Head Groups Of Amphiphiles Research Articles

Red Circularly Polarized Luminescence from Dimeric H-Aggregates of Acridine Orange by Chiral Induction.

Understanding the mechanism of chirality transfer from a chiral surface to an achiral molecule is essential for designing molecular systems with tunable chiroptical properties. These aspects are explored herein using l- and d-isomers of alkyl valine amphiphiles, which self-assemble in water as nanofibers possessing a negative surface charge. An achiral chromophore, acridine orange, upon electrostatic binding on these surfaces displays mirror-imaged bisignated circular dichroism and red-emitting circularly polarized luminescence signals with a high dissymmetry factor. Experimental and computational investigations establish that the chiroptical properties emerge from surface-bound asymmetric H-type dimers of acridine orange, further supported by fluorescence lifetime imaging studies. Specifically, atomistic molecular dynamics simulations show that the experimentally observed chiral signatures have their origin in van der Waals interactions between acridine orange dimers and the amphiphile head groups as well as in the extent of solvent exposure of the chromophore.

Role of Sn(II) in Mediating the Formation and Organization of a Langmuir Monolayer.

The influence of the Sn(II) ion on the formation and morphology of an arachidic acid (AA) monolayer was investigated using Langmuir film formation technology, pressure-area (Π-A) isotherm measurements, and Brewster angle microscopy (BAM). Our findings indicate that AA Langmuir monolayers exhibit organization that depends on subphase pH and Sn2+ concentration. There are multiple equilibria that are relevant to the complexation of AA monolayers, and the balance of Sn(OH)n equilibria and Sn(AA)n equilibria gives rise to unusual monolayer structural effects. With Sn2+ in the subphase, the AA monolayer exhibits an isotherm characterized by the absence of a collapse point and with a pH-dependent change in isotherm shape not consistent with the formation of an ordered solid phase. The amphiphile headgroup equilibrium mediates the absence of collapse seen experimentally and the ability of the monolayer to retain organization at a surface pressure of ca. 70 mN/m. BAM images show that the morphology of the monolayer depends on the Sn2+ concentration, consistent with several species of Sn(AA)n, where n = 1, 2, or 3, contributing to the overall monolayer order.

Mechanism behind Polysorbates' Inhibitory Effect on P-Glycoprotein.

Much effort has been invested in the search for modulators of membrane transport proteins such as P-glycoprotein (P-gp) to improve drug bioavailability and reverse multidrug resistance in cancer. Nonionic surfactants, a class of pharmaceutical excipients, are known to inhibit such proteins, but knowledge about the exact mechanism of this inhibition is scarce. Here, we perform multiscale molecular dynamics simulations of one of these surfactants, polysorbate 20 (PS20), to reveal the behavior of such compounds on the molecular level and thereby discover the molecular mechanism of the P-gp inhibition. We show that the amphiphilic headgroup of PS20 is too hydrophobic to partition in the water phase, which drives the binding of PS20 to the amphiphilic drug-binding domain of P-gp and thereby causes the inhibition of the protein. Based on our findings, we conclude that PS20 primarily inhibits P-gp through direct binding to the drug-binding domain (DBD) from the extracellular leaflet.

Asphaltene destabilization in the presence of dodecylbenzene sulfonic acid and dodecylphenol

Asphaltenes are the molecules in crude oil that can be dissolved in aromatic solvents, such as toluene, but will precipitate in presence of n-alkanes, such as heptane. There is an immense number of different molecules in crude oil that are classified as asphaltenes. The effect of amphiphile head group on asphaltene destabilization and aggregation was investigated. Experimental results show that Dodecylphenol (DDCP) delayed asphaltene aggregation in all 3 crude oils investigated. On the other hand, Dodecylbenzenesulfonic Acid (DBSA) delayed detection of asphaltene aggregation in two crude oils and accelerated the detection of aggregation in one crude oil.

