Oligomeric cholates: amphiphilic foldamers with nanometer-sized hydrophilic cavities

The hydroxyl at the C-3 of cholic acid was converted to an amino group, and the resulting amino-functionalized cholic acid was used as a monomer to prepare amide-linked oligomeric cholates. These cholate oligomers fold into helical structures with nanometer-sized hydrophilic internal cavities in solvent mixtures consisting of mostly nonpolar solvents such as carbon tetrachloride or ethyl acetate/hexane and 2-5% of a polar solvent such as methanol or DMSO. The conformations of the foldamers were studied by UV, fluorescence, fluorescence quenching, and fluorescence resonance energy transfer. The nature of the polar/nonpolar solvents and their miscibility strongly influenced the folding reaction. Folding was cooperative, as evidenced by the sigmoidal curves in solvent denaturation experiments. The folded conformers became more stable with an increase in the chain length. The folding/unfolding equilibrium was highly sensitive toward the amount of polar solvent. One percent variation in the solvent composition could change the folding free energies by 0.5-1.4 kcal/mol.     

Solvent-induced amphiphilic molecular baskets: unimolecular reversed micelles with different size, shape, and flexibility

Amphiphilic molecular baskets were obtained by attaching facially amphiphilic cholate groups to a covalent scaffold (calix[4]arene or 1,3,5-2,4,6-hexasubstituted benzene). In a solvent mixture consisting of mostly a nonpolar solvent (i.e., CCl4) and a polar solvent (i.e., DMSO), the hydrophilic faces of cholates turned inward to form a reversed-micelle-like conformer whose stability was strongly influenced by the number of the cholates and the topology of the scaffold. Preferential solvation of the hydrophilic faces of cholates within the molecule by the polar solvent was cooperative and gave the fundamental driving force to the conformational change. The reversed-micelle-like conformer was most stable in structures that allowed multiple cholates to form a microenvironment that could efficiently enrich the polar solvent molecules from the bulk solvent mixture.     

Solvent-tunable binding of hydrophilic and hydrophobic guests by amphiphilic molecular baskets

[reaction: see text] Responsive amphiphilic molecular baskets were obtained by attaching four facially amphiphilic cholate groups to a tetraaminocalixarene scaffold. Their binding properties can be switched by solvent changes. In nonpolar solvents, the molecules utilize the hydrophilic faces of the cholates to bind hydrophilic molecules such as glucose derivatives. In polar solvents, the molecules employ the hydrophobic faces of the cholates to bind hydrophobic guests. A water-soluble basket can bind polycyclic aromatic hydrocarbons including anthracene, pyrene, and perylene. The binding free energy (-deltaG) ranges from 5 to 8 kcal/mol and is directly proportional to the surface area of the aromatic hosts. Binding of both hydrophilic and hydrophobic guests is driven by solvophobic interactions.     

Water-dispersible, uniform nanospheres by heating-enabled micellization of amphiphilic block copolymers in polar solvents

Uniform nanospheres with tunable size down to 30 nm were prepared simply by heating amphiphilic block copolymers in polar solvents. Unlike reverse micelles prepared in nonpolar, oily solvents, these nanospheres have a hydrophilic surface, giving them good dispersibility in water. Furthermore, they are present as individual, separated, rigid particles upon casting from the solution other than continuous thin films of merged micelles cast from micellar solution in nonpolar solvents. These nanospheres were generated by a heating-enabled micellization process in which the affinity between the solvent and the polymer chains as well as the segmental mobility of both hydrophilic and hydrophobic blocks was enhanced, triggering the micellization of the glassy copolymers in polar solvents. This heating-enabled micellization produces purely well-defined nanospheres without interference of other morphologies. The micelle sizes and corona thickness are tunable mainly by changing the lengths of the hydrophobic and hydrophilic blocks, respectively. The heating-enabled micellization route for the preparation of polymeric nanospheres is extremely simple, and is particularly advantageous in producing rigid, micellar nanospheres from block copolymers with long glassy, hydrophobic blocks which are otherwise difficult to prepare with high efficiency and purity. Furthermore, encapsulation of hydrophobic molecules (e.g., dyes) into micelle cores could be integrated into the heating-enabled micellization, leading to a simple and effective process for dye-labeled nanoparticles and drug carriers.     

