Binding of Fatty Acid Amide Amphiphiles to Bovine Serum Albumin: Role of Amide Hydrogen Bonding

The study of protein–surfactant interactions is important because of the widespread use of surfactants in industry, medicine, and pharmaceutical fields. Sodium <i>N</i>-lauroylsarcosinate (SL-Sar) is a widely used surfactant in cosmetics, shampoos. In this paper, we studied the interactions of bovine serum albumin (BSA) with SL-Sar and sodium <i>N</i>-lauroylglycinate (SL-Gly) by use of a number of techniques, including fluorescence and circular dichroism spectroscopy and isothermal titration calorimetry. The binding strength of SL-Sar is stronger than that of structurally similar SL-Gly, which differs only by the absence of a methyl group in the amide nitrogen atom. Also, these two surfactants exhibit different binding patterns with the BSA protein. The role of the amide bond and hence the surfactant headgroup in the binding mechanism is discussed in this paper. It was observed that while SL-Sar destabilized, SL-Gly stabilized the protein structure, even at concentrations less than the critical micelle concentration (cmc) value. The thermodynamics of surfactant binding to BSA was studied by use of ITC. From the ITC results, it is concluded that three molecules of SL-Sar in contrast to only one molecule of SL-Gly bind to BSA in one set of binding sites at room temperature. However, on increasing temperature four molecules of SL-Gly bind to the BSA through H-bonding and van der Waals interactions, due to loosening of the BSA structure. In contrast, with SL-Sar the binding process is enthalpy driven, and very little structural change of BSA was observed at higher temperature

Vesicle Formation by l‑Cysteine-Derived Unconventional Single-Tailed Amphiphiles in Water: A Fluorescence, Microscopy, and Calorimetric Investigation

Two new l-cysteine-derived zwitterionic amphiphiles with poly­(ethylene glycol) methyl ether (mPEG) tail of different chain lengths were synthesized and their surface activity and self-assembly properties were investigated. In aqueous phosphate buffered solution of pH 7.0, the amphiphiles were observed to form stable unilamellar vesicles, the bilayer membrane of which is constituted by the mPEG chains. The vesicle phase was characterized by a number of methods including fluorescence spectroscopy, dynamic light scattering, and transmission electron microscopy. The thermodynamics of self-assembly was also studied by isothermal titration calorimetry through measurements of the standard Gibbs free energy change (Δ<i>G</i>°_m), standard enthalpy change (Δ<i>H</i>°_m) and standard entropy change (Δ<i>S</i>°_m) of micellization. The self-assembly process was found to be entropy-driven, which implies that the mPEG chain behaves like a hydrocarbon tail of conventional surfactants. The effects of pH, temperature, salt, and aging time on the bilayer stability were also investigated. Encapsulation and pH-triggered release of model hydrophobic and hydrophilic drugs is demonstrated

An Unconventional Zwitterionic Bolaamphiphile Containing PEG as Spacer Chain: Surface Tension and Self-Assembly Behavior

Monolayer lipid membrane formation based on self-assembly of bolaamphiphiles containing hydrophobic spacer are well-established in the literature, but monolayer vesicle formation by so-called hydrophilic poly­(ethylene glycol) (PEG) spacer has not been reported to date. Here, a novel l-cysteine-derived bolaamphiphile with PEG as spacer has been developed and characterized. The interfacial properties and the solution behavior of the amphiphile were investigated in pH 7.0 at 25 °C. The self-assembly properties of the bolaamphiphile in aqueous buffer were investigated by using different techniques, such as surface tensiometry, fluorescence spectroscopy, UV–vis spectroscopy, isothermal titration calorimetry, dynamic light scattering, transmission electron microscopy, and atomic force microscopy. Surprisingly, despite having so-called polar spacer in between two polar head groups, it exhibits formation of microstructures in aqueous buffer as well as in water at 25 °C. The molecule undergoes self-organization leading to the formation of monolayer vesicles with hydrodynamic diameters between 100 and 250 nm in a wide range of concentration. The thermodynamic parameters clearly suggest that the aggregate formation is mainly driven by the hydrophobic effect. The monolayer vesicles were found to form at a very low concentration (≥0.63 mM) and within a wide pH range (2–10). The vesicles exhibit excellent shelf life at physiological temperature

