Complexes between â-Cyclodextrin and Aliphatic Guests asNew Noncovalent Amphiphiles: Formation and

Physicochemical StudiesTzvetana Bojinova,† Yannick Coppel,‡ Nancy Lauth-de Viguerie,*,† Alain Milius,§

Isabelle Rico-Lattes,† and Armand Lattes†

Laboratoire IMRCP, UMR CNRS 5623, Universite Paul Sabatier, 118 route de Narbonne,31062 Toulouse Cedex 04, France, Laboratoire de Chimie de Coordination, UPR CNRS 8241,

205 route de Narbonne, 31077 Toulouse Cedex 04, France, and SEPPIC, 75 Quai d’Orsay,75321 Paris Cedex 07, France

Received January 27, 2003. In Final Form: March 31, 2003

The aim of this work was to develop new sugar nonionic surfactants from raw materials of plant origin.These nonionic surfactants are based on the noncovalent association between cyclodextrins (CDs) and fattyalcohols or fatty acids. We describe here (i) the preparation of various complexes between â-cyclodextrin(â-CD) and fatty alcohols or fatty acids, (ii) the evaluation of the surfactive properties of the complexes,and (iii) the structure of one of them which presents interesting surfactive properties. Among the preparedcomplexes, the â-CD/alcohol complexes present high surface tension efficiencies compared with â-CD/acidcomplexes. The surfactive properties of the â-CD/alcohol complexes are influenced by the length of thehydrocarbon chain and reach an excellent efficiency for guests having 10-12 carbon atoms. For the complexbetween â-cyclodextrin and undec-10-en-1-ol, the inclusion mode in aqueous solution was described bynuclear magnetic resonance techniques. The results showed a 1:1 stoichiometry and a dynamic processexchanging the two possible orientations of the guest relative to the â-CD.

IntroductionNonionic surfactants based on sugars have many

prospects and actual applications in both chemistry andbiochemistry.1-4 In addition to performance, there is agrowing demand for surfactants which are also environ-mentally friendly and produced from renewable resources.In particular, alkylpolyglucosides (APGs) are being in-creasingly developed,5-9 as in addition they have gooddermatological compatibility and biodegradability. Al-though effective at low temperatures, their developmentis nevertheless limited by their hydrophilic/lipophilicbalance (HLB) which does not reach values as high asthose obtained with ethylene oxide derivatives.

The aim of this work was to develop new sugar-basednonionic surfactant derivatives from cyclodextrins (CDs).We used the ability of CDs to form inclusion complex-es10,11 with a variety of guest molecules to obtain newnoncovalent surfactants in which the nonionic polar-headis constituted by the cyclodextrin (Figure 1).

For the preparation of complexes,12 fatty alcohols andfatty carboxylic acids with different lengths were retainedas guests and different cyclodextrins, three native (R-, â-,and γ-) and two modified cyclodextrins (HP-CD and Me-CD), as hosts. We present here the results concerning theâ-CD complexes: (i) their preparation and the proof oftheir existence, (ii) their surfactant activity, and (iii) acomplete study of the structure of one of these newnoncovalent amphiphilic compounds by the techniques ofNMR titration13,14 and rotating-frame Overhauser effectspectroscopy (ROESY) experiments.15,16

* To whom correspondence should be addressed. Phone: 00.33.5.61.55.61.35. Fax: 00.33.5.61.55.81.55. E-mail: viguerie@chimie.ups-tlse.fr.

† Laboratoire IMRCP, UMR CNRS 5623, Universite Paul Sa-batier.

‡ Laboratoire de Chimie de Coordination, UPR CNRS 8241.§ SEPPIC.(1) Rico-Lattes, I.; Lattes, A. Colloids Surf., A 1997, 123-124, 37-

18.(2) Blanzat, M.; Massip, S.; Speziale, V.; Perez, E.; Rico-Lattes, I.

Langmuir 2001, 17, 3512-3514.(3) Houlmont, J.-P.; Vercruysse, K.; Perez, E.; Rico-Lattes, I.; Bordat,

P.; Treilhou, M. Int. J. Cosmet. Sci. 2001, 23, 363-368.(4) Blanzat, M.; Perez, E.; Rico, I.; Lattes, A.; Gulik, A. Chem.

