Letter pubs.acs.org/Langmuir
Perfluorinated Alcohols and Acids Induce Coacervation in Aqueous Solutions of Amphiphiles Morteza G. Khaledi,* Samuel I. Jenkins,† and Shuang Liang Department of Chemistry, North Carolina State University, 2620 Yarborough Street, Raleigh, North Carolina 27695-8204, United States ABSTRACT: We have discovered that water-miscible perfluorinated alcohols and acids (FA) can induce simple and complex coacervation in aqueous solutions of a wide range of amphiphilic molecules such as synthetic surfactants, phospholipids, and bile salts as well as polyelectrolytes. This unique phenomenon seems to be nearly ubiquitous, especially for complex coacervate systems composed of mixed catanionic amphiphiles. In addition, coacervation and aqueous phase separation were observed over a wide range of surfactants concentrations and for different mole fractions of the oppositely charged amphiphile.
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INTRODUCTION The self-assembly of amphiphilic molecules and the subsequent formation of a variety of microstructures in aqueous media such as micelles, vesicles, lamellae, and coacervates are of fundamental and practical importance in a wide range of disciplines.1−3 Hydrophobic, electrostatic, and steric effects play significant roles as driving forces and/or are determinants of the structures of such molecular assemblies. Although certain types of aggregation such as micelles and vesicles formation are commonly observed for broad groups of amphiphilic molecules, coacervation remains a relatively rare form of organization. The term coacervation is derived from the Latin prefix co- and the Latin word acervus that means to come together in a heap. It was first introduced by Bungenberg-de Jong and Kruyt and refers to a phenomenon involving the assembly of certain amphiphilic molecules or colloids that leads to the formation of liquid−liquid phase separation. One phase is rich in the amphiphile or colloids (coacervate phase) and is immiscible with the other phase that is lean in amphiphile or colloids.4 Coacervates are conveniently divided into simple and complex, where simple coacervates are typically made of a single amphiphilic component or mixtures of similarly charged amphiphilic molecules that phase separate with each amphiphile concentrating into the separate phases.5−15 Coacervation and phase separation in the purely aqueous medium occur only under specific conditions and depend on a number of parameters such as the molecular structure, concentration, and/or mole fraction of amphiphiles as well as parameters such as the temperature, ionic strength, and pH. Mixtures of oppositely charged polyions or polyelectrolytes (e.g., charged polymers and biomacromolecules such as proteins and polysaccharides) form complex coacervates more readily than surfactants.5−15 The formation of complex © 2013 American Chemical Society
coacervates from mixtures of oppositely charged surfactants in purely aqueous media seems to be more in the realm of exception than rule. Complex coacervates are even less common for surfactants and are composed of oppositely charged amphiphiles that form catanionic complexes, followed by phase separation of the aqueous medium.16−18 The addition of a perfluorinated alcohol or acid can reverse that trend and in general facilitates the formation of coacervates and liquid− liquid phase separation. Coacervation is most commonly observed in water where the colloidal-rich coacervate phase contains a high concentration of water but is immiscible with the colloidal−lean aqueous phase. In principle, the phenomenon of coacervate formation and liquid−liquid phase separation is not limited to pure water and can occur in other solvents. In this first report, we demonstrate that the presence of a small percentage of a perfluorinated alcohol such as trifluoroethanol (TFE) or hexafluoroisopropanol (HFIP) or perfluorinated carboxylic acids such as trifluoroacetic acids (TFA), pentafluoropropionic acids (PFPA), and heptafluorobutyric acid (HFBA) induces coacervation and liquid−liquid phase separation in the aqueous media of a broad range of different classes of amphiphilic molecules with diverse molecular structures and compositions.
