Phase behavior and molecular thermodynamics of coacervation in oppositely charged polyelectrolyte/surfactant systems: a cationic polymer JR 400 and anionic surfactant SDS mixture

Coacervation in mixtures of polyelectrolytes and surfactants with opposite charge is common in nature and is also technologically important to consumer health care products. To understand the complexation behavior of these systems better, we combine multiple experimental techniques to systematically study the polymer/surfactant binding interactions and the phase behavior of anionic sodium dodecyl sulfate (SDS) surfactant in cationic JR 400 polymer aqueous solutions. The phase-behavior study resolves a discrepancy in the literature by identifying a metastable phase between the differing redissolution phase boundaries reported in the literature for the surfactant-rich regime. Isothermal titration calorimetry analyzed within the framework of the simple Satake-Yang model identifies binding parameters for the surfactant-lean phase, whereas a calculation for polymer-bound micelles coexisting with free micelles is analyzed in the surfactant-rich redissolution regime. This analysis provides a preliminary understanding of the interactions governing the observed phase behavior. The resulting thermodynamic properties, including binding constants and the molar Gibbs free energies, enthalpies, and entropies, identify the relative importance of both hydrophobic and electrostatic interactions and provide a first approximation for the corresponding microstructures in the different phases. Our study also addresses the stability and metastability of oppositely charged polyelectrolytes and surfactant mixtures.     

Micellization of cationic gemini surfactant and its interaction with DNA in dilute brine

The micellization of cationic gemini surfactant trimethylene-1,3-bis (dodecyldimethylammonium bromide) (12-3-12·2Br) was investigated and critical micelle concentrations (CMC) and thermodynamic parameters were evaluated as functions of ionic strength and temperature. The micellization of 12-3-12·2Br is entropically driven and thermodynamically favored. Raising the temperature slightly increases the CMC, while increasing the ionic strength lowers the CMC. A multi-technique study of the 12-3-12·2Br/DNA interaction and its dependence on ionic strength, temperature and DNA concentration were presented. DNA with loose coil conformation, necklace-like structure, highly ordered toroidal aggregates and coexisting of large aggregates and small structures in DNA/12-3-12·2Br system were observed. Critical aggregation concentrations (CAC), interaction saturation concentrations (C(2)), and associated thermodynamic parameters were determined. The screening effect of salt decreases the DNA/12-3-12·2Br electrostatic attraction, but favors the formation of free 12-3-12·2Br micelles or aggregates on the DNA chain. DNA acts as a separate phase contacting with the surfactant molecules and therefore CAC is independent of DNA concentration. Increasing DNA concentration postpones the appearance of free micelle in bulk phase, consequently increases the C(2). Finally an interaction mechanism between 12-3-12·2Br and DNA was proposed.     

Aggregation behavior and interaction of an amphiphilic drug imipramine hydrochloride with cationic surfactant cetyltrimethylammonium bromide: light scattering studies

The aggregation behavior and interaction of an amphiphilic antidepressant drug imipramine (IMP) hydrochloride with the cationic surfactant cetyltrimethylammonium bromide (CTAB) have been studied using light scattering (both static and dynamic) techniques. Due to rigid tricyclic hydrophobic moiety present in the molecule, the drug shows interesting association behavior. The static light scattering measurements show that the self-association of IMP commenced above a well-defined critical micellar concentration (CMC), which decreases with increasing the mole fraction of the CTAB surfactant. Both the excess Gibbs energy (ΔG(ex)) and the Gibbs energy of micellization (ΔG(M)°) are negative, and decrease with increasing mole fraction of the surfactant. The hydrodynamic diameters (d(h)) of the micellar aggregates were also evaluated using the dynamic light scattering measurements. The data indicate formation of larger aggregates by IMP and CTAB due to mixed micellization and subsequent micellar growth. The results have been analyzed using different models (viz., Clint, Motomura, Rosen, Rubingh, etc.) for mixed micelle formation.     