Commun. 2003, 244-245 and references cited therein.(5) Andree, H.; Middelhauve, B. Tenside, Surfactants, Deterg. 1991,

28, 413-418.(6) Andree, H.; Tesmann, H. SOFW J. 1995, 121, 598-611.(7) Busch, P.; Hensen, H.; Tesmann, H. Tenside, Surfactants, Deterg.

1993, 30, 116-121.(8) Perez, E.; Rico-Lattes, I.; Lattes, A.; Godefroy, L. French Patent

No. 9708461, June 20, 1997, STEPAN.(9) Hill, K.; Von Rybinski, W.; Stoll, G. Alkyl polyglucosides:

technology, properties and applications; VCH: New York, 1997.

(10) Wenz, G. Angew. Chem., Int. Ed. Engl. 1994, 33, 803-822.(11) Rekharsky, M. V.; Inoue, Y. Chem. Rev. 1998, 98, 1875-1917.(12) Milius, A.; Trouve, G.; Boiteux, J.-P.; Bojinova, T.; de Viguerie,

N.; Poinsot, V.; Rico-Lattes, I. French Patent No. 0107499, June 8,2001; extended PCT/FR02/01876, June 4, 2002, Air-Liquide-SEPPIC.

(13) Connors, K. Binding Constants. The Measurement of MolecularComplex Stability; John Wiley & Sons: New York, 1987.

(14) Fielding, L. Tetrahedron 2000, 56, 6151-6170.(15) Botsi, A.; Yannakopoulou, K.; Perly, B.; Hadjoudis, E. J. Org.

Chem. 1995, 60, 4017-4023.(16) Botsi, A.; Yannakopoulou, K.; Hadjoudis, E. Carbohydr. Res.

1993, 241, 37-46.

Figure 1. Covalent and noncovalent amphiphiles.

5233Langmuir 2003, 19, 5233-5239

10.1021/la030030q CCC: $25.00 © 2003 American Chemical SocietyPublished on Web 05/20/2003

Experimental Section

â-Cyclodextrin (â-CD) (purity, 99%) was purchased fromRoquette, France, and was used as received. The water content,determined by thermogravimetric analysis and the Karl Fischertechniques, was â-CD‚9.7H2O. Alcohols and acids (octan-1-ol,decan-1-ol, undec-10-en-1-ol, dodecan-1-ol, hexadecan-1-ol,docosan-1-ol, and dodecan-1-oic, tetradecan-1-oic, hexadecan-1-oic, octadecan-1-oic, and docosan-1-oic acids) (98% or 99%) werepurchased from Aldrich Chemical Co. and were used withoutfurther purification. Deuterium oxide (99.6% D2O) was manu-factured by Euriso-top (CEA Saclay, France). The water usedwas ultrapure, obtained with a Pur1te Select Analyst HP (SELI,France) apparatus working at a resistivity of 16 MΩ‚cm.

Complex Preparation. The inclusion complexes were pre-pared using the suspension method. The general method isindicated below.

General Method. An aqueous equimolecular suspension ofâ-CD(∼600-700 g‚L-1) and guest was heated at 55 °C under mech-anical stirring (300 t‚min-1) for 1-18 h. The resulting suspensionwas freeze-dried, leading to the complex as a white powder.

Differential Scanning Calorimetry (DSC) Measure-ments. The thermograms of the various products were recordedon a differential scanning calorimeter (model PYRIS 1DSC,Perkin-Elmer). About 15 mg of sample was placed in a pinholedaluminum sample pan (50 µL, Perkin-Elmer B 0143017 model)and heated at a rate of 10 °C/min in the range of -30 to 200 °Cunder a stream of nitrogen. For undec-10-en-1-ol, which is liquidat ambient temperature, the sample pan was stored at -18 °Cfor 3 days before analysis.

