Understanding interactions of plasticisers with a phospholipid monolayer.

The use of DEHP (diethylhexyl phthalate) is now banned for most applications in Europe; the exception is for blood bags, where its toxicity is overshadowed by its ability to extend the storage life of red blood cells. Another plasticiser, BTHC (butanoyl trihexyl citrate), is used in paediatric blood bags but does not stabilise blood cells as effectively. Interactions between plasticisers and lipids are investigated with a phospholipid, DMPC, to understand the increased stability of blood cells in the presence of DEHP as well as bioaccumulation and identify differences with BTHC. Mixed monolayers of DMPC and DEHP or BTHC were studied on Langmuir troughs where surface pressure/area isotherms can be measured. Neutron reflection measurements were made to determine the composition and structure of these mixed layers. A large amount of plasticiser can be incorporated into a DMPC monolayer but once an upper limit is reached, plasticiser is selectively removed from the interface at high surface pressures. The upper limit is found to occur between 40-60 mol% for DEHP and 20-40 mol% for BTHC. The areas per molecule are also different with DEHP being in the range of 50-100 Å2 and BTHC being 65-120 Å2. Results indicate that BTHC does not fit as well as DEHP in DMPC monolayers which could help explain the differences observed with regards to the stability of blood cells.

Competitive Adsorption of a Monoclonal Antibody and Nonionic Surfactant at the PDMS/Water Interface.

Interfacial adsorption of monoclonal antibodies (mAbs) can cause structural deformation and induce undesired aggregation and precipitation. Nonionic surfactants are often added to reduce interfacial adsorption of mAbs which may occur during manufacturing, storage, and/or administration. As mAbs are commonly manufactured into ready-to-use syringes coated with silicone oil to improve lubrication, it is important to understand how an mAb, nonionic surfactant, and silicone oil interact at the oil/water interface. In this work, we have coated a polydimethylsiloxane (PDMS) nanofilm onto an optically flat silicon substrate to facilitate the measurements of adsorption of a model mAb, COE-3, and a commercial nonionic surfactant, polysorbate 80 (PS-80), at the siliconized PDMS/water interface using spectroscopic ellipsometry and neutron reflection. Compared to the uncoated SiO2 surface (mimicking glass), COE-3 adsorption to the PDMS surface was substantially reduced, and the adsorbed layer was characterized by the dense but thin inner layer of 16 Å and an outer diffuse layer of 20 Å, indicating structural deformation. When PS-80 was exposed to the pre-adsorbed COE-3 surface, it removed 60 wt % of COE-3 and formed a co-adsorbed layer with a similar total thickness of 36 Å. When PS-80 was injected first or as a mixture with COE-3, it completely prevented COE-3 adsorption. These findings reveal the hydrophobic nature of the PDMS surface and confirm the inhibitory role of the nonionic surfactant in preventing COE-3 adsorption at the PDMS/water interface.

Surfactant induced gelation of TEMPO-oxidized cellulose nanofibril dispersions probed using small angle neutron scattering.

In this work, we studied TEMPO-oxidized cellulose nanofibril (OCNF) suspensions in the presence of diverse surfactants. Using a combination of small angle neutron scattering (SANS) and rheology, we compared the physical properties of the suspensions with their structural behavior. Four surfactants were studied, all with the same hydrophobic tail length but different headgroups: hexaethylene glycol mono-n-dodecyl ether (C12EO6, nonionic), sodium dodecyl sulfate (SDS, anionic), cocamidopropyl betaine (CapB, zwitterionic), and dodecyltrimethylammonium bromide (DTAB, cationic). Contrast variation SANS studies using deuterated version of C12EO6 or SDS, or by varying the D2O/H2O ratio of the suspensions (with CapB), allowed focusing only on the structural properties of OCNFs or surfactant micelles. We showed that, in the concentration range studied, for C12EO6, although the nanofibrils are concentrated thanks to an excluded volume effect observed in SANS, the rheological properties of the suspensions are not affected. Addition of SDS or CapB induces gelation for surfactant concentrations superior to the critical micellar concentration (CMC). SANS results show that attractive interactions between OCNFs arise in the presence of these anionic or zwitterionic surfactants, hinting at depletion attraction as the main mechanism of gelation. Finally, addition of small amounts of DTAB (below the CMC) allows formation of a tough gel by adsorbing onto the OCNF surface.

