Hydrocarbon

pubs.acs.org/Langmuir © 2011 American Chemical Society

Giant Brainlike Aggregates from New Fluorocarbon/Hydrocarbon Hybrid Cationic Surfactants Mamadou Oumar,†,‡ Elisabeth Taffin de Givenchy,† Samba Yand
e Dieng,‡ Sonia Amigoni,† and Fr
ed
eric Guittard*,† †

Universit
e de Nice-Sophia Antipolis, Laboratoire de Chimie des Mat
eriaux Organiques et M
etalliques, Parc Valrose, 06108 Nice Cedex 2, France, and ‡D
epartement de Chimie, Facult
e des Sciences et Techniques, Universit
e Cheikh Anta Diop, Dakar, S
en
egal Received October 13, 2010. Revised Manuscript Received December 13, 2010

A rapid synthetic procedure in two steps from perfluoroalkylethyl iodide derivatives led to 18 novel ammonium type hybrid surfactants of the general formula: RF(CH2)2S(CH2)2Nþ(CH3)2RHBr- (RF = C4F9, C6F13, C8F17; RH = C4H9, C6H13, C8H17, C10H21, C12H25, C14H29). These hybrid surfactants exhibited very low surface tension (from 16 to 25 mN/ m) as well as low critical micellar concentration until 1.5  10-5 mol/L. A special focus was made on aggregation phenomenon as giant multilamellar “brainlike” vesicles were observed via cryogenic scanning electron microscopy (cryoSEM) and transmission electron microscopy (TEM; with a contrast agent) suggesting a high encapsulation ability and a very important specific surface of these particular organizations.

Introduction A lot of research effort is devoted to the progress in the molecular design of new surfactant molecules, in particular for medical or health care applications.1-4 Specifically, the ability of these surfactant systems to self-assemble was particularly studied for the development of drug delivery systems,5,6 templating applications,7 or nanoreactors.8 Inventive systems such as multicompartment micelles formed by polymeric surfactants9,10 or by catanionic associations11-13 have been developed. Among them, hydrocarbon/fluorocarbon hybrid surfactants are strong associative surfactants and their mutual phobicity induces the creation of nonconventional interactions and aggregates. Very stable vesicles can be observed along with some peculiar intermediate structures such as threadlike micelles trans*To whom correspondence should be addressed. Telephone: þ33 (0)4 92 07 6159. Fax: þ33 (0)4 92 07 6156. E-mail: [email protected].

(1) Riess, J. G. Curr. Opin. Colloid Interface Sci. 2009, 14, 294 and references therein. (2) Massi, L.; Guittard, F.; Levy, R.; Duccini, Y.; Geribaldi, S. Eur. J. Med. Chem. 2003, 38, 519. (3) Massi, L.; Guittard, F.; Levy, R.; Duccini, Y.; Geribaldi, S Eur. J. Med. Chem. 2009, 44, 1615. (4) Caillier, L.; Taffin de Givenchy, E.; Levy, R.; Vandenberghe, Y.; Geribaldi, S.; Guittard, F. J. Colloid Interface Sci. 2009, 332, 201. (5) McKelvey, C. A.; Kaler, E. W.; Zasadzinski, J. A. N.; Coldren, B.; Jung, H. T. Langmuir 2000, 16, 8285. (6) Hashimoto, Y.; Sugawara, M.; Masuko, T.; Hojo, H. Cancer Res. 1983, 43, 5328. (7) Antonietti, M. Curr. Opin. Colloid Interface Sci. 2001, 6, 244. (8) Vriezema, D. M.; Comellas Aragones, M.; Elemans, J. A. A. W.; Cornelissen, J. J. L. M.; Rowan, A. E.; Nolte, R. J. M. Chem. Rev., 2005, 105, 1445 and references therein. (9) Kotzev, A.; Laschewsky, A.; Adriaensens, P.; Gelan, J. Macromolecules 2002, 35, 1091. (10) Lodge, T. P.; Rasdal, A.; Li, Z.; Hillmyer, M. A. J. Am. Chem. Soc. 2005, 127, 17608. (11) Silva, B. F. B.; Marques, E. F.; Olsson, U.; Pons, R. Langmuir 2010, 26, 3058. (12) Pasc-Banu, A.; Stan, R.; Blanzat, M.; Perez, E.; Rico-Lattes, I.; Lattes, A.; Labrot, T.; Oda, R. Colloids Surf., A 2004, 242, 195. (13) Blanco, E.; Olsson, U.; Ruso, J. M.; Schulz, P. C.; Prieto, G.; Sarmiento, F. J. Colloid Interface Sci. 2009, 331, 522. (14) Oda, R.; Huc, I.; Danino, D.; Talmon, Y. Langmuir 2000, 16, 9761. (15) Matsuoka, K.; Yoshimura, T.; Bong, M.; Honda, C.; Endo, K. Langmuir 2008, 24, 5676.