Determination of the Free Guest Quantity in the PreparedSamples. For the calibration curve, physical mixtures (totalweight, 1 g) were prepared by simple homogenization of theweighed guest and â-CD with various mass percentages of guestof 1-100% [(mguest/mmixture) × 100]. Then about 15 mg of samplewas analyzed.

The melting of free guest present in the sample was associatedwith an endothermal effect characterized by a Tonset (°C) and afusion enthalpy in joules per gram of sample. From the measuredvalue of ∆Hf of the guest and from the calibration curve, theweight of noncomplexed guest in each sample was calculated.

Tensiometry. The measurements were made with a droptensiometer (KRUSS GmbH) model DSA 10-Mk2 at 25 °C andrepeated on a Prolabo (tensiomat no. 3) apparatus using thestirrup detachment method.

Minimum Surface Tensions (γmin). Aqueous solutions of eachcomplex at its saturated concentration were prepared at 25 °Cusing the solid quantitative complexes prepared as describedabove. Saturated aqueous solutions of guest and â-CD were alsoprepared at 25 °C. The surface tensions (γmin) of these saturatedsolutions were measured at 25 °C.

1H NMR Analysis. NMR measurements were recorded at318 K in D2O on a Bruker AMX400 spectrometer. All chemicalshifts for 1H are relative to TMS using 1H (residual) chemicalshifts of the solvent as a secondary standard. Relaxation periodsof 30 s were used to obtain reliable integration data in 1H spectra.

1H NMR Titration Experiments. A stock solution of â-CD (10-2

mol‚L-1) in D2O was prepared. It was distributed into severalaliquots, and increasing quantities of alcohol were added to givehost/guest molar ratios of 1:0.2, 1:0.4, 1:0.6, 1:0.8, 1:1, 1:2, 1:3,and 1:5. The suspensions obtained were vigorously stirred atroom temperature for 1 min and stored at 318 K for 2 days.

1H 2D-ROESY. Two-dimensional 1H-1H T-ROESY experi-ments were acquired with mixing times of 200, 300, and 500 ms.Twenty-four scans for each of the 256 t1 values were collectedwith 4096 points. The spectra were obtained from suspensionsof CD/undec-10-en-1-ol in a 1:2 ratio in D2O. A 1D selectiveGROESY experiment17 with a mixing time of 300 ms wasperformed with 1600 transients. A 1D selective total correlationspectroscopy (TOCSY)-ROESY experiment18 with TOCSY andROESY mixing times of 60 and 300 ms was obtained with 6400transients.

Selective pulses used were Gaussian truncated at the 1% levelwith durations as short as possible. Gradients were sine shapedin all experiments with durations of 1 ms.

Results and DiscussionComplex Preparation. The inclusion complexes were

prepared from equimolecular aqueous suspensions of â-CDand alcohol or carboxylic acids using the usual suspensionmethod.12-19 The alcohols chosen were octan-1-ol, decan-1-ol, undec-10-en-1-ol, dodecan-1-ol, hexadecan-1-ol, anddocosan-1-ol, and the carboxylic acids were dodecan-1-oic, tetradecan-1-oic,hexadecan-1-oic, octadecan-1-oic, anddocosan-1-oic acids.

To verify if complexation takes place, DSC was used.DSC allows comparison of the thermal behavior for thecomplexes and for the pure components (host and guest)and enables the formation of complex to be checked byvisualizing the disappearance of the characteristic peakof the guest.20 The DSC traces of each pure guest showonly the melting peak of the substance characterized bya Tonset (°C) and a fusion enthalpy in joules per gram ofsample (Table 1). Pure â-CD has no defined melting peaksbut a thermal rise near 300 °C attributed to its decom-position and a broad thermal rise between 120 and 160°C corresponding to its dehydration.21 The DSC curves(not recorded up to 200 °C) of â-CD-guest physicalmixtures show two endothermic peaks, one correspondingto the fusion of the guest and the other corresponding todehydration from â-CD. Figure 2 depicts the thermogramsof â-CD (1), of pure undec-10-en-1-ol (2), the physicalmixture undec-10-en-1-ol/â-CD 1:6 (3), partially complexedundec-10en-1-ol (4), and a 1:1 complex (5). The disap-pearance of the DSC peak corresponding to the fusion ofthe guest indicates the formation of new species which isevidence for complexation leading to a solid compound inwhich the guest is totally complexed (trace 5). In trace 4,the area of the fusion peak of the guest (peak A)corresponds to the fusion enthalpy in joules per gram ofsample. From this value, which is proportional to the massof guest present in the physical mixture (Figure 3), theamount of free guest can be determined from the area ∆Hfof this peak compared with that of the melting peak of thepure guest using the relation above:

