J. Phys. Chem. B 2007, 111, 10713-10722
10713
Diversifying the Solid State and Lyotropic Phase Behavior of Nonionic Urea-Based Surfactants Celesta Fong,*.† Darrell Wells,† Irena Krodkiewska,† Asoka Weerawardeena,† Jamie Booth,‡,§ Patrick G. Hartley,† and Calum J. Drummond†,| CSIRO Molecular & Health Technologies, Bag 10, Clayton South, VIC 3169, Australia, Applied Science, RMIT, Melbourne, VIC 3001, Australia, CSIRO Manufacturing and Materials Technology, Bag 33, Clayton South, VIC 3169, Australia, and CSIRO Industrial Physics, P.O. Box 218, Lindfield, NSW 2070, Australia ReceiVed: February 15, 2007; In Final Form: June 19, 2007
The solid state and lyotropic phase behavior of 10 new nonionic urea-based surfactants has been characterized. The strong homo-urea interaction, which can prevent urea surfactants from forming lyotropic liquid crystalline phases, has been ameliorated through the use of isoprenoid hydrocarbon tails such as phytanyl (3,7,11,15tetramethyl-hexadecyl) and hexahydrofarnesyl (3,7,11-trimethyl-dodecyl) or the oleyl chain (cis-octadec-9-enyl). Additionally, the urea head group was modified by attaching either a hydroxy alkyl (short chain alcohol) moiety to one of the nitrogens of the urea or by effectively “doubling” the urea head group by replacing it with a biuret head group. The solid state phase behavior, including the liquid crystal-isotropic liquid, polymorphic, and glass transitions, is interpreted in terms of molecular geometries and probable hydrogen-bonding interactions. Four of the modified urea surfactants displayed ordered lyotropic liquid crystalline phases that were stable in excess water at both room and physiological temperatures, namely, 1-(2-hydroxyethyl)-1-oleyl urea (oleyl 1,1-HEU) with a 1D lamellar phase (LR), 1-(2-hydroxyethyl)-3-phytanyl urea (Phyt 1,3-HEU) with a 2D inverse hexagonal phase (HII), and 1-(2-hydroxyethyl)-1-phytanyl urea (Phyt 1,1-HEU) and 1-(2-hydroxyethyl)-3-hexahydrofarnesyl urea (Hfarn 1,3-HEU) with a 3D bicontinuous cubic phase (QII). Phyt 1,1-HEU exhibited rich mesomorphism (QII1, QII2, LR, LU, and HII), as did one other surfactant, oleyl 1,3-HEU (QII1, QII2, LR, LU, and HII), in the study group. LU is an unusual phase which is mobile and isotropic but possesses shear birefringence, and has been very tentatively assigned as an inverse sponge phase. Three other surfactants exhibited a single lyotropic liquid crystalline phase, either LR or HII, at temperatures >50 °C. The 10 new surfactants are compared with other recently reported nonionic urea surfactants. Structureproperty correlations are examined for this novel group of self-assembling amphiphiles.
Introduction Utilizing the self-assembly of amphiphilic molecules in water to create hydrophilic and hydrophobic domains has long been an active area of scientific research and end use applications. Rich mesomorphism is displayed by many surfactants, with the one-dimensional (1D) lamellar liquid crystalline phase (LR) arguably the best characterized, as it plays a major role in biological systems. More complex, higher order phases such as the 2D inverse hexagonal phase (HII) have also received attention, in part because of an ability to promote membrane fusion and to participate in transbilayer transport.1,2 Amphiphiles such as dioleoylphosphatidylethanolamime (DOPE) that adopt the HII phase at physiological temperatures have been employed in “fusogenic” lipid-based drug delivery systems.3-5 Also, the 3D inverse bicontinuous cubic phases (QII) of glyceryl monooleate (GMO) and phytantriol (3,7,11,15-tetramethyl-1,2,3hexadecanetriol) have been studied, as their high internal surface area and stability against dilution are of interest for pharmaceutical and cosmetic applications.6-14 * To whom correspondence should be addressed. E-mail: Celesta.fong@ csiro.au. Phone: +61-3-95452608. Fax: +61-3-9545-8106. † CSIRO Molecular & Health Technologies. ‡ RMIT. § CSIRO Manufacturing and Materials Technology. | CSIRO Industrial Physics.
The non-lamellar 2D and 3D phase structures have been well described in the literature15-20 and will be only briefly overviewed here. The inverse bicontinuous cubic phase of GMO is perhaps the best characterized and may be described as a bilayer of surfactant infinitely curved in three dimensions and wrapped around two continuous, noncontacting water networks. In contrast, the inverse hexagonal phase has two-dimensional order and comprises inverse cylindrical micelles in a hexagonally close packed array. Several factors including local and global packing constraints dictate the structure of surfactant self-assembly phases.15,18,19,21 The molecular packing of surfactant molecules in water is determined by the competing interactions of the polar head groups and alkyl chains, whereby the shape factor or critical packing parameter (CPP) is defined as CPP) V/a0lc, where lc is the effective length of the surfactant chain, a0 is the effective surfactant head group area (determined by the balance of interchain attractive and head group repulsive interactions), and V is the average volume occupied by a surfactant molecule. For the inverse HII and QII structures described above, CPP > 1 compared to 1/2 e CPP e 1 for bilayers.21 Simplistically then, the shape factor required for promoting inverse phases is a wedge shaped molecule, that is a molecule with a relatively small head group with respect to the hydrophobe volume. These molecular factors, together with composition and environmental
10.1021/jp071324d CCC: $37.00 Published 2007 by the American Chemical Society Published on Web 08/17/2007
10714 J. Phys. Chem. B, Vol. 111, No. 36, 2007
Fong et al.
