The Crystalline Sponge Method in Water

The crystalline sponge method entails the elucidation of the (absolute) structure of molecules from a solution phase using single-crystal X-ray diffraction and eliminates the need for crystals of the target compound. An important limitation for the application of the crystalline sponge method is the instability of the available crystalline sponges that can act as host crystals. The host crystal that is most often used decomposes in protic or nucleophilic solvents, or when guest molecules with Lewis basic substituents are introduced. Here a new class of (water) stable host crystals based on f-block metals is disclosed. It can be shown that these hosts not only increase the scope of the crystalline sponge method to a wider array of solvents and guests, but that they can even be applied to aqueous solutions containing hydrophilic guest molecules, thereby extending the crystalline sponge method to the important field of water-based chemistry.     

Interfacial Modification and Structural Transitions Induced by Guest Molecules Solubilized in U‐Type Nonionic Microemulsions

Abstract

Alcohols and polyols are essential components (in addition to the surfactant, water, and oil) in the formation of U‐type self‐assembled nano‐structures, (sometimes called L‐phases or U‐type microemulsions). These microemulsions are characterized by large isotropic regions ranging from the oil side of the phase diagram up to the aqueous corner. The isotropic oily solutions of reverse micelles (“the concentrates”) can be diluted along some dilution lines with aqueous phase to the “direct micelles” corner via a bicontinuous mesophases (i.e., two structural transitions). This dilution takes place with no phase separations or occurrence of liquid crystalline phases. The structural transitions were determined by viscosity, conductivity, and pulsed gradient spin echo NMR (PGSE NMR), and are not visible to the eye. Two guest nutraceutical molecules (lutein and phytosterols) were solubilized, at their maximum solubilization capacity, in the reversed micellar solutions (L₂ phase) and were further diluted with the aqueous phase to the aqueous micellar corner (L₁ phase). Structural transitions (for the two types of molecule) from water‐in‐oil to bicontinuous microstructures were induced by the guest molecules. The transitions occurred at an earlier stage of dilution, at a lower water content (20 wt.% aqueous phase), than in the empty (blank) microemulsions (transitions at 30 wt.% aqueous phase). The transitions from the bicontinuous microstructure to the oil‐in‐water microemulsions were retarded by the solubilizates and occurred at later dilution stage at higher aqueous phase contents (50 wt.% aqueous region for empty microemulsion and >60 wt.% for solubilized microemulsion). As a result, the bicontinuous isotropic region, in the presence of the guest molecules, becomes much broader. It seems that the main reason for such “guest‐induced structural transitions” is related to a significant flattening and enhanced rigidity of the interface. The guest molecules of the high molecular volume are occupying high volume fraction of the interface (when the solubilization is maximal).     

A novel lyotropic liquid crystal formed by triphilic star-polyphiles: hydrophilic/oleophilic/fluorophilic rods arranged in a 12.6.4. tiling

Triphilic star-polyphiles are short-chain oligomeric molecules with a radial arrangement of hydrophilic, hydrocarbon and fluorocarbon chains linked to a common centre. They form a number of liquid crystalline structures when mixed with water. In this contribution we focus on a hexagonal liquid crystalline mesophase found in star-polyphiles as compared to the corresponding double-chain surfactant to determine whether the hydrocarbon and fluorocarbon chains are in fact demixed in these star-polyphile systems, or whether both hydrocarbon and fluorocarbon chains are miscible, leading to a single hydrophobic domain, making the star-polyphile effectively amphiphilic. We report SANS contrast variation data that are compatible only with the presence of three distinct immiscible domains within this hexagonal mesophase, confirming that these star-polyphile liquid crystals are indeed hydrophilic/oleophilic/fluorophilic 3-phase systems. Quantitative comparison with scattering simulations shows that the experimental data are in very good agreement with an underlying 2D columnar (12.6.4) tiling. As in a conventional amphiphilic hexagonal mesophase, the hexagonally packed water channels (dodecagonal prismatic domains) are embedded in a hydrophobic matrix, but that matrix is split into oleophilic hexagonal prismatic domains and fluorophilic quadrangular prismatic domains.     

