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Amino Acid Based Cationic Surfactants in Aqueous Solution: Physicochemical Study and Application of Supramolecular Chirality in Ketone Reduction Sangita Roy, Debapratim Das, Antara Dasgupta, Rajendra Narayan Mitra, and Prasanta Kumar Das* Department of Biological Chemistry, Indian Association for the Cultivation of Science, Jadavpur, Kolkata 700 032, India Received June 10, 2005. In Final Form: July 28, 2005 The present study provides a molecular understanding of the origin of the chirality in aqueous micelles and its correlation with the proficiency of stereoselective ketone reduction. The effects of varied headgroup architecture on the surface-active properties as well as on other microstructural parameters were studied and correlated to the structural differences of these naturally occurring amino acid containing surfactants (1-4). Micropolarity sensed by pyrene showed that the micelles prepared using 1-4 are mostly hydrated; particularly large headgroup size surfactant produces more polar environment. A theoretical study was done to quantify the varied spatial dissymmetry for all four surfactants. Asymmetric reduction of prochiral ketones was carried out at the aqueous micellar interface of these chiral amphiphiles by exploiting the supramolecular chirality as evidenced from a circular dichroism study. The enantioselectivity of the reduction process is rationally improved through increase in spatial dissymmetry and steric constraint imposed at the micellar interface by the polar head of surfactants.
Introduction Spurred by the ever growing demand for enantiopure pharmaceuticals,1 agricultural and other specialty chemicals, the current world of chemistry is paying much attention to design alternative routes to synthesize enantiopure products.2 The chemical industries are also under immense pressure to reduce the use of volatile organic solvents and to develop environmentally safe chemical processes. To seek a better alternative, selforganized aggregates are gaining exponential importance due to their potential biocompatibility as well as compartmentalizing ability, which have been utilized in several chemical processes.3,4 Enantioselective transformations in the micellar aggregates have already started to gain importance owing to the possible structural variation in the polar headgroup of basic building blocksurfactants, using naturally occurring chiral synthons.5 A molecular level understanding of the origin of su* To whom correspondence should be addressed. E-mail: bcpkd@ iacs.res.in. (1) Stinson, S. C. Chem. Eng. News 1998, 76, No. 38. (2) Blaser, H. U.; Schmidt, E., Eds.; Asymmetric Catalysis on Industrial Scale; Wiley-VCH: Weinheim, Germany, 2003. (3) (a) Tascioglu, S. Tetrahedron 1996, 52, 11113. (b) Fendler, J. H.; Catalysis. In Micellar and Macromolecular Systems; Academic Press: New York, 1975. (c) Fendler, J. H. Chem. Rev. 1987, 87, 877. (d) Bacaloglu, R.; Bunton, C. A.; Cerichelli, G.; Ortega, F. J. Phys. Chem. 1989, 93, 1490. (e) Bacaloglu, R.; Bunton, C. A.; Ortega, F. J. Phys. Chem. 1989, 93, 1497. (f) Brinchi, L.; Profio, P. D.; Germani, R.; Savelli, G.; Bunton, C. A. Langmuir 1997, 13, 4583. (g) Menger, F. M.; Elrington. A. R. J. Am. Chem. Soc. 1991, 113, 9621. (h) Peresypkin, A. V.; Menger, F. M. Org. Lett. 1999, 1, 1347. (4) (a) Das, D.; Roy, S.; Das, P. K. Org. Lett. 2004, 6, 4133. (b) Bunton, C. A.; Savelli, G. Adv. Phys. Org. Chem. 1986, 22, 213. (5) (a) Andriamanampisoa, R.; Boyer, B.; Lamaty, G.; Roque, J. P. J. Chem. Soc. Chem. Commun. 1986, 597. (b) Heath, J. G.; Arnett, E. M. J. Am. Chem. Soc. 1992, 114, 4500. (c) Shinitzky, M.; Haimovitz, R. J. Am. Chem. Soc. 1993, 115, 12545. (d) Morr, M.; Fortkamp, J.; Ruhe, S. Angew. Chem., Int. Ed. 1997, 36, 2460. (e) Sommerdijk, N. A. J. M.; Buynsters, P. J. J. A.; Akdemir, Geurts, H. D. G.; Pistorius, A. M. A.; Feiters, M. C.; Nolte, R. J. M.; Zwanenburg, B. Chem. Eur. J. 1998, 4, 127. (f) Bella, B. J. S.; Mancini, G.; Langmuir 1999, 15, 8025.