1668 DOI: 10.1021/la1041184

forming into bilayers or vesicles,14 nanocage aggregates,15 polyhedral vesicles,16,17 or multicompartiment micelles.18 These hybrid structures are of growing interest, as they are known to combine19-23 the so particular surface properties generally induced both by the fluorinated tail and the gemini structure (two tailed surfactants)24 without facing the low water solubility often encountered for highly fluorinated compounds. Furthermore, hybrid fluorocarbon/hydrocarbon structures allow the surfactants to emulsify either fluorinated or hydrocarbon fluids25 and to be used in a wide range of applications.26 In biomedical applications, for example, even if partially fluorinated surfactants have a strong tendency to accumulate in living organisms and in the environment, from a biological point of view, many F-surfactants, including F-alkylated phospholipids, sugars, polyols, and amino acids, have shown acute toxicities and hemolytic activities that were significantly lower than those of their H-alkylated analogues.1 Their properties are also unequaled in such a domain as the formation of water/supercritical carbon dioxide type microemulsions.27 However, studies on hybrid cationic fluorinated surfactants are rare due to the difficulty in their synthesis. In this work, we wanted to study the aggregation behavior of new cationic hybrid surfactants noted as S-HnFm and shown in Figure 1. They possess, in the same structure, a polar quaternary ammonium head and two (16) Dubois, M.; Lizunov, V.; Meister, A.; Gulik-Krywicki, T.; Verbavatz, J.-M.; Perez, E.; Zimmerberg, J.; Zemb, T. Proc. Natl. Acad. Sci. U.S.A. 2004, 101, 15082. (17) Gonzalez-P
erez, A.; Schmutz, M.; Waton, G.; Romero, M. J.; Krafft, M. P. J. Am. Chem. Soc. 2007, 129, 756. (18) Unsal, H.; Aydogan, N. Langmuir 2009, 25, 7884. (19) Dieng, S. Y.; Sz€onyi, S.; Jouani, M.; Watzke, H. J.; Cambon, A. Colloids Surf., A 1995, 98, 43. (20) Oda, R.; Huc, I.; Danino, D.; Talmon, Y. Langmuir 2000, 16, 9759. (21) Ohno, A.; Kushiyama, A.; Kondo, Y.; Teranaka, T.; Yoshino, N. J. Fluorine Chem. 2008, 129, 577. (22) Yoshimura, T.; Ohno, A.; Esumi, K. Langmuir 2006, 22, 4643. (23) Aydogan, N.; Aldis, N.; Guvenir, O. Langmuir 2003, 19, 10726. (24) Rosen, M. J.; Tracy, D. J. J. Surfactants Deterg. 1998, 1, 547. (25) Yoshino, N.; Hamano, K.; Omiya, Y.; Kondo, Y.; Ito, A.; Abe, M. Langmuir 1995, 11, 466. (26) Kondo, Y.; Yoshino, N. Curr. Opin. Colloid Interface Sci. 2005, 10, 88. (27) Dupont, A.; Eastoe, J.; Martin, L.; Steytler, D. C.; Heenan, R. K.; Guittard, F.; Taffin de Givenchy, E. Langmuir 2004, 20, 9960.

Published on Web 01/11/2011

Langmuir 2011, 27(5), 1668–1674

Oumar et al.

