Dodecyl Ether Research Articles

Molecular simulation on solubilization of fullerene C60 by C12E6 nonionic surfactants

ABSTRACT Coarse grained simulations were adopted to describe the encapsulation and dispersion of fullerene C 60 by hexaoxyethylene dodecyl ether (C 12 E 6 ) surfactants. The self-organised structures of C 12 E 6 molecules in water were captured and the characteristics of micelles composed of different number of C 12 E 6 molecules were analysed. We found that C 60 molecules alone or in clusters can spontaneously translate into the hydrophobic core of micelles. One monomeric C 60 can explore the hydrocarbon-chain region of the micelles with different sizes, and two different preferential locations of C 60 are observed. The small C 60 clusters can disaggregate after entering the micelle. Larger C 60 clusters can penetrate into the micelle as solid-like nanoparticles, although they are partially disaggregated. When investigating the self-assembly of C 12 E 6 surfactants and C 60 molecules, we found that it is very difficult to disperse C 60 in the micelle monomolecularly. At high molar ratio of C 12 E 6 /C 60 , colloidal nanoC 60 aggregates form with C 12 E 6 surfactants adsorbed on the surface. Our simulations provide an explanation for the different observations in fullerene solubilization in micellar solutions and give a guideline for further solubilization of pristine fullerene or small hydrophobic molecules with surfacant micelles, which is helpful for the design of new micelle-based delivery vehicles.

Self-assembly of mixed surfactants sodium dodecylsulfate and polyethylene glycol dodecyl ether in aqueous solutions

The thermodynamic behavior of mixed systems containing the anionic surfactant sodium dodecyl sulfate (SDS) and the nonionic surfactant polyethylene glycol dodecyl ether (Brij L4) in aqueous solutions was investigated. Electrical conductivity and interfacial tension measurements were employed to investigate the concentration-dependent properties of these surfactant mixtures. Two main experiments were conducted: i) constant ratio experiment: the overall surfactant concentration was varied while maintaining a fixed ratio between SDS and Brij L4. It was shown that the critical micelle concentration (CMC) determined from electrical conductivity measurements does not indicate the formation of the first mixed micelles as observed using tensiometry, but the point from which the adsorption of counterions by the existing micelles became important. By using the Regular Solution Theory (RST), it was found that the interaction between SDS and Brij L4 is synergistic, driven by dipole-ion interactions of the hydrophilic regions of the two surfactants. ii) Fixed SDS concentration while increase the Brij L4 concentration: the resulting electrical conductivity exhibited non-trivial behavior which complexity arose from simultaneous phenomena of incorporation of free SDS molecules into the micelles as Brij L4 concentration increased, leading to a decrease in electrical conductivity; liberation of some adsorbed counterions from the mixed micelles to the solution, which increases the conductivity and increase of viscosity due to Brij L4 further addition that leads to a sequential decrease in electrical conductivity.

Molecular insight into the effect of the number of introduced ethoxy groups on the calcium resistance of anionic-nonionic surfactants at the oil/water interface

The salinity seriously affects the recovery efficiency of surfactant flooding, and it is demonstrated the introduced ethoxy (EO) groups can enhance the interfacial activity of surfactants at harsh salinity via various experimental methods. In this study, sodium dodecyl sulfate (SDS) and sodium dodecyl ether sulfate (AES) are selected to investigate the effects of EO group number on the salt resistance of surfactants at the air/water interface by experiments and molecular dynamics (MD) simulation method. Optical microscopy and static multiple light scattering results show that the AES stabilized emulsions with Ca2+ ions have better stability than those of SDS, which is further explored by molecular MD simulation method. The interface formation energy (IFE) and self-diffusion coefficients (Dα) are calculated to systematically study the effects of introduced EO group number on calcium resistance of surfactants. The interaction between surfactants and Ca2+ ions at the oil/water interface is evaluated by the potential of mean of force (PMF) and the radial direction functions (RDF), which is confirmed by the calculation of molecular electrostatic potential (MEP) and coordination number. The simulation results indicate that the introduced EO groups can combine Ca2+ ions to fabricate salt bridge via intermolecular or intramolecular interactions to highly improve the calcium resistance of surfactants. The present work proposes a microcosmic perspective of the roles of EO group number on the calcium resistance of AES at the oil/water interface.

