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We herein report 13 protic ionic liquids (PILs) as tunable solvation media to regulate the internal lyotropic liquid crystalline mesophase of monoolein-based nanoparticles. A range of nanostructures, including inverse bicontinuous cubic, inverse hexagonal, and sponge/lamellar mesophases, were produced and verified by synchrotron small-angle X-ray scattering. Notably, manipulating the cation/anion structures of the PILs can alter the monoolein packing behavior and cause a sequential phase transition (hexagonal → cubic → lamellar) in the nanoparticles. The solvent channels inside the nanoparticles were enlarged up to 40% under certain PIL-water conditions, making these materials prospective for encapsulation of large molecules. Finally, a freeze-drying study demonstrated the ability of PILs to preserve nanostructure upon reconstitution of the nanoparticles compared to that in pure water. This study opens a new route for fine-tuning lyotropic liquid crystalline structures using PILs, which circumvents issues encountered using conventional salts.

Cubosomes with an internal three-dimensional (3D) periodic and porous particulate nanostructure have emerged as a promising drug delivery system for hydrophobic small molecules as well as large biomolecules over the past several decades. Limited understanding of their safety profiles and biodistribution, however, hinders clinical translation. This study used monoolein-based cubosomes stabilized by Pluronic F127 and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[maleimide(polyethylene glycol)] polymers to encapsulate paclitaxel (PTX) as a model drug and investigated the in vitro cytotoxicity, in vivo acute response, and whole body biodistribution of the developed nanoparticles. Comparison of the PTX and nanoparticle cytotoxicity in two-dimensional and 3D spheroid cell models revealed distinct differences, with the cells in the 3D model found to be more tolerable to unloaded PTX as well as the PTX-loaded nanoparticle form. One-time intraperitoneal (i.p.) injection of unloaded cubosomes were generally well tolerated up to 400 mg/kg. Using the A431 skin cancer xenograft model, in vivo imaging studies showed the preferential accumulation of PTX-loaded cubosomes at the tumor sites following i.p. injection. Lastly, average tumor size was reduced by approximately 50% in the nanoparticle-based treatment group compared to the unloaded PTX drug group. The study provides significant information on the biological response of cubosomes and highlights their potential as a versatile drug delivery platform for safe and effective delivery of chemotherapeutic drugs.

The potential of gene therapy has not yet been realized, largely due to difficulties in the targeted delivery of DNA to tissues and cells. Lipid-based nanovectors are of potential use in gene therapy due to their ability to enhance fusion with cellular membranes and transport the large polyanionic DNA molecules into the cytoplasm. While the research to date has mainly focused on liposome-based vectors, recently, nonlamellar phases with more complex internal architectures based on hexagonal or cubic symmetry have received increasing research attention due to their fusogenic properties, which may promote uptake of the DNA into the cell. Herein, we have carried out a fundamental physicochemical study to systematically analyze the encapsulation and release of nonfunctional double-stranded (ds) DNA fragments within monoolein (MO)-based cationic lipid phases of cubic symmetry (cationic cubic phases) and their dispersed submicron particles (cationic cubosomes). MO-based cationic cubic phases, both as the bulk phase and cubosomes, were formulated using six different cationic lipids, and their nanostructure was characterized in a high-throughput manner by synchrotron small-angle X-ray scattering (SAXS). dsDNA encapsulation was confirmed using agarose gel electrophoresis, and the effect on the internal nanostructure, size, and morphology of the cubosomes was investigated using synchrotron SAXS, dynamic light scattering, and cryo-transmission electron microscopy. Synchrotron radiation circular dichroism confirmed that the structure of the dsDNA fragments was unaffected by encapsulation within the cationic cubosome. The use of commercially available dsDNA ladders consisting of a controlled mixture of dsDNA fragments allowed us to determine release rates as a function of fragment size in a reasonably high throughput manner. An improved understanding of the loading capacity and release profile of nonfunctional biomolecules in cationic cubosomes will assist in the design of novel lipid nanovectors for gene delivery.

Herein, we demonstrate a method for the functionalization of cubic phase lipid nanoparticles (cubosomes) with a series of magnetite (Fe3O4), copper oxide (Cu2O), and silver (Ag) nanocrystals, with prospective applications across a wide range of fields, including antimicrobial treatments. The resulting cubosomes are characterized using small-angle X-ray scattering and dynamic light scattering, demonstrating the retention of a typical cubic phase structure and particle size following nanocrystal encapsulation at concentrations up to 20% w/w. Cryogenic transmission electron microscopy reveals significant loading and association of each nanocrystal type with both monoolein- and phytantriol-based cubosomes. The antibiotic potential of these hybrid nanoparticles is demonstrated for the first time; cubosomes with embedded silver nanocrystals display a high level of antimicrobial activity against both Gram-positive and Gram-negative bacteria, with observed minimum inhibitory concentration values ranging from 15.6-250 μg/mL. Lastly, total internal reflection fluorescence microscopy is used to visualize cubosome-bacteria interactions, suggesting the involvement of particle interactions as a delivery mechanism.