Understanding the Stabilizing Effect of Histidine on mAb Aggregation: A Molecular Dynamics Study.

Histidine, a widely used buffer in monoclonal antibody (mAb) formulations, is known to reduce antibody aggregation. While experimental studies suggest a nonelectrostatic, nonstructural (relating to secondary structure preservation) origin of the phenomenon, the underlying microscopic mechanism behind the histidine action is still unknown. Understanding this mechanism will help evaluate and predict the stabilizing effect of this buffer under different experimental conditions and for different mAbs. We have used all-atom molecular dynamics simulations and contact-based free energy calculations to investigate molecular-level interactions between the histidine buffer and mAbs, which lead to the observed stability of therapeutic formulations in the presence of histidine. We reformulate the Spatial Aggregation Propensity index by including the buffer-protein interactions. The buffer adsorption on the protein surface leads to lower exposure of the hydrophobic regions to water. Our analysis indicates that the mechanism behind the stabilizing action of histidine is connected to the shielding of the solvent-exposed hydrophobic regions on the protein surface by the buffer molecules.

In-Membrane Nanostructuring of Cationic Amphiphiles Affects Their Antimicrobial Efficacy and Cytotoxicity: A Comparison Study between a De Novo Antimicrobial Lipopeptide and Traditional Biocides.

Cationic biocides have been widely used as active ingredients in personal care and healthcare products for infection control and wound treatment for a long time, but there are concerns over their cytotoxicity and antimicrobial resistance. Designed lipopeptides are potential candidates for alleviating these issues because of their mildness to mammalian host cells and their high efficacy against pathogenic microbial membranes. In this study, antimicrobial and cytotoxic properties of a de novo designed lipopeptide, CH3(CH2)12CO-Lys-Lys-Gly-Gly-Ile-Ile-NH2 (C14KKGGII), were assessed against that of two traditional cationic biocides CnTAB (n = 12 and 14), with different critical aggregation concentrations (CACs). C14KKGGII was shown to be more potent against both bacteria and fungi but milder to fibroblast host cells than the two biocides. Biophysical measurements mimicking the main features of microbial and host cell membranes were obtained for both lipid monolayer models using neutron reflection and small unilamellar vesicles (SUVs) using fluorescein leakage and zeta potential changes. The results revealed selective binding to anionic lipid membranes from the lipopeptide and in-membrane nanostructuring that is distinctly different from the co-assembly of the conventional CnTAB. Furthermore, CnTAB binding to the model membranes showed low selectivity, and its high cytotoxicity could be attributed to both membrane lysis and chemical toxicity. This work demonstrates the advantages of the lipopeptides and their potential for further development toward clinical application.

An insight into the thermo-thickening behavior of wormlike micellar solutions based on ultra-long-chain surfactants.

Generally, the solution viscosity of wormlike micelles (WLMs) assembled from common surfactants decreases upon an increase in the temperature, following the Arrhenius law. However, abnormal thermo-thickening behavior has been repeatedly observed for WLMs formed by ultra-long-chain (≥C18) surfactants. It would be useful to unravel the mechanism behind this phenomenon. Here, three C22-tailed surfactants with an erucyl tail, two of them containing carboxylate or sulfonate head groups (UC22DAB and UC22DAS) and a cationic one with an iodide counterion (UC22DAI), and two C18-tailed betaines with olemido- and stearamidopropyl hydrophobic chains (UC18DAS and C18DAS) were characterised in terms of their viscosity and viscoelastic behavior with increasing temperature to examine the roles of head groups, tail length and tail nature. Their micellar structures were elucidated at various temperatures using small angle neutron scattering (SANS), small angle neutron X-ray scattering (SAXS) and molecular dynamics simulation. It is found that the thermo-thickening behavior of ultra-long-chain surfactants is ascribed to the prolonged persistence length and increased entanglement points. When the temperature is increased, an increase in viscosity is always accompanied by a longer persistent length, thus a larger hydrodynamic volume. The iceberg structure around the hydrophobic tail of surfactants can be destroyed at high temperatures leading to the self-assembly of these surfactants. In this self-assembly process, compared to cationic surfactants, zwitterionic surfactants can form WLMs more readily due to weak electrostatic repulsions between their head groups; the longer tails give the surfactants enhanced hydrophobicity to form WLMs with a long breaking time; the cis-unsaturation and the resulting kink in the hydrophobic tails give the surfactants good solubility, which is not conducive to the formation of micelles. In brief, the zwitterionic, longer tail and saturated tail surfactants can form WLMs with a prolonged persistence length at elevated temperatures.