Vesicle-to-Micelle Transition in Aqueous Solutions of l‑Cysteine-Derived Carboxylate Surfactants Containing Both Hydrocarbon and Poly(ethylene glycol) Tails

In our recent reports, we have shown that when a poly­(ethylene glycol) (PEG) chain is covalently linked to any ionic group, the resultant molecule behaves like an amphiphile. Depending upon the nature of ionic head groups, they self-assemble to form micelles or vesicles, in which the PEG chain constitutes the micellar core or vesicle bilayer. In this study, we intend to examine what happens when both hydrocarbon (HC) and PEG chains are attached to a carboxylate head group. Therefore, we have synthesized two novel amphiphiles in which a PEG and a HC chain is covalently linked to l-cysteine. The surface activities and the solution behavior of the sodium salts of these amphiphiles were investigated at neutral pH. The amphiphiles self-organize to form large unilamellar vesicles in dilute solutions, which transformed into small micelles at higher concentrations. The HC chains of the molecules have been shown to constitute the bilayer membrane of the vesicles and core of micelles. In acidic pH, the amphiphiles were found to form large disklike micelles. The thermodynamic parameters of self-assembly formation were also measured by isothermal titration calorimetry. The vesicle and micelle formation was found to be spontaneous and thermodynamically favorable. The thermal stability of the micelles at neutral and acidic pH was studied. The addition of cholesterol was observed to increase the physical stability of vesicles

Organogelation by 4‑(<i>N</i>‑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-(<i>N</i>-tetradecanoyl)­aminohydroxybutanoic acid amphiphiles in a series of organic solvents and compared with those of the corresponding unsubstituted amphiphile 4-(<i>N</i>-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 ¹H 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

l‑Cysteine-Derived Ambidextrous Gelators of Aromatic Solvents and Ethanol/Water Mixtures

A series of l-cysteine-derived double hydrocarbon chain amphiphilic gelators l-(3-alkyl-carbamoylsulfanyl)-2-(3-alkylurido)­propionic acid with different hydrocarbon chain lengths (C6–C16) was designed and synthesized. These gelators efficiently gelate only aromatic solvents. The gelation ability increased with the increase of chain length up to C14, but then it dropped with further increase of chain length. The C12 and C14 derivatives also gelled ethanol/water mixtures. The gels were characterized by a number of methods, including FT-IR, NMR, and XRD spectroscopy, electron microscopy, and rheology. The amphiphiles were observed to form either flat lamellar or ribbonlike aggregates in aromatic solvents as well as in ethanol/water mixtures. The gelation in all the solvents employed was observed to be thermoreversible. The gel-to-sol transition temperature as well as mechanical strength of the organogels were observed to increase with the hydrocarbon chain length. Both types of gels of C8–C16 amphiphiles have gel-to-sol transition temperatures above the physiological temperature (310 K). FT-IR and variable temperature ¹H NMR measurements suggested that van der Waals interactions have major contribution in the gelation process. The gel-to-sol transition temperature and mechanical strength of the organogels in ethanol/water mixtures was observed to be higher than those of benzene organogel

Physicochemical Characterization and Self-Assembly Studies on Cationic Surfactants Bearing mPEG Tail

Poly­(ethylene glycol), PEG, is normally coupled to hydrophobic molecules to produce nonionic surfactants. However, there is no report so far on cationic surfactants in which PEG chain acts as a hydrophobic tail. In this work, two novel cationic amphiphiles containing a poly­(ethylene glycol) monomethyl ether (mPEG) tail of different lengths linked to a cationic headgroup were synthesized to investigate their surface activity and self-assembling properties. The amphiphiles were shown to be surface-active with low critical micelle concentration (cmc). It has been found that although mPEG chain is hydrophilic as compared to hydrocarbon chain of equivalent length, the cmc values are lower than that of cetyltrimethylammonium chloride, a commercial cationic surfactant. The cationic surfactants have been shown to have antimicrobial activity. The fluorescence probe studies and the thermodynamic data have shown that the self-assembly is due to strong van der Waals interaction between mPEG chains as well as hydrophobic effect. The single-tailed cationic surfactants spontaneously self-assembled to form small unilamellar vesicles with hydrodynamic diameter in the range of 20–50 nm. The vesicles were characterized by fluorescence probe technique, dynamic light scattering, transmission electron microscopy, and confocal fluorescence microscopy. We have also studied encapsulation of model drugs by the vesicles and pH-triggered release kinetics