Well-dispersed graphene toward robust lubrication via reorganization of sliding interface

Excellent lubrication performance of graphene lubricant is mostly attributed to the dispersion of graphene and forming of tribo-film. Herein, diethylene glycol dodecyl ether (E2C12) functionalized graphene oxide (E2C12-GO) was successfully prepared by simple esterification. The physicochemical properties of as-prepared samples were characterized by a series of characterization methods. E2C12-GO with flat edge and high-level spacing possesses high dispersion stability in PAO 20 base oil. Compared with base oil, 0.08 wt% E2C12-GO could achieve the reduction of average friction coefficient and wear rate by 30 % and 57 % at 150 N, respectively. Even with each long-term friction, E2C12-GO could still maintain the state of robust low friction coefficient. Meanwhile, the addition of E2C12-GO can significantly improve the load-bearing capacity (PB value and PD value) of base oil. The excellent tribological properties of E2C12-GO were attributed to high dispersion and high layer spacing, as well as the reorganization of sliding interface. Prospectively, the E2C12-GO shows promising potential as a multi-functional oil-based lubricating additive in industrial applications.

Polyethylene Glycol Dodecyl Ether as Interfacial Modifier for Improving Efficiency of Perovskite Solar Cells

The rapid development of the perovskite solar cell (PSC) makes its best research efficiency comparable with that of silicon solar cells. However, the large‐scale application of PSCs still faces the dual challenges of improving efficiency and stability. Herein, an interfacial modifier of polyethylene glycol dodecyl ether (Brij) with ether group (C–O–C) and long alkyl chain is introduced into the interface of the perovskite layer and hole transport layer. It is demonstrated that the interaction of the ether group on Brij with uncoordinated lead ions on the perovskite passivates the point defects and reduces carrier recombination. The introduction of Brij tunes the energy gradient among electron transport layer/perovskite layer/hole transport layer and promotes the carrier extraction and transportation. The long alkyl chain of Brij covers the surface of perovskite and effectively improves the moisture resistance of perovskite films and the environmental stability of devices. Under an optimal Brij concentration, the modified perovskite solar cell achieves the best power conversion efficiency of 22.57%, along with improved environmental stability, while the pristine device obtains an efficiency of 20.66%.

Adsorption process and mechanisms of AEO-3/dodecane mixed collector on low-rank coal surface driven by water flow: A non-equilibrium molecular dynamics simulation study

During coal slime flotation, the collector is adsorbed to the coal in the form of fine oil droplets in the turbulent slurry. And understanding the adsorption behavior of collector oil droplets on the coal surface is important for the development of efficient collector. In this study, the adsorption process and mechanism of triethylene glycol dodecyl ether (AEO-311triethylene glycol dodecyl ether.)/dodecane mixed collector oil droplet (MCOD22mixed collector oil droplet.) on the surface of low-rank coal driven by water flow were investigated by non-equilibrium molecular dynamics simulations. The changes of the mass center velocity of MCOD, contact area and interaction energy between MCOD and coal during the simulation were analyzed, and the adsorption process was divided into the adhesion stage, spreading stage and equilibrium stage. The kinetic reason for the adsorption of AEO-3 molecules at the interface was found. The pushing of oil droplet by the water flow caused the AEO-3 molecules to be slowly pressed into the contact interface between the oil droplet and coal, and the adsorption occurred. The presence of polar oxygen-containing functional groups on the AEO-3 molecule makes it much more strongly adsorbed on low-rank coal than dodecane. Water molecules play an important role in the adsorption process of AEO-3 with coal, and the bridging action of water molecules that enables indirect adsorption of collector with coal was proposed. The water molecule connects AEO-3 and coal molecules, which cannot form hydrogen bond due to the distance, through hydrogen bonding, and inserts between alcohol oxygen, ether oxygen and carbonyl oxygen, which are originally mutually exclusive, so that the three of them (OAEO-3, H2O and Ocoal) are connected together through hydrogen bonding (OAEO-3…H-O-H…Ocoal), and the stability of AEO-3 adsorption on coal surface is greatly enhanced. The presence of strong indirect electrostatic interactions between polar collector and coal generated by the bridging action of water molecules proves that it is the strong electrostatic interactions that are the reason for the strong flotation performance of polar collector on low-rank/oxidized coals.