Structural investigation of sulfobetaines and phospholipid monolayers at the air-water interface.

Mixtures of sulfobetaine based lipids with phosphocholine phospholipids are of interest in order to study the interactions between zwitterionic surfactants and the phospholipids present in cell membranes. In this study we have investigated the structure of mixed monolayers of sulfobetaines and phosphocholine phospholipids. The sulfobetaine used has a single 18-carbon tail, and is referred to as SB3-18, and the phospholipid used is DMPC. Surface pressure-area isotherms of the samples were used to determine whether any phase transitions were present during the compression of the monolayers. Neutron and X-ray reflectometry were then used to investigate the structure of these monolayers perpendicular to the interface. We found that the average headgroup and tail layer thickness was reasonably consistent across all mixtures, with a variation of less than 3 Å reported in the total thickness of the monolayers at each surface pressure. However, by selective deuteration of the two components of the monolayers, it was found that the two components have different tail layer thicknesses. For the mixture with equal compositions of DMPC and SB3-18 or with a higher composition of DMPC the tail tilts were found to be constant, resulting in a greater tail layer thickness for SB3-18 due to its longer tail. For the mixture higher in SB3-18 this was not the case, the tail tilt angle for the two components was found to be different and DMPC was found to have a greater tail layer thickness than SB3-18 as a result.

Small-angle neutron scattering from mixtures of long- and short-chain 3-alkyl-1-methyl imidazolium bistriflimides.

The preparation of mixtures of ionic liquids (ILs) represents an attractive strategy to tune their properties, an important aspect of which is to understand how the structure of the bulk varies with composition. In this study, small-angle neutron scattering (SANS) was used to probe mixtures of methylimidazolium-based ionic liquids [Cnmim][Tf2N] with [C2mim][Tf2N]) (n = 4, 6, 8 and 10) and of [Cmmim][Tf2N] with [C12mim][Tf2N] (m = 2, 4, 6 and 8). Mixtures were prepared in both contrasts, which is to say that one component would be fully hydrogenated while the other was fully deuterated, and vice versa. Data were fitted using a range of appropriate models, of which the Teubner-Strey model provided most useful information and the pure materials showed a nascent Polar Non-polar Peak (PNPP) for n = 6, which became more evident as n increased. In the mixtures [Cnmim]x[C2mim]1-x[Tf2N], the PNPP was evident for n = 10 and 8, nascent for n = 6 and absent for n = 4, with percolation showing a very strong dependence on the chain length of the added IL, [Cnmim][Tf2N]. In contrast, while the ability of [C12mim][Tf2N] to form percolated structures was damped when mixed with [Cmmim][Tf2N], as m increased from 2 to 6, this effect was less strong. However, data obtained for mixtures of [C12mim][Tf2N] and [C8mim][Tf2N], both of which percolate as pure materials, did not fit easily in any of the models applied to the previous systems and gave results that depended on the contrast used. Complementary small-angle X-ray scattering (SAXS) data, however, showed the expected evolution and behaviour of the PNPP, COP and CP, revealing that the unexpected observations were due to an adventitious matching out of isotopic contrasts. As well as revealing details of the structures of these IL mixtures, the results also point to complementary strategies for generating bulk percolated structures as a function of cation chain length.

Cryogenic wormlike micelles.

Cryogenic wormlike micellar solutions which possess a freezing point far below 0 °C while retaining rheological properties similar to those of ordinary wormlike micellar solutions are fabricated from the self-assembly of a C22-tailed monounsaturated zwitterionic surfactant, erucyl dimethyl amidopropyl betaine, in an ethylene glycol/water co-solvent at subzero temperature. Such fluids may find potential applications in fields where viscoelasticity is highly desired at subfreezing temperatures.

Correction: Cryogenic wormlike micelles.

