Albumin Proteins as Delivery Vehicles for PFAS Contaminants into Respiratory Membranes.

Poly- and perfluoroalkyl substances (PFAS) are a family of chemicals that have been used in a wide range of commercial products. While their use is declining, the prevalence of PFAS, combined with their chemical longevity, ensures that detectable levels will remain in the environment for years to come. As such, there is a pressing need to understand how PFAS contaminants interact with other elements of the human exposome and the consequences of these interactions for human health. Using serum albumin as a model system, we show that proteins can bind PFAS contaminants and facilitate their incorporation into model pulmonary surfactant systems and lipid bilayers. Protein-mediated PFAS delivery significantly altered the structure and function of both model membrane systems, potentially contributing to respiratory dysfunction and airway diseases in vivo. These results provide valuable insights into the synergistic interaction between PFAS contaminants and other elements of the human exposome and their potential consequences for human health.

The partitioning of primary alcohols into the aggregates of gemini amphiphiles determined from diffusion NMR experiments.

The partition constants (p-values) of primary alcohols in solutions containing aggregates of symmetric gemini surfactants of the family N,N'-dimethyl, N-dialkyl-α,ω-alkanediammonium dibromide (m-s-m = symmetric gemini surfactants) have been computed from the measured values of their diffusion coefficients obtained from NMR-diffusion experiments. From the p-values, both mole-fraction and concentration-based partition coefficients and Gibbs energies of transfer for the alcohols from the bulk D2O phase to the gemini aggregate phase have been calculated. As expected, the Gibbs energy of transfer decreased linearly with an increase in the alcohol carbon length for each of the primary alcohol/gemini amphiphile series studied. The Gibbs transfer energy increment per CH2 for the alcohols was consistent for all the alcohol/gemini amphiphile series and was in excellent agreement with the values measured for the same primary alcohol series in conventional single-headed, single-tailed surfactants. Surprisingly, the partition coefficients of the alcohols in the symmetric gemini aggregates exhibited little, if any, dependence on the spacer length of the gemini amphiphiles and were remarkably consistent as the length of the main surfactant chain increased at constant spacer length. When these results are compared to the partition coefficients of the same alcohols in corresponding monomeric surfactants, we observe little difference in the thermodynamic driving forces governing the transfer of alcohols from water to the aggregates of either monomeric or symmetric gemini surfactants.

Lactate shuttling as an allostatic means of thermoregulation in the brain.

Lactate, the redox-balanced end product of glycolysis, travels within and between cells to fulfill an array of physiologic functions. While evidence for the centrality of this lactate shuttling in mammalian metabolism continues to mount, its application to physical bioenergetics remains underexplored. Lactate represents a metabolic "cul-de-sac," as it can only re-enter metabolism by first being converted back to pyruvate by lactate dehydrogenase (LDH). Given the differential distribution of lactate producing/consuming tissues during metabolic stresses (e.g., exercise), we hypothesize that lactate shuttling vis-à-vis the exchange of extracellular lactate between tissues serves a thermoregulatory function, i.e., an allostatic strategy to mitigate the consequences of elevated metabolic heat. To explore this idea, the rates of heat and respiratory oxygen consumption in saponin-permeabilized rat cortical brain samples fed lactate or pyruvate were measured. Heat and respiratory oxygen consumption rates, and calorespirometric ratios were lower during lactate vs. pyruvate-linked respiration. These results support the hypothesis of allostatic thermoregulation in the brain with lactate.

m-s-m cationic gemini and zwitterionic surfactants - a thermodynamic analysis of their mixed micelle formation.

Micelle formation enthalpies (Δmic H values) have been calorimetrically determined at 298 K for three sets of mixed zwitterionic/cationic gemini systems consisting of N-dodecyl-N,N-dimethyl-3-ammonio-1-propanesulfonate (ZW3-12) and a series of structurally related gemini surfactants, the N,N'-bis(dimethyldodecyl)-α,ω-alkanediammonium dibromide (12-s-12) systems. From the experimental and the estimated ideal micelle formation enthalpies, the excess enthalpies were obtained. The degrees of nonideality of the interaction in the mixed micelle (ß m) from our previous work was used along with the excess enthalpy values to determine excess thermodynamic quantities of the surfactants in the mixed system according to Regular Solution Theory (RST) and Motomura's theory. The excess enthalpies for the ZW3-12/12-4-12 were positive in magnitude and rose sharply when small amounts of the zwittergent were distributed into the gemini micelles. The excess enthalpies for the ZW3-12/12-5-12 and the ZW3-12/12-6-12 systems were also >0 kJ mol-1, and as a function of zwittergent composition, were quite different to those of the ZW3-12/12-4-12 mixed micelles. These results indicate that the heat of mixed micelle formation is strongly dependent on electrostatic interactions and the structure of the surfactants involved, specifically, the length of the tether group for the 12-s-12 gemini surfactants. From the calorimetric data and the application of RST and Motomura's theory, we have obtained estimates of the excess Gibbs energy and entropy of mixing. An analysis of the three thermodynamic properties suggests that the relative contributions of enthalpic and entropic effects to nonideal behavior for mixed micelles involving gemini surfactants are strongly dependent on the gemini structure.

