Facial Amphiphiles Research Articles

Smaller Building Blocks Form Larger Assemblies: Aggregation Behavior of Biaryl-Based Dendritic Facial Amphiphiles

Synthesis and micellar behavior of biaryl-based benzyl ether dendritic molecules prepared from a new biaryl building block are described. The key objective of the study is to tune the size of individual dendritic molecules and investigate its effect on aggregation behavior of the resulting micelle-like assemblies. We show that the functional group placement in the building block influences flexibility of the dendritic backbone and interior volume available for packing the hydrophobic groups, which is reflected in different aggregation behavior and aggregate size of the two types of micellar assemblies.

Nanofibers from self-assembly of an aromatic facial amphiphile with oligo(ethylene oxide) dendrons

Novel block facial amphiphiles consisting of a laterally extended aromatic segment and oligo(ethylene oxide) dendrons as a flexible segment were synthesized in a stepwise fashion and their aggregation behavior was investigated in aqueous solution; self-assembly into elongated nanofibers with a uniform diameter of 7 +/- 0.5 nm and lengths up to several hundred nanometers was observed.

A Non-Steroidal Facial Amphiphile

This paper gives the synthesis of an unusual non-steroidal amphiphile consisting of a large rigid molecule that possesses two water-solubilizing sulfates on one face and an extended hydrophobic surface on the other. The properties of this compound have been examined by X-ray analysis, light and cryo-electron microscopy, surface tension, conductivity, microrheology, and NMR. Aqueous solutions behave quite differently from those of a conventional amphiphile with long linear and flexible chains (e.g., sodium dodecyl sulfate). Thus, there is evidence that the facial amphiphile self-assembles to form viscous networks, but without the traditional critical micelle concentration, as if assembly is a stepwise process. Emulsions of toluene in water promoted by the facial amphiphile are stable for many months. In contrast to conventional surfactants, the NMR peaks are obliterated in aqueous solutions of the facial amphiphile. Both X-ray and cryo-HRSEM data suggest a lamellar morphology.

Cholic Acid-Derived Facial Amphiphiles with Different Ionic Characteristics

A cholate derivative with three epoxide groups was synthesized from cholic acid by allylation followed by epoxidation. Ring opening of the epoxides by various nucleophiles yielded facial amphiphiles with anionic, cationic, or nonionic functional groups. The critical micelle concentrations of these amphiphiles largely depend on the number of charged groups on the molecule. A facial amphiphile with pH-tunable micellization was prepared. Its aggregation behavior changes abruptly at pH = 7.6-6.6 as a result of protonation of its amino groups.

A Short Synthesis of Methyl 3α,7α,12α-Triaminocholanoate, the ‘Triaza-Analogue’ of Methyl Cholate

Triamine 2a, a facial amphiphile and precursor for anion receptors, has been prepared in just four steps from the inexpensive steroid cholic acid.

Structure-Activity Relationships of Diastereomeric Lysine Ring Size Analogs of the Antimicrobial Peptide Gramicidin S: MECHANISM OF ACTION AND DISCRIMINATION BETWEEN BACTERIAL AND ANIMAL CELL MEMBRANES

Structure-activity relationships were examined in seven gramicidin S analogs in which the ring-expanded analog GS14 [cyclo-(VKLKVdYPLKVKLdYP)] is modified by enantiomeric inversions of its lysine residues. The conformation, amphiphilicity, and self-association propensity of these peptides were investigated by circular dichroism spectroscopy and reversed phase high performance liquid chromatography. (31)P nuclear magnetic resonance spectroscopic and dye leakage experiments were performed to evaluate the capacity of these peptides to induce inverse nonlamellar phases in, and to permeabilize phospholipid bilayers; their growth inhibitory activity against the cell wall-less mollicute Acholeplasma laidlawii B was also examined. The amount and stability of beta-sheet structure, effective hydrophobicity, propensity for self-association in water, ability to disrupt the organization of phospholipid bilayers, and ability to inhibit A. laidlawii B growth are strongly correlated with the facial amphiphilicity of these GS14 analogs. Also, the magnitude of the parameters segregate these peptides into three groups, consisting of GS14, the four single inversion analogs, and the two multiple inversion analogs. The capacity of these peptides to differentiate between bacterial and animal cell membranes exhibits a biphasic relationship with peptide amphiphilicity, suggesting that there may only be a narrow range of peptide amphiphilicity within which it is possible to achieve the dual therapeutic requirements of high antibiotic effectiveness and low hemolytic activity. These results were rationalized by considering how the physiochemical properties of these GS14 analogs are likely to be reflected in their partitioning into lipid bilayer membranes.

Interfacial micellar structures from novel amphiphilic star polymers.