Contact mechanics of nanometer-scale molecular contacts: correlation between adhesion, friction, and hydrogen bond thermodynamics

Using a scanning force microscope, adhesion forces have been measured between carboxylic acid terminated self-assembled monolayers in different nonpolar solvents or in two-component liquid mixtures consisting of a polar solvent (ethyl acetate or acetone) in heptane. The adhesion forces measured in pure acetone and ethyl acetate were small (0.24 nN) but increased logarithmically as the concentration of the polar solvent decreased to reach a maximum value (2.77 nN), equal to that measured in pure heptane, and for lower concentrations of polar solvent, the adhesion force remained constant. This behavior is identical to that observed for association constants measured for the formation of 1:1 H-bonded complexes between dilute solutes in solvent mixtures. The transition between the solvent-dependent and -independent regimes occurs at a polar solvent concentration corresponding to 1/K(S), where K(S) is the equilibrium constant for solvation of a carboxylic acid by the polar solvent in heptane. A simple model, in which the solvation of the carboxylic acid groups may be estimated by considering the concentration and polarity of functional groups in the liquid, accurately predicts values of K(S) that were found to correlate very well with the observed solvent-dependence of the adhesion force. Friction-load relationships were measured using friction-force microscopy. In pure acetone and ethyl acetate, a linear friction-load relationship was observed, in agreement with Amontons' law. However, as the concentration of polar solvent was reduced, a nonlinear relationship was observed and the friction-load relationship was found to fit the Derjaguin-Müller-Toporov (DMT) model for single asperity contacts. For pure heptane and a range of other nonpolar liquids with identical dielectric constants, the friction-load relationship was described by DMT mechanics. Exceptionally, for perfluorodecalin, Johnson-Kendall-Roberts mechanics was observed. These observations may be rationalized by treating the friction force as the sum of load-dependent and shear contributions. Under conditions of low adhesion, where the carboxylic acid surface is solvated by polar solvent molecules, the shear term is negligible and the sliding interaction is dominated by load-dependent friction. As the degree of solvation of the carboxylic acid groups decreases and the adhesion force increases, the shear friction contribution increases, dominating the interaction for media in which the adhesion force is greater than ca. 0.6 nN.     

Delivering octadecylphosphonic acid self-assembled monolayers on a Si wafer and other oxide surfaces

We describe a simple experimental approach for delivering self-assembled monolayers (SAMs) of octadecylphosphonic acid (OPA) on many oxide surfaces using a nonpolar medium with a dielectric constant around 4 (e.g., trichloroethylene). This approach readily results in the formation of full-coverage OPA SAMs on a wide variety of oxide surfaces including cleaved mica, Si wafer, quartz, and aluminum. Especially, the availability of delivering full-coverage OPA SAM on a Si wafer is unique, as no OPA SAMs at all could be formed on a Si wafer when using a polar OPA solution. The reason a nonpolar solvent is superior lies in the very fact that the hydrophilic OPA headgroup tends to escape from the nonpolar solution and is thus enriched at the medium-air interface. It is these OPA headgroups seeking a hydrophilic surface that make possible the well-controlled OPA monolayer on an oxide surface.     

Tuning the sensitivity of a foldamer-based mercury sensor by its folding energy

A fluorescent sensor for Hg2+ was obtained by incorporation of two methionine units into a cholate hexamer and by attaching a Dansyl group at the chain end. Folding could be made highly favorable or unfavorable in different solvents. Because folding was required to bring the sulfur groups together to chelate the mercury ion, binding affinity of the foldamer and, thus, its sensitivity as a sensor, could be tuned over broad ranges (at least 5 orders of magnitude) by solvent changes.     

Large-scale preparation of five polar polyphenols including three isomers from Phyllanthus emblica Linn. by preparative high-speed counter-current chromatography

The separation of polar compounds is challenging work due to poor retention and insufficient selectivity. In the present study, an efficient strategy for large-scale preparation of five polar polyphenols including three isomers from Phyllanthus emblica Linn has been established by preparative high-speed counter-current chromatography. Macroporous resin column chromatography was used for the enrichment of the polar polyphenols. However, sugar and other ultra-polar impurities were co-washed out with the targets. Liquid-liquid extraction with ethyl acetate/water (1/1, v/v) solvent system was developed to remove the ultra-polar impurities with a clearance rate of 95%. Finally, the targets were introduced to preparative high-speed counter-current chromatography for separation using ethyl acetate/n-butanol/acetic acid/water (2/7/1/10, v/v/v/v) solvent system. As a result, 191 mg of Mucic acid 1,4-lactone 5-O-gallate, 370 mg of β-Glucogallin, 301 mg of Gallic acid, 195 mg of Mucic acid 1,4-lactone 3-O-gallate and 176 mg of Mucic acid 1,4-lactone 2-O-gallate with purity higher than 98% were obtained from 1.5 g of sample. Mucic acid 1,4-lactone 3-O-gallate, Mucic acid 1,4-lactone 3-O-gallate, and Mucic acid 1,4-lactone 2-O-gallate are isomers. The results showed that high-speed counter-current chromatography could be well developed for the separation of polar compounds from natural products.     