Thermotropic Liquid Crystals Formed by Intermolecular Hydrogen Bonding Interactions

The role of hydrogen bonding in the formation or stabilization of liquid crystalline phases has only recently been appreciated. Following the first, wellestablished examples of liquid crystal formation from the dimerization of aromatic carboxylic acids, through hydrogen bonding, several classes of compounds have recently been synthesized, the liquid crystalline behavior of which is also dependent on intermolecular hydrogen bonds between similar or dissimilar molecules. In this review the main classes of compounds exhibiting liquid crystallinity due to hydrogen bonding are presented to show the diversity of organic compounds that can be used as building elements in liquid crystals. The molecules are either of the rigid-rod anisotropic or amphiphilic types such as molecules appropriately functionalized with pyridyl and carboxyl groups, whose interaction leads to the formation of liquid crystals; amphiphilic carbohydrates and amphiphilic and bolaamphiphilic compounds with multiple hydroxyl groups whose dimerization or association is indispensable for the formation of liquid crystals; and certain amphiphilic carboxylic acids with monomeric or polymeric mesogens and amphiphilic-type compounds bearing different moieties, whose interaction may lead to the formation of mesomorphic compounds. Associated with the macroscopic display of liquid crystalline phases is the supramolecular structure, and therefore rather extended discussion of these structures are included in this review.     

Linker molecules in surfactant mixtures

Linker molecules are amphiphiles that segregate near the microemulsion membrane either near the surfactant tail (lipophilic linkers) or the surfactant head group (hydrophilic linkers). The idea of the lipophilic linkers was introduced a decade ago as a way to increase the surfactant–oil interaction and the oil solubilization capacity. Long chain (>9 tail carbons) alcohols were first used as lipophilic linkers. Later it was found that the solubilization enhancement plateaus (saturates) above a certain lipophilic linker concentration. Hydrophilic linkers have been recently introduced as a way to compensate for the saturation effect observed for lipophilic linkers. Hydrophilic linkers are surfactant-like molecules with 6–9 tail carbons that coadsorb with the surfactant at the oil/water interface, thereby increasing the surfactant–water interaction, but have a poor interaction with the oil phase due to their short tail. A special synergism emerges when combining hydrophilic and lipophilic linkers, which further increases the solubilization enhancement over lipophilic linkers alone. We will discuss the profound impact of linker molecules on interfacial properties such as characteristic length, interfacial rigidity and dynamics (coalescence, solubilization and relaxation experiments) of the interface. We also demonstrate how these properties affect the performance of cleaning formulations designed around linker molecules. We describe linker-based formulations for a wide range of oils, including highly hydrophobic oils (e.g. hexadecane) that have proven very hard to clean. We also report on the use of ‘extended’ surfactants as an alternative to self-assembled linker systems.     

Interactions of charged porphyrins with nonionic triblock copolymer hosts in aqueous solutions

The extent and locus of solubilization of guest and self-assembling surfactant host molecules in aqueous solutions are influenced by a variety of hydrophobic and hydrophilic interactions, as well as by more specific interactions between the various species present. By using a combination of two-dimensional heteronuclear 13C[1H] NMR correlation experiments with pulsed-gradient NMR diffusion and proton cross-relaxation measurements, the locations and distributions of porphyrin guest molecules have been established unambiguously with respect to the hydrophobic and hydrophilic moieties of a triblock copolymer species in solution. The interactions of tetra(4-sulfonatophenyl)porphyrin with the poly(propylene oxide) (PPO) and the poly(ethylene oxide) (PEO) segments of amphiphilic PEO-PPO-PEO triblock copolymer species have been measured as functions of solution conditions, including temperature and pH. The porphyrin/PEO-PPO-PEO interactions are established to be selective and adjustable according to the different temperature-dependent hydrophilicities or hydrophobicities of the PEO and PPO triblock copolymer components. Furthermore, such interactions influence the self-assembly properties of the block-copolymer amphiphiles in solution by stabilizing molecular porphyrin/PEO-PPO-PEO complexes well above the critical micellization temperature of the triblock copolymer species under otherwise identical conditions.     

Fluorescence turn on by cholate aggregates

Bile salts, including sodium cholate (NaCh), are amphiphilic molecules with a concave hydrophilic side and a convex hydrophobic side. By forming aggregates in aqueous solution, these natural surfactants fulfill vital biological roles in the solubilization of cholesterol, lipids, and fat-soluble vitamins and thus are involved in the transport and absorption of important biological molecules. Following our success with the encapsulation of fluorescent protein chromophore (FP) analogs by synthetic hydrophobic and hydrophilic hosts, based upon substitution patterns, we now report the binding and turn on of other analogs by bile salt aggregates, observations which may lead to new tools for studying trafficking in these important systems.     

刚棒-线团分子的自组装研究进展

超分子化学领域的自组装研究是近年来研究的热点,对这种由一种或多种结构单元自发聚集而成具有一定尺寸和结构的过程研究已经取得了重大进展.以亲水基团和亲脂基团为主要构成单元的两亲性分子在自组装领域中的表现优异于其他分子,其亲水的刚性棒状基团和疏水的柔性线团基团通过不同方法共同构成了各种类型的刚柔两亲性分子,而在水溶液中自组装...     