m-s-m Cationic Gemini and Zwitterionic Surfactants-Spacer-Dependent Synergistic Interactions.

Critical micelle concentration (cmc) values were determined for the mixed zwitterionic/cationic gemini systems of N-dodecyl- N, N-dimethyl-3-ammonio-1-propanesulfonate (ZW3-12)/ N, N'-bis(dimethyldodecyl)-α,ω-alkanediammonium dibromide (12-s-12) systems. The cmc values for the mixed systems were determined through conductivity measurements. The degree of nonideality of the interaction in the mixed micelle (ßm), for each system, was determined according to Rubingh's nonideal solution theory. In most cases, the systems exhibited negative deviations (-ßm values) at high surfactant mole fractions of zwittergent (αZW3-12). Specifically, the ZW3-12/12-4-12 system displayed -ßm values at αZW3-12 ≥ 0.5, while both the ZW3-12/12-5-12 and the ZW3-12/12-6-12 systems displayed -ßm values over the entire mole fraction range. Except for the low mole fraction range in the 12-4-12 system, these mixed surfactant systems demonstrated almost identical behavior to the n-dodecyltrimethylammonium bromide/12-2-12 system studied by Bakshi et al. providing further evidence that ZW3-12 tends to behave as a cationic surfactant in mixed surfactant systems. The manner in which the cosurfactants aggregate in the micelles was determined via two-dimensional (2D) NOESY spectroscopy. In the case of both the ZW3-12/12-5-12 and the ZW3-12/12-6-12 systems, the 2D NOESY spectra exhibited strong cross peaks between the gemini and zwitterionic surfactants over the entire micellar composition range. In the case of the ZW3-12/12-4-12 system, little cross peak intensity was observed between the gemini and the zwitterionic surfactant at low micellar compositions of the zwittergent. The results suggest some micelle demixing is occurring between the gemini and the zwittergent certain micellar composition ranges, a phenomenon rarely associated with hydrocarbon surfactants.

The micellar and surface properties of a unique type of two-headed surfactant--pentaerythritol based di-cationic surfactants.

The surface properties of some families of cationic two-headed surfactants based on a pentaerythritol backbone are described. The compounds have the following general structure (1), where R' are head groups and R are linear alkyl groups ranging from octyl to tetradecyl. The syntheses of these compounds has been published in detail previously. Critical micelle concentrations (cmc values) of these two-headed surfactants have been determined and compared to conventional ionic surfactants and gemini surfactants of similar structure. In addition, the surface activity of these two-headed surfactants, expressed as the C20 value and the surface tension at the cmc, have been determined. Transmission electron microscopy has been used to examine the morphology of the aggregates formed by these amphiphiles. In general, when compared to conventional ionic and two-headed surfactants, these new two-headed surfactants exhibit a remarkable efficiency in the tendency to self-assemble and are significantly more surface active than their conventional counterparts [structure: see text].

Nonaromatic hydrotropic cationic ammonium salts as a rheology modifier for an anionic/zwitterionic surfactant mixture.

In this article, we report additive-induced micellar growth and rheology modification for mixtures of anionic (sodium dodecyl sulfate, SDS) and zwitterionic (N-alkylated glycine derivative, Empigen BB or EBB) surfactants. Two nonaromatic hydrotropic salts (hexyltrimethylammonium bromide, C6TAB, and/or dibutylenebis(dimethylbutylammonium bromide), 4-4-4) are used as novel additives to induce micellar growth in these systems. Nuclear magnetic resonance (NMR), photon correlation spectroscopy (PCS), transmission electron microscopy (TEM), the Weissenberg effect, and rheology measurements were employed to assess mixed micelle formation, micellar growth, and rheology modifications. Finally, the manner in which the surfactants and hydrotropes self-assemble into aggregates has also been deduced from 2D NMR NOESY measurements. In this study, both hydrotropic ions have been found to contribute to similar structural modifications in the mixed micelles of the anionic and zwitterionic surfactants. However, the extent of the rheology modification in solution is found to be quite different when the gemini hydrotrope (4-4-4) versus the monomeric hydrotrope (C6TAB) is employed.