Photostability of the sunscreening agent 4-tert-butyl-4′-methoxydibenzoylmethane (avobenzone) in solvents of different polarity and proticity

The most widely used UVA absorber in broad-spectrum sunscreens is 4-tert-butyl-4′-methoxydibenzoylmethane (avobenzone). However, the photostability of avobenzone is solvent-dependent. The aim of this work was to investigate the photostability of avobenzone in solvents of different polarity and proticity. Four solvents were employed, namely, cyclohexane, ethyl acetate, dimethylsulfoxide and methanol. The cause of the instability of avobenzone in these solvents was determined by means of UV spectroscopy, high performance liquid chromatography, gas chromatography–mass spectrometry and nuclear magnetic resonance spectroscopy. The effect of oxygen on the photo-instability was also determined. Avobenzone was found to lose absorption efficacy as a result of photoisomerisation from the enol to the keto form and/or photodegradation to form photoproducts that absorb principally in the UVC region, depending on the solvent. It was found to be essentially photostable in the polar protic solvent methanol but photoisomerised in the polar aprotic solvent dimethylsulfoxide. In the nonpolar solvent cyclohexane, it photodegraded appreciably. Both photoisomerisation and photodegradation occurred to a similar extent in the moderately polar aprotic solvent ethyl acetate. Photoisomerisation occurred only in the presence of oxygen whereas photodegradation occurred irrespective of oxygen. This knowledge is important in order to achieve the correct formulation for sunscreens incorporating avobenzone.     

Separation of three polar compounds from Rheum tanguticum by high‐speed countercurrent chromatography with an ethyl acetate/glacial acetic acid/water system

The separation of polar compounds by high‐speed countercurrent chromatography is still regarded as a challenge. In this study, an efficient strategy for the separation of three polar compounds from Rheum tanguticum has been successfully conducted by using high‐speed countercurrent chromatography. X‐5 macroporous resin chromatography was used for the fast enrichment of the target compounds. Then, the target fraction was directly introduced into high‐speed countercurrent chromatography for separation using ethyl acetate/glacial acetic acid/water (100:1:100, v/v/v) as the solvent system. Consequently, three polar compounds including gallic acid, catechin, and gallic acid 4‐O‐β‐d ‐(6′‐O‐galloyl) glucoside were obtained with purities higher than 98%. The results showed glacial acetic acid could be such an appropriate regulator for the ethyl acetate/water system. This study provides a reference for the separation of polar compounds from natural products by high‐speed countercurrent chromatography.     

Imidazolium‐embedded iodoacetamide‐functionalized silica‐based stationary phase for hydrophilic interaction/reversed‐phase mixed‐mode chromatography

A novel imidazolium‐embedded iodoacetamide‐functionalized silica‐based stationary phase has been prepared by surface radical chain‐transfer polymerization. The stationary phase was characterized by Fourier transform infrared spectrometry, thermogravimetric analysis, and element analysis. Fast and efficient separations of polar analytes, such as nucleosides and nucleic acid bases, water‐soluble vitamins and saponins, were well achieved in hydrophilic interaction chromatography mode. Additionally, a mixed mode of hydrophilic interaction and reversed‐phase could be also obtained in the analysis of polar and nonpolar compounds, including weak acidic phenols, basic anilines and positional isomers, with high resolution and molecular‐planarity selectivity, outperforming the commercially available amino column. Moreover, simultaneous separation of polar and nonpolar compounds was also achieved. In conclusion, the multimodal retention capabilities of the imidazolium‐embedded iodoacetamide‐functionalized silica‐based column could offer a wide range of retention behavior and flexible selectivity toward hydrophilic and hydrophobic compounds.     