Electrophoretic properties of complexes between DNA and the cationic surfactant cetyltrimethylammonium bromide

We use agarose gel electrophoresis to characterize how the monovalent catioinic surfactant cetyltrimethylammonium bromide (CTAB) compacts double-stranded DNA, which is detected as a reduction in electrophoretic DNA velocity. The velocity reaches a plateau at a ratio R = 1.8 of CTAB to DNA-phosphate charges, i.e., above the neutralization point, and the complexes retain a net negative charge at least up to R = 200. Condensation experiments on a mixture of two DNA sizes show that the complexes formed contain only one condensed DNA molecule each. These CTAB-DNA globules were further characterized by time-resolved measurements of their velocity inside the gel, which showed that CTAB does not dissociate during the migration but possibly upon entry into the gel. Using the Ogston-model for electrophoresis of spherical particles, the measured in-gel velocity of the globule is quantitatively consistent with CTAB having two opposite effects, reduction of both the electrophoretic charge and DNA coil size. In the case of CTAB the two effects nearly cancel, which can explain why opposite velocity shifts (globule faster than uncomplexed DNA) have been observed with some catioinic condensation agents. Dissociation of the complexes by addition of anionic surfactants was also studied. The DNA release from the globule was complete at a mixing ratio between anionic and cationic surfactants equal to 1, in agreement with equilibrium studies. Circular DNA retained its supercoiling, and this demonstrates a lack of DNA nicking in the compaction-release cycle which is important in DNA transfection and purification applications.     

Biophysical and biochemical properties of a binary lipid mixture for DNA transfection

The phase and miscibility behavior of a triple-chain phosphatidylcholine (TPHPC) and a single-chain surfactant (CTAB) were investigated in aqueous dispersions and in monolayers at the air/water interface. CTAB can be incorporated in the TPHPC monolayer because of its complementary molecule shape and reduces the tilt angle of TPHPC. The type of phases and the phase sequence (L2 - LS) are the same in the pure TPHPC monolayer and in the TPHPC/CTAB (80:20 mol:mol) mixture. No indication of any ordering of adsorbed DNA was observed. In the aqueous dispersions, TPHPC exhibits an inverted hexagonal phase above the chain melting. The addition of 30 mol% CTAB leads to the appearance of a lamellar Lalpha phase. The binding of DNA to the mixture is obvious but this is accompanied by a separation of the two lipids what is supported by monolayer experiments. The system has no long-term stability. The main reason seems to be not only the stronger interaction of DNA with CTAB, but also especially the unexpected weak interaction between CTAB and TPHPC. The transfection efficiency is lower compared with lipofectamine. The main disadvantage of this system is the cytotoxicity of CTAB, which could not be lowered by incorporation of CTAB in the TPHPC bilayer.     

Adsorption of cationic surfactants on covered hanging mercury drop electrode surface of variable area

Cetyldimethylbenzylammonium chloride (CDBACl) or cetyltrimethylammonium bromide (CTAB) is preadsorbed on mercury and used as substrate. The adsorptive stripping voltammetry with the two-step procedure is used. The mercury droplet with the preadsorbed surfactant is expanded in aqueous solutions of KCl, KBr, CTAB, CDBACl, or cetylethyldimethylammonium bromide (CEDAB). The surface area was increased from 0.0022cm(2) up to 0.0571cm(2). The surfactant molecules are maintained close to each other and in the vicinity of the electrode by the applied electric field. The expanding of the droplets resulted in a reorientation of the adsorbed molecules depending on the surfactant surface concentration. In some cases, condensed films were observed. Differences were noticed in the adsorption and desorption potential region. A linear increase in the capacitance current with the surface area was found in all cases up to a maximum increase in the surface area. Partly disorganized films were also observed. In some cases, defects were noticed during expansion. In one case, fractal structure was observed.     