pramolecular chirality in these self-assemblies is steadily increasing.6,7 “Traditionally, a lack of symmetry is considered to be a signature of chirality” as aptly described by Nandi and Vollhardt.6 In the self-assembled structure, the supramolecular chirality can emerge through noncovalent organized packing of molecular components.7 Several attempts were made to employ this manifested chirality in stereoselective transformations8 including the asymmetric reduction of prochiral ketones in chiral aqueous micelles and reverse micelles.9 However, the observed enantioselectivity induced only by the chiral surfactants for the reduction of aryl alkyl ketones using NaBH4 was found to be meager [the enantiomeric excess (ee) was varied from 1.7 to 17.7%].9 This lack of stereoselectivity may originate from (i) improper design of the surfactants as well as (ii) the flexibility of the self-organized aggregates leading to a chiral interface not being rigid enough to provide stable asymmetric complexes.10 Thus, the urge to understand the molecular origin of chirality became essential in deciphering the structural arrangements of self-aggregates. To this end, Nandi and Bagchi put forward a quantitative assessment of the large-scale chirality through the effective pair potential (EPP) calculation.11 (6) Nandi, N.; Vollhardt, D. Chem. Rev. 2003, 103, 4035. (7) (a) Rowan, A. E.; Nolte, R. J. M.; Angew. Chem., Int. Ed. 1998, 37, 63. (b) Lehn, J. M. In Supramolecular Chemistry, Concepts and Perspectives; VCH: Weinheim, Germany, 1995. (c) Nandi, N.; Vollhardt, D. Thin Solid Films 2003, 433, 12. (8) (a) Diego-Castro, M. J.; Hailes, H. C. J. Chem. Soc. Chem. Commun. 1998, 1549. (b) Zhang, Y.; Wu, W. Tetrahedron: Asymmetry 1997, 8, 3575. (c) Zhang, Y.; Wu, W. Tetrahedron: Asymmetry 1997, 8, 2723. (d) Wu, W.; Zhang, Y, Tetrahedron: Asymmetry 1998, 9, 1441. (e) Diego-Castro, M. J.; Hailes, H. C.; Lawrence, M. J. J. Colloid Interface Sci. 2000, 234, 122. (9) (a) Goldberg, S. I.; Baba, N.; Green, R. L.; Pandiar, R.; Stowers, J. J. Am. Chem. Soc. 1978, 100, 6768. (b) Zhang, Y. M.; Fan, W.; Lu, P.; Wang, W. Synth. Commun. 1988, 18, 1495. (c) Zhang, Y. M.; Sun, P. Tetrahedron: Asymmetry 1996, 7, 3055. (10) Schmitzer, A.; Perez, E.; Rico-Lattes, I.; Lattes, A. Tetrahedron Lett. 1999, 40, 2947. (11) (a) Nandi, N.; Bagchi, B. J. Am. Chem. Soc. 1996, 118, 11208. (b) Nandi, N.; Bagchi, B. J. Phys. Chem. A 1997, 101, 1343.
