The phase separation of immiscible surfactants in mixed monolayer films provides an approach to physically manipulate important properties of thin films, including surface morphology, microscale composition, and mechanical properties. In this work, we predict, based upon existing miscibility studies and their thermodynamic underpinnings described in the literature, the miscibility and film morphology of mixed monolayers comprised of behenic acid (C21H43COOH) and perfluorotetradecanoic acid (C13F27COOH) in various molar ratios. Predictions are tested using a combination of experimental surface characterization methods for probing miscibility and film morphology at the solid/air and air/water interfaces. Film components were immiscible and phase-separated into chemically well-defined domains under a variety of experimental conditions, with monolayer morphology consistent with initial predictions. The extensibility of these basic predictions to other systems is discussed in the context of using these works for different perfluorinated surfactant molecules.

The miscibility and film structure of mixed Langmuir monolayer films composed of an anionic gemini N,N,N',N'-dialkyl-N,N'-diacetate ethylenediamine surfactant (Ace(12)-2-Ace(12)) with perfluorotetradecanoic acid (CFCOOH; PF) have been investigated using a variety of thermodynamic and structural characterization methods. The two film components were found to be miscible in monolayers at the air-water interface over a range of compositions and at all but the lowest surface pressures, with attractive interactions occurring between the two components. While pure PF monolayers formed crystalline lattices with hexagonal symmetry and with the surfactant tails oriented normal to the underlying water subphase, the pure gemini surfactant formed amorphous films with little tendency to orient at the subphase. In mixed films with mole ratios of PF:Ace(12)-2-Ace(12) < 2.5, the miscibility of the two components resulted in a nearly complete loss of crystallinity of the PF, though films at higher mole fractions of PF showed some residual crystallinity, albeit with lattice structures that were significantly different from that of pure PF. Miscibility and film structure in this mixed system are discussed in comparison with other mixed gemini surfactant systems in the literature as well as binary mixtures of phospholipids or monomeric fatty acids with PF.

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A new member of the N,N,N′,N′-dialkyl-N,N′diacetate ethylenediamine family of anionic gemini surfactants has been synthesized, and its miscibility with the model perfluorocarbon, perfluorotetradecanoic acid (PF), has been investigated in monolayer films at the air−water interface. Thermodynamics of mixing and the accompanying changes in the mixed film structure have been probed using a combination of compression isotherm measurements supported by Brewster angle microscope imaging and X-ray scattering measurements, and results have been compared with those collected for a previously studied, shorter tail chain variant of the surfactant. Thermodynamic measurements showed that the gemini surfactant and perfluorotetradecanoic acid were immiscible, with weak repulsive interactions, manifesting as small positive deviations from ideal mixing, observed between the two film components. Films were highly textured, with micrometer-scale, phase-separated domains readily detectable. Grazing incidence X-ray diffraction measurements showed that the gemini surfactant was disordered in the monolayers, whereas the perfluorocarbon formed discrete crystallites in the disordered matrix. Despite the small deviations from ideal mixing detected in the thermodynamic measurements, the X-ray measurements indicated that the presence of the gemini perturbs the PF crystal lattice from that of pure PF. Finally, X-ray reflectivity measurements showed that the addition of equimolar PF to the gemini monolayer induces a significant increase in the nominal head group thickness of the film, suggesting that interactions between the two surfactants can lead to structural rearrangements of gemini's head group near to the water surface.

Gemini surfactants are promising molecules utilized as non-viral gene delivery vectors. However, little is known about their cellular uptake and distribution after they release their therapeutic cargo. Therefore, we quantitatively evaluated the cellular uptake and distribution of three gemini surfactants: unsubstituted (16-3-16), with pyridinium head groups (16(Py)-S-2-S-16(Py)) and substituted with a glycyl-lysine di-peptide (16-7N(GK)-16). We also assessed the relationship between cellular uptake and distribution of each gemini surfactant and its overall efficiency and toxicity. Epidermal keratinocytes PAM212 were treated with gemini surfactant nanoparticles formulated with plasmid DNA and harvested at various time points to collect the enriched nuclear, mitochondrial, plasma membrane and cytosolic fractions. Gemini surfactants were then extracted from each subcellular fraction and quantified using a validated flow injection analysis-tandem mass spectrometry (FIA-MS/MS) method. Mass spectrometry is superior to the use of fluorescent tags that alter the physicochemical properties and pharmacokinetics of the nanoparticles and can be cleaved from the gemini surfactant molecules within biological systems. Overall, a significantly higher cellular uptake was observed for 16-7N(GK)-16 (17.0%) compared with 16-3-6 (3.6%) and 16(Py)-S-2-S-16(Py) (1.4%), which explained the relatively higher transfection efficiency of 16-7N(GK)-16. Gemini surfactants 16-3-16 and 16(Py)-S-2-S-16(Py) displayed similar subcellular distribution patterns, with major accumulation in the nucleus, followed by the mitochondrion, cytosol and plasma membrane. In contrast, 16-7N(GK)-16 was relatively evenly distributed across all four subcellular fractions. However, accumulation within the nucleus after 5hr of treatment was the highest for 16(Py)-S-2-S-16(Py) (50.3%), followed by 16-3-16 (41.8%) and then 16-7N(GK)-16 (33.4%), possibly leading to its relatively higher toxicity.