Temperature-dependent vesicle formation of aqueous solutions of mixed cationic and anionic surfactants

The phase behavior of aqueous solutions of mixed cetyltrimethylammonium bromide (CTAB) and sodium octyl sulfate (SOS) was examined at different temperatures (20, 30, 40, and 50 degrees C). While stable vesicles were formed in a narrow composition range on the SOS-rich side at 20 degrees C, the range widened remarkably when the temperature was raised to 30 degrees C. Thus, the vesicle region extended to cover almost the entire composition range, CTAB:SOS = 0.5:9.5-5.0:5.0, at the total surfactant concentrations of 50-70 mM on the SOS-rich side. To analyze the temperature dependence of this phase behavior of the mixed surfactant system, DSC and fluorescence polarization measurements were performed on the system. The experimental findings obtained revealed that pseudo-double-tailed CTAB/SOS complex, the major component of the bimolecular membrane formed by the surfactant mixture, undergoes a gel (Lbeta)-liquid crystal (Lalpha) phase transition at about 26 degrees C. This phenomenon was interpreted as showing that the bimolecular membrane has no curvature and is rigid and easy to precipitate at temperatures below the phase transition point, whereas it has a curvature and is loose enough to disperse in the solution as vesicles at temperatures above the phase transition point. Vesicles formed by the anionic/cationic surfactant complex were then stable at temperatures above the phase transition temperature of the complex.     

Phase behavior and thermodynamics of a mixture of cationic gemini and anionic surfactant

We present the phase behavior and thermodynamics of the catanionic mixture of the gemini surfactant hexanediyl-alpha,omega-bis(dodecyldimethylammonium bromide), designated here as 12-6-12Br(2), and sodium dodecyl sulfate (SDS) over the full range of composition, at the water-rich corner. Visual and turbidity measurements of the mixtures provide some basic macroscopic information on phase behavior. The structure of the aggregates formed spontaneously in the mixtures has been observed with TEM. As the molar fraction of SDS, X(SDS), is increased, at constant total surfactant concentration, the aggregation morphologies change gradually from gemini-rich micelles, through multiphase regions containing a precipitate (catanionic surfactant) and a vesicle region, to SDS-rich micelles. From isothermal titration calorimetry measurements, the phase boundaries and corresponding enthalpy changes for phase transitions have been obtained. The formation of the different microstructures, in particular, the spontaneously formed vesicles in the SDS-rich side, is discussed on the basis of geometric and electrostatic effects occurring in the SDS-gemini mixture.     

Interaction between biosurfactant surfactin and cationic surfactant cetyl trimethyl ammonium bromide in mixed micelle

An anionic/cationic mixed surfactant aqueous system of surfactin and cetyl trimethyl ammonium bromide (CTAB) at different molar ratios was studied by surface tension and fluorescence methods (pH 8.0). Various parameters that included critical micelle concentration (cmc), micellar composition (X ₁), and interaction parameter (β ^m) as well as thermodynamic properties of mixed micelles were determined. The β ^m was found to be negative and the mixed system was found to have much lower cmc than pure surfactant systems. There exits synergism between anionic surfactin and cationic CTAB surfactants. The degree of participation of surfactin in the formation of mixed micelle changes with mixing ratio of the two surfactants. The results of aggregation number, fluorescence anisotropy, and viscosity indicate that more packed and larger aggregates were formed from mixed surfactants than unmixed, and the mixed system may be able to form vesicle spontaneously at high molar fraction of surfactin.     

A Cryo-TEM Study of Protein-Surfactant Gels and Solutions

Oppositely charged globular protein and surfactant systems, such as lysozyme-sodium dodecyl sulfate (SDS) and ovalbumin-dodecyltrimethylammonium chloride (DOTAC) form precipitate, gel, and colorless solution in water over a wide concentration range. Bluish solutions are also recognized in connection with the redissolution of precipitate as well as prior to the gel formation. For the lysozyme-SDS system the bluish solution has been suggested to consist of finely dispersed gel particles in solution. The oppositely charged bovine serum albumin (BSA)-DOTAC-water system forms only a large, clear solution phase and a narrow, bluish solution region within a very limited surfactant concentration range. In the lysozyme-SDS system the formation of protein-surfactant aggregates and their growth and breakdown are studied in detail by cryogenic-transmission electron microscopy (cryo-TEM) method. In particular a series of samples with an increased surfactant concentration at fixed 4 wt% of lysozyme is studied. Imaging of the bluish solution at different protein concentrations exhibits large aggregates in the form of rod-like, sheet-like, and star-like objects which are attributed to the gel. At excess amounts of SDS, in the colorless solution, only small objects are detected. In the ovalbumin-DOTAC-water and BSA-DOTAC-water systems large aggregates are also observed in the bluish solutions. Colorless solutions for these two systems show the presence of small objects in the cryo-TEM micrographs. Ultrathin sections of the lysozyme and ovalbumin gels fixed with OsO(4) also show the presence of aggregated structures as judged from the transmission electron microscopy observations. Copyright 2000 Academic Press.     