10.1021/la051548s CCC: $30.25 © 2005 American Chemical Society Published on Web 09/30/2005
Amino Acid Based Cationic Surfactants Chart 1
Langmuir, Vol. 21, No. 23, 2005 10399 Table 1. Critical Micellar Concentration (cmc), Surface Area per Headgroup (Amin), and Micropolarity Values (I1/I3) for Surfactants (1-4) surfactant 1 2 3 4
On the basis of this approach, rational molecular designing of chiral surfactants deserves serious investigation as this offers excellent opportunity for tailoring their aggregation behavior, physicochemical properties,12 and its application in stereoselective processes. Herein, we have synthesized four amino acid based chiral surfactants (1-4, Chart 1) where the molecular chirality has been tuned efficiently by changing the headgroup geometry of the surfactants. EPP calculation for all four surfactants (1-4) delineates significant alteration in spatial dissymmetry arising out of chiral intermolecular interactions in the close packed aggregates. The structural modification of 1-4 also could lead to changes in aggregate morphology by means of electrostatic interaction, which is reflected in the varying extent of induced supramolecular chirality as evidenced from their circular dichroism (CD) spectra. Such chirality was efficiently employed in stereoselective ketone reduction where the observed ee (41%) in aqueous micelle of 3 is the highest ever found in any micelle mediated ketone reduction. In the present paper, we tried to establish the structurefunction relationship between the supramolecular chirality and the efficiency of stereoselective ketone reduction. Experimental Section Materials. Amberlyst A-26 chloride ion-exchange resin was obtained from BDH, U.K. High performance liquid chromatography (HPLC) grade solvents were purchased from Qualigens and SpectroChem, India. Silica gel of 60-120 mesh from SRL, India, was used for the column chromatography, and thin-layer chromatography was performed on Merck precoated silica gel 60-F254 plates. All other reagents and solvents were purchased from SRL, India. 1H NMR spectra were recorded on an Avance 300 MHz (BRUKER) spectrometer. Mass spectrometric data were acquired by electron spray ionization (ESI) technique using 2570 eV in a Q-tof-Micro Quadruple mass spectrophotometer, Micromass. Optical rotations were measured in Perkin-Elmer LC 341 model polarimeter. Fluorescence spectra were recorded with a Perkin-Elmer LS55 luminescence spectrometer. Circular dichroism (CD) spectra were recorded in a Jasco J-600C spectropolarimeter. HPLC was performed using a Shimadzu LC-10 AT series liquid chromatograph. Identities of the reduced alcohols were confirmed with the pure alcohols (procured from Aldrich Chemical Co. or synthesized). Methods. Syntheses of Surfactants (Chart 1, 1-4). Bocprotected L-amino acids (10 mmol) were coupled with nhexadecylamine (11 mmol) using N,N-dicyclohexylcarbodiimide (DCC, 11 mmol) as the coupling reagent in the presence of 4-N,N(dimethylamino)pyridine (DMAP, 11 mmol). Deprotections of Bocgroups were carried out using trifluoroacetic acid (TFA, 4 equivalent) in dry DCM. After 2 h of stirring, solvents were removed on a rotary evaporator and the mixture was taken in ethyl acetate. The ethyl acetate part was thoroughly washed with aqueous 10% sodium carbonate solution followed by brine to neutrality. The organic parts were dried over anhydrous sodium sulfate and concentrated to get the corresponding amines. The (12) (a) Lindman, B.; Wennerstrom, H. Top. Curr. Chem. 1980, 87, 1. (b) Holmberg, K.; Jo¨nsson, B.; Krongerg, B.; Lindman, B. Surfactants and Polymers in Aqueous Solution, 2nd ed.; John Wiley & Sons: New York, 2003. (c) Schnur, J. M. Science 1993, 262, 1669. (d) Menger, F. M.; Keiper, J. S. Angew. Chem., Int. Ed. 2000, 39, 1906.
104 × cmc, (M) 104 × cmc, (M) (tensiometry) (fluorescence) 4.29 2.12 1.76 1.29
4.85 2.46 1.95 1.48
Amin (nm2)
I1/I3a
0.69 ( 0.02 1.13 ( 0.01 1.16 ( 0.03 1.26 ( 0.03
1.02 1.08 1.15 1.13
a Intensity ratio due to first and third vibronic peak of pyrene steady-state fluorescence I1/I3 indicate the micropolarity at the micellar interface.