The different inclusion complexes prepared were obtainedwith 0-5% (w/w) of free guest.12 The stirring time

(17) Dalvit, C. J. Magn. Reson., Ser. A 1995, 113, 120-123.(18) Gradwell, M. J.; Kogelberg, H.; Frenkiel, T. A. J. Magn. Reson.

1997, 124, 267-270.

(19) Szente, L.; Szejtli, J.; Szeman, J.; Kato, L. J. Inclusion Phenom.Mol. Recognit. Chem. 1993, 16, 339.

(20) Preiss, A.; Mehnert, W.; Fromming, K.-H. J. Inclusion Phenom.Mol. Recognit. Chem. 1994, 18, 331.

(21) Szejtli, J. Cyclodextrins. In Comprehensive SupramolecularChemistry; Atwood, J. L., Davies, J. E. D., MacNicol, D. D.; Vogtle, F.,Eds.; Pergamon: Oxford, 1996; Vol. 3, pp 189-205.

Table 1. Fusion Temperatures (Tf in °C) and FusionEnthalpies (∆Hf) of the Different Guests

guest molecule Tf (°C) ∆H (J/g)

CH3(CH2)11OH 26.2 203 ( 0.09CH3(CH2)15OH 51.4 236.0 ( 0.03CH3(CH2)17OH 61.9 253.0 ( 0.15CH3(CH2)21OH 73.0 259.5 ( 0.08CH2dCH(CH2)9OH -3.4 178.0 ( 0.05CH3(CH2)10COOH 47.0 175.7 ( 0.09CH3(CH2)12COOH 56.4 206.2 ( 0.09CH3(CH2)14COOH 64.1 205.4 ( 0.05CH3(CH2)16COOH 71.0 211.2 ( 0.09

%MInot-complexed )∆HMIfree

∆HMIpure

× 100

5234 Langmuir, Vol. 19, No. 13, 2003 Bojinova et al.

necessary for the quantitative complexation increasedwith the length of the hydrocarbon chain.

Surfactant Properties of the Complexes. To evalu-ate the surfactive properties of the complexes prepared,the minimum surface tensions (γmin) of aqueous solutionsof each complex were measured at 25 °C and comparedwith those determined for aqueous solutions of thecorresponding guest alone (Figure 4). The surface tensions

of saturatedaqueoussolutionsofguestand â-CDmeasuredat 25 °C are given in Table 2. In all cases, these valueswere determined from aqueous solutions of complex orguest obtained at their saturated concentration at 25 °C.As shown in Figure 4, the best surface tension efficienciesare obtained for â-CD/alcohol complexes.

The interfacial tensions of saturated solutions of guestalone increased with the length of the hydrocarbon chain

Figure 2. Schematic typical DSC curves recorded between -30 and 200 °C. (1) Pure â-CD; dehydration of â-CD (peak B). (2) Pureundec-10-en-1-ol (peak A: Tf ) -3.4 °C and ∆H ) 169.3 J/g). (3) Physical mixture of 50% undec-10-en-1-ol and 50% â-CD (w/w)(peak A: Tf guest ) -3.4 °C and ∆H ) 85 J/g). (4) Undec-10-en-1-ol partially complexed (peak A: Tf guest ) -3.4 °C and ∆H ) 5.2J/g). (5) Complex; disappearance of peak A.

Figure 3. Fusion enthalpy (joules/gram) corresponding to themelting peak of the guest (undec-10-en-1-ol) versus the weightpercentage of guest in various â-CD-guest physical mixtures.

