Criss‐cross amphiphilic polymers and analogous model systems

A new class of amphiphilic polymers carrying two pendant docosyl (C22) chains, located at periodic intervals that are separated by PEG chains of varying lengths, was synthesized via a simple melt‐transesterification polymerization, using dimethyl, 2,5‐didocosyloxyterephthalate as one of the monomers. DSC, variable temperature FT‐IR, and WAXS studies demonstrated that immiscibility between the pendant docosyl units and the backbone PEG segments drives their self‐segregation; this results in the crystallization of the pendant docosyl segments and the generation of a lamellar morphology with the alkyl segments and the PEG chains occupying alternate layers. Based on the study of model criss‐cross amphiphiles that resemble the polymer repeat unit, it is postulated that the chains reconfigure such that both the docosyl chains fold to one side of the terephthalate unit while the PEG segments form a loop on the other side; these chains then organize in a bilayer to form the lamellar structure. The simplicity of the synthesis and the rather unique properties of these polymers suggests that such a design could be translated to develop other interesting functional materials that could exploit the immiscibility‐driven microphase separation for the generation of sub‐10 nm domains; these could have potential applications, such as in membranes, solid polymer electrolyte formulations, and so forth. © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2018 , 56, 1554–1563     

Microtubules from Fluorinated Phosphorylated Amphiphiles in Aqueous/Alcoholic and Non-Aqueous Solvents

Abstract

Phospholipids are known to self-organize into bilayer membranes and liposomes. Recently, much attention has also been focussed on highly ordered cylindrical, bilayer-based hollow microstructures usually called tubules, that form, for example, from diacetylenic phosphatidylcholines [1]. However, despite the potential of these new supramolecular architectures in both fundamental and applied area, only few tubule-forming surfactants have been reported yet. We have shown that the driving force required to form and stabilize coiled membranes in water can be brought by fitting amphiphiles with a single fluorinated chain, without need for rigid segments, hydrogen bonding between polar head or chiral centers [2,3].     

Specific binding structures of dendrimers on lipid bilayer membranes

Dissipative particle dynamics simulations are used to study the specific binding structures of polyamidoamine (PAMAM) dendrimers on amphiphilic membranes and the permeation mechanisms. Mutually consistent coarse-grained (CG) models both for PAMAM dendrimers and for dimyristoylphosphatidylcholine (DMPC) lipid molecules are constructed. The PAMAM CG model describes correctly the conformational behavior of the dendrimers, and the DMPC CG model can properly give the surface tension of the amphiphilic membrane. A series of systematic simulations is performed to investigate the binding structures of the dendrimers on membranes with varied length of the hydrophobic tails of amphiphiles. The permeability of dendrimers across membranes is enhanced upon increasing the dendrimer size (generation). The length of the hydrophobic tails of amphiphiles in turn affects the dendrimer conformation, as well as the binding structure of the dendrimer-membrane complexes. The negative curvature of the membrane formed in the dendrimer-membrane complexes is related to dendrimer concentration. Higher dendrimer concentration together with increased dendrimer generation is observed to enhance the permeability of dendrimers across the amphiphilic membranes.     

Self‐Assembled Vesicles with Functionalized Membranes

Biological membranes play a key role for the function of living organisms. Thus, many artificial systems have been designed to mimic natural cell membranes and their functions. A useful concept for the preparation of functional membranes is the embedding of synthetic amphiphiles into vesicular bilayers. The dynamic nature of such noncovalent assemblies allows the rapid and simple development of bio‐inspired responsive nanomaterials, which find applications in molecular recognition, sensing or catalysis. However, the complexity that can be achieved in artificial functionalized membranes is still rather limited and the control of their dynamic properties and the analysis of membrane structures down to the molecular level remain challenging.     

Gemini peptide lipids with ditopic ion-recognition site. Preparation and functions as an inducer for assembling of liposomal membranes

Gemini amphiphiles having two peptide lipid units and a spacer group connected at the polar heads were synthesized. A gemini peptide lipid bearing l-histidyl residues, hydrophobic double-chain segments, and a tri(oxyethylene) spacer performed as an inducer of the reversible assembling of liposomal membranes through ditopic ion recognition toward transition metal ions and alkali metal ions. The vesicular assembling behavior induced by the gemini peptide lipids was sensitive to the structural difference in the amino acid residue and the spacer group of the lipids.     