Complexation of DNA with cationic gemini surfactant in aqueous solution

Interactions between DNA and the cationic gemini surfactant trimethylene-1,3-bis(dodecyldimethylammonium bromide) (12-3-12) in aqueous solution have been investigated by UV-vis transmittance, zeta potential, and fluorescence emission spectrum. Complexes of DNA and gemini surfactant are observed in which the negative charges of DNA are neutralized by cationic surfactants effectively. The DNA-induced micelle-like structure of the surfactant due to the electrostatic and hydrophobic interactions is determined by the fluorescence spectrum of pyrene. It is found that the critical aggregation concentration (CAC) for DNA/12-3-12 complexes depends little on the addition of sodium bromide (NaBr) because of the counterbalance salt effect. However, at high surfactant concentration, NaBr facilitates the formation of larger DNA/surfactant aggregates. Displacement of ethidium bromide (EB) by surfactant evidently illustrates the strong cooperative binding between surfactant and DNA. In contrast to that in the absence of surfactant, the added NaBr at high surfactant concentration influences not only the binding of surfactant with DNA, but also the stability of DNA/EB complex.     

OBSERVATION OF DNA PARTIAL DENATURATION BY ATOMIC FORCE MICROSCOPY

Atomic force microscopy was used to investigate the DNA-cetyltrimethylammonium bromide (CTAB) complexes adsorbed on highly ordered pyrolytic graphite (HOPG). These complexes, at low concentrations, can automatically spread out on the surface of HOPG. The DNA-CTAB complexes display a typically extended structure rather than a globular structure. Partially denaturated DNA produced by binding CTAB to DNA is directly observed by AFM with high resolution. The three-dimensional resolution of partially denaturated DNA obtained by AFM is not available by any other technique at present.     

Co-adsorption of carboxymethyl-cellulose and cationic surfactants at the air-water interface

We investigated the interaction between an anionic polyelectrolyte (carboxymethylcellulose) and cationic surfactants (DTAB, TTAB, and CTAB) at the air/water interface, using surface tension, ellipsometry, and Brewster angle microscopy techniques. At low surfactant concentration, a synergistic phenomenon is observed due to the co-adsorption of polyelectrolyte/surfactant complexes at the interface, which decreases the surface tension. When the surfactant critical aggregation concentration (cac) is reached, the adsorption saturates and the thickness of the adsorbed monolayer remains constant until another characteristic surfactant concentration, C0, is reached, at which all the polymer charges are bound to surfactant in bulk. Above C0, the absorbed monolayer becomes much thicker, suggesting adsorption of bulk aggregates, which have become more hydrophobic due to charge neutralization.     

Electrospinning of polymer-free nanofibers from cyclodextrin inclusion complexes

The electrospinning of polymer-free nanofibers from highly concentrated (160%, w/v) aqueous solutions of hydroxypropyl-β-cyclodextrin (HPβCD) and its inclusion complexes with triclosan (HPβCD/triclosan-IC) was achieved successfully. The dynamic light scattering (DLS) and rheology measurements indicated that the presence of considerable HPβCD aggregates and the high solution viscosity were the key factors in obtaining electrospun HPβCD and HPβCD/triclosan-IC nanofibers without the use of any polymeric carrier. The HPβCD and HPβCD/triclosan-IC solutions containing 20% (w/w) urea yielded no fibers but only beads and splashes because of the depression of the self-aggregation of the HPβCD. The inclusion complexation of triclosan with HPβCD was studied by isothermal titration calorimetry (ITC) and turbidity measurements. The characteristics of the HPβCD and HPβCD/triclosan-IC nanofibers were investigated by Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), X-ray diffraction (XRD), and differential scanning calorimetry (DSC). It was found that the electrospinning of HPβCD/triclosan-IC solution having a 1:1 molar ratio was optimal for obtaining nanofibers without any uncomplexed guest molecules.     