Article

Figure 1. Variation in the electrical conductivity with the surfactant concentration exemplified for the surfactant series with an H-octyl tail (S-F4H8, S-F6H8, and S-F8H8). Scheme 1. Synthesis of Hybrid Surfactantsa

a

(i) HS(CH2)2N(CH3)2 3 HCl, NaOH, CH3CN, TBAHS, 80 °C; (ii) CH3(CH2)n-1Br, 100°C.

hydrophobic chains: a semifluorinated tail and hydrocarbon one. We have designed these surfactants, so they can be readily synthesized in two steps from commercially available perfluoroalkyl iodides allowing easy variation of the length of either the fluorinated or the hydrocarbon tail (Figure 1). The new hybrid surfactants we describe in this paper are readily achieved in two steps from commercially available semifluorinated iodine derivatives 1-3 (Scheme 1). This rapid synthesis allows varying both the lengths of the fluorocarbon and the hydrocarbon chains. Eighteen new surfactants coded S-FmHn (where m is the number of fluorinated carbons and n the number of hydrocarbons in the second hydrophobic tail), all having good water solubility, were thus studied, highlighting the contribution of each part of the molecule to the physicochemical properties. The tuning of fluorinated and hydrocarbon chain lengths was used to optimize the aggregation properties that are highlighted by cryoSEM and TEM studies.

Experimental Section For the synthesis of hybrid surfactants, 2-(dimethylamino)ethanethiol hydrochloride, tetrabutylammonium hydrogen sulfate (TBAHS), alkyl bromides, and all chemicals (NaOH, acetonitrile, ethyl ether, MgSO4) were purchased from Aldrich and used without Langmuir 2011, 27(5), 1668–1674

further purification. 2-Perfluoroalkylethyl iodides were provided by Atofina. Unless specified, the solvents were of unpurified reagent grade. Confirmation of the structures of the intermediates and products was obtained by nuclear magnetic resonance (NMR) realized with a Bruker W-200 MHz instrument, mass spectrometry (MS) using a Thermo TRACEGC instrument from Thermofischer Corp. fitted with an Automass III Multi spectrometer (electron ionization at 70 eV), and infrared spectroscopy (FT-IR) using a 3100 FTIR microscope from Perkin-Elmer.

Synthesis of the Semifluorinated Tertiary Amines 4, 5, and 6. In a 250 mL round-bottom flask, 28.2 mmol of 2-(dimethylamino)ethanethiol chloride and 56.4 mmoL of NaOH were diluted in 20 mL of water. Then, 500 mg of TBAHS, the phase transfer catalyst, in 20 mL of acetonitrile was added. The solution was vigorously stirred for 30 min at room temperature. Then 28.2 mmol of perfluoroalkylethyl iodide was added, and the solution was heated at 80 °C for 48 h. The water/acetonitrile solution was extracted five times with diethyl ether. The organic phase was dried over MgSO4, and then the solvent was evaporated. The amines were then purified by distillation in a kughelrorh apparatus to give colorless liquids (yields: 4, 78%; 5, 82%; 6, 64%). The yield is lower for the F-octyl derivative as expected. Indeed, it is well-known that the reactivity of semifluorinated compounds decreases with the number of perfluorinated carbons; DOI: 10.1021/la1041184

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Article

Oumar et al. Scheme 2. Phase Transfer Mechanism of Step 1

this is mainly due to a decrease in solubility in the conventional solvents uses in organic synthesis. The experiments were reproduced several times. In all cases, the yields were reproducible ((3%).

General Procedure for the Synthesis of the Hybrid Surfactants 7-24 (S-FmHn). In a 100 mL round-bottom flask, 10 mmol of tertiary amine 4, 5, or 6 was reacted with 20 mmol of alkyl bromide used both as a reagent and solvent. The reaction was conducted for 24 h at 100 °C. The solution was then cooled to room temperature, and 20 mL of diethyl ether was added, leading to the precipitation of the desired ammonium. The precipitate was filtrated and abundantly washed with diethyl ether. The ammoniums were collected as white solids. Yields were from 70 to 92% depending on the length of the fluorinated tail and the hydrocarbon part (detailed yields and characterizations can be found in the Supporting Information). Krafft Temperatures. In order to determine the Krafft temperatures (KT), aqueous solutions of surfactants at a concentration of 5 times the CMC were prepared and placed in a refrigerator at 5 °C for at least 24 h. In a general procedure, the temperature of the precipitated system is raised gradually by using a thermostat bath with a temperature uncertainty of (0.05 °C under constant stirring and the conductance κ was measured using a digital conductivity meter (Consort C831). The Krafft temperature is the temperature where the conductance versus temperature plot shows an abrupt change in slope.28 This temperature is the same as that required to completely dissolve the hydrated solid surfactant, judged visually to be the point of complete clarification of the system. In our case, all the surfactant solutions were already clear at 5 °C. KT < 5 °C confirms a great water solubility at ambient temperature for all the surfactant studied.

