A Molecular Dynamics Investigation of Compressed Aqueous Alkanoate Monolayers

Molecular dynamics are conducted on a dodecanoic acid monolayer/aqueous surface. Surface pressure is controlled by imposing constant-volume conditions for series of lengths of the square slab constituting the MD cell. The response of the alkanoate chains to the pressure is followed by examining various computed quantities that monitor their conformational order. These include atom-pair radial distribution functions, chain torsional angles, energies, atomic densities perpendicular to the interface, diffusivities and atomic plots. These quantities lead to chain separations which in the range 4-5 Å implying order when the alkanoate chains have a mean area of 0.18 nm 2.     

Amphiphile-induced tubular budding of the bilayer membrane

Amphiphile-induced tubular budding of the erythrocyte membrane was studied using transmission electron microscopy. No chiral patterns of the intramembraneous particles were found, either on the cylindrical buds, or on the tubular nanoexovesicles. In agreement with these observations, the tubular budding may be explained by in-plane ordering of anisotropic membrane inclusions in the buds where the difference between the principal membrane curvatures is very large. In contrast to previously reported theories, no direct external mechanical force is needed to explain tubular budding of the bilayer membrane.     

Synthesis and mesogenic properties of a Y-shaped glyco-glycero-lipid

We synthesised a new glyco-glycero-lipid [1,3-di-O-(beta-D-glucopyranosyl)-2-deoxy-2-amino-N-palmitoyl-sn-glycerol] with a Y-shaped structure bearing two sugar head groups and only one fatty acid chain. Instead of an ester linkage between the glycerol and the fatty acid an amido function was introduced. The mesogenic properties were investigated using polarising microscopy and are discussed with respect to similar compounds. The lyotropism was measured using the contact preparation method and small-angle neutron-scattering.     

Amphiphiles for supercritical CO2

A semi-fluorinated hybrid amphiphile, pentadecafluoro-5-dodecyl (F7H4) sulfate, has been shown to form reversed micelles in dense CO₂; the aggregates evolve to form water-in-CO₂ (w/c) microemulsion droplets on addition of water. Aggregation structures in these w/c phases have been characterised by small-angle neutron scattering (SANS), showing the presence of cylindrical droplets, which change into dispersed lamellar phases at even higher water loadings. Other systems are also introduced, being high internal phase emulsions (HIPEs) with brine, and liquid and supercritical CO₂, stabilized by certain commercially available nonylphenol ethoxylates (Dow Tergitol NP-, and Huntsman Surfonic N- amphiphiles). These dispersions have been characterised by SANS for the first time. Quantitative analyses of the HIPEs SANS profiles show that they behave similarly to hydrocarbon-water emulsion analogues, with regard to total interfacial areas and the effects of amphiphile concentration on the underlying structures. Finally, the advantages and disadvantages of both approaches for controlling the physico-chemical properties of liquid/supercritical CO₂ in potential applications are compared and contrasted. These results highlight the importance of using specially designed CO₂-philic amphiphiles for generating self-assembly structures in dense CO₂.     

Stability of Model Membranes in Extreme Environments

The first forms of cellular life required a source of amphiphilic compounds capable of assembling into stable boundary structures. Membranes composed of fatty acids have been proposed as model systems of primitive membranes, but their bilayer structure is stable only within a narrow pH range and low ionic strength. They are particularly sensitive to aggregating effects of divalent cations (Mg+2, Ca+2, Fe+2) that would be present in Archaean sea water. Here we report that mixtures of alkyl amines and fatty acids form vesicles at strongly basic and acidic pH ranges which are resistant to the effects of divalent cations up to 0.1 M. Vesicles formed by mixtures of decylamine and decanoic acid (1:1 mole ratio) are relatively permeable to pyranine, a fluorescent anionic dye, but permeability could be reduced by adding 2 mol% of a polycyclic aromatic hydrocarbon such as pyrene. Permeability to the dye was also reduced by increasing the chain length of the amphiphiles. For instance, 1:1 mole ratio mixtures of dodecylamine and dodecanoic acid were able to retain pyranine dye during and following gel filtration. We conclude that primitive cell membranes were likely to be composed of mixtures of amphiphilic and hydrophobic molecules that manifested increased stability over pure fatty acid membranes.     

Improved activity of enzymes in mixed cationic reverse micelles with imidazolium-based surfactants

This work reports the significant enhancement in performance of interfacially active enzymes, Chromobacterium viscosum (CV) lipase and horseradish peroxidase (HRP) in mixed reverse micelles of cetyltrimethylammonium bromide (CTAB) and imidazolium-based amphiphiles having varying tail lengths. Lipase activity in these mixed systems was always higher than that in the individual cationic reverse micelles of CTAB or any imidazolium surfactant, highest being observed in the mixed system of CTAB (50 mM) and 6 (1-tetradecyl-3-methyl imidazolium bromide, 40 mM)/water/isooctane/n-hexanol (0.24 M), second-order rate constant, k2=1301+/-5 cm3 g(-1)s(-1), approximately 200% higher compared to that in CTAB and approximately 65% more than the most popular AOT-microemulsion. Activity increased with concentration of imidazolium surfactant and also with its alkyl tail length. To have a more profound view on the structure-activity relationship, CTAB was replaced by cetyltriethylammonium bromide (CTEAB) and cetyltripropylammonium bromide (CTPAB) with subsequent increase in the headgroup size. The generalized influence of these mixed cationic systems on surface-active enzyme was also verified using HRP, where the activity improved approximately 100%. This enhancement in enzyme activity is presumably due to the activating effect of the imidazolium cation in the enzymatic reactions by improving the nucleophilicity of interfacial water in vicinity of enzyme through hydrogen bonding.     