Interactions of l-arginine with Langmuir monolayers of common phospholipids at the air-water interface

The interactions of l-arginine (l-arg) with Langmuir monolayers of three most common phospholipids, which are sodium salt of dipalmitoylphosphatidylglycerol (DPPG), dipalmitoylphosphatidylcholine (DPPC) and dipalmitoylphosphatidylethanolamine (DPPE), have been investigated at the air-water interface. The surface pressure-area (π-A) isotherms of these monolayers have been measured with a film balance and monolayer morphology has been observed by a Brewster angle microscopy (BAM). The DPPG monolayers on pure water do not show any phase transition but show irregular shaped condensed phases formed just after evaporation of the solvent at 20 °C. However, this monolayer on l-arg solution subphase indicates a first-order phase transition from liquid expanded to liquid condensed (LE-LC) phases and forms LC domains at the same temperature. With an increase in the l-arg concentration in the subphase up to 5.0 × 10−4 M, the π-A shows an overall increasingly greater expansion in the molecular area. All of the π-A isotherms recorded on ≥5.0 × 10−4 M l-arg solution subphases almost coincide with each other. These changes in the phase behavior have been explained by the fact that l-arg having guanidinium cationic group undergoes strong hydrogen bonding interaction with the anionic phosphatidylglycerol (PG-) head group. The bonding between two molecules is further strengthened by electrostatic attraction between cationic l-arg and anionic PG- ions. The BAM observation of the monolayer morphology supports this explanation. On the other hand, a very negligible interaction has been observed between l-arg and DPPC or DPPE monolayers. The π-A isotherms in the presence of l-arg for both the amphiphiles show a very little expansion only in the LE phase region, but coincide in the so called solid phase region. The monolayer morphology of both the monolayers also supports these results. This little effect of expansion in the LE region may be explained by the ion-pair formation between cationic l-arg and anionic head groups in the monolayers at lower pressures. However, due to compression at high pressure, the l-arg molecules are squeezed out from the amphiphile head groups.

Nucleotide-Selective Templated Self-Assembly of Nanoreactors under Dissipative Conditions.

Nature adopts complex chemical networks to finely tune biochemical processes. Indeed, small biomolecules play a key role in regulating the flux of metabolic pathways. Chemistry, which was traditionally focused on reactions in simple mixtures, is dedicating increasing attention to the network reactivity of highly complex synthetic systems, able to display new kinetic phenomena. Herein, we show that the addition of monophosphate nucleosides to a mixture of amphiphiles and reagents leads to the selective templated formation of self-assembled structures, which can accelerate a reaction between two hydrophobic reactants. The correct matching between nucleotide and the amphiphile head group is fundamental for the selective formation of the assemblies and for the consequent up-regulation of the chemical reaction. Transient stability of the nanoreactors is obtained under dissipative conditions, driven by enzymatic dephosphorylation of the templating nucleotides. These results show that small molecules can play a key role in modulating network reactivity, by selectively templating self-assembled structures that are able to up-regulate chemical reaction pathways.

Nucleotide‐Selective Templated Self‐Assembly of Nanoreactors under Dissipative Conditions

AbstractNature adopts complex chemical networks to finely tune biochemical processes. Indeed, small biomolecules play a key role in regulating the flux of metabolic pathways. Chemistry, which was traditionally focused on reactions in simple mixtures, is dedicating increasing attention to the network reactivity of highly complex synthetic systems, able to display new kinetic phenomena. Herein, we show that the addition of monophosphate nucleosides to a mixture of amphiphiles and reagents leads to the selective templated formation of self‐assembled structures, which can accelerate a reaction between two hydrophobic reactants. The correct matching between nucleotide and the amphiphile head group is fundamental for the selective formation of the assemblies and for the consequent up‐regulation of the chemical reaction. Transient stability of the nanoreactors is obtained under dissipative conditions, driven by enzymatic dephosphorylation of the templating nucleotides. These results show that small molecules can play a key role in modulating network reactivity, by selectively templating self‐assembled structures that are able to up‐regulate chemical reaction pathways.