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EXPERIMENTAL SECTION
Materials. Sodium dodecyl sulfate (SDS) and cetyl trimethyl ammonium bromide (CTAB) were purchased from Affymetrix USB products (Cleveland, OH) and were ultrapure. Dodecyltrimethylammonium bromide (DTAB, 99%) was purchased from Sigma. 1,1,1,3,3,3-Hexafluoro-isopropanol(HFIP, ≥99%) was purchased Received: July 26, 2012 Revised: January 2, 2013 Published: February 8, 2013 2458
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from TCI America. 2,2,2-Trifluoroethanol(TFE), extra pure, was purchased from Acros Organics. Zwitterionic phospholipid dipalmitoylphosphatidyl choline(DPPC) and anionic phospholipid dipalmitoylphosphatidyl glycerol(DPPG) were purchased from Avanti Polar Lipids. Tris and sodium phosphate, monobasic, were purchased from Acros Organics. Sodium Sulfate (anhydrous) was purchased from Sigma. Hydrochloric acid, certified ACS Plus, was received from Fisher Chemical. Methods. Light Microscopy. The coacervate phases of 10% (w/w, 347 mM) SDS [10% (w/w, 274 mM) CTAB, 15% HFIP v/v] and 10% (347 mM) SDS [10% (324 mM) DTAB, 15% HFIP] have been examined by light microscopy. The samples are prepared at room temperature. After centrifugation and separation of the two phases, the bottom coacervate phases are observed by light microscopy. Phase Diagram Experiments. Phase diagrams were created to elucidate the compositions of surfactant and fluoroalcohol at which coacervate formation and aqueous phase separation occur. These would aid in the preparation of the systems used in other analyses. All of the concentrations used for the phase diagrams were made from stock solutions of either 250 or 500 mM SDS, CTAB, SHS, or DTAB . A 1.0 mL quantity of 1:1 (equimolar) SDS/CTAB was added to a 1.5 mL centrifuge tube. The solvent modifier (TFE) was added incrementally, and then the solutions were vortex mixed and centrifuged for 10 min. Occasionally, solids and viscous coacervates were sonicated to facilitate mixing prior to centrifugation. The visual state of the solution was recorded after equilibration. The phase diagrams were plotted as the volume percentage of fluoroalcohol versus the total surfactant concentration. The concentrations were calculated by assuming ideal mixing because TFE mixes nearly ideally with water, which makes them very close estimates. Coacervate Volume Analysis. The goal of this experiment was to determine the volume of the coacervate as the surfactant concentration varied. Stock solutions (375 mM) of SDS and CTAB were added to 15 mL collecting tubes that had volume graduations of 0.1 mL (Nasco, Fort Atkinson, WI). They were subsequently diluted with DI water and TFE to obtain the desired concentrations. Rubber stoppers and Parafilm were used to seal the top before mixing by inversion. The tubes were centrifuged and then allowed to sit and equilibrate overnight. The volumes of the coacervate and the total solution were recorded. The experiment was conducted in triplicate. Quantitation of Total Surfactant Content. A gravimetric approach was used to determine the amount of total surfactant in each phase. The water and fluoroalcohol were evaporated at a temperature just below 100 °C that was chosen so that the samples did not boil violently, which could result in sample loss. The solutions were prepared in a similar manner to those used in the coacervate volume analysis above. The coacervate phase was isolated by removing the aqueous phase with a Pasteur pipet. Sample vials (4 mL) were heated to ∼90 °C in an oven. They were then removed and allowed to cool to room temperature for 1 h before being weighed. Aliquots (1 mL) of the aqueous phases were added to separate vials, and 200 μL aliquots of the coacervate phases were added and the total weight was recorded. ( For a few solutions with small coacervates or difficult to sample coacervates (i.e., not on the bottom), 100 or 75 μL aliquots were used.) The solvents were evaporated in the oven for 10 days before being removed, cooled for 1 h, and reweighed. The remaining weight in excess of the original vial weight should be attributable to the