Modeling solubilization of oil mixtures in anionic microemulsions II. Mixtures of polar and non-polar oils

Polar/amphiphilic oils, called lipophilic linkers, are sometimes added to oil-water-ionic surfactant microemulsions in order to increase the solubilization of hydrophobic oils. The solubilization increase has been well documented for a number of systems. However, mathematical models to calculate the solubilization increase have been proposed only for optimum microemulsions (i.e., middle phase microemulsions solubilizing equal volumes of oil and water). In this paper we propose a model, which predicts solubilization enhancement for non-optimum microemulsion systems as well. The model is an extension of the net-average curvature model of microemulsion. The net-average curvature model is combined with a surface activity model to account for the increased palisade layer solubilization due to the presence of the polar/amphiphilic oil component. New non-linear mixing rules are also incorporated to account for the optimum salinity and the characteristic length variation of the anionic surfactant microemulsion as a function of the lipophilic linker concentration. The model predicts the effect of the lipophilic linker and the electrolyte concentration on the oil solubilization in accordance with the experimental results.     

Stimuli-responsive supramolecular nanocapsules from amphiphilic calixarene assembly

We synthesized tetrameric amphiphilic molecules based on a calixarene building block that self-assembles into a tunable and stable aggregation structure in aqueous solution. The amphiphilic calixarene molecules with a small hydrophilic part were observed to assemble into a vesicular structure that decreases significantly in diameter with only small increases in the hydrophilic chain length. Further increasing the chain length induced the collapse of the vesicles into spherical micelles. Remarkably, the vesicles were also observed to transform into small globular micelles at lower pH, which can be used to trigger the release of the encapsulated hydrophilic guest molecules.     

用共轭亚油酸构筑层状液晶的药物传递系统

在水相中用共轭亚油酸(CLA)及其钠盐(SCL)构筑层状液晶相,并考察了其药物缓释行为.借助偏光显微镜并辅以目测确定CLA/SCL/H2O三元相图中的层状液晶相区,然后用偏光显微镜、小角X射线散射仪和旋转流变仪获得层状液晶的偏光织构、相参数和流变参数等,证实其适用于药物传递系统(DDS).采用透析法研究了负载亲水性药物5-氟尿嘧啶或亲油性药物姜黄素的层状液晶的释药曲线,结果表明,该类层状液晶对2种药物均有良好的缓释能力.     

Water-in-water (W/W) emulsions

Water-in-water (W/W) emulsions are colloidal dispersions of an aqueous solution into another aqueous phase. Such dispersions can be formed in mixtures of at least two hydrophilic macromolecules, which are thermodynamically incompatible in solution, generating two immiscible aqueous phases. W/W emulsions are much less known than conventional oil-in-water or water-in-oil emulsions, despite the fact that phase separation in aqueous mixtures is highly common. The thermodynamics and the phase behavior of segregative phase separation in mixtures of hydrophilic polymers have focused a great attention, with many excellent scientific reports in the literature. However, the kinetic stability of water-in-water emulsions is generally difficult to control, since amphiphilic molecules do not adsorb on water-water interfaces. Consequently, surfactants are not good stabilizers for W/W emulsions, and until recently, only a limited number of scientific studies have dealt with the formation and stabilization of emulsions in aqueous two-phase systems. Recent advances and successful results in the stabilization of these emulsions, by alternative mechanisms, have triggered a renewed interest. Nowadays, fast progress is being made in formation and stabilization methods, and new knowledge is rapidly acquired, opening a wide range of novel possibilities for practical applications. Interestingly, highly stable water-in-water emulsions can be formulated using fully biocompatible and edible components, and consequently, these emulsions can be used in food formulations, among many other interesting applications. This review describes the general background of research in the field, and focuses on recent scientific advances, including phase behavior, formation, stability and kinetic aspects, as well as applications such as formation of microgels, encapsulation and drug delivery.     

Chemical Programming of the Domain of Existence of Liquid Crystals

This work illustrates how enthalpy and entropy changes responsible for successive phase transitions of cyanobiphenyl‐based liquid crystals can be combined to give cohesive free energy densities. These new parameters are able to rationalize and quantify the demixing of the melting and clearing processes that occur in thermotropic liquid crystals. Minor structural variations at the molecular level can be understood as pressure increments that alter either the melting or clearing temperatures in a predictable way. This assessment of microsegregation operating in amphiphilic molecules paves the way for the chemical programming of the domain of existence of liquid‐crystalline phases.     