Nonlamellar lyotropic liquid crystalline (LLC) lipid nanomaterials have emerged as a promising class of advanced materials for the next generation of nanomedicine, comprising mainly of amphiphilic lipids and functional additives self-assembling into two- and three-dimensional, inverse hexagonal, and cubic nanostructures. In particular, the lyotropic liquid crystalline lipid nanoparticles (LCNPs) have received great interest as nanocarriers for a variety of hydrophobic and hydrophilic small molecule drugs, peptides, proteins, siRNAs, DNAs, and imaging agents. Within this space, there has been a tremendous amount of effort over the last two decades elucidating the self-assembly behavior and structure-function relationship of natural and synthetic lipid-based drug delivery vehicles in vitro, yet successful clinical translation remains sparse due to the lack of understanding of these materials in biological bodies. This review provides an overview of (1) the benefits and advantages of using LCNPs as drug delivery nanocarriers, (2) design principles for making LCNPs with desirable functionalities for drug delivery applications, (3) current understanding of the LLC material-biology interface illustrated by more than 50 in vivo, preclinical studies, and (4) current patenting and translation activities in a pharmaceutical context. Together with our perspectives and expert opinions, we anticipate that this review will guide future studies in developing LCNP-based drug delivery nanocarriers with the objective of translating them into a key player among nanoparticle platforms comprising the next generation of nanomedicine for disease therapy and diagnosis.

The bicontinuous lipidic cubic phase (LCP), which is based on the fundamental structure of the lipid bilayer, is increasingly used in a range of applications including drug delivery, in meso crystallization of membrane proteins, biosensors, and biofuel cells. The majority of LCPs investigated to date have been formulated from a single lipid or a combination of two lipids in water. Such systems lack tunability, with only a narrow range of lattice parameters adopted. In addition, the lipid bilayer of these materials lacks the complexity of natural cell membranes, which are composed of hundreds of different lipids and which may be essential to retaining the functionality of proteins embedded within them. In this work, we investigate the phase behavior of quaternary lipid-water systems consisting of three different lipids (monoolein-cholesterol-phospholipid) and water using a combination of experimental and simulation techniques. This study provides a large library of lipidic materials with bilayer compositions, which more effectively mimic the native cell membrane and significantly increased tunability based on nanostructural parameters such as lattice parameter, aqueous channel size, and bilayer thickness. Importantly, the library contained several extremely swollen cubic phases with a maximum lattice parameter of up to 342.5 Å. Many of these cubic phases were successfully dispersed into highly swollen cubosomes. The swollen cubic phases described in this article contain only uncharged lipids and are therefore particularly useful for applications with a high salt concentration, including encapsulation of larger therapeutic proteins and peptides for in vivo delivery, or for the crystallization of large membrane proteins such as GPCRs.(1).

The transition between the lyotropic liquid crystalline lamellar and the bicontinuous cubic mesophase drives multiple fundamental cellular processes involving changes in cell membrane topology, including endocytosis and membrane budding. While several theoretical models have been proposed to explain this dynamic transformation, experimental validation of these models has been challenging because of the short-lived nature of the intermediates present during the phase transition. Herein, we report the direct observation of a lamellar-to-bicontinuous cubic phase transition in nanoscale dispersions using a combination of cryogenic transmission electron microscopy and static small-angle X-ray scattering. The results represent the first experimental confirmation of a theoretical model which proposed that the bicontinuous cubic phase originates from the center of a lamellar vesicle then propagates outward via the formation of interlamellar attachments and stalks. The observation was possible because of the precise control of the lipid composition to place the dispersion systems at the phase boundary of a lamellar and a cubic phase, allowing for the creation of long-lived structural intermediates. By the surveying of the nanoparticles using cryogenic transmission electron microscopy, a complete phase transition sequence was established.

Mesophase structures of self-assembled lyotropic liquid crystalline nanoparticles are important factors that directly influence their ability to encapsulate and release drugs and their biological activities. However, it is difficult to predict and precisely control the mesophase behavior of these materials, especially in complex systems with several components. In this study, we report the controlled manipulation of mesophase structures of monoolein (MO) and phytantriol (PHYT) nanoparticles by adding unsaturated fatty acids (FAs). By using high throughput formulation and small-angle X-ray scattering characterization methods, the effects of FAs chain length, cis-trans isomerism, double bond location, and level of chain unsaturation on self-assembled systems are determined. Additionally, the influence of temperature on the phase behavior of these nanoparticles is analyzed. We found that in general, the addition of unsaturated FAs to MO and PHYT induces the formation of mesophases with higher Gaussian surface curvatures. As a result, a rich variety of lipid polymorphs are found to correspond with the increasing amounts of FAs. These phases include inverse bicontinuous cubic, inverse hexagonal, and discrete micellar cubic phases and microemulsion. However, there are substantial differences between the phase behavior of nanoparticles with trans FA, cis FAs with one double bond, and cis FAs with multiple double bonds. Therefore, the material library produced in this study will assist the selection and development of nanoparticle-based drug delivery systems with desired mesophase.

Polyampholytic copolymers have been synthesized via reversible addition–fragmentation chain transfer (RAFT) polymerization of protic ionic liquid monomers. The monomers were prepared by acid–base proton exchange between acid and basic precursor conjugates, each containing one or more vinyl pendant groups. The polymerization, which was carried out without additional solvents present, led to high molecular weight glassy polymers, which were stable in the form of bulk viscous liquid ionic complexes. Various polyampholytes belonging to both linear and cross-linked families were prepared by judiciously varying the molecular structure of the acid precursor. Furthermore, by using solid-state NMR, the molecular arrangement of the polymeric backbone was identified, highlighting the presence of copolymers with both random and alternating copolymer chains which in the latter case involves a regularly alternating acid monomer, whereas the base occurs as a random sequence with the average and most probable number of m...