Correction for 'Cryogenic wormlike micelles' by Hongyao Yin et al., Soft Matter, 2019, 15, 2511-2516.

Blooming of Smectic Surfactant/Plasticizer Layers on Spin-Cast Poly(vinyl alcohol) Films.

The blooming of sodium dodecyl sulfate (SDS) and the influence of plasticizer (glycerol) on the surfactant distribution in poly(vinyl alcohol) (PVA) films have been explored by neutron reflectometry (NR) and ion beam analysis techniques. When in binary films with PVA, deuterated SDS (d25-SDS) forms a surface excess corresponding to a wetting layer of the surfactant molecules at the film surface. The magnitude of this surface excess increased significantly in the presence of the plasticizer, and the surfactant was largely excluded from the PVA subphase. NR revealed smectic nanostructures for both SDS and glycerol components within this surface excess in plasticized films. This combined layer comprises surfactant lamellae, separated by interstitial glycerol-rich layers, which is only formed in the plasticized films and persists throughout the surface excess. Atomic force microscopy micrographs of the film surfaces revealed platelike structures in the plasticized PVA, which were consistent with the rigid defects in the surfactant-rich lamellae. The formation of these structures arises from the synergistic surface segregation of SDS and glycerol, evidenced by surface tensiometry. Cloud point analysis of bulk samples indicates a transition at ∼55% water content, below which phase separation occurs in ternary films. This transition is likely to be necessary to form the thick wetting layer observed and therefore indicates that film components remain mobile beyond this point in the drying process.

Temperature Resistant Binary SLES/Nonionic Surfactant Mixtures at the Air/Water Interface.

Surface compositions of adsorbed monolayers at the air/water interface, formed from binary surfactant mixtures in equilibrium, have been studied using neutron reflectivity at three discrete temperatures: 10, 25, and 40 °C. The binary compositions studied are sodium lauryl dodecyl ether sulfate (SLES EO3)/C12E n, where n = 6 and 8, at a fixed concentration of 2 mM with and without the addition of 0.1 M NaCl. Without NaCl, the nonionic surfactant dominates at the interface and nonideal mixing behavior is observed. This is modeled using the pseudophase approximation with a quadratic expansion of the free energy of mixing. The addition of 0.1 M NaCl screens the charge interaction between the surfactants and drives the surface composition of each system closer to that of the bulk composition. However, model fits to both the micelles and surface layers suggest that nonideal mixing is still taking place, although it is difficult to establish the extent of nonideality due to the limited data quality. The effect of temperature changes on the surface adsorption and composition of the surfactant mixtures is minimal and within error, with and without NaCl, but the critical micelle concentrations are significantly affected. This indicates the dominant influence of steric hindrances and surfactant charge interactions in determining interfacial behavior for these surfactants, relative to the temperature changes. The study also highlights the delicate effect of a relatively small change in the number of EO groups on mixing behavior.

Structural Features of Reconstituted Cuticular Wax Films upon Interaction with Nonionic Surfactant C12E6.

The interaction of nonionic surfactant hexaethylene glycol monododecyl ether (C12E6) with a reconstituted cuticular wheat wax film has been investigated by spectroscopic ellipsometry and neutron reflection (NR) to help understand the role of the leaf wax barrier during pesticide uptake, focusing on the mimicry of the actions adjuvants impose on the physical integrity and transport of the cuticular wax films against surfactant concentration. As the C12E6 concentration was increased up to the critical micelle concentration (CMC = 0.067 mM), an increasing amount of surfactant mass was deposited onto the wax film. Alongside surface adsorption, C12E6 was also observed to penetrate the wax film, which is evident from the NR measurements using fully protonated and chain-deuterated surfactants. Furthermore, surfactant action upon the model wax film was found to be physically reversible below the CMC, as water rinsing could readily remove the adsorbed surfactant, leaving the wax film in its original state. Above the CMC, the detergency action of the surfactant became dominant, and a significant proportion of the wax film was removed, causing structural damage. The results thus reveal that both water and C12E6 could easily penetrate the wax film throughout the concentration range measured, indicating a clear pathway for the transport of active ingredients while the removal of the wax components above the CMC must have enhanced the transport process. As the partial removal of the wax film could also expose the underlying cutaneous substrate to the environment and undermine the plant's health, this study has a broad implication to the roles of surfactants in crop care.