surfactant. Attenuated Total Reflectance−Fourier Transform Infrared (ATRFTIR) Spectroscopy Analysis. The ATR-FTIR method was used to determine the amount of TFE found in each phase for the SDS− CTAB system. The samples were prepared by mixing 1:1 224 mM SDS and 224 mM CTAB, 1:1 250 mM SDS and 250 mM CTAB, in small vials with addition of different TFE volume to get total final concentration of surfactants 179 mM. TFE was added in a volume ratio of 0.25:1 (20% v/v) and 0.4:1 (29% v/v) to create the coacervates. The aqueous and coacervate phases were separated from one another with a Pasteur pipet. In addition to the coacervate samples, the ATR-FTIR spectra of water, 250 mM SDS, 250 mM
CTAB, and TFE were obtained for peak recognition and calibration plots. All spectra were collected using a Bio-Rad (Hercules, CA) Digilab FTS-3000 Fourier transform infrared (FT-IR) spectrometer with a mounted crystalline germanium attenuated total internal reflection (ATR) sampling attachment (Pike Technologies Inc., MIRacle Single Reflection ATR, Madison, WI). The infrared light is focused onto the photodiode of a liquid-nitrogen-cooled, narrow-band mercury− cadmium−telluride (MCT) detector. The spectra presented are an average of 1 accumulation of 64 scans. All spectra were recorded at room temperature, approximately 23 ± 1 °C with a resolution of 2 cm−1. The spectra were converted into absorbance units by taking the negative of the log ratio of a sample spectrum to that of an air spectrum. Karl Fischer Water Analysis. The water concentrations for both aqueous and coacervate phases of 179 mM as total concentration for SDS and CTAB (1:1), 20% TFE v/v, and 29% TFE v/v have been determined by the Karl Fischer titration method using 701 KF Titrino (Metrohm Ltd.; Herisau, Switzerland). Volumetric one-component KF titration was tested where methanol was the solvent and HYDRANAL Composite 5 (Sigma-Aldrich) was the reactant. Samples (25 μL) were titrated in triplicate for both aqueous and coacervate phases of 20 and 29% TFE samples. The samples were prepared at room temperature, and then the solutions were vortex mixed and centrifuged. The tubes were allowed to sit and equilibrate overnight.
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RESULTS AND DISCUSSION Table 1 lists a summary of a variety of simple and complex coacervate systems that have been made in this laboratory thus Table 1. Perfluoro-Alcohol/Acid-Induced Coacervate (PFAIC) Systems Table 1A. Complex Perfluoro-Alcohol/Acid Induced Coacervates (ComplexPFAIC) group I II III
anionic amphiphile
cationic surfactant
surfactants: sodium alkane sulfates DTAB, (SDS, SHS, SOS, and DBSA) CTAB, OTAB anionic phospholipids: DPPG DTAB and CTAB bile acid salts: SC and SDC DTAB and CTAB
coacervator TFE, HFIP, TFA, PFPA, HFBA HFIP
TFE, HFIP, TFA, PFPA, HFBA IV perfluorinated surfactant: PFOA CTAB HFIP V polyelectrolytes: sodium salt of DTAB and TFE, HFIP, PAA and PMA CTAB TFA, PFPA, HFBA Table 1B. Simple-Perfluoro-Alcohol Induced Coacervates (Simple-PFAIC) VI zwitterionic surfactant: DMMAPS TFE, HFIP, VII zwitterionic phospholipid: DPPC HFIP VIII anionic phospholipid: DPPG HFIP IX cationic surfactants (DTAB and CTAB) at pH HFIP >7.0 X anionic surfactants: SDS + HCl HFIP XI nonionic surfactants: Triton X-100 and X-114 HFIP
far. The initial discovery was the formation of the complex coacervates composed of mixed anionic SDS and cationic CTAB surfactants over a wide range of surfactant concentrations and TFE (see below). To achieve an understanding of the scope of the perfluoroalcohol/acid-induced coacervation phenomenon, we screened a library of different types of amphiphiles ranging from analogs of SDS and CTAB and then expanded the selections to other classes of amphiphiles such as bile salts, phospholipids, zwitterionic surfactants, nonionic surfactants, and charged 2459
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Figure 1. Images of a mixture of 100 mM SDS and 100 mM CTAB (1:1) in water (image 1) and in the presence of HFIP (2−5) and HFBA (image 6) serving as coacervators. Light microscopy images of coacervate phases in SDS−CTAB−HFIP (7) and SDS−DTAB−HFIP (8).