Obtaining well-diffracting crystals of membrane proteins, which is crucial to the molecular-level understanding of their intrinsic three-dimensional structure, dynamics, and function, represents a fundamental bottleneck in the field of structural biology. One of the major advances in the field of membrane protein structural determination was the realization that the nanostructured lipidic cubic phase (LCP) environment constitutes a membrane mimetic matrix that promotes solubilization, stabilization, and crystallization of specific membrane proteins. Despite two decades passing since the introduction of LCP-based membrane protein crystallization, the research community’s understanding of the processes that drive protein nucleation and macromolecular assembly in the LCP generally remains limited. In the current study, we present a detailed, systematic investigation into the relationship between the chemical structure of the lipid, the physical properties of the ensuing mesophase, the translational diffusion...

For evolving biological and biomedical applications of hybrid protein?lipid materials, understanding the behavior of the protein within the lipid mesophase is crucial. After more than two decades since the invention of the in meso crystallization method, a protein-eye view of its mechanism is still lacking. Numerous structural studies have suggested that integral membrane proteins preferentially partition at localized flat points on the bilayer surface of the cubic phase with crystal growth occurring from a local fluid lamellar L? phase conduit. However, studies to date have, by necessity, focused on structural transitions occurring in the lipid mesophase. Here, we demonstrate using small-angle neutron scattering that the lipid bilayer of monoolein (the most commonly used lipid for in meso crystallization) can be contrast-matched using deuteration, allowing us to isolate scattering from encapsulated peptides during the crystal growth process for the first time. During in meso crystallization, a clear decrease in form factor scattering intensity of the peptides was observed and directly correlated with crystal growth. A transient fluid lamellar L? phase was observed, providing direct evidence for the proposed mechanism for this technique. This suggests that the peptide passes through a transition from the cubic QII phase, via an L? phase to the lamellar crystalline Lc phase with similar layered spacing. When high protein loading was possible, the lamellar crystalline Lc phase of the peptide in the single crystals was observed. These findings show the mechanism of in meso crystallization for the first time from the perspective of integral membrane proteins.

Nanostructured bicontinuous lipidic cubic phases are used for the encapsulation of proteins in a range of applications such as in meso crystallization of transmembrane proteins and as drug delivery vehicles. The retention of the nanoscale order of the cubic phases subsequent to protein incorporation, as well as retention of the protein structure and function, is essential for all of these applications. Herein synthetic peptides (WALP21, WALPS53, and WALPS73) with a common α-helical hydrophobic domain, but varying hydrophilic loop size, were designed to systematically examine the effect of peptide structure and charge on bicontinuous cubic phases. The effect of the cubic phases on the secondary structure of the peptides was also investigated. The incorporation of the WALP peptides in cubic phases formed by a range of lipids showed that hydrophobic mismatch of the peptides with the lipid bilayers, the hydrophilic domain size, and peptide charge were all significant factors determining the response of the lipid nanomaterial to protein insertion. As charge repulsion had the most significant effect on the phase transitions observed, we suggest that buffer pH and salt concentration must be carefully considered to ensure cubic mesophase retention. Importantly, the WALP peptides were found to have a different conformation depending on the local lipid environment. Such structural changes could potentially affect membrane protein function, which is crucial for both current and prospective applications.

Lipidic bicontinuous cubic mesophases with encapsulated amphiphilic proteins are widely used in a range of biological and biomedical applications, including in meso crystallization, as drug delivery vehicles for therapeutic proteins, and as biosensors and biofuel cells. However, the effect of amphiphilic protein encapsulation on the cubic phase nanostructure is not well-understood. In this study, we illustrate the effect of incorporating the bacterial amphiphilic membrane protein Ag43, and its individual hydrophobic β(43) and hydrophilic α(43) domains, in bicontinuous cubic mesophases. For the monoolein, monoalmitolein, and phytantriol cubic phases with and without 8% w/w cholesterol, the effect of the full length amphiphilic protein Ag43 on the cubic phase nanostructure was more significant than the sum of the individual hydrophobic β(43) and hydrophilic α(43) domains. Several factors were found to potentially influence the impact of the hydrophobic β(43) domain on the cubic phase internal nanostructure. These include the size of the hydrophobic β(43) domain relative to the thickness of the lipid bilayer, as well as its charge and diameter. The size of the hydrophilic α(43) domain relative to the water channel radius of the cubic mesophase was also found to be important. The secondary structure of the Ag43 proteins was affected by the hydrophobic thickness and physicochemical properties of the lipid bilayer and the water channel diameter of the cubic phase. Such structural changes may be small but could potentially affect membrane protein function.

Lyotropic liquid crystalline nanoparticle dispersions are of interest as delivery vectors for biomedicine. Aqueous dispersions of liposomes, cubosomes, and hexosomes are commonly stabilized by nonionic amphiphilic block copolymers to prevent flocculation and phase separation. Pluronic stabilizers such as F127 are commonly used; however, there is increasing interest in using chemically reactive stabilizers for enhanced functionalization and specificity in therapeutic delivery applications. This study has explored the ability of 1,2-distearoyl-sn-glycero-3-phosphoethanolamine conjugated with poly(ethylene glycol) (DSPE-PEGMW) (2000 Da ≤ MW ≤ 5000 Da) to engineer and stabilize phytantriol-based lyotropic liquid crystalline dispersions. The poly(ethylene glycol) (PEG) moiety provides a tunable handle to the headgroup hydrophilicity/hydrophobicity to allow access to a range of nanoarchitectures in these systems. Specifically, it was observed that increasing PEG molecular weight promotes greater interfacial curvature of the dispersions, with liposomes (Lα) present at lower PEG molecular weight (MW 2000 Da), and a propensity for cubosomes (QII(P) or QII(D) phase) at MW 3400 Da or 5000 Da. In comparison to Pluronic F127-stabilized cubosomes, those made using DSPE-PEG3400 or DSPE-PEG5000 had enlarged internal water channels. The toxicity of these cubosomes was assessed in vitro using A549 and CHO cell lines, with cubosomes prepared using DSPE-PEG5000 having reduced cytotoxicity relative to their Pluronic F127-stabilized analogues.