Orientation and Location of the Cyclotide Kalata B1 in Lipid Bilayers Revealed by Solid-State NMR

Cyclotides are ultra-stable cyclic disulfide-rich peptides from plants. Their biophysical effects and medically interesting activities are related to their membrane-binding properties, with particularly high affinity for phosphatidylethanolamine lipids. In this study we were interested in understanding the molecular details of cyclotide-membrane interactions, specifically with regard to the spatial orientation of the cyclotide kalata B1 from Oldenlandia affinis when embedded in a lipid bilayer. Our experimental approach was based on the use of solid-state 19F-NMR of oriented bilayers in conjunction with the conformationally restricted amino acid L-3-(trifluoromethyl)bicyclopent-[1.1.1]-1-ylglycine as an orientation-sensitive 19F-NMR probe. Its rigid connection to the kalata B1 backbone scaffold, together with the well-defined structure of the cyclotide, allowed us to calculate the protein alignment in the membrane directly from the orientation-sensitive 19F-NMR signal. The hydrophobic and polar residues on the surface of kalata B1 form well-separated patches, endowing this cyclotide with a pronounced amphipathicity. The peptide orientation, as determined by NMR, showed that this amphipathic structure matches the polar/apolar interface of the lipid bilayer very well. A location in the amphiphilic headgroup region of the bilayer was supported by 15N-NMR of uniformly labeled protein, and confirmed using solid-state 31P- and 2H-NMR. 31P-NMR relaxation data indicated a change in lipid headgroup dynamics induced by kalata B1. Changes in the 2H-NMR order parameter profile of the acyl chains suggest membrane thinning, as typically observed for amphiphilic peptides embedded near the polar/apolar bilayer interface. Furthermore, from the 19F-NMR analysis two important charged residues, E7 and R28, were found to be positioned equatorially. The observed location thus would be favorable for the postulated binding of E7 to phosphatidylethanolamine lipid headgroups. Furthermore, it may be speculated that this pair of side chains could promote oligomerization of kalata B1 through electrostatic intermolecular contacts via their complementary charges.

Exploring architectures at the nanoscale: the interplay between hydrophobic twin lipid chains and head groups of designer peptide amphiphiles in the self-assembly process and application.

The self-assembly of peptide amphiphiles (PAs) is found to be governed by the hydrophobic interactions induced by the hydrophobic groups/number of alkyl chains and the hydrophilic head groups. In this study, an assessment of the nanostructures formed by the self-assembly of simple twin chained PAs was carried out and compared to their single chain/short analogues. The spectroscopic and microscopic analysis revealed the fact that the twin chained amphiphiles had a high inclination to form β-sheet nanofibers and further towards hydrogelation. The mixture of twin chained PAs also exhibited cooperative self-assembly with improved aggregation behavior, although not much augmentation in β-type structuring was found. In contrast, the single chain/short analogue containing PAs showed very less of β-sheet type structures to a lesser extent and no hydrogelating behavior but resulted in mostly random conformations. The increase in the number or alteration of polar head groups in double chained PAs induced higher extent of β-type conformation and better gelling capability due to the combined hydrophobic effect of the twin chains. The overall results delineated the dominance of hydrophobic interactions. Finally, calcium phosphate bio-mineralization was done in the hydrogels of twin chained PAs with the aim of developing future biomaterials.

Molecular Origins of Mesoscale Ordering in a Metalloamphiphile Phase.

Controlling the assembly of soft and deformable molecular aggregates into mesoscale structures is essential for understanding and developing a broad range of processes including rare earth extraction and cleaning of water, as well as for developing materials with unique properties. By combined synchrotron small- and wide-angle X-ray scattering with large-scale atomistic molecular dynamics simulations we analyze here a metalloamphiphile–oil solution that organizes on multiple length scales. The molecules associate into aggregates, and aggregates flocculate into meso-ordered phases. Our study demonstrates that dipolar interactions, centered on the amphiphile headgroup, bridge ionic aggregate cores and drive aggregate flocculation. By identifying specific intermolecular interactions that drive mesoscale ordering in solution, we bridge two different length scales that are classically addressed separately. Our results highlight the importance of individual intermolecular interactions in driving mesoscale ordering.

Organogelation by 4-(N-tetradecanoyl)aminohydroxybutyric acids: effect of hydrogen-bonding group in the amphiphile head.