produced amines (1 equivalent) were quarternized with excess iodomethane using anhydrous potassium carbonate (2.2, 2.2, 1.1, and 2.2 equivalent for 1-4, respectively) and a catalytic amount of 18-crown-6-ether in dry DMF for 2 h. The reaction mixtures were taken in ethyl acetate and washed with aqueous sodium thiosulfate and brine solution, respectively. The concentrated ethyl acetate parts were crystallized from methanol/ether to obtain solid quarternized iodides, which were then subjected to ion exchange on an Amberlyst A-26 chloride ion-exchange resin column to get the pure desired surfactant. Overall yields were in the range of 70-80%. Syntheses of Pure Alcohols [1-(p-Methylphenyl)methanol, 1-Phenyl 2-methylpropanol, 1-Phenylpentanol]. The racemic pure alcohols of the prochiral ketones were synthesized conventionally by NaBH4 reduction of the corresponding ketones in methanol. 1H NMR (300 MHz, CDCl ) and elemental analysis of the 3 synthesized compounds: (1-Hexadecylcarbamoyl-ethyl)-trimethylammonium chloride (1). δ ) 0.87 (t, 3H), 1.24-1.16 (br, 26H), 1.61-1.56 (d, 3H), 1.74 (br, 2H), 3.28-3.21 (m, 2H), 3.33 (s, 9H), 5.69-5.65 (t, 1H). E.A: calculated for C22H47N2OCl: C, 67.57; H, 12.11; N, 7.16. Found: C, 67.41; H, 11.79; N, 6.91. MS (ESI) calcd. m/z ) 355.34; found 355.1259 (M+). 1-Hexadecylcarbamoyl-2-phenyl-ethyl)-trimethylammonium chloride (2). δ ) 0.80 (t, 3H), 1.08-1.18 (br, 28H), 2.82-2.86 (m, 2H), 3.15-3.18 (m, 2H), 3.4 (s, 9H), 5.63-5.68 (t, 1H), 7.18-7.26 (m, 5H). E.A: calculated for C28H51N2OCl: C, 71.99; H, 11.00; N, 6.00. Found: C, 71.72; H, 11.09; N, 5.92. MS (ESI) calcd. m/z ) 431.37; found 431.1137 (M+). 2-Hexadecylcarbamoyl-1,1-dimethyl-pyrrolidinium chloride (3). δ ) 0.86 (t, 3H), 1.16-1.30 (br, 26H), 1.561-0.61 (br, 4H), 3.21-3.26 (m, 2H), 3.28 (s, 3H), 3.39 (s, 3H), 3.49-3.55 (m, 2H), 5.60 (t, 1H). E.A: calculated for C23H47N2OCl: C, 68.53; H, 11.75; N, 6.95. Found: C, 68.23; H, 11.61; N, 6.65. MS (ESI) calcd. m/z ) 367.34; found 367.4124 (M+). [2-(1H-Indole-3-yl)-1-hexadecylcarbamoyl-ethyl-trimethyl-ammonium chloride (4). δ ) 0.83 (t, 3H), 0.97-0.99 (br, 2H), 1.11-1.32 (br, 24H), 1.66-1.73 (br, 2H), 2.82-2.91 (m, 2H), 3.20-3.24 (m, 2H), 3.31 (s, 9H), 5.60 (br, 1H), 7.01-7.06 (br, 1H), 7.29-7.31 (d, 2H), 7.41 (d, 1H), 7.48-7.51 (d, 1H). E.A: calculated for C30H52N3OCl: C, 71.18; H, 10.35; N, 8.30. Found: C, 71.28; H, 10.43; N, 8.35. MS (ESI) m/z. calcd (for C30H52N3O, the 4° ammonium ion, 100%) 470.41, found 470.5699(M+). 1-Phenyl-2-methylpropanol. δ ) 1.01 (t, 6H), 2.04 (m, 1H), 4.36 (d, 1H), 7.24-7.36 (m, 5H). E.A: calculated for C10H14O: C, 79.96; H, 9.39. Found: C, 79.39; H, 9.67. 1-Phenylpentanol. δ ) 0.87 (t, 3H), 1.16-1.32 (m, 4H), 1.591.71 (m, 2H), 4.51-4.55 (t, 1H), 7.13-7.37 (m, 5H). E.A: calculated for C11H16O: C, 80.44; H, 9.82. Found: C, 80.15; H, 9.72. 1-(p-Methylphenyl)methanol. δ ) 1.32-1.39 (t, 3H), 2.212.27 (s, 3H), 4.77 (m, 1H), 4.55-4.51 (t, 1H), 6.93 (d, 2H), 7.26 (d, 2H). E.A: calculated for C11H16O: C, 79.37; H, 8.88. Found: C, 79.12; H, 8.59. Surface Tension Measurement. The critical micellar concentration (cmc) values of the surfactants in Chart 1 were measured using a tensiometer (Jencon, India) applying Du Nou¨y ring method at 25 ( 0.1° C in water. The cmc values were determined (Table 1) by plotting surface tension (γ) vs concentration of surfactant with the accuracy of (2% in duplicate experiments.