In meso crystallization uses bicontinuous cubic lipidic mesophases as matrices for the crystallization of membrane proteins. In this work, we look at the impact of a screen specifically marketed as compatible with the cubic mesophase, the Cubic crystallization screen (Emerald BioSystems), on the cubic mesophases formed by three different lipids: monoolein, monopalmitolein, and phytantriol. The Cubic screen was found to be compatible with cubic mesophase retention under most crystallization conditions for all three lipids studied. The effect of the individual components comprising the multicomponent screen was deconvoluted in two ways. Initially, the effect of specific poly(ethylene glycol) (PEG) and salt components on the cubic mesophase was determined using small-angle X-ray scattering (SAXS). The effect of high-molecular-weight (Mw) PEG was shown to dominate the phase behavior within the screen. The effect of additional salts present within the screen becomes important for low Mw PEG molecules. Finally,...

Force-separation measurements between Giardia lamblia cysts and an inorganic oxide (silicate glass) have been obtained by using an atomic force microscope (AFM). The cysts are compressible on the scale of the loads applied during force measurement, with the surface compressibility expressed in terms of an interfacial spring constant (K(int)). The force of interaction prior to this Hookean region, on approach, is long-range and repulsive. The long-range force has been compared to models of the electrical double layer as well as an electrosteric layer. The comparison has led to the conclusion that the cyst surface can be described as a polyelectrolyte brush at intermediate separations (5-115 nm from linear compliance) with an electrical double layer often observed at larger separations. The dependence of the interaction force on surface retraction suggests that tethering between the cyst and siliceous surface can occur. The variation of the interaction with pH and upon variation with ionic strength has also been assessed. The information gained from the measurement of the interaction between G. lamblia and this model sandlike surface informs water treatment processes. Similar studies have been performed by us for the Cryptosporidium parvum (C. parvum) oocyst system to which this work is compared.

The development of biomedical nanoparticulate materials for use in diagnostics is a delicate balance between performance, particle size, shape, and stability. To identify materials that satisfy all of the criteria it is useful to employ automated high-throughput (HT) techniques for the study of these materials. The structure and performance of surfactant templated mesoporous silica is very sensitive to a wide number of variables. Variables, such as the concentration of the structure-directing agent, the cosolvent and dopant ions and also the temperature and concentration of quenching all have an influence on the structure, surface chemistry, and therefore, the performance of the mesoporous silica nanoparticles generated. Using an automated robotic synthetic platform, a technique has been developed for the high-throughput preparation of mesoporous silica and gadolinium-doped silicate (gadoliniosilicate) nanoparticulate MRI contrast agents. Twelve identical repeats of both the mesoporous silica and gadolinosilicate were synthesized to investigate the reproducibility of the HT technique. Very good reproducibility in the production of the mesoporous silica and the gadolinosilcate materials was obtained using the developed method. The performance of the gadolinosilicate materials was comparable as a T(1) agent to the commercial MRI contrast agents. This HT methodology is highly reproducible and an effective tool that can be translated to the discovery of any sol-gel derived nanomaterial.

A protocol is presented for the high-throughput (HT) production of lyotropic liquid crystalline phases from libraries of lipids and lipid mixtures using standard liquid dispensing robotics, implementing methods that circumvent the problems traditionally associated with handling the highly viscous cubic phase. In addition, the ability to structurally characterize lipidic phases and assess functionality for membrane proteins contained within cubic phases, in a HT manner, is demonstrated. The techniques are combined and exemplified using the application of membrane protein crystallization within lipidic cubic phases.

Protic ionic liquids (PILs) have been evaluated as additives in protein crystallization trials. Ten ionic liquids were incorporated as additives along with the JCSG+ sparse matrix screen for the crystallization of lysozyme, glucose isomerase, and trypsin. When used as additives, the PILs were identified to influence the crystallization of these globular proteins. Crystal structures obtained for lysozyme with each of the 10 PILs under identical conditions showed no change in the crystal structure of the protein; however, in three of the ten cases fragments of the ionic liquids were observed to be incorporated within the protein.

Protic ionic liquids (PILs) have been shown to provide media for small amphiphilic molecule self-assembly into periodic 3D geometries. The ability of phytantriol and monoolein to self-assemble into ordered 3D nanostructures analogous to structures observed in aqueous solvents has been demonstrated. Monoolein in ethanolammonium formate (EOAF) formed the double diamond lyotropic liquid crystalline cubic mesophase, and phytantriol formed the gyroid cubic mesophase at 25 °C. The monoolein cubic mesophase was successfully dispersed in excess PIL, forming nanostructured nanoparticles, and imaged by cryo-transmission electron microscopy. The self-assembled materials reported herein can be considered for soft-templating of material structures during synthesis, as encapsulation and controlled release media, as carrier particles in transport phenomena, and as supports for catalysts where the process conditions require a nonaqueous environment.