Influence of the Surfactant Structure on Photoluminescent π-Conjugated Polymer Nanoparticles: Interfacial Properties and Protein Binding.

π-Conjugated polymer nanoparticles (CPNs) are under investigation as photoluminescent agents for diagnostics and bioimaging. To determine whether the choice of surfactant can improve CPN properties and prevent protein adsorption, five nonionic polyethylene glycol alkyl ether surfactants were used to produce CPNs from three representative π-conjugated polymers. The surfactant structure did not influence size or yield, which was dependent on the nature of the conjugated polymer. Hydrophobic interaction chromatography, contact angle, quartz crystal microbalance, and neutron reflectivity studies were used to assess the affinity of the surfactant to the conjugated polymer surface and indicated that all surfactants were displaced by the addition of a model serum protein. In summary, CPN preparation methods which rely on surface coating of a conjugated polymer core with amphiphilic surfactants may produce systems with good yields and colloidal stability in vitro, but may be susceptible to significant surface alterations in physiological fluids.

Exploring the bulk-phase structure of ionic liquid mixtures using small-angle neutron scattering.

Small-angle neutron scattering experiments, supported by molecular dynamics simulations, have been performed on a range of compositions of the [C2mim]1-x[C12mim]x[Tf2N] ionic liquid mixture system. Isotopic contrast variation, through selective deuteration of both cations, has been used to assist in fitting the data to different scattering models. These data, and subsequent fitting, show that the structure of the ionic liquid mixtures changes substantially as a function of composition. Mixtures where x < 0.32 are dominated by aggregates of amphiphilic [C12mim]+ ions in the relatively polar [C2mim][Tf2N] solvent. Compositions where x > 0.32 can be described as bicontinuous, containing networks of both polar and non-polar domains, where the C12 chains of the [C12mim]+ ions percolate through the system to form a continuous non-polar sub-phase. Temperature-dependent scattering experiments suggest that there is relatively little change in bulk structure in these liquids between 20 and 60 °C. The presence of water, however, does influence some aspects of the liquid structure in a composition that is rich in [C2mim][Tf2N] (where x = 0.24).

Adsorption of Methyl Ester Sulfonate at the Air-Water Interface: Can Limitations in the Application of the Gibbs Equation be Overcome by Computer Purification?

We describe a new laboratory synthesis of the α-methyl ester sulfonates based on direct sulfonation of the methyl ester by SO3 introduced from the vapor phase. This was used to synthesize a chain deuterated sample of αC14MES, which was then used to measure the surface excess of αC14MES directly at the air/water interface over a wide range of concentration using neutron reflection. The adsorption isotherm could be fitted to an empirical equation close to a Langmuir isotherm and gave a limiting surface excess of (3.4 ± 0.1) × 10-6 mol m-2 in the absence of added electrolyte. The neutron-measured surface excesses were combined with the integrated Gibbs equation to fit the variation in surface tension with concentration (σ-ln C curve). The fit was exact provided that we used a prefactor consistent with the counterion at the surface being an impurity divalent ion, as has previously been found for sodium diethylhexylsulfosuccinate (aerosol OT or AOT) and various perfluorooctanoates. The critical micelle concentration (CMC) was determined from this fit to be 2.4 ± 0.3 mM in the absence of electrolyte. In the presence of 100 mM NaCl, this contamination was suppressed and the σ-ln C curve could be fitted using the integrated Gibbs equation with the expected prefactor of 1. The new data were used to reinterpret measurements by Danov et al. on an unpurified sample of αC14MES for which computer refinement was used to try to eliminate the effects of the impurities.

Effects of length and hydrophilicity/hydrophobicity of diamines on self-assembly of diamine/SDS gemini-like surfactants.