thymol blue is primarily concentrated in the cationic-rich coacervate bottom phase whereas its partition coefficient in the anionic-rich system (image 5) is smaller as evident from the appearance of the yellowish color in the top aqueous phase. Image 6 illustrates the effect of adding a perfluorinated acid, HFBA, that surprisingly resulted in the formation of three separate phases. The dye is more concentrated in the bottom phase than in the middle phase as evident from the different shades. The third (top) phase is colorless. The bottom phase probably contains higher concentrations of the surfactants and/ or HFBA than the middle phase and the top phase that is aqueous-rich and lean in colloids. The coacervate systems induced by perfluorinated acids are currently under investigation. Light microscopy images of the complex coacervate phases in the presence of 15% HFIP v/v show the formation of spherical particles (or droplets) with diameters varying from 1 to 7 μm in SDS−CTAB (image 7) and from 2 to 3.5 μm in SDS−DTAB (image 8). Note that the particles (or droplets) coalesce and their sizes grow with time. The formation of complex coacervates from oppositely charged polyelectrolytes (proteins, polysaccharides, or synthetic polyions) is more common than those involving surfactants because of the existence of multiple charge groups on the former molecules.9−14 Complex coacervate formation has been reported for a limited combination of oppositely charged surfactants under a specific, narrow range of concentrations. In nearly all reported cases in the literature, complex coacervation via charged surfactants occurred at specific mole fractions when one of the two oppositely charged surfactants were present in excess. For example, Xiao et al.16 studied mixtures of sodium dodecyl sulfate (SDS) and dodecyltriethylammonium bromide (DTeAB). Complex coacervation and liquid−liquid phase separation were observed in two small regions, where one of the two surfactants was in excess, either a cationic- or anionicrich mixture. At all other mole fractions and concentrations, the mixtures exist as a single liquid phase or liquid/solid phases. Note that cationic surfactant DeTAB has a triethyl moiety in the headgroup, which is different from the more common and commercially available cationic surfactants with the trimethyl moiety in the headgroup such as CTAB or DTAB used in this study. Other workers have also reported similar behavior to that reported by Xiao et al. for different mixed catanionic systems composed of specific combinations of oppositely charged surfactants, for example, mixtures of cetyl trimethyl ammonium bromide (CTAB) and sodium dodecyl sulfonate (SDSu)17 and mixtures of DTAB and alkyldiphenyloxide disulfonate
polymers (polyelectrolytes). Five different groups of complex perfluoro-alcohol/acid induced coacervates (complex-PFAIC) composed of mixed, oppositely charged amphiphiles (Table 1A) and six groups of simple perfluoro-alcohol/acid induced coacervates (simple-PFAIC) made of a single amphiphile (Table 1B) have been discovered. The different groups are recognized on the basis of different classes of amphiphiles, for example, those made of synthetic surfactants, polyelectrolytes (charged polymers), and bile salts. Note that each group contains multiple types of coacervates made of different analogs. For example, the group I complex-PFAIC (Table 1A) represents different combinations of anionic and cationic surfactants with different chain lengths (SDS, SHS, SOS + DTAB or CTAB) or a hydrophobic tail (DBSA) that remarkably could be combined in various mole fractions over a broad range of concentrations. Images 2−6 in Figure 1 illustrate some examples of the complex coacervation between two oppositely charged surfactants: anionic sodium dodecyl sulfate (SDS) and cationic cetyltrimethyl ammonium bromide (CTAB). Mixtures of oppositely charged surfactants form catanionic complexes at or near equimolar ratios that are typically insoluble in aqueous media even at low concentrations. Image 1 illustrates a mixture of 100 mM SDS and CTAB in water that expectedly formed a white precipitate. Image 2 shows that the addition of 9% v/v HFIP to the 100 mM SDS−CTAB (1:1) mixture results in the solubilization of the precipitate and the formation of two phases in the aqueous media. A dye, methylene blue (MB), was added for a better visualization of the phase separation and solute distribution (partitioning) into the coacervate bottom phase (Figure 1, images 2, 3, and 6). Increasing the HFIP concentration to 27% results in a decrease in the partition coefficient of MB in the