The nanostructure of a series of 20 protic ionic liquids (PILs) has been investigated using small- and wide-angle X-ray scattering (SAXS and WAXS). The PILs contained alkylammonium, dialkylammonium, trialkylammonium, and cyclic ammonium cations combined with organic or inorganic anions. The presence of hydroxyl and methoxy substituents on the alkyl chains of the cations was also explored. Many of the PILs showed a nanostructure resulting from segregation of the polar and nonpolar components of the ionic liquid. It was found that this segregation was enhanced for longer alkyl chains, with a corresponding increase in the length scale, whereas the presence of hydroxyl groups on the alkyl chains led to much less ordered liquids. The broad range of protic ionic liquids studied allowed several structure-property relationships to be established. The solvophobic effect was shown to be dependent on the nanostructure of the PILs. These PILs support amphiphile self-assembly, and it was shown that the less structured PILs had more "water-like" behavior in the diversity of lyotropic liquid-crystal phases supported, and the thermal stability ranges for these phases.

The n-acylethanolamides (NAEs) are a family of naturally occurring monoethanolamide containing lipids that display a variety of interesting biological properties. In this study, some physicochemical properties of a series of saturated monoethanolamide lipids with increasing hydrocarbon chain length (lauroyl, myristoyl, palmitoyl, and stearoyl) have been investigated. Temperature induced phase transitions for these NAEs indicate that both the monoethanolamide headgroups and the unsaturated hydrophobic tails play a role in the melting behavior of these lipids. All four lipids examined demonstrate the presence of at least three different polymorphic crystal forms. Transitions in crystal structure can be induced via heating and visualized with polarized optical microscopy. At room and physiological temperature, the four NAEs are solid lamellar crystalline materials. All four molecules form lyotropic liquid crystalline phases in water, albeit at relatively high temperatures, including the lamellar liquid crystalline phase and at least two isotropic phases. Lamellar crystalline palmitoyl monoethanolamide was dispersed as solid lipid nanoparticles (SLNs). The cytotoxicity of these SLNs toward human mammary epithelial cells (HMEpiC) and the MCF7 breast cancer cell line was assessed at physiological temperature. The palmitoyl monoethanolamide SLNs showed little to no toxicity to the HMEpiC even at a concentration of 30 microM. At concentrations above 3 microM, the HMEpiC population was reduced by less than 15%, while the MCF7 population was reduced by approximately 20-30%. The endogenous nature and natural medicinal properties make this series of lipids ideal candidates for further investigation as solid lipid nanoparticle drug delivery systems.

Lanthanide salts of phytanic acid, an isoprenoid-type amphiphile, have been synthesized and characterized. Elemental analysis and FTIR spectroscopy were used to confirm the formed product and showed that three phytanate anions are complexed with one lanthanide cation. The physicochemical properties of the lanthanide phytanates were investigated using DSC, XRD, SAXS, and cross-polarized optical microscopy. Several of the hydrated salts form a liquid-crystalline hexagonal columnar mesophase at room temperature, and samarium(III) phytanate forms this phase even in the absence of water. Select lanthanide phytanates were dispersed in water, and cryo-TEM images indicate that some structure has been retained in the dispersed phase. NMR relaxivity measurements were conducted on these systems. It has been shown that a particulate dispersion of gadolinium(III) phytanate displays proton relaxivity values comparable to those of a commercial contrast agent for magnetic resonance imaging and a colloidal dispersion of europium(III) phytanate exhibits the characteristics of a fluorescence imaging agent.

Eight lanthanide(III) oleates have been prepared and characterized. The chelation and self-assembly structures of these rare-earth oleates have been studied by elemental analysis, Fourier transfer infrared spectroscopy (FTIR), and X-ray powder diffraction (XRD) analysis. Elemental analysis and FTIR results indicate that three oleate anions are complexed with one lanthanide cation and, with the exception of anhydrous cerium(III) oleate, form either a mono- or a hemihydrate. The X-ray analysis showed that the neat lanthanide soaps have a lamellar bilayer structure at room temperature. The thermal behavior has been investigated by cross-polarized optical microscopy (POM), differential scanning calorimetry (DSC), and thermogravimetric analysis (TGA). POM scans showed that all the lanthanide oleates form a lamellar phase in the presence of excess water. Small-angle X-ray scattering (SAXS) and XRD were used to investigate the internal structure of the bulk lanthanide oleates in excess water, and these X-ray results confirmed that the lanthanide oleates do not swell in water. Select lanthanide oleates were dispersed in water to form nonswelling lamellar submicrometer particles, confirmed by dynamic light scattering (DLS) and synchrotron SAXS measurements. NMR results indicated that colloidal dispersions of lanthanide oleates containing paramagnetic ions, such as gadolinium(III), terbium(III), and dysprosium(III), have a significant effect on the longitudinal (T(1)) and transverse (T(2)) relaxation times of protons in water. Time-resolved fluorescence measurements have demonstrated that colloidal dispersions of europium(III) oleate exhibit strong luminescence. The rare earth metal soaps exemplify the potential of self-assembled chelating amphiphiles as contrast agents in medical imaging modalities such as magnetic resonance imaging (MRI) and fluorescence imaging.

The self-assembly, solid state and lyotropic liquid crystalline phase behavior of a series of endogenous n-acylethanolamides (NAEs) with differing degrees of unsaturation, viz., oleoyl monoethanolamide, linoleoyl monoethanolamide, and linolenoyl monoethanolamide, have been examined. The studied molecules are known to possess inherent biological function. Both the monoethanolamide headgroup and the unsaturated hydrophobe are found to be important in dictating the self-assembly behavior of these molecules. In addition, all three molecules form lyotropic liquid crystalline phases in water, including the inverse bicontinuous cubic diamond (Q(II)(D)) and gyroid (Q(II)(G)) phases. The ability of the NAE's to form inverse cubic phases and to be dispersed into ordered nanostructured colloidal particles, cubosomes, in excess water, combined with their endogenous nature and natural medicinal properties, makes this new class of soft mesoporous amphiphile self-assembly materials suitable candidates for investigation in a variety of advanced multifunctional applications, including encapsulation and controlled release of therapeutic agents and incorporation of medical imaging agents.