An amphiphilic heteroarm star polymer containing 12 alternating hydrophobic/hydrophilic arms of polystyrene (PS) and poly(acrylic acid) (PAA) connected to a well-defined rigid aromatic core was studied at the air-water and the air-solid interfaces. At the air-water interface, the molecules spontaneously form pancakelike micellar aggregates which measure up to several microns in diameter and 5 nm in thickness. Upon reduction of the surface area per molecule to 7 nm2, the two-dimensional micelles merged into a dense monolayer. We suggest that confined phase separation of dissimilar polymer arms occurred upon their segregation on the opposite sides of the rigid disklike aromatic core, forcing the rigid cores to adopt a face-on orientation with respect to the interface. Upon transfer onto solid supports the PS chains face the air-film interface making it completely hydrophobic, and the PAA chains were found to collapse and form a thin flattened underlayer. This study points toward new strategies to create large 2D microstructures with facial amphiphilicity and suggests a profound influence of star molecular architecture on the self-assembly of amphiphiles at the air-water interface.

Synthesis and hierarchical self-assembly of cavity-containing facial amphiphiles.

The synthesis and aggregation behavior of cavity-containing facial amphiphiles is described. The molecules consist of a glycoluril-based rigid cavity functionalized with two water-soluble benzoate groups. By specific molecular recognition processes in water, the amphiphilic hosts self-assemble in a hierarchical process to form arrays of molecules. Depending on the counterions, these arrays can be assembled into well-defined aggregates of mesoscopic size. The size and shape of the aggregates can be tuned by variations in the size and substitution pattern of the cavities of the host molecules.

Thermodynamics of Micellization of Cholic Acid Based Facial Amphiphiles Carrying Three Permanent Ionic Head Groups

This paper describes a series of cholic acid based facial amphiphiles carrying three ionic headgroups. Their micellization behavior in water was studied as a function of spacer length and alkyl tail length: both were found to have a small influence on the critical micellization concentration (cmc). Isothermal titration calorimetry was used to gain information on the thermodynamics of micellization. These surfactants show rather normal temperature-dependent behavior: Gibbs energy of micellization is almost constant, cmc increases, and enthalpy of micellization decreases with temperature, and both entropy and enthalpy contribute to the micellization.

Enantiomeric Self-Recognition of a Facial Amphiphile Triggered by [{Pd(ONO2)(en)}2] We thank the NIH (GM61854) and the University of Maryland for generous financial support. We thank Professor Dorothy Beckett and Dr. Peter Schuck for assistance with the analytical ultracentrifuge and Professor Sandra Greer for access to the density meter. L.I. is a Cottrell Scholar of Research Corporation. en=1,2-ethylenediamine

Enantiomeric Self-Recognition of a Facial Amphiphile Triggered by [{Pd(ONO2)(en)}2] We thank the NIH (GM61854) and the University of Maryland for generous financial support. We thank Professor Dorothy Beckett and Dr. Peter Schuck for assistance with the analytical ultracentrifuge and Professor Sandra Greer for access to the density meter. L.I. is a Cottrell Scholar of Research Corporation. en=1,2-ethylenediamine

Enantiomeric Self-Recognition of a Facial Amphiphile Triggered by [{Pd(ONO2)(en)}2] We thank the NIH (GM61854) and the University of Maryland for generous financial support. We thank Professor Dorothy Beckett and Dr. Peter Schuck for assistance with the analytical ultracentrifuge and Professor Sandra Greer for access to the density meter. L.I. is a Cottrell Scholar of Research Corporation. en=1,2-ethylenediamine

Die Selbsterkennung von Enantiomeren wird durch die Zugabe von [Pd(ONO2)(en)2] 2 (en=1,2-Ethylendiamin) zu einer wässrigen Lösung von (±)-1 ausgelöst. Als Ergebnis dieses Prozesses erhält man wohldefinierte 2:2-Aggregate (12⋅22 und (ent-1)2⋅22). Der Einsatz der Ultrazentrifugierung als analytische Methode zur Bestimmung des Molekulargewichts und der Stöchiometrie bei Synthesestudien zur Selbstorganisation wird näher beleuchtet.

ChemInform Abstract: Anionic Facial Amphiphiles from Cholic Acid.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Anionic facial amphiphiles from cholic acid.

[structure:see text] Anionic facial amphiphiles have been prepared from cholic acid. These compounds offer antipodes of recently reported cationic amphiphiles derived from cholic acid. The synthesis of the anionic amphiphiles was accomplished in few steps from a common intermediate. In contrast to many other anionic facial amphiphiles, the cholic acid derived amphiphiles appeared to aggregate at relatively low concentration.

The "Triamino-analogue" of Methyl Cholate; A Practical, Large-Scale Synthesis

The triamino steroids 2 are in demand as facial amphiphiles and starting materials for supramolecular chemistry. 2 (R = Me) is now available from cholic acid 1 in substantial quantities via a new, high-yielding procedure.