Spontaneously Formed Robust Steroidal Vesicles: Physicochemical Characterization and Interaction with HSA

Self-assembled multimolecular aggregates, such as vesicles, have earned tremendous attention for their applications as model membranes and drug delivery systems. Over the past decades, enormous efforts have been dedicated to the development of stable and biocompatible vesicles that form spontaneously in aqueous solution. With the aim of preparing highly stable vesicles, we herein report the physicochemical characterization of a novel cholesterol-based chiral surfactant with l-alanine headgroup. Different techniques, such as surface tensiometry, fluorescence spectroscopy, dynamic light scattering, UV–vis spectroscopy, transmission electron microscopy, and confocal fluorescence microscopy were employed to investigate the self-assembly properties of the aforementioned single-tailed steroidal surfactant in aqueous solution. The surfactant molecule is weakly surface-active, but self-assembles to form unilamellar vesicles facilitated by the strong hydrophobic association of the cholesterol moieties, above a very low critical aggregation concentration. The vesicles are fairly stable with respect to aging, temperature, and pH of the aqueous medium. Additionally, the vesicles were found to fuse together, leading to large unilamellar vesicles. The intervesicular fusion pertaining to high stability of the vesicles could be ascribed to large hydrophobic interactions among steroidal skeletons. Furthermore, the interaction of the vesicles with human serum albumin is also investigated

Spontaneously Formed Robust Steroidal Vesicles: Physicochemical Characterization and Interaction with HSA

Self-assembled multimolecular aggregates, such as vesicles, have earned tremendous attention for their applications as model membranes and drug delivery systems. Over the past decades, enormous efforts have been dedicated to the development of stable and biocompatible vesicles that form spontaneously in aqueous solution. With the aim of preparing highly stable vesicles, we herein report the physicochemical characterization of a novel cholesterol-based chiral surfactant with l-alanine headgroup. Different techniques, such as surface tensiometry, fluorescence spectroscopy, dynamic light scattering, UV–vis spectroscopy, transmission electron microscopy, and confocal fluorescence microscopy were employed to investigate the self-assembly properties of the aforementioned single-tailed steroidal surfactant in aqueous solution. The surfactant molecule is weakly surface-active, but self-assembles to form unilamellar vesicles facilitated by the strong hydrophobic association of the cholesterol moieties, above a very low critical aggregation concentration. The vesicles are fairly stable with respect to aging, temperature, and pH of the aqueous medium. Additionally, the vesicles were found to fuse together, leading to large unilamellar vesicles. The intervesicular fusion pertaining to high stability of the vesicles could be ascribed to large hydrophobic interactions among steroidal skeletons. Furthermore, the interaction of the vesicles with human serum albumin is also investigated

Thermoreversible as Well as Thermoirreversible Organogel Formation by l‑Cysteine-Based Amphiphiles with Poly(ethylene glycol) Tail

We report here the gelation behavior of two novel l-cysteine-based amphiphiles bearing a poly­(ethylene glycol) tail. The amphiphiles were found to form transparent organogels in both apolar and aprotic polar solvents at reasonably low concentrations. In chloroform, dichloromethane, and benzene solvents, the organogels are formed at room temperature without the requirement of heating–cooling cycle due to strong hydrogen-bonding interaction between gelator molecules. The swelling kinetics, however, becomes faster on heating. Unlike most organogels of low-molecular-mass gelators, these organogels do not exhibit a gel-to-sol transition on heating but instead become rigid when heated. Surprisingly, in polar solvents, the gelation required a heating–cooling cycle, and the sol-to-gel transition was found to be reversible. The gelation abilities of the amphiphiles were correlated with the hydrogen-bonding parameters of the solvents. Intermolecular H-bonding interaction was found to be the major driving force for the organogelation. The morphology of the organogels was investigated by the use of optical as well as electron microscopy and was found to be dependent on the nature of solvent. The mechanical strengths of the organogels were studied by rheological measurements