A novel method for the preparation of hierarchically porous LiFePO4 electrode materials for lithium ion batteries has been investigated. A meso/macroporous carbon monolith, a conductive framework, was prepared and infiltrated with the LiFePO4 precursors to increase the electrode/electrolyte interface and improve the rate capability of the battery. The final LiFePO4/carbon monoliths feature a meso/macroporous hierarchical structure. The monoliths were calcined at increasing temperatures, from 650 to 800 °C, to determine the structural and sintering effects on the electrochemical properties of the materials. The samples were characterized using SEM, TEM, nitrogen sorption, and XRD analysis prior to electrochemical testing. The results showed that the capacity of the LiFePO4/carbon electrodes achieved 82% of the theoretical capacity at 0.1C discharge rate.

Future nanoscale soft matter design will be driven by the biological paradigms of hierarchical self-assembly and long-lived nonequilibrium states. To reproducibly control the low-energy self-assembly of nanomaterials for the future, we must first learn the lessons of biology. Many cellular organelles exhibit highly ordered cubic membrane structures. Determining the mechanistic origins of such lipid organelle complexity has been elusive. We report the first observation of the complete sequence of major transformations in the conversion from a 1D lamellar membrane to 3D inverse bicontinuous cubic nanostructure. Characterization was enabled by adding a steric stabilizer to dispersions of lipid nanoparticles which increased the lifetime of very short-lived nonequilibrium intermediate structures. By using synchrotron small-angle X-ray scattering and cryo-transmission electron microscopy we observed and characterized initial lipid bilayer contacts and stalk formation, followed by membrane pore development, pore evolution into 2D hexagonally packed lattices, and finally creation of 3D bicontinuous cubic structures.

Porous LiFePO4 has been prepared via a solution-based templating technique. Beads of poly(methyl methacrylate) were synthesized with diameters of 100, 140, and 270 nm and used to form colloidal crystal templates to produce LiFePO4, which featured pores spanning from 10 to 100 nm. The use of colloidal crystal templates allowed an examination of the effects of pore size on the electrochemical properties. The templated LiFePO4 samples were fully characterized using SEM, TEM, XRD, Rietveld analysis, and nitrogen sorption prior to electrochemical testing. The materials with the largest pores, around 100 nm diameter, gave the best discharge capacities, with 160 mA h g−1 at 0.1C and 115 mA h g−1 at 5C being achieved. This compares with a theoretical discharge capacity of 170 mA h g−1.

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.

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.

The homo-interaction between urea moieties residing in close proximity to each other generally results in very strong intermolecular hydrogen bonding. The bifurcated hydrogen bonding exhibited by n-alkyl substituted ureas means that for those urea surfactants possessing medium and long hydrocarbon chain substituents the crystal to isotropic liquid melting point is high and the solubility in water is very low, compared to other similar chain length nonionic surfactants. In addition, saturated n-alkyl urea surfactants do not form lyotropic liquid crystalline phases in water. In this work the strong intermolecular hydrogen bonding of the urea headgroup has been ameliorated through the introduction of unsaturated hydrocarbon chains, viz., oleyl (cis-octadec-9-enyl), linoleyl (cis, cis-octadec-9,12-dienyl), and linolenyl (cis, cis, cis-octadec-9,12,15-trienyl) with one, two, and three carbon double bonds, respectively. Unsaturation in the C18 urea surfactants lowers the melting point and promotes an inverse hexagonal phase, in oleyl urea-water and linoleyl urea-water systems, which is thermodynamically stable in excess water. As the degree of unsaturation is increased to three in linolenyl urea, there is a tendency for autoxidation/polymerization. The occurrence of an inverse hexagonal phase in the nonionic urea surfactant-water systems has been rationalized in terms of both local molecular and global self-assembled aggregate packing constraints.

The thermotropic and lyotropic phase behavior of 1- and 5-decyl urea, and 1-, 2-, 4-, and 6-dodecyl urea have been studied. This allowed the effect of positional isomerism to be examined. Intermolecular hydrogen bonding by the urea moiety is the dominant factor in determining the solid-state thermal behavior and crystal solubility boundary of these linear nonionic surfactants. The positional isomers where the urea moiety was not situated at the terminus of the hydrocarbon chain exhibited higher melting points than the 1-alkyl ureas. This has been rationalized by postulating interdigitated chains in the solid state. In the urea surfactant-water systems, three phases are observed, viz. crystalline solid, a dilute aqueous solution of the alkyl urea, and an isotropic liquid. The last two phases coexist in the low-surfactant, high-temperature region of the binary phase diagram. An overview of structure-property correlations for linear nonionic urea surfactants is presented in light of the new physicochemical data obtained for the decyl urea and dodecyl urea positional isomers.

The strong intramolecular hydrogen bonding of urea is ameliorated, through select structural modifications to hydrocarbon chain substituents, resulting in surfactant self-assembly and the formation of a lyotropic liquid crystalline (inverse hexagonal) phase that is thermodynamically stable in excess water. The nanostructured bulk phase can be dispersed in water to form nanoparticles (“colloidosomes”).