coacervate phase, as evident from the appearance of the light-blue color in the top aqueous phase (image 3). As can be seen, the phase boundary is not as distinct and is at a slightly higher HFIP concentration (>30%) when the two phases merge into one liquid phase (not shown). HFIPinduced complex coacervate formation also occurs at several other anionic/cationic mole ratios. Two examples are illustrated in images 4 and 5 (dyed with thymol blue) for a cationic-rich 30 SDS:70 CTAB and an anionic rich 70 SDS:30 CTAB mixture at 100 mM total SDS−CTAB concentration and 9% HFIP, respectively. Note that the thymol blue solution has a yellowish color that indicates a pH value between ∼3 and 8. The colorless top phase in image 4 suggests that anionic dye 2460
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Figure 2. Phase diagram of mixtures of cationic and anionic surfactants (1:1 mol ratio) with different chain lengths and TFE-forming complex coacervates: (A) SDS−CTAB, (B) SHS−DTAB, (C) SDS−DTAB, and (D) a simple coacervate made of zwitterionic surfactant DMMAPS and TFE. Abbreviations: tL, turbid liquid; S, solid; G, gel; C, coacervate; wG, white gel-like; cG, clear gel-like; C/L, liquid−liquid two-phase systems with the coacervate top phase and aqueous bottom phase; L/C, liquid−liquid two-phase systems with the top aqueous phase and bottom coacervate phase; and L, single liquid phase.
(DPDS).18 In both CTAB-SDSu and DTAB-DPDS systems, the formation of complex coacervates also occurred over a defined, narrow range of mole fractions where either the cationic or anionic surfactant was present in excess. At a 1:1 mol ratio, aqueous catanionic mixtures form solid precipitates. To the best of our knowledge, mixtures of SDS−CTAB and SDS−DTAB would not form coacervates at any mole fraction or concentration in purely aqueous solutions. Thus, it is quite remarkable that the inclusion of a small amount of a perfluorinated alcohol or acid induces coacervation in mixtures of any two catanionic mixtures with different combinations of chain lengths and mole fractions and over a wide range of concentration, from a few millimolar to several hundred millimolar. Figure 2A−C illustrates the effect of the addition of TFE on the phase behavior of three mixtures of catanionic surfactants (1:1 mol ratio) with different combinations of chain lengths. Figure 2A shows the behavior for anionic SDS with a 12-carbon chain length combined with the cationic 16-carbon chain surfactant, CTAB. Figure 2B depicts the behavior when anionic 16-carbon chain surfactant SHS is combined with the 12-carbon cationic surfactant DTAB; and in Figure 2C, both the anionic and cationic surfactants have the same C-12 chain lengths. In spite of some subtle differences, there are striking similarities among the three systems. In all cases, mixing the
two oppositely charged surfactants resulted in the formation of a white precipitate in pure water. At lower TFE concentrations, the mixtures exist in several forms such as a turbid liquid and/ or mixtures of solid, liquid, gel, and/or coacervate. At TFE concentrations of around 15−16% v/v for the two systems with different chain length combinations (C12/C16) and around 12−13% TFE when the two surfactants have the same chain length (C12/C12), the complete transition to two liquid−liquid phases (shown as C/L and L/C in Figure 2) takes place where one phase is the coacervate (C) and the other phase is the surfactant-lean aqueous phase (shown as L in Figure 2). Note that the coacervate formation and aqueousphase separation occur over a broad range of total surfactant concentration from a few millimolar to several hundred millimolar. At higher TFE concentrations (above ∼30−35% v/v), the liquid−liquid phases dissolve into a single liquid phase (shown as L). Remarkably, the minimum TFE concentration for transition to a liquid−liquid two-phase system is nearly independent of the total surfactant concentration for all three systems. In the two systems with a chain-length mismatch (C12/C16), the coacervate is initially the top phase (marked as C/L in Figure 2) and then at higher concentrations of TFE the coacervate forms as the bottom phase (denoted as L/C) in the liquid− 2461
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Figure 3. Effect of total surfactant concentration on (A) SDS−CTAB (1:1) coacervate volume with 29% v/v TFE, (B) surfactant concentration in the SDS−CTAB (1:1) coacervate phase at 20% TFE (red) and 29% TFE (blue), and (C) surfactant concentration in the aqueous phase of liquid− liquid systems of SDS−CTAB (1:1) with 20% TFE (red) and 29% TFE (blue).
