon the esterification of the OH groups at the 6-position among three OH positions, the compound was insoluble in water because of the very high lipophilicity of CF2CF2CF3 groups. In particular, γ-CD-F has an apparent solubility in liquid carbon dioxide. The solubility of γ-CD-F in dense CO2 was studied in the temperature range of 35-60 °C and at pressures up to 250 bar. A given amount of γ-CD-F was placed in the view cell, and CO2 was then added. The cell was then heated to the specified temperature, and more CO2 was charged while the contents were mixed using a magnetic stirrer. The pressure was then increased by moving the piston forward until all of the γ-CD-F was dissolved, giving an optically clear, one-phase, homogeneous solution. The cloud point was defined as the lowest CO2 pressure at which the compound became completely dissolved. The optically transparent one-phase region is above each curve in the plot in Figure 4. The results in Figure 4 indicate that γ-CD-F is soluble in CO2 in these conditions. For example, 1 wt % of γ-CD-F is soluble above 179 bar at 40 °C. It is well-known that fluoroalkyls are highly CO2-philic, so the solubility of CD in CO2 was obtained by the introduction of fluoroalkyl esters at one of rims. This implies that γ-CD-F can be utilized as a host molecule to form inclusion complexes in CO2, which has very poor solvent character. The inclusion reaction of γ-CD-F with AOT, a noted doublechain surfactant, was attempted in CO2. The surfactant AOT is practically insoluble in carbon dioxide and exists in solution as a waxy solid up to high pressures (25-100 °C and 400 bar).16 A small quantity of AOT was weighed onto the sapphire
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Figure 5. Dissolution of AOT in liquid CO2 at 22 °C and 345 bar: photographs taken (a) after 3 min with γ-CD-F, (b) after 60 min with γ-CD-F, and (c) after 12 h without γ-CD-F.
Figure 6. DSC curves for (a) AOT, (b) γ-CD-F, (c) physical mixture of AOT and γ-CD-F, and (d) complex of AOT and γ-CD-F in liquid CO2.
window, a 2-fold molar excess of γ-CD-F was placed in the high-pressure cell, and the cell was assembled. Upon addition of CO2, γ-CD-F dissolved rapidly, forming a transparent CO2 phase. The AOT on the sapphire window became a waxy solid in 2 min (Figure 5a). The AOT disappeared with time and dissolved completely in 1 h (Figure 5b). For comparison, the experiment was conducted without γ-CD-F in CO2 under the same conditions. The waxy shape of AOT on the sapphire window did not change after 24 h (Figure 5c). Thus, it is obvious that AOT can be dissolved in CO2 with the help of γ-CD-F. When the cell was depressurized, the complex was deposited on the interior of the cell as a yellowish film. To better understand the formation of a complex between AOT and γ-CD-F in CO2, the complex was subjected to DSC analysis. Samples were heated from 20 to 300 °C at a rate of 10 °C min-1 under nitrogen. In Figure 6, typical DSC curves of AOT, γ-CDF, and their physical mixture and complex are presented. AOT is very hygroscopic, so it was freeze-dried thoroughly before use. The endothermic peak at 160-180 °C for AOT (Figure 6a) is due to the melting of AOT. This kind of melting peak was also observed in the DSC curves for the sample physically mixed at the same ratio of γ-CD-F and AOT (Figure 6c). However, the complex from CO2 did not show an endothermic peak corresponding to the melting of AOT (Figure 6d). This behavior indicates that AOT can form a complex with γ-CD-F by inclusion at the molecular level. X-ray diffraction analysis was performed using an X’Pert-MPD system (Philips, Eindhoven, The Netherlands). All of the peaks of γ-CD-F, AOT, and the complex in the XRD pattern were broad, indicating an amorphous state. The profiles for the complex, the physical mixture, and γ-CD-F were not distinguishable from each other.
Figure 7. DSC curves for (a) N-lauroylsarcosine sodium salt, (b) γ-CD-F, (c) physical mixture of N-lauroylsarcosine sodium salt and γ-CD-F, and (d) complex of N-lauroylsarcosine sodium salt and γ-CD-F in liquid CO2.