The long-ranged attractions between hydrophobic amorphous fluoropolymer surfaces are measured in water with and without dissolved air. An atomic force microscope is used to obtain more than 500 measured jump-in distances, which yields statistically reliable results. It is found that the range of the attraction and its variability is generally significantly decreased in deaerated water as compared to normal, aerated water. However, the range and strength of the attraction in deaerated water remain significantly greater than the van der Waals attraction for this system. The experimental observations are consistent with (1) nanobubbles being primarily responsible for the long-ranged attraction in normal water, (2) nanobubbles not being present in deaerated water when the surfaces are not in contact, and (3) the attraction in the absence of nanobubbles being most probably due to the approach to the separation-induced spinodal cavitation of the type identified by Bérard et al. [J. Chem. Phys. 1993, 98, 7236]. It is argued that the measurements in deaerated water reveal the bare or pristine hydrophobic attraction unobscured by nanobubbles.

Molecular dynamics simulations of monolayers of nonionic, poly(ethylene oxide) based surfactants are reported. Specifically, alcohol ethoxylates and alkylphenol ethoxylates are compared in terms of the varying architecture of the molecules for the development of a structure-behavior relationship. Interfacial density profiles are used to assess the structure of the monolayers, the penetration of water and oil into the monolayers, and the solvation of the hydrophiles and hydrophobes. Chain conformational descriptors are used to examine the molecular structure of the surfactants. The simulations revealed that monolayers of alcohol ethoxylates are considerably more diffuse than their alkylphenol counterparts, with the packing being governed by the size of the hydrophile. With the exception of the branched alcohol ethoxylate, the intermixing of the bulk phases within monolayers of alcohol ethoxylates increases with increasing hydrophile length. By comparison, the packing of alkylphenol ethoxylates within the monolayer is governed by the aromatic nucleus in the molecule. No specific interaction is observed between the aromatic rings of neighboring molecules. Monolayers of alkylphenol ethoxylates are more compact than their alcohol counterparts, resulting in more effective separation of the bulk water and oil phases.

Aqueous solution conditions have been chosen so that a globular gelling food protein, ovalbumin, is adsorbed on a molecularly smooth muscovite mica surface. Atomic force microscope (AFM) fluid-tapping and electrical double layer imaging modes and force mapping have been used to characterize the heat-induced aggregation mechanism and surface properties of the protein. At a solution concentration of 0.5 μg/mL, single globular structures, which were consistent with the dimensions of ovalbumin monomers, were observed with the fluid-tapping imaging mode. Heat treatment caused protein aggregation and produced larger globular structures. At a solution concentration of 20 μg/mL, a protein film was formed and the electrical double layer mode of imaging revealed that the heat-induced globular aggregates were more heterogeneous than the native protein. The heterogeneity of the heat-treated ovalbumin film was also apparent from the effective film thickness maps derived from the force data obtained on approach of the ...

The two chiral isomers of the surfactant (±)-2-dodecyl β-d-glucoside have been prepared, and their thermotropic and lyotropic liquid crystalline behavior has been studied. Mixtures of the two pure diastereomers were prepared in known ratios to examine the effect of chiral purity on these properties using the techniques of differential scanning calorimetry and polarized light optical microscopy. It was found that the (+)-diastereomer produced crystalline and liquid crystalline phases in the presence and absence of water, which were more thermally stable than the (−)-diastereomer. The transition temperatures were reduced with increasing amounts of the (−)-diastereomer, but eutectic-like behavior was not exhibited, indicating metastable cosolubility. The large differences in thermotropic and lyotropic phase behavior may be due to the gross changes in molecular shape resulting from the very subtle difference in structure. This change in shape is likely to affect the molecular packing and headgroup interaction...

The force of interaction between pairs of silica colloids in aqueous electrolyte has been measured using an atomic force microscope . The measured force of interaction has been compared to predictions based on the Derjaguin, Landau, Verwey, and Overbeek (DLVO) theory, and only partial agreement has been obtained. Specifically, the force−separation data is entirely repulsive, failing to manifest the attraction predicted from the van der Waals interaction. The experimental decay length of the repulsive force was found to be in good agreement with the predicted Debye length, implicating an electrical double layer interaction. At low electrolyte concentration (

A series of six dodecyl glucopyranoside surfactants, each with a single glucopyranoside headgroup attached sequentially along the chain from carbon 1 to carbon 6, have been prepared in order to systematically simulate “branching” in glucose-based surfactants. The thermotropic and lyotropic liquid crystalline properties of the series have been investigated, as well as the hard soil detergency of these surfactants. The introduction of “branching” into the alkyl chain strongly affects the packing of the molecules into crystals and liquid crystalline structures, thereby influencing the thermotropic properties and the surfactant/water binary phase diagrams. Attachment of the headgroup at the terminal carbon or at carbon 2 does not appreciably influence the surfactant behavior, while attachment at carbon 3, 4, 5, or 6 results in very different behavior from that of either 1 or 2. This discontinuous change is reflected in the detergency behavior of the surfactants and can be attributed to the change in length an...

Force−separation measurements between a deformable, rough, biological surface (Cryptosporidium parvum) and an inorganic oxide (silica) have been obtained using the atomic force microscope. The system was chosen because oocysts of C. parvum have been associated with waterborne outbreaks of disease, and one of the main barriers to oocyst contamination of drinking waters is provided by sand-bed filtration. The oocysts are shown to be significantly rough on the scale of Derjaguin−Landau−Verwey−Overbeek forces and have been found to be compressible on the scale of the loads applied during force measurement. The surface compressibility is reported in terms of an interfacial spring constant. The force of interaction prior to this Hookean region is long-range and repulsive. The long-range force has been compared to models of the electrical double layer force (based on the measured ζ-potentials and bulk electrolyte concentration) as well as an electrosteric force (treating the surface as a polyelectrolyte brush). ...