Integrated Conversion of Lignocellulosic Biomass to Bio-Based Amphiphiles using a Functionalization-Defunctionalization Approach

Concerns over the sustainability and end-of-life properties of fossil-derived surfactants have driven interest in bio-based alternatives. Lignocellulosic biomass with its polar functional groups is an obvious feedstock for surfactant production but its use is limited by process complexity and low yield. Here, we present a simple two-step approach to prepare bio-based amphiphiles directly from hemicellulose and lignin at high yields (29 % w/w based on the total raw biomass and >80 % w/w of these two fractions). Acetal functionalization of xylan and lignin with fatty aldehydes during fractionation introduced hydrophobic segments and subsequent defunctionalization by hydrogenolysis of the xylose derivatives or acidic hydrolysis of the lignin derivatives produced amphiphiles. The resulting biodegradable xylose acetals and/or ethers, and lignin-based amphiphilic polymers both largely retained their original natural structures, but exhibited competitive or superior surface activity in water/oil systems compared to common bio-based surfactants.     

含萘（2,6）生色基的合成双分子膜研究

本文首次了报道系列单链、2,6-取代萘刚性生色基的双亲化合物C_nNaph(2,6)C_4N~+(CH_3)_3(n=16,12,7,4),C_(12)Naph(2,6)PO_4~-和C_(12)Naph(2,6)C_4N~+(CH_3)_2CH_2CH_2OH的合成。分别用AEM、~1HNMR和DSC考察了该系列化合物在稀水溶液中的自组织行为、聚集体内分子运动和物相变化。当n≥7时,该系列双亲化合物在稀水溶液中可自组织形成双分子层结构,亲水基团的种类直接影响双亲分子的自组织形态。     

Entropic interfaces in hard-core model amphiphilic mixtures

We investigate bulk and interfacial properties of a recently proposed hard-body model for a ternary mixture of amphiphilic particles, spheres and needles using density functional theory. The simple model amphiphiles are formed by bonding a vanishingly thin needle tail radially to a hard-sphere head group. Such particles provide a natural amphiphile when added to a binary mixture of spheres and needles. As all interactions are hard, we seek to find whether amphiphilic effects can be driven by entropy without the need to invoke attractive interactions. In order to assess the amphiphilic character of the model we first examine the spatial and orientational distribution of the amphiphiles at the free interface between demixed needle-rich and amphiphile-rich fluid phases of the binary amphiphile-needle subsystem. We then consider the free interface between sphere-rich and needle-rich phases upon adding amphiphiles with low concentration to the demixed system. In both cases the orientational distribution of the particles in the interface provides strong evidence that amphiphilic properties can arise purely from geometrical packing effects.     

Photochemically induced disturbance of the alkyl chain packing in vesicular membranes

In previous reports, we presented the synthesis and properties of double-tailed azobenzene-substituted phosphate amphiphiles (Kuiper et al. Synthesis 2003, 695 and Kuiper et al. Langmuir 2004, 20, 1152). We also reported that an ion channel can be regulated by trans-cis isomerization of these amphiphiles, which were incorporated in the membrane (Folgering et al. Langmuir 2004, 20, 6985). In the present study, the effect of trans-cis isomerization of both single- and double-tailed azobenzene-substituted amphiphiles on the aggregation and packing behavior has been studied. The phase transition temperature of a membrane and the thermal half-life times of the cis azobenzene-substituted amphiphiles in membranes have been measured. Furthermore, the synthesis and properties of single-tailed azobenzene-substituted phosphate amphiphiles are described and compared with those of the double-tailed analogues. The single-tailed azobenzene-substituted phosphates have a low solubility in water and form micelles, sheets, and crystals. In all cases the trans-cis isomerization leads to a disturbance of the chain packing. Both single- and double-tailed cis azobenzene-substituted phosphates lowered the main phase transition temperature of bilayer membranes. The effect increased when the azobenzene moiety was situated closer to the head group. Accordingly, the half-life times of the cis azobenzene group was shorter when the azobenzene group was positioned closer to the head group for both the single- and double-tailed amphiphiles. Interestingly, the thermal cis-trans isomerization of the single-tailed azobenzene-substituted phosphates was faster in a DOPC membrane than that for the free monomer in aqueous solution.     

