1384
J. Phys. Chem. B 2007, 111, 1384-1392
Synthesis and Mesophases of Glycerate Surfactants C. Fong,*,† D. Wells,† I. Krodkiewska,† J. Booth,‡,§ and P. G. Hartley† CSIRO Molecular and Health Technologies, Bag 10, Clayton South, VIC, 3169, Australia, and Applied Science, Royal Melbourne Institute of Technology, Melbourne, VIC, 3001, Australia ReceiVed: September 12, 2006; In Final Form: NoVember 2, 2006
In the quest to rationally design novel mesophase systems the challenge remains to deconvolute the relationship between structure, composition, and function. In the current study, novel glycerol-derived surfactants with high negative interfacial areas and a preference for inverse phase behavior have been targeted and synthesized. This has been achieved by application of the rule-of-thumb afforded by the critical packing parameter (CPP), namely, that inverse phase behavior is favored by wedge-shaped molecules with relatively small head group versus chain volume. Highly splayed hydrophobes with exaggerated cross section such as oleyl (cis-octadec9-enyl) hexahydrofarnesyl (3,7,11-trimethyl-dodecyl) and phytanyl (3,7,11,15-tetramethyl-hexadecyl) were particularly successful for this purpose across many variations of head group. The phase behavior of the binary system in water of many of these surfactants is relatively simple. Typically, cubic or inverse hexagonal phases exist at the interface with water with the inverse micellar phases present at lower hydration. The inverse liquid crystalline phases were present for a broad range of temperatures and compositions.
Introduction Supramolecular self-assembly amphiphiles with biomimetic structural motifs and surface ligand functionalities are providing a new generation of “smart” materials. The desire to manipulate such behavior has fuelled a resurgence in the study of lyotropic liquid crystalline phase behavior. Submicrometer dispersions of liposomes, cubosomes, hexosomes, and their bulk mesophases offer nanometer to micrometer domains for encapsulation,1-6 release,7-19 and structure templating.20,21 However, an advantage of nonlamellar architectures such as the inverse bicontinuous cubic and inverse hexagonal phases is the increased surface area generated by their inherent nanostructure. Such mesophase materials are also much more robust when compared to liposomal delivery technologies by virtue of their semirigid periodicity. In particular, much attention has focused upon the inverse cubic and hexagonal phases of monoolein (GMO, glyceryl monooleate) and, more recently, phytantriol (3,7,11,15-tetramethyl-hexadecan-1,2,3-triol) as these can exist in equilibrium with excess water over a wide range of compositions and temperatures.22,23 They can therefore retain their structure when diluted either in particulate or bulk form. This is a critical feature for delivery applications which require administration of the materials in dispersion form.24,25 The mesophase formed by a surfactant is, to a large extent, determined by the interplay between surfactant head group, tail geometry, and volume.26 These molecular factors, together with composition and environmental parameters, determine the mesophases’ behavior and nanostructure and ultimately impact upon their resultant performance and functionality. Despite the interest in these materials, relatively few systematic attempts * Author to whom correspondence should be addressed. E-mail:
[email protected]. Phone: 61-3-9545-2608. † CSIRO Molecular and Health Technologies. ‡ Royal Melbourne Institute of Technology. § Current address: CSIRO Materials and Manufacturing Technology, Bag 33, Clayton South, VIC 3169, Australia.
have been made to produce and study new surfactants that exhibit dilutable mesophase behavior. In the quest to rationally design novel mesophase systems the challenge remains to deconvolute the relationship between structure, composition, and function. Some insight into these relationships may be gained from the family of monoacylglycerides (MAGs) for which Caffrey and co-workers22,27-33 and Lutton34 have derived structure-property relationships for the homologous series monomyristolein (C14) to monoerucin (C22). Monoolein (C18) is a member of this family. Several members of this family, in particular, the unsaturated derivatives, exhibit inverse bicontinuous cubic and hexagonal phases that are robust to dilution. This type of lyotropic phase behavior is relatively rare for single-chained surfactants, and only a small number of other surfactant systems demonstrate a capacity for dilution in this way. Apart from the MAGs and phytantriol, Hato and co-workers have illustrated a dilutable inverse hexagonal phase for 1-glyceryl phytanyl ether.35-39 Recent work in our laboratory has expanded the range of dilutable mesophase-forming surfactants to include urea-,40,41 substituted urea-,42 and glycerate (1,2 dihydroxy propionic acid)based systems.43 In general, the observations from these studies highlight the importance of molecular geometry in determining mesophase behavior. These effects are conveniently approximated by the critical packing parameter (CPP). The CPP predicts mesophase behavior based on the curvature of the surfactant-water interface, resulting from local packing constraints due to the volume (ν), cross-sectional area of the surfactant head group (a0), and the hydrophobe length (l)26
CPP ) ν/a0l Of particular relevance to this study is the prediction that small head groups and bulky hydrophobes deliver CPP values greater than 1, implying mean negative interfacial curvature and, therefore, inverse mesophase structures.
