Chelating DTPA amphiphiles: ion-tunable self-assembly structures and gadolinium complexes

A series of chelating amphiphiles and their gadolinium (Gd(iii)) metal complexes have been synthesized and studied with respect to their neat and lyotropic liquid crystalline phase behavior. These amphiphiles have the ability to form ion-tunable self-assembly nanostructures and their associated Gd(III) complexes have potential as magnetic resonance imaging (MRI) contrast enhancement agents. The amphiphiles are composed of diethylenetriaminepentaacetic acid (DTPA) chelates conjugated to one or two oleyl chain(s) (DTPA-MO and DTPA-BO), or isoprenoid-type chain(s) of phytanyl (DTPA-MP and DTPA-BP). The thermal phase behavior of the neat amphiphiles was examined by differential scanning calorimetry (DSC), thermogravimetric analysis (TGA) and cross polarizing optical microscopy (POM). Self-assembly of neat amphiphiles and their associated Gd complexes, as well as their lyotropic phase behavior in water and sodium acetate solutions of different ionic strengths, were examined by POM and small and wide angle X-ray scattering (SWAXS). All neat amphiphiles exhibited lamellar structures. The non-complexed amphiphiles showed a variety of lyotropic phases depending on the number and nature of the hydrophobic chain in addition to the ionic state of the hydration. Upon hydration with increased Na-acetate concentration and the subtle changes in the effective headgroup size, the interfacial curvature of the amphiphile increased, altering the lyotropic liquid crystalline structures towards higher order mesophases such as the gyroid (Ia3d) bicontinuous cubic phase. The chelation of Gd with the DTPA amphiphiles resulted in lamellar crystalline structures for all the neat amphiphiles. Upon hydration with water, the Gd-complexed mono-conjugates formed micellar or vesicular self-assemblies, whilst the bis-conjugates transformed only partially into lyotropic liquid crystalline mesophases.     

Lyotropic liquid crystal engineering-ordered nanostructured small molecule amphiphile self-assembly materials by design

Future nanoscale soft matter design will be guided to a large extent by the teachings of amphiphile (lipid or surfactant) self-assembly. Ordered nanostructured lyotropic liquid crystalline mesophases may form in select mixtures of amphiphile and solvent. To reproducibly engineer the low energy amphiphile self-assembly of materials for the future, we must first learn the design principles. In this critical review we discuss the evolution of these design rules and in particular discuss recent key findings regarding (i) what drives amphiphile self-assembly, (ii) what governs the self-assembly structures that are formed, and (iii) how can amphiphile self-assembly materials be used to enhance product formulations, including drug delivery vehicles, medical imaging contrast agents, and integral membrane protein crystallisation media. We focus upon the generation of 'dilutable' lyotropic liquid crystal phases with two- and three-dimensional geometries from amphiphilic small molecules (225 references).     

Nonionic diethanolamide amphiphiles with unsaturated C18 hydrocarbon chains: thermotropic and lyotropic liquid crystalline phase behavior

The neat and lyotropic liquid crystalline phase behavior of three nonionic diethanolamide amphiphiles with C18 hydrocarbon chains containing one, two or three unsaturated bonds has been examined. This has allowed the effect of degree of unsaturation on the phase behavior of diethanolamide amphiphiles to be investigated. Neat linoleoyl and linolenoyl diethanolamide undergo a transition from a glassy liquid crystal to a liquid crystal at ～-85 °C, while neat oleoyl diethanolamide undergoes a transition at ～-60 °C to a liquid crystalline material before re-crystallizing at -34 °C. Oleoyl diethanolamide then undergoes a third transition from a crystalline phase to a smectic liquid crystalline phase at ～5 °C. In the absence of water, the transition temperature from a smectic liquid crystal to an isotropic liquid decreases with increasing unsaturation. The addition of water results in the formation of a lamellar phase (L(α)) for all three amphiphiles. The lamellar phase is stable under excess water conditions up to temperatures of at least 70 °C. Approximate partial binary amphiphile-water phase diagrams generated for the three unsaturated C18 amphiphiles indicate that the excess water point for each amphiphile occurs at ～60% (w/w) amphiphile.     

Ionic liquids as amphiphile self-assembly media

In recent years, the number of non-aqueous solvents which mediate hydrocarbon-solvent interactions and promote the self-assembly of amphiphiles has been markedly increased by the reporting of over 30 ionic liquids which possess this previously unusual solvent characteristic. This new situation allows a different exploration of the molecular "solvophobic effect" and tests the current understanding of amphiphile self-assembly. Interestingly, both protic and aprotic ionic liquids support amphiphile self-assembly, indicating that it is not required for the solvents to be able to form a hydrogen bonded network. Here, the use of ionic liquids as amphiphile self-assembly media is reviewed, including micelle and liquid crystalline mesophase formation, their use as a solvent phase in microemulsions and emulsions, and the emerging field of nanostructured inorganic materials synthesis. Surfactants, lipids and block co-polymers are the focus amphiphile classes in this critical review (174 references).     