Figure 4. Minimum surface tensions (γmin) of aqueous solutions of each complex or corresponding guest obtained at their saturatedconcentration at 25 °C.

Table 2. Surface Tensions of Aqueous SaturatedSolutions of CDs and Guests at 25 °C

guest moleculesaturated concentration inwater (mol‚L-1) at 25 °C γ (mN‚m-1)

â-CD 1.4 × 10-2 72octan-1-ol 3.20 × 10-3 30decan-1-ol 2.5 × 10-4 36undec-10-en-1-ol 7.2 × 10-5 50dodecan-1-ol 9.1 × 10-6 62octadecan-1-ol <10-6 72hexadecan-1-ol <10-6 72dodecanoic acid 3.1 × 10-4 59tetradecanoic acid 4.6 × 10-6 72hexadecanoic acid 2 × 10-6 72octadecanoic acid 2 × 10-6 72

â-Cyclodextrin Complexes Langmuir, Vol. 19, No. 13, 2003 5235

(Table 2). The interfacial tensions measured for shorteralcohols are low due to their greater miscibility with water.For the alcohols having chain lengths from 10 to 12 carbonatoms, we observed an appreciable difference betweenthe surfactive efficiencies of the guest alone and of thecorresponding complexes and also remarkable surfacetension values. For alcohols with longer chains, thecomplexes are no longer sufficiently soluble in water.

This interesting surface activity cannot be due to thealcohol or CD alone because saturated solutions of â-CDand the alcohol considered do not present comparablesurfactive efficiencies. It is possible to determine a criticalaggregation concentration by measuring the variation ofthe surface tension versus log [C] where the concentrationindicated ([C]) was that for the complex considering nodecomplexation occurred. For example, the graphs of γversus log [C] obtained for the studies of the complexesâ-CD/undec-10-en-1-ol and â-CD/dodecan-1-ol give a “criti-cal aggregation concentration” of about 1.9 × 10-4 and 9.1× 10-5 M, respectively (Figure 5).

To understand why these complexes have a remarkablesurface tension efficiency, the study of their structure wasprimordial. The techniques of NMR titration10,11 andROESY experiments15,16 give a lot of information.

We chose to present here a complete study of thestructural analysis of the complex between undec-10-en-1-ol and â-CD. We opted for undec-10-en-1-ol for tworeasons: (i) it is used in various industrial applicationssuch as beauty care, laundry care, soap, and householdcleaners; (ii) the functional groups at each extremity ofthis alcohol, for example, the hydroxyl group on C1 andthe double bond on C10, allowed us to explore whichfunction takes part in the complexation and providedinformation on the structure of this noncovalent surfac-tant.

1H NMR Studies. 1H NMR is the technique most widelyused to obtain information about inclusion modes andgeometries. It is very useful to provide evidence for theformation of inclusion complexes in solution, since thiswill affect the proton environment in both the host andguest and will hence be reflected by chemical shiftvariations of protons from both species.

Variation of 1H Signals upon Complexation. The inclu-sion of a guest molecule in a CD generally provokes achange in the environment of only the protons inside thecavity (Figure 6). Therefore, in the present case, com-parison of the 1H NMR spectra of the â-CD mixed with theundec-10-en-1-ol dissolved in D2O (with various â-CD/alcohol ratios) and those of free â-CD under the sameconditions provides clear answers regarding inclusion

(Figure 7, Table 3). Specifically, the internal H-3 and H-5protons are more sensitive (significant upfield shifts) tothe complexation effect than the H-1, H-2, or H-4 protonslocated on the outside of the host cavity. The signal of theprotons H-6ab is also shifted upfield but less than for theH-5 and H-3 protons. This indicates that guest moleculesonly interact with the functional groups of the cavity ofthe â-CD moiety. The shifts of these protons to high fielddisplay increasing shielding during complex formation,as a result of the release of the water molecules from thecavity which are replaced by the apolar alkyl chain of theguest.22

Stoichiometry of the Complex. Measurements of chemi-cal shift changes as a function of guest and host concen-trations (so-called NMR titrations) were performed todetermine the stoichiometry of the â-CD/undecenol com-plex. This method consists of titrating a â-CD solution inD2O with the neat guest and plotting the resulting ∆δ’sversus the molar host/guest ratio.23,24 Upon guest addition,progressive chemical shift variations were observed forthe resonance of each compound, indicating a fast ex-change process at the NMR time scale, that is, peaks aredetected at an intermediate chemical shift between freeand bound compound resonances.