A matrix of anomerically pure glucose-based surfactants have been synthesized and their thermotropic and lyotropic liquid crystalline phase behavior, and air-aqueous solution interfacial adsorption were investigated. The surfactants, which represent the major components of the Fischer synthesis products, were the n-octyl, n-decyl and n-dodecyl homologues of alkyl α-d- and β-d-glucoside and alkyl β-d-maltoside. The matrix allowed the investigation of the effects of alkyl chain length, headgroup polymerization, and anomeric configuration on the surfactants' physicochemical properties. Increasing the alkyl chain length increases the hydrophobicity and the dispersion interaction between surfactant molecules, as one would expect, resulting in greater thermal stability of thermotropic and lyotropic phases. Phase transition temperatures are influenced significantly by the anomeric configuration in the shorter octyl derivatives, but to a lesser extent in the longer alkyl chain derivatives. The effect of increasin...

An atomic force microscope (AFM) has been used to measure the force of interaction between individual biological microspheres (oocysts of Cryptosporidium parvum) and an amorphous silica surface (hydrolyzed AFM tip). One of the main barriers to oocyst contamination of drinking waters is provided by sand-bed filtration. The AFM tip has been functionalized to silica in order to investigate the interaction between oocysts and model sand (siliceous) particles at the most fundamental level. The AFM force curves have been compared and contrasted with the ζ-potentials of silica particles and oocysts obtained from electrophoretic mobility measurements. It has been concluded that there is a steric interaction between the silica surface and the oocyst material, in addition to electrical double-layer and van der Waals interaction. The proteinaceous materials on the surface of the oocysts are considered to be responsible for the steric interaction. The magnitude of the steric interaction is little changed by varying t...

An atomic force microscope has been employed to measure the force of interaction between a micron-sized colloidal sphere and a flat plate, both coated with a copolymer of perfluoro(2,2-dimethyl-1,3-dioxole) and tetrafluoroethylene (Teflon AF1600) in water, glycerol, formamide, ethylene glycol, ethylammonium nitrate, formic acid, ethanol, methanol, diiodomethane, 1-bromonaphthalene, hexadecane, and hexane. A long-range force of attraction was measured in water and, with the exception of the n-alkanols and n-alkanes, all the organic liquids. The results indicate that there is a macroscopic long-range attraction between solvophobic surfaces that has a different origin from that of the hydrophobic interaction observed at the molecular level. The results also indicate that there is a “solvophobic force” that is not due to either orientational ordering propagated by hydrogen bonds, electrostatic (or polarization) effects, or condensates of “loosely attached” surface material; all mechanisms that have been invok...

The thermal properties of n-hexyl, n-heptyl, and n-octyl urea, in the temperature range of 20 °C to the melting point, have been determined. The melting points of the three n-alkyl ureas, and the enthalpies for this crystalline solid to isotropic liquid transition, are similar. The urea headgroup interaction clearly dominates the melting behavior with only a minor contribution from alkyl chain interaction. The n-alkyl urea solubility in water, partial binary surfactant−water phase diagrams, and surface activity at the air−water interface have also been determined. The strong intermolecular hydrogen bonding existing in the crystalline state results in a relatively low solubility and a high crystal solubility boundary for each of the n-alkyl ureas. In surfactant−water mixtures, in the temperature range of 20−98 °C, three phases have been observed, viz., crystalline solid, a dilute aqueous solution of n-alkyl urea, and an isotropic liquid that is considered to be rich in n-alkyl urea but contains water as we...

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AFM force measurements were carried out between a silica colloid sphere and an alumina flat crystal over a wide pH range and in both 110-4and 110-3M KNO3aqueous solutions. Microelectrophoresis and streaming potential experiments were performed on the silica colloid sample and the alumina plate, respectively. The potentials measured by the different techniques were in very good agreement. The results clearly indicate that AFM force measurements can be used to accurately determine diffuse layer potentials of metal oxide materials under these solution conditions.

Surface free energies have been calculated for solid fluorocarbon materials by employing a method that utilizes dielectric data and theoretical predictions of van der Waals (dispersion) interactions. Excellent agreement between the results of direct force measurements and those of the theory for retarded van der Waals interactions supports the methodology. Two relatively new fluorocarbon polymers have been identified as having the lowest known surface free energies of all bulk homogeneous polymeric solids. This study provides confirmation that estimates of solid surface free energies based on contact angle measurements with dispersive organic liquids depend on the dielectric properties of both the liquids and the solid.

A theoretical description is presented for the macroscopic contact angle (θ) of a solid/vapor/aqueous solution interface when the solid surface is ionizable and relatively hydrophobic. The contact angle is related to the free energy of formation of the ionizable surface in aqueous solution. Therefore, the theoretical approach takes into account the electrostatic free energy of charging the surface and the change in the free energy associated with the acid-base reactions of the surface sites. It is shown that the dependence of θ on pH depends on the number ofionizable surface sites per unit area, the intrinsic acid-base dissociation constant (K a i ) of the surface sites, and the background electrolyte. The negative free energy change which accompanies the acid-base reactions dominates over the positive electrostatic free energy of charging the surface ; therefore, the overall free energy of ionization is negative, and the ionized surfaces are more wettable than the uncharged surfaces. The theoretical description is applied to experimental values of θ as a function of pH, measured on heptylamine plasma polymer surfaces in the presence of either 1 or 10 mM NaCl. The theoretical fit to the advancing and sessile contact angles indicates that the plasma polymer surface contains ca. 4±1x10 17 amines/m 2 and the pK a i of the amine groups is ca. 6. The surface site density is in accord with values obtained by derivatization techniques, and the pK a i is consistent with a low effective dielectric constant for the polymer-water interfacial microenvironment.