Design, synthesis and self-association behavior of water soluble self complementary facial amphiphiles

Self-complementary facially amphiphilic derivatives of glycoluril are useful building blocks for hydrophobic self-assembly in water; we describe the design, synthesis and characterization of six dimeric self-assembled structures with values of KS up to 1840 M–1 in pD 7.4 buffered D2O.

Formation of Columnar and Lamellar Lyotropic Mesophases by Facial Amphiphiles with Protic and Lipophilic Solvents

The influence of water, formamide, and n-dodecane on the liquid crystalline properties of several rodlike 4,4‘‘-bis(decyloxy)-p-terphenyl derivatives incorporating nonionic hydrophilic groups in a central position was investigated by polarizing microscopy and X-ray scattering. Up to three different rectangular columnar mesophases have been found for molecules with large hydrophilic groups with increasing concentrations of protic solvents. Remarkably only one lattice parameter changes in dependence on the mesophase type and the number of solvent molecules coordinated to the polar groups. We propose that the columns represent ribbons consisting of the rigid terphenyl units, separated laterally by the segregated regions of the hydrophilic groups, whereby the three different columnar mesophases should result from an anisotropic swelling of the polar regions on addition of solvents. Lipophilic solvents (dodecane) destabilize the columnar phases and replace them by smectic layer structures (SA phases).

Selective Cationic Binding at the Air−Water Interface by Thin Films of Rigid Amphiphiles Bearing Laterally Attached Crown Ether Moieties

Three 4,4-didecyloxy-p-terphenyl derivatives with laterally attached crown ether units of different ring size [(1,4,7,10-tetraoxacyclododecyl)-,(1,4,7,10,13-pentaoxacyclopentadecyl)-, and (1,4,7,10,13,16-hexaoxacyclooctadecyl)-2-methyl 2,5-bis(4-decyloxyphenyl)benzoate] have been synthesized, and their Langmuir films were investigated by means of a film balance. They form well-ordered thin films when spread at the air-water interface which are characterized by two sharp breaks in their surface pressure-area isotherms separated by a large plateau. The lateral pressure in the plateau region-in which the molecules undergo a first-order phase transition with formation of a defined triple layer-significantly increases on enhancing the number of oxyethylene units in the crown ether units. Additionally, it depends on the type and concentration of alkali metal ions (Li + , Na + , K + , Rb + , Cs + ) in the subphase. Cations which fit the cavity of the appended crown ethers most significantly stabilize the films. It seems that the surface pressure in the plateau region is reminiscent of the binding constants of alkali metal ions to the crown ether units. This shows that facial amphiphiles could represent an interesting new platform for the investigation of guest-host interactions and molecular recognition processes at the air-water interface.

The “triamino-analogue” of methyl cholate; a facial amphiphile and scaffold with potential for combinatorial and molecular recognition chemistry

The triamino steroid 2 is synthesized from cholic acid ( 1), and found to possess little tendency to aggregate at pH 5 – 6 in aqueous solution. 2 and/or related derivatives are expected to find use in the synthesis of receptors and combinatorial libraries, and as “contrafacial amphiphiles” for drug delivery across cell membranes.

Design and Synthesis of Molecular Umbrellas

This paper describes the design and synthesis of a series of conjugates derived from cholic acid, spermidine, and 5-(dimethylamino)-1-naphthalenesulfonyl (dansyl), which effectively shield the dansyl moiety from water. Direct coupling of cholic acid to both terminal amino groups of spermidine, and attachment of the environmentally-sensitive dansyl moiety to the remaining secondary amine, yields a “molecular umbrella” (Ia) whose fluorescent properties (λmax and emission intensity) reflect a nonpolar microenvironment in water and one that is relatively polar in intermediate dimethoxyethane/water mixtures. Comparison of Ia with analogous “single-walled” (II) and “no-walled” (III) umbrellas further indicates that a minimum of two walls is necessary in order to have “umbrella-like” properties. Examination of the fluorescent properties of a related double-walled umbrella, bearing a flexible (2-hydroxyethyl)carbamate moiety at the C-3 position of the sterol (Ib), reveals that “umbrella-like” properties are present even when facial amphiphilicity is not rigorously maintained; however, the molecule's ability to shield the fluorophore, as judged by its relative emission intensity, is diminished. “Methyl-capping” of the (2-hydroxyethyl)carbamate (i.e., Ic) enhances the umbrella's ability to provide a hydrophobic shelter in water. A tetra-walled analogue of Ia, bearing four cholic acid units (i.e., IV), has been synthesized and its dansyl group found to have reduced exposure toward water. The potential utility of molecular umbrellas in the area of drug delivery is briefly discussed.

Mesogenic Properties of Amphiphilic Liquid Crystals with an Unusual Head‐Group Topology

The lateral fixing of calamitic mesogens through hydrogen bonding of facial amphiphiles is a novel way of generating smectic materials with a broad mesomorphic region. Compound 1 is an example of this amphiphile and represents a new type of liquid-crystalline carbohydrate. R = OC10H21.