Critical Micellar Concentration (CMC) and Surface Tension (γs). The critical micellar concentrations were deter-

mined from conductimetry measurements29 at 25 °C using a conductimeter apparatus (mentioned above). The surface tensions at the CMC values were determined, at 25 °C, by the Wilhemy plate method using a Kr€ uss K100 tensiometer.30 Dynamic Light Scattering. Particles size and polydispersity were measured at 25 °C using a Zetasizer Nano-S model 1600 (28) Moroi, Y. Micelles, Theoretical and Applied Aspects; Plenum: New York, 1992. Tsuji, K. Surface Activity, Principles, Phenomenon, and Applications; Academic Press: New York, 1992; Ch. 2, p 15. (29) Staehler, K.; Selb, J.; Barthelemy, P.; Pucci, B.; Candau, F. Langmuir 1998, 14, 4765. (30) Pallas, N. R.; Pethica, B. A. Colloids Surf. 1989, 36, 369.

1670 DOI: 10.1021/la1041184

(Malvern Instruments Ltd.) equipped with a He-Ne laser (λ = 633 nm, 4.0 mW). The aqueous solutions were prepared using demineralized water and were filtered through a 0.45 μm filter. Measurements were repeated several weeks after preparation, and no modification of the sizes was visualized. The time-dependent correlation function of the scattered light intensity was measured at a scattering angle of 173° relative to the laser source (backscattering detection). The Stokes radius (RS) of the particles was estimated from their diffusion coefficient (D) using the StokesEinstein equation D = kBT/6πηRS, where kB is Boltzmann’s constant, T is the absolute temperature, and η is the viscosity of the solvent. Microscopic Observations. Cryogenic scanning electron microscopy (cryo-SEM) images were obtained with a FESEM 6700F JEOL microscope (Japan). One drop of the sample was rapidly frozen in nitrogen slush at -220 °C and transferred under vacuum in the cryofracture apparatus (Alto 2500 GATAN UK) chamber where it was fractured at -100 °C and maintained at this temperature during 7 min for sublimation. It was then metallized with AuPd and introduced in to the microscope chamber where it was maintained at -100 °C during the observation. Transmission electron microscopy (TEM) images were obtained using a Philips CM12 transmission electron microscope in negative contrast: a drop of the surfactant solution was deposited on a Formvarcoated copper grid. This drop was thrown out with a contrasting agent solution drop (1 wt % aqueous solution of uranyl acetate), and then excess liquid was blotted away with filter paper. All observations were made in low dose mode and at an accelerating voltage of 80 kV to prevent the melting of the sample. To ensure reproducibility, the selection of micrographs presented in this Article was chosen from a large number of negatives.

Results and Discussion 1. Synthesis. The studied surfactants are synthesized in two steps from N,N-dimethyl aminoethylthiol hydrochloride and commercially available semifluorinated iodine derivatives 1-3. The use of N,N-dimethyl aminoethylthiol hydrochloride derivative as a precursor is a quite convenient choice in the idea of a systematic study, as it allows variation of both the length of the hydrocarbon and the fluorocarbon chains straightforwardly. In the resulting cationic surfactants, the perfluorinated tail is linked to the quaternary ammonium head via a CH2CH2-S-CH2CH2 linker; the presence of the sulfur atom is not expected to disrupt the surface properties as demonstrated in the hydrocarbon series Langmuir 2011, 27(5), 1668–1674

Oumar et al.

Article Table 1. Physicochemical Parameters of the Surfactant Aqueous Solutions

compd

S-FmHn

Mp (°C)

KT (°C)a

CMC (mol/L)

γs (mN/m)

ΔGag° (KJ/Mol)

R

β

7 8 9 10 11 12

S-F4H4 S-F4H6 S-F4H8 S-F4H10 S-F4H12 S-F4H14

139 150 192 190 182 178