Specific interactions of tryptophan with phosphatidylcholine and digalactosyldiacylglycerol in pure and mixed bilayers in the dry and hydrated state

Amphiphilic solutes play an important role in the desiccation tolerance of plant cells, because they can reversibly partition into cellular membranes during dehydration. Their effects on membrane stability depend on their chemical structure, but also on the lipid composition of the host membrane. We have shown recently that tryptophan destabilizes liposomes during freezing. The degree of destabilization depends on the presence of glycolipids in the membranes, but not on the phase preference (bilayer or non-bilayer) of the lipids in mixtures with the bilayer lipid phosphatidylcholine. Here, we have investigated the influence of tryptophan on the phase behavior and intermolecular interactions in dry and hydrated bilayers made from the phospholipid egg phosphatidylcholine and the plant chloroplast glycolipid digalactosyldiacylglycerol, or from a mixture (1:1) of these lipids, using Fourier-transform infrared spectroscopy. To distinguish effects of the hydrophobic ring structure of tryptophan from those of the amino acid moiety, we also performed experiments with the hydrophilic amino acid glycine. Our data show that there are specific interactions between tryptophan and either phospholipid or glycolipid in the dry state, as well as H-bonding interactions between the lipids and both solutes. In the rehydrated state, the H-bonding interactions between amino acids and lipids are mostly replaced by interactions between water and lipids, while the hydrophobic interactions between lipids and tryptophan mostly persist.     

Minimum requirements of hydrophobic and hydrophilic features in cationic peptide antibiotics (CPAs): pharmacophore generation and validation with cationic steroid antibiotics (CSAs)

Cationic peptide antibiotics (CPAs) are known to possess amphiphilic structure, by virtue of which they display lytic activity against bacterial cell membranes. Naturally occurring antimicrobial peptides contain a large number of amino acid residues, which limits their clinical applicability. Recent studies indicate that it is possible to decrease the chain-length of these peptides without loss of activity, and suggest that a minimum of two positive ionizable (hydrophilic) and two bulky groups (hydrophobic) are required for antimicrobial activity. By employing the HipHop module of the software package CATALYST, we have translated these experimental findings into 3-D pharmacophore models by finding common features among active peptides. Positively ionizable (PI) and hydrophobic (HYD) features are the important characteristics of compounds used for pharmacophore model development. Based on the highest score and the presence of amphiphilic structure, two separate hypothesis, Ec-2 and Sa-6 for Escherichia coli and Staphylococcus aureus, respectively, were selected for mapping analysis of active and inactive peptides against these organisms. The resulting models not only provided information on the minimum requirement of PI and HYD features but also indicated the importance of their relative arrangement in space. The minimum requirement for PI features was two in both cases but the number of HYD features required in the case of E. coli was four while for S. aureus it was found to be three. These hypotheses were able to differentiate between active and inactive CPAs against both organisms and were able to explain the experimental results. The hypotheses were further validated using cationic steroid antibiotics (CSAs), a different class of facial amphiphiles with same mechanism of antimicrobial action as that of CPAs. The results showed that CSAs also require similar minimum features to be active against both E. coli and S. aureus. These studies also indicate that the minimum feature requirements may be conserved for different strains of the same organism. Figure shows the mapping of an active cationic peptide antibiotic (CPA) mapped to the most acceptable hypothesis Sa6 against S. aureus     

A minimalistic tetrapeptide amphiphile scaffold for transmembrane pores with a preference for sodium

Synthetic channels or pores that are easy to synthesize, stable and cation-selective are extremely attractive for the development of therapeutics and materials. Herein, we report a pore developed from a small tetrapeptide scaffold that shows a preference for sodium over lithium/potassium. The sodium selectivity is attributed to the appended oligoether tail at the C-terminus. A peptide dimer is proposed as the predominant cation-transporting pore. Such pyridine containing stable pores can be potentially utilized for the pH modulated ion transport.     

Synthesis and evaluation of N-alkyl-9-aminoacridines with antibacterial activity

A series of 9-alkylaminoacridines were synthesized and evaluated for activity against two strains of methicillin-resistant and one strain of methicillin-sensitive Staphylococcus aureus. Results are presented that show a clear structure activity relationship between the N-alkyl chain length and antibacterial activity with peak MIC₉₉ values of 2–3 μM for alkyl chains ranging from 10 to 14 carbons in length. Although prior work has linked the function of acridine-based compounds to intercalation and topoisomerase inhibition, the present results show that 9-alkylaminoacridines likely function as amphiphilic membrane-active disruptors potentially in a similar manner as quaternary ammonium antimicrobials.