Influence of intraparticle cross-linking on polymer diffusion in latex films prepared from secondary dispersions

In this work, we synthesized surfactant-free latex dispersions of nanoparticles (NPs) based upon emulsification of a preformed proprietary BASF polymer (MnGPC = 5000 g/mol, Ð = 3, denoted as Pol), in which the —COOH groups were partially neutralized by ammonia. To obtain useful coatings with polymers of such low molecular weight (MW), we approached this problem through the reaction of carboxylated polymer dispersions with neopentyl glycol diglycidyl ether (NGDE, 20 to 60 mol% based on carboxyl groups) to increase the MW and to introduce gel content. We employed AFM to monitor the influence of cross-link density on the surface roughness and found the presence of cross-links increases the resistance of particles to deformation. Fluorescence resonance energy transfer (FRET) measurements were carried out to determine the extent of polymer mixing upon film formation. Our most important finding is that the gel content substantially limited the extent of molecular mixing at long annealing times or in corresponding solvent-cast films. In parallel, we carried out a series of similar reactions on the secondary dispersion particles with a monoepoxide, consisting of a mixture of dodecyl and tetradecyl glycidyl ether. This reaction maintained the size and size distribution of the latex particles. These polymers had no gel content, but the reaction with the epoxide lowered the Tg of the polymer. FRET studies showed a pronounced influence of Tg on the rates of polymer diffusion in these films.

Ferrihydrite nanoparticles entrapped in shear-induced multilamellar vesicles

HypothesisFerrihydrite (Fh) nanoparticles are receiving considerable scientific interest due to their large reactive surface areas, crystalline structures, and nanoparticle morphology. They are of great importance in biogeochemical processes and have the ability to sequester hazardous and toxic substances. Here, the working hypothesis was to entrap fractal-like Fh nanoparticles, with a radius of gyration of 6.2 nm and a primary building block of polydisperse spheres with a radius of 0.8 nm, in a shear-induced multilamellar vesicle (MLV) state using a 40 wt% polyethylene glycol dodecyl ether surfactant. ExperimentsSmall- and Wide- Angle X-ray scattering revealed the equilibrium state of the non-ionic planar lamellar phase, the Fh dispersion, and their mixture. The MLV state was induced by using a shear flow in a Taylor-Couette geometry of a rheometer. FindingsThe nonionic surfactant initially exhibited a lamellar gel phase with two distinct d-spacings of 11.0 and 9.7 nm, which collapsed into the MLV state under shear flow. The Fh nanoparticles induced bilayer attraction by suppressing lamellar layer undulations, decreasing the d-spacing. These results are helpful in the understanding of the relationship between nanoparticle size and nanoparticle-bilayers interactions and provides insight on Fh encapsulations in a kinetically stable MLVs state.

Adsorption and Aggregation Behavior of Mixtures of Quaternary-Ammonium-Salt-Type Amphiphilic Compounds with Fluorinated Counterions and Surfactants.