Two-component membrane material properties and domain formation from dissipative particle dynamics

The material parameters (area stretch modulus and bending rigidity) of two-component amphiphilic membranes are determined from dissipative particle dynamics simulations. The preferred area per molecule for each species is varied so as to produce homogeneous mixtures or nonhomogeneous mixtures that form domains. If the latter mixtures are composed of amphiphiles with the same tail length, but different preferred areas per molecule, their material parameters increase monotonically as a function of composition. By contrast, mixtures of amphiphiles that differ in both tail length and preferred area per molecule form both homogeneous and nonhomogeneous mixtures that both exhibit smaller values of their material properties compared to the corresponding pure systems. When the same nonhomogeneous mixtures of amphiphiles are assembled into planar membrane patches and vesicles, the resulting domain shapes are different when the bending rigidities of the domains are sufficiently different. Additionally, both bilayer and monolayer domains are observed in vesicles. We conclude that the evolution of the domain shapes is influenced by the high curvature of the vesicles in the simulation, a result that may be relevant for biological vesicle membranes.     

N-methyl Benzimidazole Tethered Cholic Acid Amphiphiles Can Eradicate S. aureus-Mediated Biofilms and Wound Infections

Infections associated with Gram-positive bacteria like S. aureus pose a major threat as these bacteria can develop resistance and thereby limit the applications of antibiotics. Therefore, there is a need for new antibacterials to mitigate these infections. Bacterial membranes present an attractive therapeutic target as these membranes are anionic in nature and have a low chance of developing modifications in their physicochemical features. Antimicrobial peptides (AMPs) can disrupt the microbial membranes via electrostatic interactions, but the poor stability of AMPs halts their clinical translation. Here, we present the synthesis of eight N-methyl benzimidazole substituted cholic acid amphiphiles as antibacterial agents. We screened these novel heterocyclic cholic acid amphiphiles against different pathogens. Among the series, CABI-6 outperformed the other amphiphiles in terms of bactericidal activity against S. aureus. The membrane disruptive property of CABI-6 using a fluorescence-based assay has also been investigated, and it was inferred that CABI-6 can enhance the production of reactive oxygen species. We further demonstrated that CABI-6 can clear the pre-formed biofilms and can mitigate wound infection in murine models.     

Control of nano-micrometric twist and helical ribbon formation with gemini-oligoalanine via interpeptidic beta-sheet structure formation

Confinement of anionic oligo-alanine peptides at the surfaces of cationic membrane by ionic interaction can induce their secondary structure formation; such organized peptides reciprocally transfer their chirality to membranes with non-chiral amphiphiles and their supramolecular chiral structures can be tuned both by peptides and amphiphiles structures.     

Disorganised self-assembled monolayers (SAMs): the incorporation of amphiphilic molecules.

A new approach for designing a voltammetric selective electrode is presented. The approach is based on the formation of a disorganised inert self-assembled monolayer (SAM), in which an amphiphilic molecule is incorporated. The latter serves as the selectivity factor, which extracts the analyte. The purpose of these experiments is to study the parameters that affect the capability of a monolayer to host amphiphiles. As model systems we focused on the incorporation of simple amphiphilic molecules (quaternary alkyl ammonium salts), electroactive amphiphiles (dialkylviologens) and a macrocycle ligand (tetramethylcyclam) into octadecyl silane monolayers formed on indium tin oxide (ITO) and purposely made disorganised alkanethiols on gold. We find that basically, the incorporation of amphiphiles into a hydrophobic inert SAM resembles a reversed stationary phase in liquid chromatography and this configuration can be used for designing selective electrodes.     

Properties of giant vesicles

We have discussed the specific properties of giant vesicles and their use as model systems for fluid interfaces and biomembranes. Recent advances in giant vesicle research include systematic measurements of visco-elastic parameters as a function of membrane composition, experiments with water-soluble amphiphiles and active membranes, as well as the investigation of hydrodynamic interactions. Notably, it has finally been possible to measure spontaneous curvatures of membranes for a variety of different systems. Experimentally, spontaneous curvature has been a somewhat obscure quantity so far. Furthermore, vesicles have been used to construct bioelectronic devices and new classes of vesicles made of polymers were introduced.     