Phase behavior of polyion-surfactant ion complex salts: effects of surfactant chain length and polyion length

The aqueous phase behavior of a series of complex salts, containing cationic surfactants with polymeric counterions, has been investigated by visual inspection and small-angle X-ray scattering (SAXS). The salts were alkyltrimethylammonium polyacrylates, CxTAPAy, based on all combinations of five surfactant chain lengths (C6, C8, C10, C12, and C16) and two lengths of the polyacrylate chain (30 and 6 000 repeating units). At low water contents, all complex salts except C6TAPA6000 formed hexagonal and/or cubic Pm3n phases, with the hexagonal phase being favored by lower water contents. The aggregate dimensions in the liquid crystalline phases changed with the surfactant chain length. The determined micellar aggregation numbers of the cubic phases indicated that the micelles were only slightly aspherical. At high water contents, the C6TAPAy salts were miscible with water, whereas the other complex salts featured wide miscibility gaps with a concentrated phase in equilibrium with a (sometimes very) dilute aqueous solution. Thus, the attraction between oppositely charged surfactant aggregates and polyions decreases with decreasing surfactant chain length, and with decreasing polyion length, resulting in an increased miscibility with water. The complex salt with the longest surfactant chains and polyions gave the widest miscibility gap, with a concentrated hexagonal phase in equilibrium with almost pure water. A decrease in the attraction led to cubic-micellar and micellar-micellar coexistence in the miscibility gap and to an increasing concentration of the complex salt in the dilute phase. For each polyion length, the mixtures for the various surfactant chain lengths were found to conform to a global phase diagram, where the surfactant chain length played the role of an interaction parameter.     

DNA‐Surfactant Interactions. Compaction,Condensation, Decompaction and Phase Separation

Recent investigations of the interaction between DNA and alkyltrimethylammonium bromides of various chain lengths are reviewed. Several techniques have been used such as phase map determinations, fluorescence microscopy, and electron microscopy. Dissociation of the DNA‐surfactant complexes, by the addition of anionic surfactant, has received special attention. Precipitation maps for DNA‐cationic surfactant systems were evaluated by turbidimetry for different salt concentrations, temperatures and surfactant chain lengths. Single‐stranded DNA molecules precipitate at lower surfactant concentrations than double‐helix ones. It was also observed that these systems precipitate for very low concentrations of both DNA and surfactant, and that the extension of the two‐phase region increases for longer chain surfactants; these observations correlate well with fluorescence microscopy results, monitoring the system at a single molecule level. Dissociation of the DNA‐cationic surfactant complexes and a concomitant release of DNA was achieved by addition of anionic surfactants. The unfolding of DNA molecules, previously compacted with cationic surfactant, was shown to be strongly dependent on the anionic surfactant chain length; lower amounts of a longer chain surfactant were needed to release DNA into solution. On the other hand, no dependence on the hydrophobicity of the compacting agent was observed. The structures of the aggregates formed by the two surfactants, after the interaction with DNA, were imaged by cryogenic transmission electron microscopy. It is possible to predict the structure of the aggregates formed by the surfactants, like vesicles, from the phase behaviour of the mixed surfactant systems. The compaction of a medium size polyanion with shorter polycations was furthermore studied by means of Monte Carlo simulations. The polyanion chain suffers a sudden collapse as a function of the condensing agent concentration and of the number of charges on the molecules. Further increase of the concentration gives an increase of the degree of compaction. The compaction was found to be associated with the polycations promoting bridging between different sites of the polyanion. When the total charge of the polycations was lower than that of the polyanion, a significant translational motion of the compacting agent along the polyanion was observed, producing only a small‐degree of intrachain segregation. However, complete charge neutralization was not a prerequisite to achieve compacted forms.     