For the protons which showed the most significantvariations of chemical shift, on one hand protons H-3 andH-5 of â-CD and on the other hand the methylene protonson C3 to C7 of the guest ((CH2)5), a plot of ∆δ versus thehost/guest ratio was drawn. ∆δ corresponds to thedifference in resonance between the free and associatedcompound. The plots presented in Figure 8 reach a plateauat a 1:1 host/guest ratio, indicating that the complexformed has a 1:1 stoichiometry and that no other complexis present in aqueous solution. In addition, for mixturesin molar ratios from 1:1 to 1:5, the integration of the signalsof the host and the guest shows a ratio of 1:1 in the complex.

Three phases were present in the NMR sample: (i) theexcess alcohol as an oil at the water-air interface, (ii) the1:1 complex and the free CD in the aqueous solution, and(iii) a white precipitate which is the complex. These three-phase conditions were chosen to maintain the complexsurfactant activity. To determine the composition of theprecipitate, it was isolated and analyzed by 1H NMR inDMSO-d6 (a solvent that dissolves both the host and guest).The spectra obtained showed the characteristic signals ofthe two molecules. Upon integration of the two signals,the molar ratio was found to be 1:1. Therefore, a singlecomplex with a stoichiometry of 1:1 was obtained, andthis stoichiometry was confirmed by fast atom bombard-ment mass spectrometry (MS-FAB) and electrosprayionization (ESI).12

(22) Wilson, L. D.; Siddall, S. R.; Verrall, R. E. Can. J. Chem. 1997,75, 927-933.

(23) Carofiglio, T.; Fornasier, R.; Jicsinszky, L.; Saielli, G.; Tonellato,U.; Vetta, R. Eur. J. Org. Chem. 2002, 1191-1196.

(24) Gonzalez-Gaitano, G.; Guerrero-Martınez, A.; Ortega, F.; Tar-dajos, G. Langmuir 2001, 17, 1392-1398.

Figure 5. Variation of the surface tension (γ) in water versusthe logarithm of the calculated concentration of the complexconsidering no decomplexation has occurred.

Figure 6. â-Cyclodextrin and the inside/outside orientation ofthe protons.

5236 Langmuir, Vol. 19, No. 13, 2003 Bojinova et al.

Evidence of the significant contribution of hydrophobicinteractions to the formation of the complexes was pro-vided by the fact that complexation did not occur in sol-vents other than D2O (e.g., it did not occur in DMSO-d6).

The K values are usually determined from nonlinearleast-squares fitting of the shift changes. But in the currentwork, the presence of three phases (oil, aqueous solution,and solid) caused too many equilibria and thus too manyparameters to determine the K value with precision.

However, the remarkable upfield shifts of the internalprotons observed upon complexation (∆δmax(H-5) ) 0.106ppm and ∆δmax(H-3) ) 0.058 ppm, ∆δmax(H-6ab) ) 0.02ppm) could suggest a relatively high association constant15

(Figure 8).The results of these studies offer information regarding

the stoichiometry of the complex but provide poor infor-mation about the orientation of undecenol in the cavityof the â-CD. So, we used 2D rotating-frame 1H-1H nuclearOverhauser effect spectroscopy (2D ROESY), which isconsidered to be a reliable method for exploring theconformations of cyclodextrin/guest complexes.25