The major driving force for organogelation is known to be hydrogen bonding for gelators containing functional groups capable of forming hydrogen bond(s). In order to examine this, we have investigated the gelation behavior of two 4-(N-tetradecanoyl)aminohydroxybutanoic acid amphiphiles in a series of organic solvents and compared with those of the corresponding unsubstituted amphiphile 4-(N-tetradecanoyl)aminobutanoic acid (C14-ABA). The gelation ability of the nonhydroxyl amphiphile C14-ABA was found to be better than the hydroxyl group substituted amphiphiles. An attempt was also made to correlate gelation abilities of the amphiphiles with the solvent polarity parameters. The driving force for the gelation was studied by Fourier transform infrared and (1)H NMR spectroscopy. The organogels were characterized by electron microscopy and XRD. The thermal stability of the gels was investigated by measuring the sol-to-gel transition temperature. Rheological measurements were performed in order to determine the mechanical stability of the organogels. The gelation ability and thermal and mechanical stability of the organogels were correlated with the intermolecular hydrogen-bonding interactions between amphiphile head groups.

Self-assembly and headgroup effect in nanostructured organogels via cationic amphiphile-graphene oxide composites.

Self-assembly of hierarchical graphene oxide (GO)-based nanomaterials with novel functions has received a great deal of attentions. In this study, nanostructured organogels based on cationic amphiphile-GO composites were prepared. The gelation behaviors of amphiphile-GO composites in organic solvents can be regulated by changing the headgroups of amphiphiles. Ammonium substituted headgroup in molecular structures in present self-assembled composites is more favorable for the gelation in comparison to pyridinium headgroup. A possible mechanism for headgroup effects on self-assembly and as-prepared nanostructures is proposed. It is believed that the present amphiphile-GO self-assembled system will provide an alternative platform for the design of new GO nanomaterials and soft matters.

Specific Ion Effects in Amphiphile Hydration and Interface Stabilization

Specific ion effects can influence many processes in aqueous solutions: protein folding, enzyme activity, self-assembly, and interface stabilization. Ionic amphiphiles are known to stabilize the oil/water interface, presumably by dipping their hydrophobic tails into the oil phase while sticking their hydrophilic head groups in water. However, we find that anionic and cationic amphiphiles adopt strikingly different structures at liquid hydrophobic/water interfaces, linked to the different specific interactions between water and the amphiphile head groups, both at the interface and in the bulk. Vibrational sum frequency scattering measurements show that dodecylsulfate (DS(-)) ions do not detectably perturb the oil phase while dodecyltrimethylammonium (DTA(+)) ions do. Raman solvation shell spectroscopy and second harmonic scattering (SHS) show that the respective hydration-shells and the interfacial water structure are also very different. Our work suggests that specific interactions with water play a key role in driving the anionic head group toward the water phase and the cationic head group toward the oil phase, thus also implying a quite different surface stabilization mechanism.

Synthesis and photocatalytic property of gold nanoparticles by using a series of bolaform Schiff base amphiphiles

Gold nanoparticles were synthesized via a series of bolaform amphiphiles with hydrophilic ethyleneamine spacers and aromatic headgroups at a liquid–liquid interface. By stirring the aqueous solution containing AuCl4− ions with the chloroform solution of bolaform amphiphile, AuCl4− ions were transferred into the organic phase and reduced to gold nanoparticles. Spectral and morphological measurements indicated that these bolaform amphiphiles could serve as both capping and reducing agents. Different gold nanostructures could be obtained depending on the different spacers, headgroups of bolaform amphiphiles and the molar ratios of amphiphile to AuCl4− ions. The photocatalytic properties of as-made gold nanoparticles on the degradation of methyl orange indicated that the substituted groups and molecular structures in the amphiphiles indeed played an important role in changing the sizes of as-made gold nanoparticles and subsequently regulating their catalytic behaviors. The present work gave an original investigation of synthesis and regulation of gold nanostructures by utilizing bolaform amphiphiles with different substituted headgroups and spacers.