Solubilization of nutraceuticals into reverse hexagonal mesophases

The solubilization of four bioactive molecules with different polarities, in three reverse hexagonal (HII) systems has been investigated. The three HII systems were a typical reverse hexagonal composed of glycerol monooleate (GMO)/tricaprylin/water and two fluid hexagonal systems containing either 2.75 wt % Transcutol or ethanol as a fourth component. The phase behavior of the liquid crystalline phases in the presence of ascorbic acid, ascorbyl palmitate, D-alpha-tocopherol and D-alpha-tocopherol acetate were determined by small-angle X-ray scattering (SAXS) and optical microscopy. Differential scanning calorimetry (DSC) and Fourier-transform infrared (FT-IR) techniques were utilized to follow modifications in the thermal behavior and in the vibrations of different functional groups upon solubilizing the bioactive molecules. The nature of each guest molecule (in both geometry and polarity) together with the different HII structures (typical and fluids) determined the corresponding phase behavior, swelling or structural transformations and its location in the HII structures. Ascorbic acid was found to act as a chaotropic guest molecule, localized in the water-rich core and at the interface. The AP was also a chaotropic guest molecule with its head located in the vicinity of the GMO headgroup while its tail embedded close to the surfactant tail. D-alpha-tocopherol and D-alpha-tocopherol acetate were incorporated between the GMO tails; however, the D-alpha-tocopherol was located closer to the interface. Once Transcutol or ethanol was present and upon guest molecule incorporation, partial migration was detected.     

Attainment of Emulsions with Liquid Crystal from Marigold Oil Using the Required HLB Method

Development of new formulations for topical use and cosmetic and pharmaceutical delivery agents has increased the complexity of emulsified systems. Liquid crystals, known since the nineteenth century are the third phase of an emulsion, being responsible for increasing its stability and the solubility of substances poorly soluble in water, or the oily phase, modulating the release of drugs imprisoned in its structure and promoting hydration of the skin surface. In the present work we developed oil/water emulsions, making use of Marigold oil (Calendula officinalis L) and ethoxylated fat alcohols as surfactant. The required HLB value for marigold oil was determined to be 6.0. The surfactants were associated in lipophilic/hydrophilic pairs. The lipophilic surfactants were Ceteth‐2 and Steareth‐2 and the hydrophilic surfactants were Steareth‐20, Ceteareth‐20, Ceteareth‐5, and Ceteth‐10. To identify the liquid crystalline phases, the emulsions were analyzed by polarized light microscopy. The physical stability was evaluated by rheology and zeta potential analysis. All emulsions presented lamellar liquid crystal structures. Results showed that this type of surfactant is able to produce liquid crystal in the system, with slight difference in appearance, influencing the physical stability, according to the methods applied.     

Bicontinuous cubic phase of monoolein and water as medium for electrophoresis of both membrane-bound probes and DNA

Porous hydrogels such as agarose are commonly used to analyze DNA and water-soluble proteins by electrophoresis. However, the hydrophilic environment of these gels is not suitable for separation of important amphiphilic molecules such as native membrane proteins. We show that an amphiphilic liquid crystal of the lipid monoolein and water can be used as a medium for electrophoresis of amphiphilic molecules. In fact, both membrane-bound fluorescent probes and water-soluble oligonucleotides can migrate through the same bicontinuous cubic crystal because both the lipid membrane and the aqueous phase are continuous. Both types of analytes exhibit a field-independent electrophoretic mobility, which suggests that the lipid crystal structure is not perturbed by their migration. Diffusion studies with four membrane probes indicate that membrane-bound analytes experience a friction in the cubic phase that increases with increasing size of the hydrophilic headgroup, while the size of the membrane-anchoring part has comparatively small effect on the retardation.     

Solubilization in alkanes by alcohols as reverse hydrotropes or "lipotropes"