ROESY. The 2D ROESY spectra (Figure 9) showedcorrelations between the H-3, H-5, and H-6ab protons ofthe â-CD and the protons at the R′ and â′ positions of thedouble bond, the protons â to the hydroxyl group, and alsothe (CH2)5 protons of the undec-10-en-1-ol. There are nocorrelations observed between the protons of the doublebond and the protons of the â-CD. On the 2D ROESYspectra, a correlation was observed for the protons at theâ position relative to the hydroxyl group of the guest withprotons at 3.7-3.8 ppm. In this region, protons H-2 andH-4 of the host and the protons R to the hydroxyl groupof the guest overlap. To check if this correlation for theprotons â to the hydroxyl group of the guest could be dueto ROEs with the H-2 and H-4 protons of the â-CD or onlydue to ROEs with the protons R to the hydroxyl group ofthe guest, we performed a 1D ROESY experiment. It showsROEs between the protons â to the hydroxyl group of theguest and those R to the hydroxyl group of the guest. Italso revealed weak ROEs between the â protons and theH-3, H-5, and H-6ab protons of the host (Figure 10). Wethen did a 1D TOCSY-ROESY experiment starting byTOCSY transfer from the protons â to the hydroxyl groupwith subsequent selection of the R protons relative to thehydroxyl group. The TOCSY-ROESY experiment shows

(25) Neuhausand, D.; Williamson, M. The Nuclear Overhauser Effectin Structural and Conformational Analysis; VCH: New York, 1989.

Figure 7. 1H NMR (400 MHz) spectra in D2O at 318 K of â-cyclodextrin (10-2 mol‚L-1) alone (A) and upon addition of undec-10-en-1-ol for a â-CD/alcohol ratio of 1:1 (B).

Figure 8. Plots of ∆δ versus the host/guest ratio (1H NMR(400 MHz) spectra in D2O at 318 K of â-CD (10-2 mol‚L-1) uponaddition of undec-10-en-1-ol). ∆δ corresponds to the differencein resonance of isochromic protons between the free andassociated compound, for H-3 and H-5 of â-CD, and for fivemethylene groups at positions 3-7 of the hydrocarbon chainof the guest (CH2)5.

Table 3. Chemical Shifts in ppm of the Protons of â-CDAlone and upon Addition of Guest (for a Host/Guest

Ratio of 1:1) from 1H NMR (400 MHz) Analysis in D2O

δ (ppm) of â-CD protons alone in complex 1:1

H-1 5.210 5.209H-2 3.791 3.786H-3 4.096 4.032H-4 3.718 3.741H-5 4.006 3.884H-6 4.012 4.004

â-Cyclodextrin Complexes Langmuir, Vol. 19, No. 13, 2003 5237

only transfer from the protons R to the hydroxyl group tothe protons â and γ to the hydroxyl group of the guest. Itwas concluded that there is no correlation of the guestwith external protons (H-2 and H-4) of the CD. From theseresults, it is suggested that the hydrocarbon chain of theguest is inside the cavity, and the double bond and thehydroxyl group protrude outside. ROESY experimentsindicate spatial proximity for eight of the nine methylenegroups of the chain with the â-CD protons located in thecavity. If the chain adopts a zigzag conformation in thecomplex, that is, with the hydrocarbon chain completelyextended, its calculated length is 10.1 Å. The height ofâ-CD is however about 7.9 Å. So the guest molecule iscertainly in permanent motion in the CD cavity and adoptsa conformation which tends to occupy the whole space ofthe cavity.

Because of the conical shape of the CD, two oppositeorientations for the guest in the complex are possible(Figure 11). The ROE observed for H-3 (at the wider side)and for H-6ab protons (at the narrower side) of thecyclodextrin with the protons R to the double bond (at oneextremity) and with the protons â to the hydroxy group(at the other extremity) of the guest are not compatiblewith a single geometry. The most probable explanationfor these ROE correlations is a dynamic process ofexchange between the two possible orientations of the

guest relative to the CD. This dynamic process is fast onthe 1H NMR time scale at 318 K. Moreover, Figure 11shows that only two or three methylene groups lie outsidethe CD cavity. However, this compound having a shorthydrophobic tail and a large hydrophilic part showsexcellent surfactive properties. Similar results werereported in the literature for covalent amphiphiliccyclodextrins.22-24 Either primary or secondary hydroxylgroups of cyclodextrins selectively substituted by shorthydrophobic parts such as tert-butyldimethylsilyl26 orbenzyl26 or bromo27 substituents gave Langmuir films.Critical micellar concentrations of 2 × 10-7 and 2.8 × 10-2