Multiple Phase Inversion of Emulsions Stabilized by in Situ Surface Activation of CaCO3 Nanoparticles via Adsorption of Fatty Acids

The in situ surface activation of raw CaCO(3) nanoparticles by interaction with a series of sodium carboxylates of chain length between 6 and 12 as well as sodium 2-ethylhexylsulfosuccinate (AOT) was studied, and the impact of this on the stabilization and phase inversion of toluene-water emulsions was assessed. By using complementary experiments including measurement of particle zeta potentials, adsorption isotherms of amphiphile, and relevant contact angles, the mechanism of this activation was revealed. The results show that hydrophilic CaCO(3) nanoparticles can be surface activated by interaction with sodium carboxylates and AOT even if they are not surface-active themselves. Both the electrostatic interaction between the positive charges on particle surfaces and the negative charges of anionic amphiphile headgroups and the chain-chain interactions of the amphiphile result in monolayer adsorption of the amphiphile at the particle-water interface. This transforms the particles from hydrophilic to partially hydrophobic such that they become surface-active and stabilize oil-in-water O/W(1) emulsions and induce O/W(1) → water-in-oil W/O phase inversion, depending on the chain length of the carboxylate molecules. At high amphiphile concentration, bilayer or hemimicelle adsorption may occur at the particle-water surface, rendering particles hydrophilic again and causing their desorption from the oil-water interface. A second phase inversion, W/O → O/W(2), may occur depending on the surface activity of the amphiphile. CaCO(3) nanoparticles can therefore be made good stabilizers of both O/W and W/O emulsions once surface activated by mixing with traces of suitable anionic amphiphile.

Synthesis of glycolipopeptidic building blocks for carbohydrate receptor discovery

A class of glycolipopeptides for use as building blocks for a new type of dynamic combinatorial library is reported. The members of the library consist of a variable carbohydrate moiety, coded amino acids, and lipoamino acids in order to convert them into amphiphiles. Glycolipopeptidic amphiphiles interact through non-covalent bonding when mixed together in aqueous phase and form micelles in dynamic close-packed fluid mosaic arrays. The head groups of amphiphiles are exposed on the micelle surface, providing entities which could be screened in biological assays to find the most potent combination of building blocks in order to identify new bioactive carbohydrate ligands.

Asymmetric bolaamphiphiles from vernonia oil designed for drug delivery

AbstractThroughout the ages, fats, oils and their chemical derivatives have been used in a variety of medical applications, but currently they are becoming important as components in drug delivery systems. Liposomes (vesicles from phospholipids) are among the lipid‐based delivery systems that have been most extensively studied. However, targeting of liposomes to specific tissues is still problematic, and attempts to overcome these limitations include developments in nano‐sized monolayer vesicles made of bolaamphiphiles (compounds containing two hydrophilic headgroups at each end of an alkyl chain). This paper describes bolaamphiphile synthesis and characterization of the nano‐sized vesicles formed from the bolaamphiphiles with potential application for targeted drug delivery to the brain. The starting material for the synthesis is vernonia oil (or its fatty acids or methyl esters), which is a naturally epoxidized triacylglycerol obtained from the seeds of Vernonia galamensis. The targeting mechanism is based on the hydrolysis of the amphiphile's headgroup by an enzyme abundant in the target tissue, with subsequent release of the encapsulated drug at the target site. Preliminary experiments in mice demonstrated that the marker FITC‐dextran, which normally does not penetrate the blood brain barrier, is delivered into the brain when encapsulated in these vesicles.