Structural and dielectric behaviour of non-aqueous lyotropic mixtures: influence of amphiphile chain lengths and counter ions

This study highlights the effects of amphiphile chain length and counter ions on the self-assembly and dielectric behaviour of non-aqueous lyotropic liquid crystals. Two-dimensional hexagonal mesophase is seen for short-chain length sodium dodecyl sulphate, while lamellar and multiwall lamellar mesophases are noticed for long-chain length cetyltrimethylammonium bromide and polyoxyethylene (20) sorbitan monolaurate amphiphiles in the non-aqueous domains of ethylene glycol. A strong influence of amphiphile counter ions is seen on static dielectric constant, loss factor, relaxation frequency and relaxation time of these lyotropic mixtures. Refractive indices of these lyotropic phases are also highlighted.     

Nanostructure and amphiphile self-assembly in polar molecular solvents: amides and the "solvophobic effect"

The ability of low molecular weight amides to support amphiphile self-assembly is shown to be a general feature for this class of solvents. This report extends the number of known polar solvents which can support amphiphile self-assembly by five new amides; more than doubling the number of known amides able to serve as amphiphile self-assembly media. The formation of lyotropic liquid crystalline phases by cationic and non-ionic surfactants in these liquid amides is reported. The ability of a solvent to promote amphiphile self-assembly is governed by the "solvophobic effect" and is linked to the solvent cohesiveness. The Gordon parameter which is a measure of the solvent cohesiveness was found to provide a guide to an amides capacity to support lyotropic liquid crystalline phase diversity and thermal stability ranges of those phases. The "solvophobic effect" and steric hindrance factors were compared between amide's and protic ionic liquids possessing analogous chemical structures and also being able to promote amphiphile self-assembly.     

Many protic ionic liquids mediate hydrocarbon-solvent interactions and promote amphiphile self-assembly

A large number of protic ionic liquids (PILs) have been found to mediate solvent-hydrocarbon interactions and promote amphiphile self-assembly. Hexagonal, cubic, and lamellar lyotropic liquid crystalline phases were observed in PIL-hexadecyltrimethylammonium bromide systems. The driving force for the formation of the self-assembled aggregate structures has been attributed to an entropic contribution to the free energy of association, analogous to the hydrophobic effect in water. The specific aggregate structures formed depend upon the cationic and anionic components of the PIL and their interactions with the amphiphiles.     

Nonionic diethanolamide amphiphiles with isoprenoid-type hydrocarbon chains: thermotropic and lyotropic liquid crystalline phase behaviour

The thermotropic and lyotropic liquid crystalline phase behaviour of a series of diethanolamide amphiphiles with isoprenoid-type hydrocarbon chains (geranoyl, H-farnesoyl, and phytanoyl) has been investigated. When neat, both H-farnesoyl and phytanoyl diethanolamide form a smectic liquid crystalline structure at sub-zero temperatures. In addition, all three diethanolamides exhibit a glass transition temperature at around -73 °C. Geranoyl diethanolamide forms a lamellar crystalline phase with a lattice parameter of 17.4 ? following long term storage accompanied by the loss of the glass transition. In the presence of water, H-farnesoyl and phytanoyl diethanolamide form lyotropic liquid crystalline phases, whilst geranoyl diethanolamide forms an L(2) phase. H-farnesoyl diethanolamide forms a fluid lamellar phase (L(α)) at room temperature and up to ～ 40 °C. Phytanoyl diethanolamide displays a rich mesomorphism forming the inverse diamond (Q(II)(D)) and gyroid (Q(II)(G)) bicontinuous cubic phases in addition to an L(α) phase.     

Formation of amphiphile self-assembly phases in protic ionic liquids

A range of protic ionic liquids (PILs) have been identified as being capable of supporting the self-assembly of the nonionic surfactants myverol 18-99 K (predominantly monoolein) and phytantriol. PIL-surfactant penetration scans have provided a high throughput technique to determine which lyotropic liquid crystalline phases were formed in the 40 PIL-surfactant systems investigated. Lamellar, inverse hexagonal, and bicontinuous cubic phases that are stable in excess PIL have been observed in surfactant-PIL systems. The studied PILs possess a wide range of solvent properties, including surface tension and viscosity. The nature of the formed amphiphile self-assembly phases is discussed in terms of the PIL structure and solvent properties.     