Figure 1. Surfactant hydrophobes and head group structural units.
Figure 2. Energy minimized representations of the (a) oleyl, (b) phytanyl, and (c) hexahydrofarnesyl chain with a urea head group.
parameters, determine the mesophase behavior and nanostructure, to ultimately impact upon performance and functionality. To date, the urea moiety represents the smallest peptide containing a head group with sufficient hydrophilicity to enable lyotropic liquid crystalline phase formation. This is a very recent discovery,22 as strong intermolecular hydrogen bonding between urea-urea head groups dominates the physicochemical properties of linear hydrocarbon ureas (including head group positional isomers) and inhibits lyotropic liquid crystalline phase formation.23,24 However, the hydrogen-bonding interaction can be ameliorated by modification of the hydrocarbon chain. The introduction of highly splayed tail groups such as unsaturated or isoprenoid hydrophobes disrupts the lateral packing of the hydrocarbon chain and exaggerates the footprint of the chain relative to the head group. This approach has been successful in promoting lyotropic mesophases in these amphiphile systems, in particular, a HII phase that is thermodynamically stable in excess water.22,25,26 This type of lyotropic phase behavior is relatively rare, with only a small number of surfactant systems previously demonstrating a capacity for dilution in this way. The formation of inverse hexagonal phases from a single chained surfactant is also unusual and is more common for double chained amphiphiles such as those from biomembrane lipids (e.g., DOPE). Apart from the urea amphiphiles, Fong et al. have also reported similar mesophase behavior for some novel
glycerate surfactants, which are structural analogues of GMO.27,28 Hato and co-workers provide the only other known example of a single chained surfactant with an inverse hexagonal phase present at ambient temperature for 1-glyceryl phytanyl ether.29 In the present work, we expand previous studies of structureproperty correlations as a function of both hydrophobe and head group modification for this new class of self-assembly amphiphiles, nonionic urea-based surfactants.22-26 Modification of the head group included the introduction of a short alkyl chain (ethyl or propyl) spacer which was aimed at disrupting intermolecular hydrogen bonding between adjacent carbonyl and -NH functionalities. To compensate for the weakly polar head group, hydroxy moieties were attached to these spacer groups. Another variation of the urea head group was biuret which comprises essentially two urea units; this was further modified using an hydroxyalkyl spacer for direct comparison with the urea analogue. Figure 1 depicts the head group and hydrophobe variations investigated, as well as the shorthand nomenclature for each of the head groups and chains. Figures 2 and 3 show the energy minimized configurations of the hydrophobes and head group orientations. In the first series of compounds, the substitution took place on the same urea nitrogen as bore the hydrophobic chain to give a 1-(2-hydroxyethyl)-1-alkyl urea (1,1-HEU). In the second series, the substitution was at the second nitrogen
Solid State and Lyotropic Phase Behavior
J. Phys. Chem. B, Vol. 111, No. 36, 2007 10715
Figure 3. Energy minimized representations (“ball and stick”) of the urea head group modifications with an oleyl tail: (a) urea; (b) 1,1-HEU; (c) 1,3-HEU; (d) 2,3-DHPU; (e) Biuret; (f) 1,1-HEBU.
to give a 3-(2-hydroxyethyl)-1-alkyl urea (1,3-HEU). A longer spacer with a propyl chain was also investigated; with its slightly increased hydrophobicity countered by an additional hydroxy group to give 1-(2,3-dihydroxypropyl)-1-alkyl urea (2,3-DHPU). In addition, the structural “dimer” of the urea head group, the biuret, was investigated, which has slightly increased size and polarity. Finally, to complete the set, the biuret with a 2-hydroxyethyl group was created to give a 1-(2-hydroxyethyl)-1alkyl biuret (1,1-HEBU). The hydrophobes selected consist of either isoprenoid type chains, namely, hexahydrofarnesyl (3,7,11-trimethyl-dodecyl) and phytanyl (3,7,11,15-tetramethyl-hexadecyl), or the unsaturated oleyl chain (cis-octadec-9-enyl). General Experimental Section General Syntheses of Alkyl Urea Surfactants. Nitrourea was synthesized by the method of Davis and Blanchard.30 The procedure involves reaction of urea nitrate with concentrated sulfuric acid. The target urea surfactant was formed from reaction of nitrourea and the appropriate amount of amine using the method of Buck and Ferry.31 The detailed synthesis and characterization of the amine precursors and target urea surfactants are provided as Supporting Information. Differential Scanning Calorimetry (DSC). DSC was performed using a Mettler 3000 system at scan rates of either 2.5 or 0.1 °C/min. The temperature calibration ((0.3 °C) of the platinum thermometer was performed with ultrahigh purity 1-hexane, water, and indium. The thermal calibration of the DSC instrument was performed by integration of the standard indium peak. The energies of the exotherms and endotherms were calculated using the Mettler 3000 software. Water Penetration into Urea-Based Surfactants. The ureabased surfactants have extremely low solubility in water (
