(1E)-1-[4-(Dimethyl­amino)phen­yl]pent-1-en-3-one

The title mol­ecule, C13H17NO, is close to planar: the dihedral angle betweent the dimethyl amino group and the benzene ring is 7.94 (19)°. No significant inter­molecular inter­actions are observed in the crystal structure

N-[4-(Ethyl­sulfamo­yl)phen­yl]acetamide

The title compound, C10H14N2O3S, crystallized with two mol­ecules (A and B) in the asymmetric unit. The terminal methyl group of the ethyl­sulfonamide moiety in mol­ecule B is disordered over two sets of sites with an occupancy ratio of 0.61 (1):0.39 (1). Both mol­ecules have L-shaped conformations. In mol­ecule A, the dihedral angles between the benzene ring and its ethyl­sulfonamide and methyl­amide substituents are 83.5 (3) and 13.34 (18)°, respectively. Equivalent values for mol­ecule B are 87.9 (3) and 6.32 (16)°, respectively. The C—S—N—C torsion angles are 66.5 (3)° for A and −64.4 (3)° for B, indicating similar twists about the S—N bonds, but in opposite senses. In the crystal, the A mol­ecules are linked by pairs of Ns—H⋯O (s = sulfonamide) hydrogen bonds, generating inversion dimers containing R 2 2(8) rings, while the B mol­ecules are linked by Ns—H⋯O hydrogen bonds into C(10) [100] chains. Finally, Na—H⋯O (a = amide) hydrogen bonds link the A-mol­ecule dimers and B-mol­ecule chains into a three-dimensional network

N-(4-Amino­phen­yl)-4-methylbenzene­sulfonamide

The title compound, C13H14N2O2S, crystallized with two independent mol­ecules in the asymmetric unit. They both have V-shaped conformations: the dihedral angles between their benzene rings are identical [45.86 (13)°] and their C—S—N—C torsion angles are similar [67.9 (3) and 70.2 (3)°]. In the crystal, the mol­ecules are linked by N—H⋯O and N—H⋯N hydrogen bonds, generating a three-dimensional network

Physical Chemistry of Gemini Surfactant Monolayers

The objective of this Ph.D. thesis research is to explore the effect of cation (Na+, Ca2+, and Fe3+) binding on monolayers comprised of two newly synthesized anionic gemini surfactants (Ace(n)-2-Ace(n), n = 11, 17; Figure 1) at the air-water and air-solid interfaces. The study was further aimed at exploring the miscibility and interactions of the Ace(n)-2-Ace(n) surfactants with perfluorotetradecanoic acid (C13F27COOH; PF) in monolayers. A combination of monolayer characterization methods, including surface pressure-area isotherms, Brewster angle microscopy (BAM) and atomic force microscopy (AFM) were used to explore the effect of ion-binding and mixing on the thermodynamics of mixing and the morphology of the monolayer films. Figure 1: Chemical structure of Ace(n)-2-Ace(n) (n = 11,17). Ace(n)-2-Ace(n) monolayers exhibited significant expansion with Na+ and Ca2+ in the sub-phase, while with Fe3+ in the sub-phase, compressed films were observed. Apparent association constants (Kapp) for Ace(n)-2-Ace(n) were smaller than the comparator phospholipids systems reported in the literature, and gemini-cation binding stoichiometries of 2:1 and 1:1 for Ca2+ and Na+ respectively were found. Multimolecular aggregates of Ace(n)-2-Ace(n) bonded to cations were observed in BAM and AFM images. Results were discussed in the context of grazing incidence X-ray diffraction (GIXD) and X-ray reflectivity (XR) measurements performed by other members of our research group. For the Ace(n)-2-Ace(n)-PF mixed monolayers, thermodynamic, morphological and X-ray scattering studies indicated that PF-Ace(12)-2-Ace(12) mixed films were miscible over a wide range of compositions at lower surface pressures. For PF-Ace(18)-2-Ace(18) mixed films, phase separation was detected at all surface pressures. GIXD and XR studies revealed that Ace(n)-2-Ace(n) forms amorphous, disordered monolayers at the air-water interface while PF forms a crystalline lattice with hexagonal symmetry. Overall the research in this thesis provides insight into fundamental interactions of this new class of gemini surfactants with metal cations in monolayers and an understanding of the physical and chemical factors that control mixing behavior in PF-Ace(n)-2-Ace(n) mixed monolayers. Future areas of research that are suggested by this work include developing new approaches for quantifying the extent of surfactant binding to metal ions in the monolayers and clarifying the precise nature of binding between Ace(n)-2-Ace(n) and metal cations

Cellular Uptake and Distribution of Gemini Surfactant Nanoparticles Used as Gene Delivery Agents

NSERC and CFIPeer ReviewedGemini 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 PAM 212 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 5 h 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

Morphology and Composition of Structured, Phase-Separated Behenic Acid–Perfluorotetradecanoic Acid Monolayer Films

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

Mixing Behavior in Binary Anionic Gemini Surfactant–Perfluorinated Fatty Acid Langmuir Monolayers

The miscibility and film structure of mixed Langmuir monolayer films composed of an anionic gemini <i>N</i>,<i>N</i>,<i>N</i>′,<i>N</i>′-dialkyl-<i>N</i>,<i>N</i>′-diacetate ethylenediamine surfactant (Ace(12)-2-Ace(12)) with perfluoro­tetradecanoic acid (C₁₃F₂₇COOH; 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