Another kind of surfactant, single-tail N-lauroylsarcosine sodium salt, was also examined to form a complex with γ-CD-F in CO2. In contrast to AOT, N-lauroylsarcosine sodium salt was soluble in pure CO2. The mixture of N-lauroylsarcosine sodium salt and γ-CD-F became homogeneous as soon as CO2 was introduced into the cell. After 18 h of stirring, the CO2 was slowly vented off, and the complex was obtained. The structure of the complex of γ-CD-F and N-lauroylsarcosine sodium salt was verified using thin-layer chromatography. The Rf values for the complex [Rf(methanol) ) 0.64], the host γ-CD-F [Rf(methanol) ) 0.70], and the guest N-lauroylsarcosine sodium salt [Rf(methanol) ) 0.83] were significantly different each other. The DSC graphs of the complex also showed similar trend to AOT, where the characteristic endothermic peak of Nlauroylsarcosine sodium salt at 145 °C was not present for the complex whereas it was apparent for the physical mixture (see Figure 7). The above results suggest that, with selective side-chain modification of CDs at smaller rims using fluoroalkyl acids, novel CO2-soluble CDs can be prepared, and water-soluble surfactants can form complexes with γ-CD-F in liquid CO2. 4. Conclusions γ-Cyclodextrins functionalized at the 6-position with perfluoro butanoate groups were prepared through the esterification reaction between γ-cyclodextrin and perfluorobutanoic acid. γ-CD-F exhibited hydrophobicity and was soluble in fluorinated solvents and densified carbon dioxide. γ-CD-F could form a complex with the water-soluble but CO2-insoluble surfactant
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AOT at the molecular level and carried the AOT into the liquid CO2 phase. The single-chain surfactant N-lauroylsarcosine sodium salt also produced a complex with γ-CD-F, which was characterized by TLC and DSC analysis. Acknowledgment This research was supported by the Program for the Training of Graduate Students in Regional Innovation, which was conducted by the Ministry of Commerce Industry and Energy of the Korean Government. This work was also supported by the Ministry of Environment as “The Eco-technopia 21 Project” Literature Cited (1) Szejtli, J. Introduction and General Overview of Cyclodextrin Chemistry. Chem. ReV. 1998, 98, 1743. (2) Van Hees, T.; Piel, G.; Evrard, B.; Otte, X.; Thunus, L.; Delattre, L. Application of supercritical carbon dioxide for the preparation of a piroxicam-cyclodextrin inclusion compound. Pharm. Res. 1999, 16, 1865. (3) Uekama, K.; Hirayama, F.; Irie, T. Cyclodextrin Drug Carrier Systems. Chem. ReV. 1998, 98, 2045. (4) Chmurski, K.; Coleman, A. W.; Jurczak, J. Direct Synthesis of Amphiphilic R-, β-, and gamma-Cyclodextrins J. Carbohydr. Chem. 1996, 15, 787. (5) Eddaoudi, M.; Baszkin, A.; Parrot-Lopez, H.; Boissonade, M.; Coleman, A. W. Divalent Cation-Cyclodextrin Interactions at the AirWater Interface. A Three-Stage Process. Langmuir 1995, 11, 13. (6) Yabe, A.; Kawabata, Y.; Niino, H.; Tanaka, M.; Ouchi, A.; Takahashi, H.; Tamura, S.; Tagaki, W.; Nakahara, H.; Fukuda, K. CisTrans Isomerization of the Azobenzenes Included as Guests in LangmuirBlodgett Films of Amphiphilic β-Cyclodextrin. Chem. Lett. 1988, 1.
(7) Granger, C. E.; Felix, C. P.; Parrot-Lopez, H. P.; Langlois, B. R.; Fluorine Containing β-Cyclodextrin: A New Class of Amphiphilic Carriers. Tetrahedron Lett. 2000, 41, 9257. (8) DeSimone, J. M.; Maury, E. E.; Menceloglu, Y. Z.; Combes, J. R.; McClain, J. B.; Romack, T. Dispersion Polymerizations in Supercritical Carbon Dioxide. Science 1994, 265, 356. (9) Banks, R. E.; Smart, B. E.; Tatlow, J. C. Organofluorine Chemistry: Principles and Commercial Applications; Plenium Press: New York, 1991. (10) Eckert, C. A.; Knutson, B. L.; Debenedetti, P. G. Supercritical Fluids as Solvents for Chemical and Materials Processing. Nature 1996, 383, 313. (11) Taylor, D. K.; Carbonell, R.; DeSimone, J. M. Opportunities for Pollution Prevention and Energy Efficiency Enabled by the Carbon Dioxide Technology Platform. Annu. ReV. Energy EnViron. 2000, 25, 115. (12) Wells, S. L.; DeSimone, J. CO2 Technology Platform: An Important Tool for Environmental Problem Solving. Angew. Chem. 2001, 40, 518. (13) O’Neill, M. L.; Cao, Q.; Fang, R.; Johnston, K. P.; Wilkinson, S. P.; Smith, C. D.; Kerschner, J. L.; Jureller, S. H. Solubility of Homopolymers and Copolymers in Carbon Dioxide. Ind. Eng. Chem. Res. 1998, 37, 3067. (14) da Rocha, S. R. P.; Dickson, J.; Cho, D.; Rossky, P. J.; Johnston, K. P. Stubby Surfactants for Stabilization of Water and CO2 Emulsions: Trisiloxanes. Langmuir 2003, 19, 3114. (15) Lim, K. T.; Hwang, H. S.; Ryoo, W.; Johnston, K. P. Synthesis of TiO2 Nanoparticles Utilizing Hydrated Reverse Micelles in CO2. Langmuir 2004, 20, 2466. (16) Yee, G. G.; Fulton, J. L.; Smith, R. D. Aggregation of Polyethylene Glycol Dodecyl Ethers in Supercritical Carbon Dioxide and Ethane. Langmuir 1992, 8, 377.
ReceiVed for reView June 16, 2005 ReVised manuscript receiVed October 25, 2005 Accepted December 6, 2005 IE050719L