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Fluorometry. Pyrene has been extensively used as a fluorescence probe to investigate the formation of hydrophobic microdomains by surfactants in aqueous solutions. The steadystate fluorescence study with pyrene (1 × 10-7 M) was utilized to determine the cmc of surfactants (1-4) and as well as micropolarity of the micellar microenvironment. The excitation wavelength was fixed at 337 nm and the emission spectra were recorded from 357 to 600 nm at 25 °C. The emission spectra of pyrene also measured at the same temperature in water and n-hexane. Circular Dichroism. CD spectra were recorded both in the micellar state as well as in the nonmicellar state (1:1 (v/v), MeOH/ H2O) for all surfactants at 25 °C in a Jasco J-600C spectropolarimeter. All of the recorded samples were in the concentration range of 1 × 10-3-5 × 10-3 M, which was actually adjusted depending on their optical density at 220-230 nm. Each CD spectral scanning was repeated five times to ensure the reproducibility. Specific Rotation. The specific rotations of the synthesized amphiphiles are as follows: [R]D ) -20.9° (MeOH) for 1; [R]D ) +15.1° (CHCl3) for 2; [R]D ) -23.8° (MeOH) for 3; [R]D ) -29.3° (CHCl3) for 4. Micelle Mediated Reduction of Ketones With NaBH4 (Detailed Procedure). In a typical experiment, to a 5 or 50 mM aqueous micellar solution (1 mL) of the respective surfactants (1-4, Chart 1) was added the required amount of the ketone dissolved in 10µL of HPLC grade acetonitrile to reach the substrate concentration of 0.5 mM. After 10 min of stirring, 10 µL of an aqueous solution of NaBH4 (3.8 mg in 1 mL) was added to the reaction mixture to attain the NaBH4 concentration of 1 mM, and it was allowed to stir at room temperature for 1 h. An aqueous solution of sodium perchlorate (1.1 equiv with respect to the concentration of the surfactant) was added to the reaction mixture to precipitate the surfactant through counterion exchange. The reaction mixture was then extracted with 2 mL of ethyl acetate and 1 mL of that organic part was taken in a microcentrifuge tube and evaporated to dryness by controlled flow of nitrogen. n-Hexane/2-propanol (200 µL; 95:5 v/v) was added to the microcentrifuge tube, and it was centrifuged for 3 min at 10 000 rpm. The supernatant liquid was then injected to the HPLC column (CHIRALCEL OD-H, 4.6 mm i.d. × 250 mm, Daicel Chemical Industries, Ltd). A 20 µL sample loop was used for the injection of the product mixtures. In all cases, n-hexane/2-propanol (95:5 v/v) was used as the mobile phase. The yield of the reactions was calculated from the product alcohol peak areas obtained from the chromatograms using the previously prepared calibration equations of the pure alcohols. The pure alcohols, purchased or synthesized, were previously injected into HPLC column in a similar concentration range to obtain the calibration equations. The detailed information of the HPLC data, including calibration equation, peak area, and chemical yields are given in the Supporting Information (Table S1). To optimize the reaction time, acetophenone was reduced in a micellar solution of 3 for 1-4 h keeping all other parameters identical. Since no notable change was observed in the stereoselectivity as well as in the yield after 1 h, all reactions were carried out for 1 h.
Results and Discussions The present study demonstrates how the rational incorporation of different substituents at the chiral head of surfactants (1-4) manipulates their spatial arrangement, which expresses the supramolecular chirality of the aggregates. The influence of this manifested chirality in the enantioselective ketone reduction and on physicochemical properties of the corresponding micelles is outlined below. Self-Aggregation in Aqueous Solution. Surface Tension Method. The cmc at the air-water interface for 1-4 was obtained from the break in the plots (Figure 1) of surface tension (γ) versus concentration of surfactants (Table 1). cmc, the most representative micellar descriptor was found to decrease with increase in headgroup size and surface area per molecule (Amin) from 1-4 in concur-
Roy et al.