The surface adsorption and aggregation behavior of a mixture of quaternary-ammonium-salt-type amphiphilic monomeric compounds (C4 FSA, C8 FSA, and C4 NTf2) or gemini compounds (C10-2-C4 FSA) and various surfactants (nonionic hexaoxyethylene dodecyl ether (C12EO6), anionic sodium dodecyl sulfate (SDS), cationic dodecyltrimethylammonium bromide (C12TAB), and zwitterionic N-dodecyl-N,N-dimethyl-3-ammonio-1-propanesulfonate (C12Sb)) was investigated. Both types of compounds contained alkyl chains of nonidentical lengths that used bis(fluorosulfonyl)imide (FSA-) or bis(trifluoromethanesulfonyl)imide (NTf2-) as counterions. The mixtures were analyzed for surface tension, viscosity, electrical conductivity, and pyrene fluorescence, in addition to evaluation by cryogenic transmission electron microscopy, small-angle X-ray scattering, and dynamic light scattering. Our results showed that the surface tension depended on the surfactant structure. For the mixture of C8 FSA and SDS, as the SDS concentration increased, the surface tension first decreased and became constant at the critical micelle concentration (CMC). In this concentration range, C8 FSA and SDS were approximately equimolar (2.5 mmol dm-3), the mixture adsorbed efficiently at the air-water interface, and vesicles and linear-type micelles were formed in the solution owing to the decreased electrostatic repulsion between the hydrophilic groups. As the SDS concentration further increased, the surface tension increased and reached another constant value. The C8 FSA at the interface was replaced by SDS and the aggregates transformed into spherical micelles. The surface tension plot of the mixture of the amphiphilic compounds and C12Sb showed a minimum at the CMC. The lowest CMC and surface tension were observed for C10-2-C4 FSA, indicating that the gemini compounds offer excellent adsorption and orientation at the air-water interface. It was revealed that the quaternary-ammonium-salt-type amphiphilic compounds in this study acted as ionic liquids on their own and as surfactants in aqueous solution. Further, they could improve the surface activity of conventional ionic surfactants.

Nanostructured fluids for polymeric coatings removal: Surfactants affect the polymer glass transition temperature

HypothesisNanostructured fluids (NSFs) based on water, organic solvents and surfactants are a valid alternative to the use of neat unconfined organic solvents for polymer coatings removal in art conservation. The physico-chemical processes underpinning their cleaning effectiveness in terms of swelling/dewetting of polymer films were identified as key in this context. The role of surfactants on polymers’ dewetting was considered to be mainly restricted to the lowering of interfacial tensions. However, recent experiments evidenced that surfactants have an important role in swelling polymer films. ExperimentsFive different amphiphiles were selected, namely: sodium dodecylsulfate, dimethyldodecyl amine oxide, hexaoxyethylene decyl ether (C9-11E6), pentadecaoxyethylene dodecyl ether (C12E15), and methyoxypentadecaoxyethylene dodecanoate (C11COE15CH3). They were combined with a carefully selected organic solvents’ mixture (1-butanol/butanone/dimethyl carbonate) to formulate new NSFs, differing for the surfactant only, and used to perform cleaning tests on surfaces coated with Paraloid B72® and Primal AC33®. Here for the first time, polymer swelling induced by surfactants was quantified and correlated with the glass transition temperature of the two polymers by differential scanning calorimetry, before and after the exposure to the fluids. Confocal laser scanning microscopy and small-angle X-ray scattering provided additional insights on the interaction mechanism. FindingsNonionics were proven more efficient than zwitterionic/ionic amphiphiles in the polymer swelling, and, overall, methyoxy pentadecaoxyethylene dodecanoate resulted the most effective among the selected surfactants. A direct relation between the effect of surfactants on the polymers’ glass transition temperature and cleaning capacity was established. This finding, fundamental to understand the interaction mechanism between NSFs and polymer coatings or paint layers, is key to achieve a selective, effective and complete removal of polymer coatings, as recently shown in the removal of vandalism and over-paintings from street art.