Mixed aggregate formation in gemini surfactant/1,2-dialkyl-sn-glycero-3-phosphoethanolamine systems.

An evaluation of the physical interactions between gemini surfactants, DNA, and 1,2-dialkyl-sn-glycero-3-phosphoethanolamine helper lipid is presented in this work. Complexation between gemini surfactants and DNA was first investigated using surface tensiometry where the surface tension profiles obtained were found to be consistent with those typically observed for mixed surfactant-polymer systems; that is, there is a synergistic lowering of the surface tension, followed by a first (CAC) and second (CMC) break point in the plot. The surfactant alkyl tail length was observed to exhibit a significant effect on the CAC, thus demonstrating the importance of hydrophobic interactions during complexation between gemini surfactants and DNA. The second study presented is an investigation of the mixing interactions between gemini surfactants and DOPE using Clint's, Rubingh's, and Motomura's theories for mixed micellar formation. The mixing interactions between the 16-3-16/16-7-16/16-12-16/16-7NH-16 gemini surfactants and DOPE were observed to be antagonistic, where the strength of antagonism was found to be dependent upon the gemini surfactant spacer group and the solution composition.

Simulations of a lattice model of two-headed linear amphiphiles: influence of amphiphile asymmetry.

Using a 2D lattice model, we conduct Monte Carlo simulations of micellar aggregation of linear-chain amphiphiles having two solvophilic head groups. In the context of this simple model, we quantify how the amphiphile architecture influences the critical micelle concentration (CMC), with a particular focus on the role of the asymmetry of the amphiphile structure. Accordingly, we study all possible arrangements of the head groups along amphiphile chains of fixed length N = 12 and 16 molecular units. This set of idealized amphiphile architectures approximates many cases of symmetric and asymmetric gemini surfactants, double-headed surfactants, and boloform surfactants. Consistent with earlier results, we find that the number of spacer units s separating the heads has a significant influence on the CMC, with the CMC increasing with s for s < N/2. In comparison, the influence of the asymmetry of the chain architecture on the CMC is much weaker, as is also found experimentally.

Synthesis of surfactants based on pentaerythritol. I. Cationic and zwitterionic gemini surfactants.

Simple strategies for the synthesis of five series of cationic gemini surfactants and one series of zwitterionic gemini surfactants from pentaerythritol have been developed. Two lipophilic groups were introduced onto pentaerythritol by alkylation of the known compound, O-benzylidenepentaerythritol, with 1-bromooctane, 1-bromodecane, 1-bromododecane, and 1-bromotetradecane. Hydrogenolysis of the benzylidene acetals gave diols which were converted into three different series of trimethylammonium derivatives. The diiodides derived from the diols could be displaced by dimethylamine, even though they are adjacent to a quaternary carbon atom. Alkylation with methyl iodide gave the first series. The iodides were easily displaced by cyanide ion and the resulting dinitriles were hydrolyzed, converted to N,N-dimethylamides, and reduced to give a second series. Oxidation of the diols to dialdehydes under Swern conditions followed by Horner-Wadsworth-Emmons reactions with diethyl N,N-dimethylcarbamoylmethylphosphonate followed by two-stage reduction gave a third series. The dialkoxides derived from the four di-O-alkylpentaerthritol diols were reacted with 2-dimethylaminoethyl chloride and 3-dimethylaminopropyl chloride in neighboring-group assisted double Williamson ether syntheses to give precursors to two more series. As expected because the neighboring group participation occurs through a four-membered-ring intermediate, considerably more vigorous conditions were required for the reactions with 3-dimethylaminopropyl chloride. 2-Diethylaminoethyl bromide was found to be less reactive than 2-dimethylaminoethyl chloride. The products were alkylated with methyl iodide and, in some cases, other alkyl halides to give cationic gemini surfactants. Alkylation of one series with ethyl bromoacetate followed by anion exchange resin catalyzed ester hydrolysis gave zwitterionic gemini surfactants. The members of all series have superior surfactant properties.

Spontaneous vesicle formation with an ionic liquid amphiphile.