溶致液晶及其在纳米结构材料合成中的应用*

有序纳米结构材料是一类具有广泛应用前景的新材料,在分离、催化、传感器等领域的应用潜力巨大。近年来,利用溶致液晶模板合成纳米结构颗粒和薄膜材料的研究取得了一系列重要进展,包括新纳米结构金属和半导体材料的合成、由过渡金属水合物与表面活性剂构建的新液晶体系、溶致液晶与其它模板结合制备具有多级孔结构的新材料、影响液晶体系及纳米结构材料有序性与稳定性的关键因素、以及纳米结构形成机理等方面的内容。本文就上述几个方面的近期研究成果进行了总结与综述,并展望了利用溶致液晶模板合成纳米结构材料需要进一步深入开展的内容,有助于化学、化学工程和材料科学等领域的相关研究工作。     

Shapes of Micelles and Molecular Geometry Synthesis and Studies on the Phase Behaviour, Surface Tension and Rheology of Rigid Rod-Like Surfactants in Aqueous Solutions

Amphiphiles with rigid rod-like hydrophobic moieties have been synthesized in order to investigate the effect of the packing restraints of such moieties on the micellar association behaviour of amphiphiles in aqueous solution. Investigations of the phase behaviour of amphiphile/water mixtures reveal that liquid-crystalline phases exist in defined temperature and concentration regimes and that they are all lamellar, regardless of the hydrophilic-hydrophobic balance of the amphiphile. For these lyotropic liquid-crystalline phases a polymorphism is observed which is similar to the polymorphism of thermotropic smectic liquid crystals. Surface tension measurements indicate critical micelle concentrations of the amphiphiles in dilute solutions which are similar to those of conventional surfactants. From rheological measurements it can be assumed that the variation of temperature and/or concentration of the solution does not influence the micellar shape. This is in contrast to the behaviour of non-ionic surfactants having a flexible hydrophobic group.     

Nonionic diethanolamide amphiphiles with saturated hydrocarbon chains: Neat crystalline and lyotropic liquid crystalline phase behavior

The solid state and lyotropic phase behavior of a series of nonionic diethanolamide amphiphiles with increasing saturated hydrocarbon chain length (lauroyl, myristoyl, palmitoyl, and stearoyl) has been examined. All four saturated diethanolamide amphiphiles form a crystalline solid with two or three different polymorphic crystalline forms at room temperature. Melting points and associated enthalpies for these four amphiphiles increased with increasing chain length. Approximate partial binary phase diagrams have been constructed for each amphiphile/water system by combining Cross-Polarized Optical Microscopy (POM) and Small-Angle X-ray Scattering (SAXS) results. In the presence of water, all four diethanolamides form an L(α) phase, between 10% and 50% water content, and an L(2) phase with decreasing hydration and increasing temperature. In addition to the L(α) and L(2) phases, the shorter chain diethanolamide amphiphiles (lauroyl and myristoyl) also display a normal micellar phase (L(1)) at higher water contents, occurring to lower temperatures than the L(α) phase. By examining the effect of subtle molecular changes on both neat and lyotropic phase behavior, amphiphiles can be designed with properties tailored to a desired application.     

Lyotropic liquid crystalline phase behaviour of a monomeric and a polymeric monosaccharide amphiphile in aqueous solution

Monomeric and polymeric amphiphiles were synthesized which exhibit lyotropic liquid crystalline phases in aqueous solution. The hydrophobic group of the monomeric surfactant is a dodecane-group esterified with acrylic acid. The hydrophilic unit is a monosaccharide derivative. By radical polymerization the monomer (N-D(-)-gluco-N-methyl-(12-acryloyloxy)-dodecane-l-amide) is converted into the corresponding polymeric surfactant. The monomer as well as the polymer exhibit a lyotropic 1.c. phase of lamellar structure. Owing to the polymerization the regime of the lamellar phase is greatly enlarged for the polymer, compared to the monomeric sufactant. These results confirm earlier investigations on non-ionic ethylene-glycol surfactants.     