Figure 1. Plots of surface tension (γ) vs concentration of surfactants 1-4 at 25 °C.
rence with the literature13 (Table 1). Amin of the surfactants (Chart 1) at the air-water interface was determined using the Gibbs Adsorption isotherm
Γmax )
1 lim dπ/d log C 4.606RT C f Ccmc
(1)
1018 N Γmax
(2)
Amin )
where π is the surface pressure calculated from the equation π ) γwater - γsolution. γ denotes the surface tension, Γmax is the maximum surface excess concentration, T is absolute temperature, R ) 8.314 J mol-1 K-1, and N is the Avogadro number. The surface excess, Γmax is calculated from the slope in π versus log [surfactant] curve using pre-cmc tensiometric data. Fluorescence Study. Pyrene monomer fluorescence emission14 was used to monitor the self-aggregation of all four surfactants (1-4) in water. Pyrene exhibits a characteristic steady-state fluorescence emission spectrum consisting of three vibronic bands (Figure 2, inset). The nature and the intensity of such fine structured bands in the pyrene fluorescence are dependent on the polarity of the environment. The intensity ratio of the first to the third band (I1/I3) was taken as a measure for the polarity of the microenvironment.14a,15 On micellization, pyrene molecules in water are preferentially located in the hydrophobic region causing an abrupt change of the I1/I3 ratio.16 The absorption and the fluorescence of the surfactants 1-4 had no effect on the steady-state fluorescence of pyrene when it was excited at 337 nm. The cmc values obtained (Table 1) from the variation in the I1/I3 ratio with the surfactant concentration (Figure 2) are in (13) (a) Tanford, C. In Hydrophobic Effect; John Wiley: New York, 1973. (b) Rosen, M. J. Surfactants and Interfacial Phenomena, 2nd ed.; Wiley: New York, 1989. (c) Laura, T.; Quina, H. F.; Seoud, O. A. E. Langmuir 2000, 16, 3119. (d) Bazito R. C.; Seoud, O. A. E. Langmuir 2002, 18, 4362. (14) (a) Kalyanasundaram, K.; Thomas, J. K. J. Am. Chem. Soc. 1977, 99, 2039. (b) Dong, D. C.; Winnik, M. A. Photochem. Photobiol. 1982, 35, 17. (c) Bhattacharya, S.; Halder, J. Langmuir 2004, 20, 7940. (d) Tan, X. L.; Zhang, L.; Zhao, S.; Li, W.; Ye, J. P.; Yu, J.-Y.; An, J.-Y. Langmuir2004, 20, 7010. (15) Fendler, J. H. Membrane Mimetic Chemistry; Wiley: New York, 1982. (16) Bohne, C.; Rednond, R. W.; Scaiano, J. C. In Photochemistry in Organized and Constrained Media; Ramammurthy, V., Ed.; VCH: New York, 1991; Chapter 3.
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Figure 3. Three-dimensional presentation of a pair of chiral molecules along with their substituents in the two perpendicular planes. Although l includes the long hydrocarbon chain and h is the hydrophilic head, grouping the same plane; a is the smallest group and b is the other group coplanar with a. The figure was adapted from ref 11a. Figure 2. Variation of I1/I3 values of pyrene steady-state fluorescence emission spectra as a function of the concentration of surfactants 1-4. Inset, representative fluorescence emission spectra of 1 × 10-7 M pyrene in aqueous cationic micellar microenvironment of surfactant 3.