A simple and effective method for the formation of stable multilamellar vesicles is reported as a potential application of ionic liquid materials (IL's) and as replacements for conventional surfactants used in such applications. The methodology is based on the various approaches for the formation of vesicles from oppositely charged surfactants. Photon correlation spectroscopy (PCS) and transmission electron microscopy (TEM) have been used to estimate the size of the aggregates; the TEM studies have also revealed morphological differences in the self-assembled systems with changing ionic liquid material. Size measurements from PCS indicate consistent growth of the ionic-liquid containing vesicles with increasing concentration of added anionic surfactant. 2D NOESY NMR spectroscopy have been used to examine the manner in which IL amphiphile self-assembles with the second surfactant in solution. A comparison has been made between the aggregates formed from hexylpyridinium tetrafluoroborate ([HexPy][BF4-])/sodium dodecylsulfate (SDS) and hexylpyridinium bromide ([HexPy][Br])/sodium dodecylsulfate (SDS).

Synergistic interactions in the mixed micelles of cationic gemini with zwitterionic surfactants: the pH and spacer effect.

Mixed micelle formation of binary cationic gemini (12-s-12, s=4, 6) and zwitterionic (N-dodecyl-N,N-dimethylglycine, EBB) surfactants has been investigated by measuring the surface tension of aqueous solution as a function of total concentration at various pH values from acidic to basic, under conditions of 298.15 K and atmospheric pressure. The results were analyzed by applying regular solution theory (RST), and Motomura's theory, which allows for the calculation of the excess Gibbs energy of micellization purely on the basis of thermodynamic equations. The synergistic interactions of all the investigated cationic gemini + zwitterionic surfactants mixtures were found to be dependent upon the pH of the solution and the length of hydrophobic spacer of gemini surfactant. The evaluated excess Gibbs free energy is negative for all the systems.

Interactions between zwitterionic and conventional anionic and cationic surfactants.

Critical micelle concentration (cmc) values have been determined for the mixed zwitterionic/anionic surfactant systems of N-dodecyl-N,N-dimethyl-3-ammonio-1-propanesulfonate (ZW3-12)/sodium dodecyl sulfate (SDS), N-dodecyl-N,N-(dimethylammonio)butyrate (DDMAB)/SDS, N-octyl-N,N-dimethyl-3-ammonio-1-propanesulfonate (ZW3-08)/sodium octyl sulfate (SOS), and the zwitterionic/cationic systems of ZW3-12/dodecyltrimethylammonium bromide (DTAB), DDMAB/DTAB. Conductivity studies and nuclear magnetic resonance (NMR) spectroscopy were the methods employed for cmc determinations. The degree of nonideality of the interaction in the micelle (beta(m)), for each system, was determined according to Rubingh's nonideal solution theory. Evidence was found for the existence of strong interactions between zwitterionic and anionic surfactants in each of the zwitterionic/anionic systems. The ZW3-08/SOS and DDMAB/SDS systems behaved synergistically at all mole fractions studied while the ZW3-12/SDS system exhibited synergistic behavior above mole fractions of 0.30. Greater negative deviations from ideal behavior were demonstrated in the DDMAB/SDS system than in the other two zwitterionic/anionic systems. The zwitterionic/cationic systems of ZW3-12/DTAB and ZW3-08/OTAB displayed only slight deviations from ideal behavior, therefore indicating near ideal mixing.

Nuclear magnetic resonance investigation of the micellar properties of two-headed surfactant systems: the disodium 4-alkyl-3-sulfonatosuccinates. 2. The dynamics of the chains comprising the interior of two-headed surfactant micelles.

The dynamics of the carbons comprising the micelles of two members of the family of two-headed surfactants, the disodium 4-alkyl-3-sulfonatosuccinates, has been determined via the application of the two-step model to the 13C relaxation rates and the nuclear Overhauser enhancements (nOe's) at 200 MHz. The NMR relaxation times, determined from the inversion recovery method, increase steadily as we descend the chain from the headgroup region. The relaxation rate profiles and the order parameters have been calculated from the two-step model for the micellar sulfosuccinate aggregates. We note that the order parameter profile and the fast motion correlation time profile for these two-headed surfactants are distinctly different from those of a typical single-headed, single-tailed surfactant such as dodecyltrimethylammonium bromide, particularly in the headgroup region of the micelle. All these results are interpreted in terms of the effect of adding a second headgroup to a single-headed, single-tailed surfactant.