10.1021/jp0659655 CCC: $37.00 © 2007 American Chemical Society Published on Web 01/19/2007
Glycerate Surfactants
J. Phys. Chem. B, Vol. 111, No. 6, 2007 1385
TABLE 1: Structural Units of the Surfactant Head Groups and Hydrophobes
a
Acyl hydrophobes have a carboxyl at C(1) of these structures.
In the current work we report on a study of the aqueous phase behavior of a series of synthetic analogues of monoolein and phytantriol, with a view to elucidating structure-property correlations within the family with respect to mesophase formation. The list of surfactants is shown in Table 1 and includes novel glycerate and glyceryl ester/ether surfactants not previously described. Figure 1 illustrates the energy-minimized configurations of each of the surfactant head groups. Specifically, we have investigated the role of head grouptail linking group, by contrasting ether and ester functionalities and the role of isoprenoid chain length by comparing phytanyl with hexahydrofarnesyl hydrophobes. In the first instance, we have investigated the effect of modifying the glyceride head group by inverting the ester bond to yield the glycerate head group. In this case, the hydrophile derives from the carboxylic acid precursor, that is, 1,2 dihydroxy propionic acid. Further, we have examined isoprenoid-based derivatives of the monoacylglycerides, namely, glyceryl phytanoate (GMP) and glyceryl hexahydrofanesoate (GMH), thereby expanding the work of Caffrey and co-workers22,28-33 and Lutton34 in this homologous series. Last, the glyceryl ether of the oleyl hydrophobe has been considered. The lyotropic binary surfactant in water behavior of these systems has been characterized using light polarizing microscopy (LPM) and small-angle X-ray scattering (SAXS). The mesomorphic behavior of these materials has been rationalized with respect to surfactant geometry. Experimental Section Surfactant Stability in Water as Determined by NMR. The stability of the glycerol-derived surfactants in water was assessed by NMR after extended storage at physiological temperatures. Under these conditions both the monoacylglyceride and monoalkylglycerates suffer from hydrolysis of the ester linkage with up to 15-20% hydrolysis identified after 1 month at elevated temperatures. OG and HFG in particular were prone to hydrolysis. Lyotropic Phase Behavior of Glycerol-Derived Surfactants. The glycerol-derived surfactants have extremely low miscibility in water with only a few fraction of a percent soluble
from ambient to 100 °C. However, above and near the melting points of the surfactants, mesomorphic behavior was observed. Water penetration scans and light polarizing microscopy were used to identify the mesophases formed as a function of temperature. With the use of a Mettler FP82HT microscope hot stage controlled by an FP90 central processor, surfactant samples were melted (where necessary) between a microscope slide and coverslip, cooled to room temperature, and water added to the edge of the coverslip. Capillary action drew the water between the two glass surfaces to surround the solidified material. This generates a concentration gradient that spans the entire range from pure water to neat surfactant such that all possible phases for the surfactant at the specific temperature were formed. With the use of an Olympus IMT-2 microscope equipped with cross polarizers, anisotropic liquid crystalline phases such as the hexagonal and lamellar phases (which are birefringent with wellcharacterized textures) can be distinguished from isotropic phases such as cubic or micellar phases, which appear transparent under cross polarizers. Differentiation between the latter is based upon the inferred viscosity, since cubic phases are viscous and gel-like. The samples were then heated at 2 °C/min or less, and phase transitions were observed. Samples were also equilibrated at a set temperature for longer periods of time to more accurately ascertain the transition temperatures. Water penetration scans were typically performed in the temperature range of 22-100 °C unless otherwise stated. Optical textures of surfactant lyotropic phases have been described in detail in the literature.44,45 While the identification of textures is not unequivocal by this method, particularly for inverse phases, the progression of phases from the interface, apparent viscosity, swelling behavior, as well as texture provide strong support for their correct assignment. The method therefore provides a rapid, qualitative assessment of the lyotropic phase behavior of a novel surfactant system from (sub)ambient to 100 °C. Small-Angle X-ray Scattering (SAXS). The structures of the bulk phases in excess water were determined using smallangle X-ray scattering. This was performed on a Bruker Nanostar SAXS system equipped with a position sensitive 2D
1386 J. Phys. Chem. B, Vol. 111, No. 6, 2007
Fong et al. TABLE 2: Lyotropic Behavior of the Glycerol-Derived Surfactants surfactant
Mp (°C)a
optical textures
temp (°C)
assignment
Monoacylglyceride Surfactants with Isoprenoid Hydrophobes GMP