agreement with those obtained from the surface tension measurements. Micropolarity (I1/I3) has been found to vary from 0.74 in a hydrophobic solvent like n-hexane to 1.37 in water, the most hydrophilic solvent. The ratios, 1.02, 1.08, 1.15, and 1.13, respectively in micelles (Table 1) of 1-4 were found to be within these two extreme values for nonpolar and polar solvent. These results in general indicate that the micelles prepared using 1-4 are mostly hydrated and notably the hydration is more in case of 3 and 4 compared to that in 1 and 2. Molecular Origin of Chirality in Self-Assemblies. Theoretical Approach. The supramolecular chirality is largely dependent upon the helical morphologies of selfaggregates, which is highly specific to the chirality of the monomer concerned.11 So, understanding the effects of chirality at the molecular level is essential as the functionality of these biomimetic systems is interrelated with their structural morphology. To this end, Nandi and Bagchi11 presented for the first time a simple approach for determining the molecular origin of the “chiralitydriven helix formation” in aqueous self-assemblies by calculating the effective pair potential (EPP) between a pair of chiral amphiphiles. According to their approach, EPP between neighboring molecules depends on the effective hard sphere diameter of the substituents at the chiral centers as well as their orientation in space and the distance between two chiral centers. It has been found that a pair of molecules having the same sense of chirality do not remain parallel in the minimum energy configuration, but rather prefer a twist between them. This angle of twist in the plane of adjacent a and b groups is designated as ΦM (please see Figure 2 in ref 11a) which primarily induces the helicity within self-aggregates, dictating the major chiral interactions (Figure 3). Owing to the comparatively larger size of the hydrophobic tail (l) and hydrophilic headgroup (h), the tilt in the plane of l and h groups is less favored and expected to have no effect in depicting the chirality. This approach of predicting the handedness of chiral microdomains in aqueous selfassemblies is finding notable importance.6,17 EPP for all four chiral amphiphiles was determined following the formulation (see the Supporting Information) developed (17) (a) Nandi, N.; Vollhardt, D. Colloid Surf. A 2001, 183-185, 67. (b) Nandi, N.; Vollhardt, D. Colloid Surf. A 2002, 198-200, 207. (c) Nandi, N.; Vollhardt, D. J. Phys. Chem. B 2002, 106, 10144. (d) Nandi, N.; Vollhardt, D. J. Phys. Chem. 2003, 107, 3464. (e) Nandi, N.; Vollhardt, D. Colloid Surf. A 2004, 250, 279.
Table 2. Effective Diameter (Å) of the Groups Attached to the Chiral Center of the Surfactants (1-4)a surfactant
l
h
a
b
ΦM
1 2 3 4
8.33 8.33 8.33 8.33
5.15 5.15 4.47 5.15
1.4 1.4 1.4 1.4
2.99 5.58 4.4 6.1
24 52 42 48
a Groups are designated as l, h, a, and b, respectively. l is the group containing the long hydrocarbon chain; h is the hydrophilic headgroup; and a and b are two other groups attached to the chiral center, b is larger than a. For surfactants 1, 2, and 4, l is -CONHC16H33 and h is N+Me3, a is H, and b is -CH3, -CH2Ph, and -CH2-indole. In surfactant 3, h is N+Me2 and b is -(CH2)3; the rest are same. The tilt angle in the plane of a and b (ΦM) is also presented.
by Nandi and Bagchi utilizing the effective diameter and Lennard-Jones energy parameter of the respective groups. The effective diameters of the groups were calculated (Table 2) by the empirical equation given by Ben-Amotz and Herschbach18 and the group increments tabulated by Bondi.19 The tilt angles, ΦM (Table 2), were obtained from the minima of the EPP plot against the orientation between adjacent groups attached to two chiral centers and the separation between them (Figure 4). The difference in the ΦM values for surfactants 1-4 (Table 2) leads to variation in their spatial dissymmetry, which is reflected in varying extent of supramolecular chirality (Figure 5) as outlined under the section Circular Dichroism. The ΦM value for 1 was significantly less than those for 2-4 (Table 2), indicating that the spatial dissymmetry mainly dependent on the relative size of the groups around the chiral center and hence the large-scale chirality is expected to be lower for 1 for than the other three surfactants. Circular Dichroism (CD). The bulk asymmetry in chiral assembly is largely affected through noncovalent molecular packing of individual components.7 The chiral molecular interactions presumably form a network of repetitive molecular unit resulting a supramolecular chiral surface.5c To ascertain the presence of supramolecular chirality in self-assemblies as predicted through EPP calculation, CD spectra of 1-4 were recorded both in aqueous solution above the cmc and in 1:1 (v/v) watermethanol solution where the surfactants are no longer in aggregated form (Figure 5). The differences in the CD spectra between the aggregated and nonaggregated form for surfactant 1 and 2 were not that distinct whereas a notable change was observed for 3 and 4. The CD spectra of these amidic surfactants are actually a superimposition of two spectra. The first one corresponds to the cotton (18) Ben-Amotz, D.; Herschbach, D. R. J. Phys. Chem. 1990, 94, 1038. (19) Bondi, A. J. Phys. Chem. 1964, 68, 441.