Phase behavior and polymerization of lyotropic phases. II. A series of polymerizable amphiphiles with systematically varied critical packing parameters

A group of polymerizable amphiphiles, with their critical packing parameters systematically varied, were studied with respect to the phase behavior and immobilization of their lyotropic liquid‐crystalline phase structures. Small‐angle X‐ray scattering and polarized light microscopy were used to study their liquid‐crystalline phases before and after photopolymerization. The liquid crystallinity of the amphiphiles depended on the contents of both oil and water in the ternary systems. Through photopolymerization, hexagonal phases could generally be immobilized, with the structural order reduced to various degrees. However, the cubic phases evolved with polymerization into another structural pattern, which was possibly related to the lamellar structure. © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 5887–5897, 2006     

Cross-linked normal hexagonal and bicontinuous cubic assemblies via polymerizable gemini amphiphiles

The synthesis and lyotropic liquid-crystalline (LLC) phase behavior of a homologous series of intrinsically cross-linkable gemini surfactants are described. These novel bis(alkyl-1,3-diene)-based phosphonium gemini amphiphiles exhibit "normal" hexagonal (H(I)), Type I bicontinuous cubic (Q(I)), and lamellar (L(alpha)) phases in water, and can be photocross-linked with retention of phase architecture in each case. On the basis of their locations on the phase diagram, their powder X-ray diffraction profiles, and the physical properties of the cross-linked materials, the Q(I) phases formed by these gemini monomers are consistent with four possible bicontinuous cubic architectures with P or I space group symmetry that have been identified previously for small molecule amphiphiles. The extent of polymerization (i.e., the degree of diene conversion) achieved in the LLC phases was determined to be in the 23% to 71% range using UV-vis spectrometry, which is more than sufficient to extensively stabilize the systems. The resulting cross-linked H(I), L(alpha), and Q(I) phases are stable up to 300 degrees C in air. To our knowledge, these reactive amphiphiles constitute the first example of a polymerizable gemini surfactant, and the first example of a cross-linkable amphiphile system that can be polymerized in both the H(I) and a Q(I) mesophase with retention of phase microstructure.     

Lyotropic liquid crystalline phases formed in ternary mixtures of 1-cetyl-3-methylimidazolium bromide/p-xylene/water: a SAXS, POM, and rheology study

The phase behavior of ternary mixtures of 1-cetyl-3-methylimidazolium bromide (C(16)mim-Br)/p-xylene/water is studied by small-angle X-ray scattering (SAXS), polarized optical microscopy (POM), and rheology measurements. Two types of lyotropic liquid crystalline phases are formed in the mixtures: hexagonal and lamellar. The structural parameters of the lyotropic liquid crystalline phases are calculated. Greater surfactant content in the sample leads to denser aggregation of the cylindrical units in the hexagonal liquid crystalline phase. The increase in lattice parameter and thickness of the water layer in lamellar phase are attributed to the increase of water content, and the area per surfactant molecule at the hydrophobic/hydrophilic interface for lamellar phase is found to be larger than that for hexagonal phase. The structural parameters of the liquid crystalline phases formed from the cetyltrimethylammonium bromide (CTAB) system are larger than those for the C(16)mim-Br system. The rheological properties of the samples are also found to be related to the structure of the liquid crystalline phases.     

Polarization transfer solid-state NMR for studying surfactant phase behavior

The phase behavior of amphiphiles, e.g., lipids and surfactants, at low water content is of great interest for many technical and pharmaceutical applications. When put in contact with air having a moderate relative humidity, amphiphiles often exhibit coexistence between solid and liquid crystalline phases, making their complete characterization difficult. This study describes a (13)C solid-state NMR technique for the investigation of amphiphile phase behavior in the water-poor regime. While the (13)C chemical shift is an indicator of molecular conformation, the (13)C signal intensities obtained with the CP and INEPT polarization transfer schemes yield information on molecular dynamics. A theoretical analysis incorporating the effect of molecular segment reorientation, with the correlation time τ(c) and order parameter S, shows that INEPT is most efficient for mobile segments with τ(c) < 0.01 μs and S < 0.05, while CP yields maximal signal for rigid segments with τ(c) > 10 μs and/or S > 0.5 under typical solid-state NMR experimental conditions. For liquid crystalline phases, where τ(c) < 0.01 μs and 0 < S < 0.3, the observed CP and INEPT intensities serve as a gauge of S. The combination of information on molecular conformation and dynamics permits facile phase diagram determination for systems with solid crystalline, solid amorphous, anisotropic liquid crystalline, and isotropic liquid (crystalline) phases as demonstrated by experiments on a series of reference systems with known phase structure. Three solid phases (anhydrous crystal, dihydrate, gel), two anisotropic liquid crystalline phases (normal hexagonal, lamellar), and two isotropic liquid crystalline phases (micellar cubic, bicontinuous cubic) are identified in the temperature-composition phase diagram of the cetyltrimethylammonium succinate/water system. Replacing the succinate counterion with DNA prevents the formation of phases other than hexagonal and leads to a general increase of τ(c).     