Figure 4. ATR-FTIR spectra of the complex coacervate of 179 mM 1:1 SDS−CTAB with 20% (red) and 29% v/v (blue) TFE. Five major peaks for TFE were observed at 1280, 1150, 1090, 950, and 828 cm−1 that were used to quantify the concentration of TFE. The inset illustrates the ATR-FTIR calibration plots for the determination of TFE at three wavenumbers.
liquid systems. However, for the system with equal chain lengths, the coacervate phase is consistently the bottom phase. When a phase is at the top, it is indicative of lower density than the bottom phase. Thus, the C/L phases in C12/C16 systems (Figure 2A,B) show that at lower TFE concentrations the density of the surfactant-rich phase (coacervate) is lower than that of the surfactant-lean, aqueous-rich phase and the trend reverses at higher TFE levels. The fact that this behavior is not observed for SDS−DTAB (both with C-12, Figure 2C) suggests that the molecular organization in the assembly of the catanionic surfactants also plays a role and the phenomenon cannot be simply explained by changes in the bulk density of the two phases. Although the microstructures of these coacervates are not known at this point, one can assume that the oppositely charged surfactants with equal chain lengths would form tighter assemblies or organizations less affected by steric effects resulting from the chain length mismatch of the C12/C16 systems (Figure 2A,B). The light microscopy results showed that the droplets of the coacervate phase of SDS− DTAB were more uniform in size than SDS−CTAB (images 7 and 8). In the SHS−DTAB system, there is a small region (shown as L + C) where the system appears as small oily droplets suspended in an aqueous medium. Finally, Figure 2D illustrates the phase diagram for a simple coacervate composed of zwitterionic surfactant DMMAPS (system V in Table 1). The phase transition to the liquid−liquid phase (L/C) occurs at a lower TFE concentration and in the TFE range where the
L/C region is narrower than those for the complex coacervates. Nevertheless, the overall patterns seem to be similar. Figure 3A shows that the volume percentage of coacervate relative to the fixed total volume of the solution increases linearly with the total surfactant concentration. The surfactant concentrations in each of the liquid−liquid phases was determined gravimetrically (as w/w %) through solvent evaporation. Figure 3B shows that the surfactant concentration in the coacervate phase does not change with the total surfactant concentration and but is dependent on the amount of TFE added: around 40% w/w surfactant at 20% v/v TFE that decreases to 25% w/w at a higher concentration of 29% v/v TFE. The fixed surfactant concentration in the coacervate phase is due to the concomitant increase in coacervate volume with the increase in the amount of surfactant. This is not the case for the surfactant-lean aqueous phase where the surfactant concentration in the phase increases linearly with the total surfactant concentration (Figure 3C). Note that the surfactant concentration in the aqueous phase ranges between 0.2 and 1.6% w/w (Figure 3C) over the same range of surfactant concentration. At lower fluoro-alcohol concentrations, as much as 80% of the total amount of surfactant is concentrated in the coacervate phase (1:1 SDS− CTAB). Given that the coacervate volume is only about 10% of the total volume of the solution, we estimate that the concentrations of the surfactants in the coacervate phase 2462
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concentrations. This situation is rather different from that of other coacervate phases that contain high concentrations of water. One might even wonder whether we can refer to these phases as coacervates. We chose to call the perfluoro-alcohol/ acid-induced phases coacervates because they follow a similar pattern to that of other coacervate phases. That is, their formation involves the assembly of amphiphilic molecules and the formation of a phase that is enriched in the amphiphiles and the solvent (water−TFE in this case), which leads to phase separation in the aqueous phase. Outlook. The underlying mechanism for perfluorinated alcohol/acid-induced coacervation is not known and might differ for simple and complex