Self-Assembling Peptide Amphiphiles for DNA Binding and Nuclear Targeting

Peptide amphiphiles can be used to create multivalent, multifunctional, self-assembled nanostructures for applications such as immunotherapy, cancer treatment, and in this case gene therapy. We have conjugated di-C16 hydrophobic tails to bZip, a thirty-eight amino acid sequence derived from the transcription factor GCN4, to promote the formation of extended micelles in solution. The peptide amphiphile headgroups adopt a high degree of alpha-helical content in the micelle corona compared to the free peptide chains as shown by circular dichroism. The hydrophobic moiety facilitates the DNA binding of bZip amphiphiles in an orthogonal arrangement similar to the native protein, in contrast to the unmodified peptide which binds via electrostatic collapse onto DNA. The peptide amphiphiles bind DNA in a cooperative fashion but do not recognize the AP 1 sequence that GCN4 binds specifically, although further modification of the monomers may enhance their biofunctionality. To implement the DNA binding peptide amphiphiles in gene therapy applications, a nuclear targeting platform is being developed by appending a hydrophobic tail to a nuclear localization signaling (NLS) peptide. The tail enhances cellular uptake of the peptide and delivery to the nucleus of HeLa cells as observed by fluorescence microscopy. Incorporating NLS peptide amphiphiles into a mixed micelle displaying DNA binding peptides or other therapeutic agents may aid in targeted delivery to the nucleus.

Physicochemical studies on the micellization behavior of cetylpyridinium chloride and triton X-100 binary mixtures in aqueous medium

Physicochemistry of micellization of binary mixtures of cetylpyridinium chloride (CPC) and Triton X-100 (TX-100) have been investigated and the data collected have been analyzed and correlated. Tensiometric, conductometric, spectrophotometric, calorimetric and polarographic methods have been employed in the study. Parameters like critical micellar concentration (CMC), counter-ion binding, energetics of micellization, interfacial surfactant adsorption and minimum area of amphiphile head groups at CMC have been determined. The diffusion coefficients of pure and mixed micelles in solution have been determined by the polarographic method. The regular solution theory of Rubingh has been considered to get information on the micellar composition and their mutual interaction (synergistic for the studied system) in solution. The packing of the monomer in micelle has been estimated to witness spherical geometry for CPC and its mixtures with TX-100, whereas the later has been found to be spheroidal. Polarographic measurements have evidenced comparable diffusion coefficients of CPC and TX-100 micelles whereas their mixed micelles have shown lower values with a minimum, at equimolar composition.

The Molecular Recognition of Dipeptide by Oligoglycyl Head Group of Amphiphile: A Quantum Chemical Study

In the present work, we presented an analysis of the unusual recognition specificity exhibited by marked difference in the binding behavior of dipeptide with amphiphilic head group when subtle relative change of N-terminal and C-terminal of the dipeptide are made. Recently, in a series of detailed experiments, binding of aqueous dipeptides, GlyX and X/Gly (X = Leu, Phe, Pro, Ala; X/ = Leu, Phe) with dialkyl oligoglycyl amphiphiles is studied [X. Cha, K. Ariga, M. Onda, and T. Kunitake, J. Am. Chem. Soc. 117, 11833 (1995)]. It is observed that GlyX are specifically bound to 2C18BGly2NH2 while X/Gly are insignificantly bound. We first studied the conformational energy variation of GlyPhe, PheGly and model of 2C18BGly2NH2 amphiphile using semi-empirical and ab-initio methods in vacuum. Using the individual energy optimized monomer structure of amphiphile and peptide, we studied the binding energy of optimized GlyPhe: amphiphile pair and PheGly: amphiphile pair structures at 1:1 and 1:2 ratio at the same level of theory using a population of structures. Binding of GlyPhe is favorable over the binding of PheGly at various levels of theory (semi-empirical and ab-initio). It is noted that the hydrogen bonding pattern in the GlyPhe binding is more effective than that in the PheGly binding. In the population of low energy structures, PheGly: amphiphile structures have more exposed area around the hydrophobic Phe group than the GlyPhe: amphiphile structures. Relatively more PheGly: amphiphile structures have intermolecular orientation unsuitable to contribute to the population of head group structures relevant in aqueous interface. Summarizing, significantly better binding capacity of GlyPhe over the PheGly with amphiphile, is due to the difference in hydrogen bonding interaction pattern, hydrophobic effect and possible orientations of the amphiphile and peptide at interface, relevant to the condensed phase monolayer structure. All the three factors cooperatively lead to favorable recognition of GlyPhe over PheGly as observed in experiment. A calculation of the ratio of the amphiphile-peptide bound complex to the initial concentration of the amphiphile indicates that the diffusional process at the peptide interfaces could be significantly influenced by hydrogen bonding.