This work studied gemini-like surfactants formed from anionic surfactant sodium dodecyl sulfate (SDS) and cationic charged bola-type diamines with hydrophilic or hydrophobic spacers of different lengths using surface tension, small angle neutron scattering, isothermal titration microcalorimetry and cryogenic transmission electron microscopy. The critical micelle concentrations (CMC) and the surface tension at CMC (γCMC) for all the diamine/SDS mixtures are markedly lower than that of SDS. The shorter diamines reduce γCMC to a greater extent regardless of the hydrophilicity/hydrophobicity of the diamines. Meanwhile, either the hydrophobic diamine with a longer spacer or the hydrophilic diamine with a shorter spacer is more beneficial to decrease CMC and leads to the transition from spherical micelles into rodlike or wormlike micelles. This is principally because of the formation of gemini-like surfactants by the electrostatic binding between SDS and the diamines, where the electrostatic repulsion between the adjacent headgroups of SDS becomes much weaker due to the electrostatic binding of oppositely charged diamine with SDS, and the longer hydrophobic spacer may also bend into the hydrophobic domain of micelles to promote micellar growth. However, the hydrophilic spacers are more compatible with the headgroup region, leading to micelles with a larger curvature. This work contributes to the understanding of the relationship between the properties of constructed gemini-like surfactants and the natures of connecting molecules, and provides guidance to efficiently improve the performance of surfactants.

Surfactant and Plasticizer Segregation in Thin Poly(vinyl alcohol) Films.

The vertical depth distributions of individual additive components [cetyltrimethylammonium bromide (CTAB), deuterated pentaethylene glycol monododecyl ether (d25-C12E5), and deuterated glycerol (d-glycerol)] in PVA films have been isolated and explored by ion beam analysis techniques and neutron reflectometry. The additives display an unexpectedly rich variety of surface and interfacial behaviors in spin-cast films. In separate binary films with PVA, both d-glycerol and CTAB were evenly distributed, whereas d25-C12E5 showed clear evidence for surface and interfacial segregation. The behavior of each surfactant in PVA was reversed when the plasticizer (glycerol) was also incorporated into the films. With increasing plasticizer content, the surface activity of d25-C12E5 systematically decreased, but remarkably, when glycerol and CTAB were present in PVA, the surface and interfacial activities of CTAB increased dramatically in the presence of glycerol. Quantification of the surface excess by ion beam analysis revealed that, in many cases, the adsorbed quantity far exceeded what could reasonably be explained by a single layer, thus indicating a wetting transition of the small molecules at the surface or interface of the film. It appears that the surface and interfacial behaviors are partly driven by the relative surface energies of the components, but are also significantly augmented by the incompatibility of the components.

Multivalent-Counterion-Induced Surfactant Multilayer Formation at Hydrophobic and Hydrophilic Solid-Solution Interfaces.

Surface multilayer formation from the anionic-nonionic surfactant mixture of sodium dodecyl dioxyethylene sulfate, SLES, and monododecyl dodecaethylene glycol, C12E12, by the addition of multivalent Al(3+) counterions at the solid-solution interface is observed and characterized by neutron reflectivity, NR. The ability to form surface multilayer structures on hydrophobic and hydrophilic silica and cellulose surfaces is demonstrated. The surface multilayer formation is more pronounced and more well developed on the hydrophilic and hydrophobic silica surfaces than on the hydrophilic and hydrophobic cellulose surfaces. The less well developed multilayer formation on the cellulose surfaces is attributed to the greater surface inhomogeneities of the cellulose surface which partially inhibit lateral coherence and growth of the multilayer domains at the surface. The surface multilayer formation is associated with extreme wetting properties and offers the potential for the manipulation of the solid surfaces for enhanced adsorption and control of the wetting behavior.

Adsorption at air-water and oil-water interfaces and self-assembly in aqueous solution of ethoxylated polysorbate nonionic surfactants.

The Tween nonionic surfactants are ethoxylated sorbitan esters, which have 20 ethylene oxide groups attached to the sorbitan headgroup and a single alkyl chain, lauryl, palmityl, stearyl, or oleyl. They are an important class of surfactants that are extensively used in emulsion and foam stabilization and in applications associated with foods, cosmetics and pharmaceuticals. A range of ethoxylated polysorbate surfactants, with differing degrees of ethoxylation from 3 to 50 ethylene oxide groups, have been synthesized and characterized by neutron reflection, small-angle neutron scattering, and surface tension. In conjunction with different alkyl chain groups, this provides the opportunity to modify their surface properties, their self-assembly in solution, and their interaction with macromolecules, such as proteins. Adsorption at the air-water and oil-water interfaces and solution self-assembly of the range of ethoxylated polysorbate surfactants synthesized are presented and discussed.