coacervates. However, the presence of both the fluorine groups and alcohol or acidic groups seems to be necessary. For example, the addition of aliphatic alcohols (methanol−octanol) or perfluorinated reagents with polar functional groups such as trifluoroacetic acid methyl ester and trifluoroethylamine did not result in coacervate formation. It should be noted that we have not exhaustively tested all combinations of perfluorinated alcohols and acids in solutions of all different types or all combinations of oppositely charged amphiphiles that induce coacervation. However, it appears that HFIP is the most effective among all listed coacervators. Interestingly, the formation of complex coacervation is more readily achieved with both perfluorinated alcohols and acids, and simple coacervation has been observed only for the alcohols, especially HFIP, thus far. Perfluorinated alcohols such as TFE, HFIP, and perfluorinated diols are known to stabilize the secondary structures (α-helix) in peptides and proteins.19−22 Although the exact mechanism for this phenomenon is unknown, it is believed that perfluoroalcohols such as TFE and HFIP form (micelle-like) clusters in aqueous media and that the clusters have a dehydration effect on the hydrophobic peptides/protein chains that, along with hydrogen bonding, serve as a driving force for α-helix formation. HFIP is more effective in stabilizing the secondary structure than TFE. In spite of obvious differences between the formation of α-helices and coacervation, it is plausible that the underlying mechanisms for fluoroalcoholinduced phenomena are similar. In fact, as the perfluorinated chain length or number of fluorine groups increases (e.g., TFE vs HFIP or TFA vs PFPA vs HFBA), the perfluorinated alcohol or acid would become a more effective coacervator, which means that it induces coacervation and aqueous phase separation at lower concentrations and for a wider range of amphiphilic solutions. The fluorine groups significantly increase the hydrogen bond donor strength/acidity as well as the hydrophobicity of the perfluoro-alcohols/acids. Thus, one can hypothesize that the fluorine and hydrogen bond donor groups play a synergistic role in the formation of coacervate and subsequent aqueous-phase separation. It is believed that coacervate systems have spongelike bicontinuous structures. Menger et al. described the bicontinuous structure of coacervates (sponge morphology) with bilayer assemblies of surfactants extending indefinitely and being highly interconnected.23 Whether the perfluoro-alcohols/acid-induced coacervate phases would have the same microstructure and organization remains to be determined.
could be in several molar ranges. This would provide very high solubilizing power for the coacervates. Attenuated total reflectance−Fourier transform infrared (ATR-FTIR) spectroscopy was used to determine the TFE concentrations in the aqueous and coacervate phases for the SDS−CTAB system. Figure 4 shows the ATR-FTIR spectrum of a complex coacervate made with solutions of 179 mM SDS and CTAB (1:1) plus 20% v/v (red) and 29% v/v (blue) TFE. Five major TFE peaks at 1280, 1150, 1090, 950, and 828 cm−1 allowed the quantitation of TFE concentration in the coacervate and aqueous phases. The concentration of water in both phases was determined by the Karl Fischer method. The concentrations of TFE and water in the coacervate and aqueous-rich phases of 179 mM SDS−CTAB at two total TFE concentrations (20 and 29%) are listed in Table 2. As expected, the concentration of Table 2. Concentration of TFE and Water in the Coacervate and Aqueous-Rich Phases of 179 mM SDS−CTAB (1:1)− TFE 20% v/v and 179 mM SDS−CTAB (1:1)−TFE 29%a coacervate phase
aqueous-rich phase
total TFE % v/v % w/wb
TFE % w/w
H2O % w/w
TFE % w/w
H2O % w/w
20/25 29/35
41.6 (±1.7) 49.3 (±1.4)
23.3 (±2.4) 33.0 (±2.1)
26.6 (±0.8) 39.2 (±1.6)
81.8 (±5.3) 71.7 (±2.3)
a Values in parentheses are 95% confidence intervals. bFor the conversion of % v/v to % w/w total TFE concentration, we have assumed that the density of an aqueous mixture of 89.5 mM SDS and 89.5 mM CTAB (1:1) would be equal to that of pure water. The actual density cannot be determined because a 1:1 mixture of SDS−CTAB in pure water would form a precipitate.