Hydrotropes in aqueous systems do not aggregate in micelles, inhibit presence of mesophases and allow significant and progressive solubilization of "insoluble" molecules in water. It was shown that n-alcohols in alkanes develop the same properties, including the power-law for maximum solubilization of "hydrophilic" molecules. The aim of this paper is to highlight properties of reverse hydrotropes or "lipotropes" by taking n-alcohol/alkane mixtures as model systems. So as to establish a clear parallel between lipotropes and hydrotropes the same methodology used to characterize hydrotropes was applied to these systems. The solubilization of solutes insoluble in alkane, i.e. water and a hydrophilic dye in dodecane, enabled by the addition of n-alcohols ( n = 2, 3, 4 and 7) was studied. In parallel, the nonmicellar aggregation state of butan-1-ol and heptan-1-ol in dodecane was investigated by small-angle X-ray scattering. By applying the Porod's treatment the specific area of the H-bond network formed by heptan-1-ol and the area occupied by hydroxyl group in this network were determined as a function of concentration. A correlation between the aggregation of alcohols in dodecane and the solubilization was made. The disrupting of concentrated mesophases by a lipotrope was illustrated by studying the effect of adding n-alcohols to water/oil/extractant ternary systems used in liquid/liquid extraction. Under some conditions the organic phase splits up into two phases: an extractant mesophase and nearly pure oil. The amount of n-alcohols required to make the extractant mesophase disappear was determined for water/alkane/malonamide extractant systems. The influence of the chain length of the n-alcohol on the efficiency as lipotrope was also experimentally studied. The trend obtained was similar to the one observed with the solubilization experiments.     

Ultrasound‐Driven Secondary Self‐Assembly of Amphiphilic β‐Cyclodextrin Dimers

The controlled secondary self‐assembly of amphiphilic molecules in solution is theoretically and practically significant in amphiphilic molecular applications. An amphiphilic β‐cyclodextrin (β‐CD) dimer, namely LA‐(CD)₂, has been synthesized, wherein one lithocholic acid (LA) unit is hydrophobic and two β‐CD units are hydrophilic. In an aqueous solution at room temperature, LA‐(CD)₂ self‐assembles into spherical micelles without ultrasonication. The primary micelles dissociates and then secondarily form self‐assemblies with branched structures under ultrasonication. The branched aggregates revert to primary micelles at high temperature. The ultrasound‐driven secondary self‐assembly is confirmed by transmission electron microscopy, dynamic light scattering, ¹H NMR spectroscopy, and Cu²⁺‐responsive experiments. Furthermore, 2D NOESY NMR and UV/Vis spectroscopy results indicate that the formation of the primary micelles is driven by hydrophilic–hydrophobic interactions, whereas host–guest interactions promote the formation of the secondary assemblies. Additionally, ultrasonication is shown to be able to effectively destroy the primary hydrophilic–hydrophobic balances while enhancing the host–guest interaction between the LA and β‐CD moieties at room temperature.     

Alignment modulation of azobenzene-containing liquid crystal systems by photochemical reactions

Recent progress in alignment modulation of azobenzene-containing liquid crystal systems by photochemical reactions has been reviewed by dividing the modulation methods into two types: phase transitions (order–disorder change) and change of liquid crystal directors (order–order change). First, photochemical phase transitions and alignment changes of liquid crystals in guest/host mixtures and polymers are summarized. Then, alignment control of liquid crystals by linearly polarized light and photoactive surface layers is discussed. Finally, recent applications of alignment change and photochemical phase transitions of liquid crystals in holographic technology and photomechanical effects are introduced. In addition, future possible applications for a variety of practical devices, such as display devices, optical switching and reversible optical image storage, are mentioned.     

Tuning in-meso-crystallized lysozyme polymorphism by lyotropic liquid crystal symmetry

Lipid-based lyotropic liquid crystals (LLCs) show great potential for applications in fields as diverse as food technology, cosmetics, pharmaceutics, or structural biology. Recently, these systems have provided a viable alternative to the difficult process of membrane protein crystallization, owing to their similarities with cell membranes. Nonetheless, the process of in-meso crystallization of proteins still remains poorly understood. In this study, we demonstrate that in-meso crystal morphologies of lysozyme (LSZ), a model hydrophilic protein, can be controlled by both the composition and symmetry of the mesophase, inferring a possible general influence of the LLC space group on the protein crystal polymorphism. Lysozyme was crystallized in-meso from three common LLC phases (lamellar, inverse hexagonal, and inverse bicontinuous cubic) composed of monolinolein and water. Different mixing ratios of mesophase to crystallization buffer were used in order to tune crystallization both in the bulk mesophase and in excess water conditions. Two distinct mechanisms of crystallization were shown to take place depending on available water in the mesophases. In the bulk mesophases, protein nuclei form and grow within structural defects of the mesophase and partially dehydrate the system inducing order-to-order transitions of the liquid crystalline phase toward stable symmetries in conditions of lower hydration. The formed protein crystals eventually macrophase separate from the mesophase allowing the system to reach its final symmetry. On the other hand, when excess water is available, protein molecules diffuse from the water channels into the excess water, where the crystallization process can take place freely, and with little to no effect on the structure and symmetry of the lyotropic liquid crystals.