Selective elimination of tumorigenic hepatic stem cells using hybrid liposomes

To avoid the risk of tumorigenesis after cell transplantation, tumorigenic stem cells should be selectively eliminated from induced pluripotent cells, embryonic stem cells, and somatic stem cells. We previously reported the presence of tumorigenic stem cells in human fetal hepatocyte-induced hepatoblasts after sodium butyrate (SB) treatment. In this study, we aimed to investigate the selective elimination of tumorigenic stem cells in human hepatoblasts using hybrid liposomes (HLs) prepared by sonicating a mixture of 90mol% l-α-dimyristoylphosphatidylcholine and 10mol% polyoxyethylene (n) dodecyl ether (C12 (EO)n, n= 23) in a buffer solution. Flow cytometric analysis revealed that the number of hepatoblasts increased by around 12-18 times in SB-treated cells compared to non-treated cells. In the colony formation assay, colonies of tumorigenic stem cells were observed in a soft agar plate after SB treatment. HL treatment for 48h resulted in a remarkable decrease in the number of colonies. HLs also induced apoptosis of tumorigenic stem cells by activating caspase-3. Flow cytometry showed a significant accumulation of HLs, including fluorescent lipids, in tumorigenic hepatic stem cells. The reappearance of tumorigenic stem cells was suppressed even in subsequent subcultures of HL-treated cells. High CYP3A4 activity was observed in a three-dimensional invitro assay. These results suggest that HL treatment could specifically eliminate tumorigenic hepatic stem cells. Incubation with HLs can be an effective culture method to maintain the quality of stem cells and reduce the risk of tumorigenesis after cell transplantation.

A case study on the partitioning of pharmaceutical compound naproxen in edible oil-water system in the presence of ionic and non-ionic surfactants

The partitioning coefficient is a physicochemical quantity which gives important information about the distribution and efficiency of bioactive compounds in various biological systems. The present work aims at detailed investigation of the partition process of drug naproxen between edible oils (olive, sunflower, sesame) and water in the presence of two differently charged surfactants consisting of SDS (sodium dodecylsulfate), DTAB (n-dodecyltrimethylammonium bromide) and non-ionic surfactant Brij 35 (polyethylene glycol dodecyl ether). The evaluation was done at atmospheric pressure and 25.0 °C by using UV–Vis spectrometric and shake-flask techniques. In this work, all the surfactants are used in a concentration below their CMC due to the turbidity that occurs in the biphasic oil-water systems in the concentrations above their CMC. The experimental results obtained indicate that the oil-water partition coefficient (Koil/w) of naproxen reduce with rising the surfactants concentration in medium irrespective of the oil employed. Moreover, these values in the surfactant media are lower in comparison with surfactant free medium. The values of standard Gibbs free energy of the transfer (ΔGw→oil∘) calculated for all binary oil-water systems have negative sign which indicates the preference of this drug for oil phase and thus spontaneous partitioning process. The surfactant effect on the partition coefficients of drug is analyzed in terms of the intermolecular interactions such as hydrogen bonding, dispersion and electrostatic forces between the drug and the surfactant.

A Green Approach of Leaching Trace Metals From Petroleum Source Rock

The extraction of trace metals (manganese, nickel, vanadium and molybdenum) from petroleum source rock using nonionic surfactant solutions with the assistance of oven heat was investigated. The results revealed that time, temperature and pH have significant influence on the extraction yields of the trace metals. The effect of sample/solvent ratio was significant for extraction of some trace metals. The optimum extraction temperature using both polyoxyethylene(23)dodecyl ether (Brij 35) and polyoxyethylene(10)dodecyl ether C12E10) solutions as extracting solvents was 150°C except nickel that had highest yield at 90°C when C12E10 solution was used. For both Brij 35 and C12E10, most of the trace metals had highest yields at 3 hr. The yields of the trace metals were more significant in acidic medium. The yields of the trace metals were significantly higher using Brij 35 than C12E10. Validation of the new oven-assisted nonionic surfactant extraction (OANSE) method using SGR-1b standard reference material revealed excellent recoveries for the trace metals except vanadium that had an average recovery, which indicates that the new method is very efficient for leaching of manganese (Mn), nickel (Ni) and molybdenum (Mo) from petroleum source rock while the recovery of vanadium can be improved in acidic medium. This study revealed that OANSE is efficient and readily available green analytical protocol for the determination of trace metals in source rock.