Protic ionic liquids: physicochemical properties and behavior as amphiphile self-assembly solvents

The physicochemical properties of 22 protic ionic liquids (PILs) and 6 protic molten salts, and the self-assembly behavior of 3 amphiphiles in the PILs, are reported. Structure-property relationships have been explored for the PILs, including the effect of increasing the substitution of ammonium cations and the presence of methoxy and hydroxyl moieties in the cation. Anion choices included the formate, pivalate, trifluoroacetate, nitrate, and hydrogen sulfate anions. This series of PILs had a diverse range of physicochemical properties, with ionic conductivities up to 51.10 mS/cm, viscosities down to 5.4 mPa.s, surface tensions between 38.3 and 82.1 mN/m, and densities between 0.990 and 1.558 g/cm3. PILs were designed with various levels of solvent cohesiveness, as quantified by the Gordon parameter. Fourteen PILs were found to promote the self-assembly of amphiphiles. High-throughput polarized optical microscopy was used to identify lamellar, hexagonal, and bicontinuous cubic amphiphile self-assembly phases. The presence and extent of amphiphile self-assembly have been discussed in terms of the Gordon parameter.     

Synthesis and lyotropic liquid crystalline behaviour of a taper-shaped phosphonic acid amphiphile

A taper-shaped phosphonic acid, 3,4,5-tris(dodecyloxy)phenylmethylphosphonic acid ( 1 ), was synthesized; its lyotropic liquid crystalline (LLC) behaviour and its ability simultaneously to order and acid-dope polyaniline were examined. It was found that the ability of 1 to form LLC phases in the presence of several hydrophilic solvents is restricted by strong intermolecular interactions between the phosphonic acid head groups (presumably H-bonding). The amphiphile exhibits poor miscibility with pure water and even with strong H-bonding organic solvents such as DMF. However, it forms a lamellar mesophase in the presence of aqueous acid. Upon deprotonation of the phosphonic acid head group with NaOH, the resulting disodium salt of the amphiphile is able to form a well defined lamellar phase with pure water. The propensity of 1 to form lamellar phases is somewhat unusual since its tapered molecular shape should direct it to form an inverted hexagonal LLC phase. These results suggest that intermolecular head group interactions are more important in determining the overall LLC behaviour of this phosphonic acid amphiphile than are the hydrophobic character and shape of the organic tail system. Compound 1 was also found to be sufficiently acidic to act as an acid dopant for the conjugated polymer polyaniline in the emeraldine base form. LLC acid 1 induces the resulting polymeric salt to form an electrically conductive LLC complex with an extended lamellar microstructure. The bulk conductivity of the resulting nanostructured polyaniline salt was found to be only in the semiconducting regime (10 -5 Scm -1 ), due to an unfavourable polyaniline chain conformation in the LLC complex.     

Lyotropic phases reinforced by hydrogen bonding

Amphiphilic guanidinium alkylbenzenesulfonates (GCnBS; n = number of carbons in the alkyl chain) exhibited lyotropic behavior in aqueous and organic solvents. The GCnBS compounds formed gel-like phases in certain cyclic organic solvents (e.g. p-xylene, cyclohexane) through the formation of swollen interdigitated lamellar phases reinforced by hydrogen bonding between the guanidinium ions and sulfonate moieties. This behavior was not observed for the homologous sodium alkylbenzenesulfonates, indicating that hydrogen bonding, mediated by the guanidinium (G) ion, was required for gel formation. Infrared spectroscopy unambiguously demonstrated the existence of the quasi-hexagonal hydrogen-bonded sheet typically adopted by G ions and the sulfonate groups in layered, solvent-free crystalline phases of the compounds, supporting lamellar structures in the gels. Small-angle X-ray scattering analysis of these gels revealed GCnBS lamellar phases with interlayer spacings (d) that increased with increasing temperature, consistent with increased absorption of solvent by the nonpolar regions of the gelator. At the lower gelator concentrations, the increase in d-spacing achieved at the higher temperatures exceeded the sum of the alkylbenzene chain lengths, suggesting either long-range interactions between the GS sheets or undulation stabilized lamellae, which have been reported in aqueous lamellar gels. The GCnBS compounds also formed lyotropic phases in water, but the phase behavior was more complex than that of the organogels. The rheology suggested gel-like behavior associated with entangled worm-like micelles at these higher concentrations. These lyotropic phases were reminiscent of crystalline layered and tubular architectures exhibited by various guanidinium organomonosulfonate compounds. These lyotropic phases expand the liquid crystal behavior observed for GS compounds beyond recently observed thermotropic smectic phases, adding to the portfolio of phase behavior exhibited by these materials.