Dispersion corrected interaction of polar and nonpolar fluids confined within carbon nanotubes: Density functional theoretical analysis using Grimme's D3 scheme

The structural and flow characteristics of fluids within carbon nanotube (CNT) is dictated by the interaction of fluid molecules within the nanocavity of CNT. Therefore, in the present study, dispersion corrected density functional theory has been used to investigate the structure and interaction of polar and nonpolar molecules within CNT. The present study shows that there is profound effect on the interaction due to dispersion. The interaction energy of the confined water was found to be reduced with increasing distance of the water molecule from the wall of the CNT. The water is preferentially adsorbed over methane due to stronger interaction with CNT over methane. Further, water is preferentially adsorbed over methanol molecule when interaction is calculated without dispersion but after inclusion of dispersion interaction, the calculated results show that the methanol–CNT interaction is stronger than that of water molecule and hence preferentially adsorbed within the CNT as revealed from MD simulation. The present calculation reveals that that the effect of CNT confinement on the IR spectra of the single file water is quite considerable compared to the IR spectra of tetrahedral bulk water cluster. Therefore, the present results might be useful for the separation of polar molecule from nonpolar molecule during fabrication of CNT‐based filter and purification system.     

Preferable solvatation of decane and benzene in 1-octanol-N,N-dimethylformamide mixed solvent

Heat effects of the dissolution of decane and benzene in a model system of 1-octanol (OctOH)-N,N-dimethylformamide are measured at 298 and 318 K using a variable temperature calorimeter with an isotermic shell. The state of hydrocarbon molecules in the mixed solvent is studied using an extended coordination model and is compared to earlier data for ethyl acetate (EtOAc), DMF, OctOH, and tetramethyl hematoporphyrin (TMHP). It is shown that the polar carboxylic groups of porphyrin are preferably solvated by amide molecules due to stronger interaction with DMF, while nonpolar aliphatic groups are solvated by alcohol molecules. We conclude that a solvate shell of aromatic benzene is strongly enriched with DMF over the range of compositions, suggesting that the weakening of the preferable solvatation of porphyrin relative to EtOAc is due primarily to the influence of nonpolar substituents.     

Control of adsorption and solubility in gradient high performance liquid chromatography 1. Principles of sudden transition gradients and elution characteristics of copolymers from styrene and methacrylates

Summary Proper retention of polymers in high performance liquid chromatography often requires injection into a starting eluent which is not a solvent for the sample under investigation. In this case, the polymer is precipitated at the top of the column. Subsequent gradient elution has to be performed by addition of an eluent with sufficient chromatographic strength and solvent power. In normal phase chromatography, it must be a solvent of high polarity. With the gradient elutions reported so far, polarity and dissolution power were simultaneously increased.The present paper reports the separate control of solvent strength and chromatographic power by applying gradient programs which include sudden addition of a moderately polar solvent. The amount of the latter does not suffice for elution, which is performed by subsequent, controlled addition of a highly polar nonsolvent. Sudden transition gradients of this kind work with, e.g.,iso-octane as a nonpolar starting eluent, tetrahydrofuran as a solvent of intermediate polarity, and methanol as a strongly polar nonsolvent. They have been applied to copolymers from styrene and ethyl methacrylate, methyl methacrylate, or methoxyethyl methacrylate.     

An amphiphilic molecular basket sensitive to both solvent changes and UV irradiation

A molecular basket was obtained by linking four cholate units to a cone-shaped calix[4]arene scaffold through azobenzene spacers. The molecule turns its polar faces inward in nonpolar solvents to bind polar molecules such as sugar derivatives. In polar solvents, the nonpolar faces turn inward, allowing the binding of hydrophobic guests such as pyrene. The molecule can also respond to UV irradiation by trans-cis isomerization of the azobenzene spacers. Response toward both solvents and UV light is fully reversible.     

Multi‐Responsive Supramolecular Gels Based on Charge Transfer Interactions

We report the co‐assembly of aromatic donor (D) and acceptor (A) molecules into purple sponge‐like supramolecular gels through susceptible charge transfer interactions with the aid of solvophobic interactions. The gel remained intact with the addition of up to 23 % (v/v) of nonpolar good solvents, such as toluene and xylene, but dissociated in the presence of <2 % (v/v) of polar solvents, such as tetrahydrofuran, ethyl acetate, and alcohols, with highly distinguishable changes of color. Notably, the gel dissolved within 1 min and the solution turned blue when 0.1 % (v/v) of methanol was added. The response to trifluoroacetic acid was extremely sensitive (i.e., the gel vanished immediately in the presence of 2 equivalents of trifluoroacetic acid), and the subsequent addition of trimethylamine could recover the purple gel. The multiple and visible response thus render the D–A gels as a potential detector for sensing complex chemical environments.     