Synthesis,physicochemical characterization,and self‐assembly of linear,dibranched, and miktoarm semifluorinated triphilic polymers

Linear, dibranched, and miktoarm amphiphiles containing both hydrophobic and fluorophilic moieties were synthesized and characterized in an attempt to elucidate the relationship between semifluorinated amphiphile structure and aggregate behavior in aqueous solution. For the linear and dibranched amphiphiles, there was an exponential decrease in critical aggregation concentration (CMC) and a logarithmic increase in core microviscosity with increasing length of the fluorocarbon segments; while the miktoarm architecture produced no notable trend in microviscosity or CMC. Furthermore, the linear and dibranched surfactants showed enhanced kinetic stability, dissociating more slowly in the presence of human serum than did either the dibranched or miktoarm amphiphiles. Finally, encapsulation studies with the hydrophobic drug paclitaxel (PTX) showed that the ability to solubilize and retain PTX increased with the presence and with the increasing size of the fluorocarbon moiety for both the linear and dibranched amphiphiles, while no such trend was observed for the miktoarm amphiphiles. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014 , 52, 3324–3336     

Synthesis and preliminary assessments of ethyl-terminated perfluoroalkyl nonionic surfactants derived from tris(hydroxymethyl)acrylamidomethane

We describe the synthesis and preliminary physicochemical and biological assessments of a new class of nonionic hybrid hydrofluoro amphiphiles derived from tris(hydroxymethyl)aminomethane (THAM). The synthesis of the hydrophobic tail of these amphiphiles is based on the preparation of an asymmetrical hydrofluorocarbon derivative containing an ethyl segment, a fluorocarbon core, and an ethyl thiol moiety. This molecule led to either THAM galactosylated monoadducts or telomers. These amphiphiles exhibit neither detergency toward cell membranes nor membrane protein denaturation.     

New Perfluoroalkylated Phosphorus Amphiphiles

Abstract

Phospholipids are the main components of biological membranes and the) spontaneously tend to self-assembly into liposomes. Synthetic double-chain so as bol amphiphiles allow the preparation of vesicles and can bc used as models of natural membranes and for preparing drug delivery systems. The formation of vesicles from single-chain perfluomalkylated phosphate or phosphoramidate amphiphiles war recently reported.¹ We present the synthesis of new fluoroalkylatcd phosphinic acid amphiphiles bearing a P-C bond and an ionic polar head promoting self-organisation We have already described the synthesis of the phosphine derivatives by one-poireaction from red phosphorus via the in situ generation of PH₃, and terminal alkenes and alkynes in basic media under sonication.² We extend this reaction to perfluoroalkena under phase uansfert catalysis.     

Chirally arranged monomeric dyes on helical bilayer membranes

Strong exciton coupling around the absorption band of monomeric dyes was induced by helical bilayer membranes formed from various L-glutamic acid-derived amphiphiles which contain three amides per molecule. The mirror-image of the circular dichroism spectra was observed by the corresponding D-isomers. No similar induction was observed by the corresponding ester-type amphiphiles which could not produce helices. It is assumed that dyes are helically arranged on helical bilayer membranes, resulting in an induction of chirality even in monomeric dyes.     

Cationic amphiphiles based on diethanolamine esters with amino acids in the polar block

A series of new cationic amphiphiles based on diethanolamine esters with Gly, βAla, GABA, Lys, Orn amino acid residues in the hydrophilic block were prepared. The sample containing the Lys residue showed the best activity against gram-positive and gram-negative bacteria. For model membranes comprising combinations of DOPC, DOPG and DOPE phospholipids, the sample can electrostatically bind to the surface of a bacterial cell and destroy it by formation of through defects.     

Polyglycerol-derived amphiphiles for the solubilization of single-walled carbon nanotubes in water: a structure-property study

A series of nonionic amphiphiles derived from polyglycerol dendrons were studied for their ability to solubilize and isolate single-walled carbon nanotubes. The amphiphiles possessed differently sized polar head groups, hydrophobic tail units, and various aromatic and non-aromatic groups between the head and tail groups. Absorbance analysis revealed that amphiphiles with anchor groups derived from pyrene were far inferior to those that possessed simple linear aliphatic tail groups. Absorbance and near-infrared fluorescence analyses revealed a weak dependence on the dendron size of the head group, but a strong positive trend in suspended nanotube density and fluorescence intensity for amphiphiles with longer tail units. Variations in the moieties linking the head and tail groups led to a range of effects on the suspensions, with linkers imparting flexibility and a bent shape that gave improved performance overall. This was illustrated most dramatically by a pair of benzamide-containing amphiphiles, the para isomer of which showed evidence in the fluorescence data of increased nanotube aggregate formation when compared with the meta isomer. In addition, statistical AFM was used to illustrate more directly the microscopic differences between amphiphiles that were effective at nanotube bundle disruption and those that were not.