Novel Therapy with Hybrid Liposomes for Orthotopic Graft Mouse Models of Glioblastoma

Hybrid Liposomes (HL25) composed of 90 mol% L-a-Dimyristoylphosphatidylcholine (DMPC) and 10 mol% polyoxyethylene(25) dodecyl ethers (C12(EO)25) were found to fuse and accumulate in the cell membranes of human brain tumor, glioblastoma, (U-87MG) cells and inhibit their growth. HL25 induced apoptosis in U-87MG cells via the release of AIF under a caspase-independent pathway. HL25 inhibited tumor enlargement in orthotopic graft mouse models of glioblastoma after crossing the blood-brain barrier.

Study on the mechanism of polyethylene oxide groups improving the foamability of anionic surfactants in hard water

Improving the foamability of anionic surfactants in hard water is essential to reduce the adding concentration and economic cost of foaming agents for dust control. In this work, sodium dodecyl sulfate (SDS) and sodium dodecyl ether sulfate (SDES) were selected to explore the mechanism of polyethylene oxide (EO) groups improving the foamability of anionic surfactants in hard water by experiments and molecular dynamics simulations. The experimental results show that SDES containing EO groups has better foaming performance in hard water compared with SDS. The simulation results indicate that the presence of EO groups can inhibit the combination of SO4− groups and Ca2+ ions at the air/water interface, which makes part of Ca2+ ions migrate from the interface layer to the bulk water. In addition, EO groups attract some Ca2+ ions to distribute around them, thereby further reducing the number of Ca2+ ions combined with SO4− groups, which helps to improve the surface activity and foamability of anionic surfactants in hard water. An increase in the number of EO groups can enlarge the interfacial thickness and the number of hydrogen bonds between surfactants and water molecules, enhancing the strength of bubble film. Moreover, the farther the EO group is from the SO4− group, the smaller the contribution to the hydration of anionic surfactants.

Aqueous phase behavior of the PEO-containing non-ionic surfactant C12E6: A molecular dynamics simulation study

HypothesisNon-ionic surfactants containing polyethylene oxide (PEO) chains are widely used in drug formulations, cosmetics, paints, textiles and detergents. High quality molecular dynamics models for PEO surfactants can give us detailed, atomic-scale information about the behavior of surfactant/water mixtures. SimulationsWe used two molecular dynamics force fields (FFs), 2016H66 and 53A6DBW, to model the simple non-ionic PEO surfactant, hexaoxyethylene dodecyl ether (C12E6). We investigated surfactant/water mixtures that span the phase diagram of starting from randomly distributed arrangements. In some cases, we also started with prebuilt, approximate models. The simulations results were compared with the experimentally observed phase behavior. FindingsOverall, this study shows that the spontaneous self-assembly of PEO non-ionic surfactants into different colloidal structures can be accurately modeled with MD simulations using the 2016H66 FF although transitions to well-formed hexagonal phase are slow. Of the two FFs investigated, the 2016H66 FF better reproduces the experimental phase behavior across all regions of the C12E6/water phase diagram.

Use of Relative Molar Sensitivity as a Specific Value for Evaluating Heptaoxyethylene Dodecyl Ether Concentrations in Methanol Solution

Relative molar sensitivity (RMS) determined using quantitative 1H NMR and HPLC with a refractive index (RI) detector was applied as a specific value for quantifying the levels of heptaoxyethylene dodecyl ether (HOEDE), a typical non-ionic surfactant, in methanol solutions. RMS was robust against changes of the analytical conditions (i.e., RI cell temperature, acetonitrile content in the mobile phase, HPLC system). Furthermore, the obtained HOEDE concentrations using a previously evaluated RMS were comparable to those obtained using a reference method for over 1 year.