Environmentally responsive molecular baskets: unimolecular mimics of both micelles and reversed micelles

[structure: see text] When four facially amphiphilic cholate derivatives are attached to a tetraaminocalixarene scaffold, the resulting molecule responds to environmental changes by rotation of the cholate units. In polar solvents, the molecule adopts a micellelike conformation with the hydrophilic alpha-faces of the cholates pointing outward. In nonpolar solvents, it turns inside out, assuming a reversed micellelike conformation with the hydrophobic beta-faces pointing outward. Switching between the two conformations is driven by solvophobic interactions and is fully reversible.     

Synthesis and solid state structure of fluorous probe molecules for fluorous separation applications

A series of colored hydrocarbon and fluorocarbon tagged 1-fluoro-4-alkylamino-anthraquinones and 1,4-bis-alkylamino-anthraquinone probe molecules were synthesized from a (fluorinated) alkyl amine and 1,4-difluoroanthraquinone to aid in the development of fluorous separation applications. The anthraquinones displayed stacking of the anthraquinone tricycle and interdigitation of the (fluorinated) alkyl chains in the solid state. Furthermore, intramolecular N-H?O hydrogen bonds forced the hydrocarbon and fluorocarbon tags into a conformation pointing away from the anthraquinone tricycle, with the angle of the tricycle plane normal and the main (fluorinated) alkyl vector ranging from 1° to 39°. Separation of the probe molecules on fluorous silica gel showed that the degree of fluorination of the probe molecules plays only a minor role with most eluents (e.g., hexane/ethyl acetate and methyl nonafluorobutyl ethers/ethyl acetate). However, toluene as eluent caused a pronounced separation by degree of fluorination for fluorocarbon, but not hydrocarbon tagged probe molecules on both silica gel and fluorous silica gel. These studies suggest that hydrocarbon and fluorocarbon tagged anthraquinones are useful probe molecules for the development of laboratory scale fluorous separation applications.     

Oligocholate foldamers as carriers for hydrophilic molecules across lipid bilayers

Three cholate foldamers were synthesized by the click reaction between an azide-functionalized cholate trimer and different dialkynyl linkers. The foldamers were labeled with pyrene groups at the ends for their conformational study. The linkers between the two tricholate fragments were found to strongly influence the conformation of the foldamers in solution, as well as their ability to transport hydrophilic molecules across lipid bilayers. The folding of the oligocholates in mixed organic solvents was studied by fluorescence and UV/Vis spectroscopy. Although these molecules could not fold permanently in lipid bilayers, they were found to translocate carboxyfluorescein readily across by a carrier-based mechanism. The transport is proposed to happen when the oligocholates adopt transiently folded structures with a hydrophobic exterior and a hydrophilic internal cavity. The transport rate strongly depended on the structure of the oligocholates and was sensitive even to the change of a single bond in a foldamer 3000 Da in MW. Better folded oligocholates in solution gave slower transport in the membranes.     

Probing the interaction of solvents with the stationary phase of C18 high-performance liquid chromatographic column material by variable-temperature dependent 129Xe nuclear magnetic resonance spectroscopy

VT (129)Xe NMR was applied to probe the interactions of solvents having different polarity indices with the stationary phase of a RP-C18 HPLC column material. It was observed that the highly polar ethylene glycol molecules do not mix with the alkyl chains of the RP-C18 stationary phase and the solvent is unable to enter the pores and the spaces between the particles. Three phases in this sample are defined as stationary/xenon phase, xenon gas phase (in the pores and the spaces between the particles) and ethylene glycol/xenon phase. In contrast to ethylene glycol, the nonpolar solvent cyclohexane was observed to be well mixed with the RP-C18 stationary phase. The capillary rise effect allows the solvent to enter the pores and the spaces between the particles. Two phases in this sample are defined as stationary/cyclohexane/xenon phase and cyclohexane/xenon phases. The properties of ethyl acetate are between those of ethylene glycol and cyclohexane. The (129)Xe NMR results show that the rational reversed phases should be conditioned from highly solvating to more polar solvents to remove the trapped air. The (129)Xe NMR results also show that pure stationary phase exists only when a highly polar solvent is used in reversed-phase chromatography. For a solvent with lower polarity, a stationary/solvent phase actually forms. This, together with the mobile phase, determines the selective factor for separating mixtures.