TFE in both the coacervate and aqueous-rich phases increased with an increase in the total TFE concentration. Interestingly, an increase in the total TFE concentration from 20 to 29% resulted in an increase in the concentration of water in the coacervate phase and a decrease in the aqueous-rich phase as evident from the data in Table 2 and the water peak at 1641 cm−1 in the ATR-IR spectrum in Figure 4. As mentioned above, the results in Figure 3B show that the concentration of surfactants in the coacervate phase is lower at higher TFE concentration. These results suggest that as the total concentration of the perfluoro-alcohol coacervator increases, both TFE and water are extracted in the coacervate phase and replace some of the surfactants that would move to the aqueous-rich phase. Thus, the chemical compositions and density of the two phases become more similar as the concentration of the fluoroalcohol coacervator increases, and at some point (>30% v/v), the two phases merge into a single phase (Figure 2). The results show that TFE is a major constituent of the coacervate phase with concentrations of around 42 and 49% w/ w when the starting total concentrations were approximately 25 and 35% w/w, respectively. The increase in TFE concentration from the original levels could be attributed to the extraction of the fluoroalcohols by the coacervate phase and/or enrichment of the fluoroalcohol due to a smaller volume of coacervate as compared to the initial total volume. Surfactants constitute the other major component of the coacervate with concentrations of around 40 and 25% w/w at total TFE concentrations of 20 and 29% v/v, respectively. Water constitutes only one-fourth or one-third of the coacervate phase composition at these TFE
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AUTHOR INFORMATION
Corresponding Author
*E-mail:
[email protected]. 2463
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Letter
Present Address
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Pfizer, 4300 Oak Park Rd, Sanford, North Carolina 27330, United States.
Notes
The authors declare no competing financial interest.
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ACKNOWLEDGMENTS We thank Mahboubeh Nejati, Nathan Weisner, and Chris Collins for their assistance in exploring the different coacervate systems in Table 1. We thank Professor Wang and Luyang Zhao for light microscopy images. We are also grateful for useful comments by an anonymous reviewer.
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ABBREVIATIONS PFAIC, perfluoro-alcohol/acid induced coacervates; SDS, sodium dodecyl sulfate; SHS, sodium hexadecyl sulfate; SOS, sodium octadecyl sulfate; DTAB, dodecyl trimethyl ammonium bromide; CTAB, cetyltrimethyl ammonium bromide; OTAB, octadecyl trimethyl ammonium bromide; TFE, trifluoroethanol; HFIP, hexafluoroisoporpanol; TFA, trifluoroacetic acid; PFPA, pentafluoro propionic acid; HFBA, hexafluoro butyric acid; DPPG, dipalmitoylphosphatidylglycerol; SC, sodium chloate; SDC, sodium deoxy cholate; PFOA, perfluoro octanoic acid; PAA, poly(acrylic acid); PMA, poly(methacrylic acid); DMMAPS, 3-(N,N-dimethylmyristylammonio)propanesulfonate; DPPC, dipalmitoylphosphatidyl choline; DBSA, dodecyl benzene sulfonic acid; MB, methylene blue
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dx.doi.org/10.1021/la303035h | Langmuir 2013, 29, 2458−2464