Distortion of surfactant lamellar phases induced by surface roughness

Self-assembly is a characteristic property of soft matter. Understanding the factors which assist or perturb this process is of great importance in many biological and industrial processes. Amphiphiles self-assemble and order into a variety of structures including well-ordered lamellar phases. The present work uses neutron reflectometry and neutron scattering to explore the effects of both interface roughness and temperature on the lamellar-phase structure of a non-ionic surfactant at a solid/liquid interface. The structure of concentrated solutions of tetraethyleneglycol dodecyl ether has been compared against a smooth surface and one with a roughness of the order of the lamellar spacing. This has been done in order to investigate the role perturbations have on the overall lamellar order, when these have length scales of the order of the interactions between neighboring lamellae. The results showed that the surfactant forms a well-ordered and aligned structure at a smooth surface, extending to a depth of several micrometers from the interface. Increasing the temperature of the sample and subsequent cooling promotes alignment and increases the number of oriented layers at the surface. The same sample forms a significantly less aligned structure against a rough surface that does not align to the same extent, even after heating. The perturbation of the structure caused by thermal fluctuations was found to be much less than that imposed by a small surface roughness.

Production of long alkyl ethers in homogeneous systems: A study of glyceryl monododecyl ethers

In this study, the etherification of glycerol was executed with dodecanol through use of homogeneous catalysts. First, a univariate study of direct condensation was executed to determine the effects of the variables reaction time, catalyst type and glycerol:dodecanol molar ratio on the dodecyl ether (DOE) and glyceryl monododecyl ether (GMDE) production. A full 23 factorial design was used to evaluate the effect of glycerol:dodecanol molar ratio, catalyst loading and temperature on the production of dodecyl ether (DOE), glyceryl monododecyl ether (GMDE) substituted on carbon 1 (C1) or carbon 2 (C2). The GMDE yield was 35% in 3 h. The experimental results indicated that rising temperature positively affected GMDE content and higher catalyst loading increased DOE production. In the case of traditional routes, Williamson synthesis produced just 5% GMDE while when applying solketal synthesis, high yield and purity of this compound were obtained, demonstrating the viability of GMDE production.

Lipid Scrambling Induced by Membrane-Active Substances

The functional roles of the lipid asymmetry of biomembranes are attracting increasing attention. This study characterizes the activity of surfactants to induce transmembrane flip-flop of lipids and thus “scramble” this asymmetry. Detergent-induced lipid scrambling of liposomes mimicking the charge asymmetry of bacterial membranes with 20 mol % of 1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-rac-glycerol in the outer leaflet only was quantified by ζ-potential measurements for octaethylene glycol dodecyl ether (C12EO8), octyl glucoside (OG), and dodecyl maltoside. Membrane leakage was separately measured by the fluorescence lifetime-based calcein leakage assay and the onset of the membrane-to-micelle transition by isothermal titration calorimetry. Partition coefficients and partial molar areas were obtained as well. For the quickly membrane-permeant C12EO8 and OG, leakage proceeds at a rather sharp threshold content in the membrane, which is well below the onset of solubilization and little dependent on incubation time; it is accompanied by fast lipid scrambling. However, unlike leakage, flip-flop is a relaxation process that speeds up gradually from taking weeks in the detergent-free membrane to minutes or less in the leaking membrane. Hence, after 24 h of incubation, 10 mol % of C12EO8 or 50 mol % of OG in the membrane suffice for virtually complete lipid scrambling, whereas leakage remains below 10% for up to 14 mol % of C12EO8 and 88 mol % of OG. There is thus a concentration window in which lipid scrambling proceeds without leakage. This implies that lipid scrambling must be considered a possible mode of action of antimicrobial peptides and other membrane-active drugs or biomolecules. A related, detergent-based protocol for scrambling the lipid asymmetry of liposomes and maybe cells without compromising their overall integrity would be a very valuable tool to study functions of lipid asymmetry.