Aggregate formation in aqueous solutions of carboxymethylcellulose and cationic surfactants

The addition of cationic surfactants to an aqueous solution of an anionic polymer, carboxymethylcellulose (carboxyMC), causes the spontaneous formation of aggregates in a certain range of concentrations. Here we studied two surfactants, dodecyl and hexadecyl trimethylammonium bromide (DTAB and CTAB, respectively). Using different techniques (light scattering, potentiometry, viscosimetry, and zetametry), we found that a simple lengthening of the surfactant tail length by four CH2 groups drastically changes the aggregate morphology, size, and charge. We explored in detail how the surfactant and polymer concentrations act on these systems.     

Cyclodextrin-surfactant coassembly depends on the cyclodextrin ability to crystallize

Full equilibrium phase diagrams are presented for two ternary systems composed of the cationic surfactant dodecyltrimethylammonium bromide (DTAB), water (D(2)O), and a cyclodextrin, either β-cyclodextrin (β-CD) or (2-hydroypropyl)-β-cyclodextrin (2HPβCD). (2)H NMR, SAXS, WAXS, and visual examination were used to determine the phase boundaries and characterize the nature of the phases formed. Additionally, diffusion (1)H NMR was used to investigate parts of the diagrams. The water solubility of 2HPβCD is 80% (w/w), whereas it is only 1.85% (w/w) for β-CD. Solubility increases for both species upon complexation with DTAB; while the increase is minute for 2HPβCD, it is dramatic for β-CD. Both systems displayed an isotropic liquid solution (L(1)) one-phase region, the extension of which differs extensively between the two systems. Additionally, the DTAB:2HPβCD:water system also comprised a normal hexagonal (H(1)) area, which was not found for the DTAB:β-CD:water system. In the DTAB:β-CD:water system, on the other hand, we found cocrystallization of DTAB and β-CD. From this work we conclude that DTAB and CD molecules form 1:1 inclusion complexes with high affinities. Moreover, we observed indications of an association of 2HPβCD to DTAB micelles in the isotropic solution phase, which was not the case for β-CD and DTAB micelles. This is, to our knowledge, the first complete phase diagrams of surfactant-CD mixtures; as a novel feature it includes the observation of cocrystallization at high concentrations.     

Compaction and decompaction of DNA induced by the cationic surfactant CTAB

A multifaceted study on the interaction of the cationic surfactant CTAB with calf thymus DNA was carried out by using different techniques. The measurements were done at different molar ratios X = [CTAB]/[DNA]. Results show the conformational change that DNA suffers due to the interaction with surfactant molecules at low molar ratios: the condensation of the polynucleotide, from an extended coil state to a globular state. The effect observed at the higher molar ratios is worth noting: the decondensation of DNA, that is, the transition from a compact state to a more extended conformation. Experimental data obtained confirm that this latter state is not exactly the same as that found in the absence of the surfactant. Attractive interactions between different parts of the molecule by ion correlation effects are the driving force to produce both the compaction and decompaction events. Results also show the importance of choosing both a proper system for the study and the most seeming measuring technique to use. The study demonstrates that, in some cases, the use of several techniques is desirable in obtaining reliable and accurate results.     

Disassembly of amyloid fibrils by premicellar and micellar aggregates of a tetrameric cationic surfactant in aqueous solution

We report a finding that not only the micelles but also the premicellar aggregates of a star-like tetrameric quaternary ammonium surfactant PATC can disassemble and clear mature β-amyloid Aβ(1-40) fibrils in aqueous solution. Different from other surfactants, PATC self-assembles into network-like aggregates below its critical micelle concentration (CMC). The strong self-assembly ability of PATC even below its CMC enables PATC to disaggregate the Aβ(1-40) fibrils far below the charge neutralization point of the Aβ(1-40) with PATC. There may be two key features of the fibril disassembly induced by the surfactant. First, the positively charged surfactant molecules bind with the negatively charged Aβ(1-40) fibrils through electrostatic interaction. Second, the self-assembly of the surfactant molecules bound onto the Aβ(1-40) fibrils disaggregate the fibrils, and the surfactant molecules form mixed aggregates with the Aβ(1-40) molecules. The result reveals a structural approach of constructing efficient disassembly agents to mature β-amyloid fibrils.