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Figure 4. Representative example of calculated effective pair potential (EPP) profile for surfactant 4. Here, EPP (U/kBT) is plotted against the difference in orientation of adjacent a and b groups, Φ2 - Φ1, as well as the separation between the chiral centers. Effective diameters of a and b groups are 1.4 Å and 6.1 Å, respectively. a/kB ) 140 K, and b/kB ) 610 K, β ) 110°, and R ) 0°.
effect of the transition dipoles of the amide bond, and the second one emerges from the supramolecular chiral assembly of the amide planes, which can be effective only in the aggregated form. The observed CD peaks due to the electronic transitions are extremely sensitive to coupling with neighboring amides.20 In presence of an organic protic solvent, like methanol, which provides a simple means
Roy et al.
for disintegrated chiral assembly, the peak magnitude decreases due to the unordered arrangement of the amide planes. Thus, in concurrence with the EPP approach, the observed supramolecular chiral interface, notably in the case of 3 and 4 might have been resulted from the increased spatial dissymmetry along with the hydrogen bonding interactions among the amide bonds. Consequently, curvature of the domain increases leading to the helical morphology of the aggregates which is in agreement with a strong band at 220-225 nm in CD spectra. In addition to the influence of spatial dissymmetry in supramolecular chirality, recent works show that the changes in the electrostatic interactions originated from the varying headgroup structures of amphiphiles also play an important role in determining the chirality of the aggregate domain.21 It was thought that the changes in chemical structure might alter the dipolar interaction among the molecules and with water in the aqueous subphase, which modifies the electrostatic interactions and consequently the domain shape. Asymmetric Ketone Reduction. As outlined in the Introduction, to hold efficient asymmetric transformations, it is essential to develop surfactants where the chiral environment generated at the interface is rigid enough to make the system more promising. Herein, we decided to carry out asymmetric reduction using a series of ketones in the aqueous chiral micelles (Scheme 1) of cationic surfactants 1-4 (Chart 1). To begin with, reduction of prochiral ketone was studied at room temperature using acetophenone (0.5 mM) as the simplest substrate in the aqueous chiral micelles of surfactant 1 (50 mM) derived from (S)-alanine. The observed ee was much less ∼3.8% (entry 1, Table 3). This may have been correlated with CD spectra of 1 (Figure 5), where no significant difference was observed between the aggregated and the nonaggre-
Figure 5. CD spectra for surfactant 1-4 was recorded in water as well as in 1:1 (v/v) aqueous methanolic solution. (- - -) represents CD spectra in water and (s) represents CD spectra in aqueous methanolic solution. Concentration used for surfactant 1 and 3 is 5 ×10-3 M while that used for 2 and 4 is 1 × 10-3 M.
Amino Acid Based Cationic Surfactants
Langmuir, Vol. 21, No. 23, 2005 10403
Scheme 1. Schematic Presentation of the Asymmetric Reduction of the Prochiral Ketones at the Chiral Micellar Interface
Table 3. NaBH4 Reduction of Ketonesa in the Aqueous Chiral Micelles at Room Temperature
entry
ketone
1
acetophenone
2
propiophenone
3
butyrophenone
4
isobutyrophenone
5
valerophenone
6
2-acetonaphthone
[surfactant] (mM) 50 5 50 5 50 5 50 5 50 5 50 5
enantiomeric excessb (%) (S) 1
2
3
4
3.8 12.0 (30)c 2.0 18.0 16.2 (41)c 29.0 3.8 6.1 6.8 2.7 7.9 23.6