M in water were found for per-2,3-carboxyethyl-â-CD andfor per-2,3-carboxyhexyl-â-CD, respectively.28

The authors consider that such surfactive propertiesmust be attributed to the following: the presence ofhydroxy groups located on one face of the CD adhering tothe air/water interface; the molecular rigidity of thecylindrical core; the presence of hydrophobic chains.Despite their very short length, quasi-impermeable hy-

(26) Hamelin, B.; Jullien, L.; Laschewsky, A.; Herve du Penhoat, C.Chem.sEur. J. 1999, 5, 546-556.

(27) Nicolis, I.; Coleman, A. W.; Charpin, P.; Villain, F.; Zhang, P.;Ling, C. C.; de Rango, C. J. Am. Chem. Soc. 1993, 115, 11596-11597.

(28) Zhang, P.; Parrot-Lopez, H.; Tchoreloff, P.; Baszkin, A.; Ling,C.-C.; de Rango, C.; Colleman, A. W. J. Phys. Org. Chem. 1992, 5, 518.

Figure 9. 1H-1H 2D ROESY spectrum of the â-CD/undec-10-en-1-ol complex in D2O at 400 MHz and Tm ) 300 ms, at 318 K.

5238 Langmuir, Vol. 19, No. 13, 2003 Bojinova et al.

drophobic layers would be formed by the part locatedoutside the cavity probably lying parallel to the air-waterinterface.

Overall, these properties also explain the surfactiveproperties of the noncovalent amphiphilic cyclodextrinsdescribed here.

ConclusionThe formation and the structure of inclusion complexes

between â-CD and fatty alcohols or fatty acids have beenstudied by different methods. Complexation was verifiedby DSC, and the measurement of minimum surface tensionat their saturated concentration showed that â-CD/alcoholcomplexes gave the best surface tension efficiencies.

The structure of the noncovalent surfactant inclusioncomplex formed in water was studied with undec-10-en-1-ol and â-CD owing to its good surfactant properties andpotential applications. The 1H NMR experiments in D2Oindicated a 1:1 stoichiometry for the complex in solution,and the trends of the chemical shifts suggest a high bindingconstant. The ROESY experiment gave information onthe position of the guest in the CD cavity. There are nodipolar interactions between the ethylenic protons or themethylene protons R to the hydroxy function of undecenol

and the protons of the â-CD. Cross-peaks for the protonsof the other methylene groups and inner protons of â-CD(H-3, H-5, and H-6ab) demonstrate the great involvementof the chain in the complexation process. The functionalgroups at the two extremities of the guest (double bondand the hydroxyl group) lie outside the â-cyclodextrincavity, and a dynamic process of exchange occurs betweenthe two possible orientations of the guest relative to thecyclodextrin. These studies show that the predominantdriving forces in the inclusion mode in aqueous solutionare due to hydrophobic effects. Probably, the extrusion ofthe water molecules from the cavity of the â-CD alsocontributes to the formation of the complex of undec-10-en-1-ol and â-CD. In this 1:1 complex, only a very shortpart of the hydrophobic chain of the guest protrudedoutside of the cavity (at the primary or at the secondaryface of â-CD). It is probably the rigidity of the core complexand the orientation of its hydrophobic part toward theair/water interface which are responsible for the excellentsurfactant activity.

Acknowledgment. We thank SEPPIC (Air-Liquide)and the ADEME for funding this project.

LA030030Q

Figure 10. (A) 1H NMR spectrum of the â-CD/undec-10-en-1-ol complex in D2O at 400 MHz and at 318 K. (B) 1H ROESY withirradiation of the CH2CH2OH (Tm ) 300 ms) and (C) enlargement of part of B.

Figure 11. The two possible orientations of undec-10-en-1-ol in the â-CD cavity.

â-Cyclodextrin Complexes Langmuir, Vol. 19, No. 13, 2003 5239