Influence of Stereochemistry on the Monolayer Characteristics of N-alkanoyl-Substituted Threonine and Serine Amphiphiles at the Air-Water Interface.

Thermodynamic and structural properties of the N-alkanoyl-substituted α-amino acids threonine and serine, differing only by one CH3 group in the head group, are determined and compared. Detailed characterization of the influence of stereochemistry proves that all enantiomers form an oblique monolayer lattice structure whereas the corresponding racemates build orthorhombic lattice structures due to dominating heterochiral interactions, except N-C16-dl-serine-ME as first example of dominating homochiral interactions in a racemic mixture of N-alkanoyl-substituted α-amino acids. In all cases, the liquid expanded-liquid condensed (LE/LC) transition pressure of the racemic mixtures is above that of the corresponding enantiomers. Phase diagrams are proposed. Using the program Hardpack to predict tilt angles and cross-sectional area of the alkyl chains shows reasonable agreement with the experimental grazing incidence X-ray diffraction (GIXD) data.

Lattice and thermodynamic characteristics of N-stearoyl-allo-threonine monolayers.

The effect of the second chiral center of diastereomeric N-alkanoyl-allo-threonine on the main monolayer characteristics has been investigated. The characteristic features of the enantiomeric and racemic forms of N-stearoyl-allo-threonine monolayers are studied on a thermodynamic basis and molecular scale. The π-A curves of the enantiomeric and racemic allo-forms show similar features to those of N-stearoyl-threonine. The compression curves are always located above the corresponding decompression curves and the decompression curves can be used as equilibrium isotherms for both the enantiomeric and racemic N-stearoyl-allo-threonine. The absolute T0-values (disappearance of the LE/LC-transition) are 4-5 K larger compared with the corresponding N-stearoyl-threonines, but the ΔT0 between the enantiomeric (d) and the racemic (dl) forms is only slightly larger than that of N-stearoyl-threonine. The difference in the critical temperatures Tc, above which the monolayer cannot be compressed into the condensed state, between the enantiomeric and the racemic forms, is quite small (ΔTc = 0.8 K) and is smaller compared to that of the corresponding threonines (ΔTc = 1.8 K). This is consistent with the dominance of the van der Waals interactions between the alkyl chains reducing the influence of chirality on the thermodynamic parameters. GIXD studies of N-stearoyl-allo-threonine monolayers provide information about the lattice structure of condensed monolayer phases on the Angstrom scale and stipulate the homochiral or heterochiral preference in the condensed phases. Comparable to N-stearoyl-threonine, the enantiomers exhibit an oblique lattice structure, whereas the racemates form a NNN tilted orthorhombic structure demonstrating the dominance of heterochiral interactions in the racemates independent of the diasteomeric structure change of the polar head group. The A0 values are characteristic for rotator phases. The smaller A0 value obtained for the racemic monolayers indicates their tighter packing caused by heterochiral interactions. The program Hardpack was used to predict the geometric parameters of possible 2-dimensional packings. For comparison with the experimental GIXD data, the two-dimensional lattice parameters and characteristic features of the enantiomeric and racemic diastereomeric stearoyl-threonine monolayers were calculated and are in reasonable agreement with the experimental GIXD data.

Influence of linkage type (ether or ester) on the monolayer characteristics of single-chain glycerols at the air-water interface.

O-1-Alkylglycerols are ubiquitous constituents in various biological materials but their biological significance is still largely unknown. So far, reports about the striking role of structural features on the interfacial properties of 1-O-alkylglycerol monolayers are quite rare. Therefore, in the present paper 1-O-alkylglycerol monolayers are comprehensively characterized on mesoscopic and molecular scales in the accessible ranges of temperature and surface pressure. Two Bragg peaks found for the condensed monolayer phase of the racemates at all pressures investigated indicate an orthorhombic structure with NN-tilted alkyl chains at lower pressures and NNN-tilted chains at higher pressures. In contrast to the continuous change of the tilt angle, as observed for many amphiphile monolayers, the tilt angle in 1-O-alkyl-rac-glycerol monolayers shows a jump-like transition from the L2 (NN tilt direction) to the Ov phase (NNN tilt direction) with the consequence of different slopes of 1/cos(t) vs. π in the two phases. This is the most striking difference to the behavior of the corresponding ester compound 1-stearoyl-rac-glycerol, having an oblique phase between the two orthorhombic phases L2 and Ov at low temperatures. The generic phase diagrams of the 1-O-alkyl-rac-glycerol and 1-acyl-rac-glycerol monolayers are essentially different. The influence of chirality on the monolayer structure is weak and becomes even weaker at high temperatures (rotator phases) and high lateral compression. The GIXD results of the enatiomeric pure compounds show the expected oblique lattice structure characterized by three Bragg peaks at almost all lateral pressures measured. The results of the GIXD studies are complemented by other monolayer characteristics such as π-A isotherms and mesoscopic domain topographies. The π-A isotherms of 1-O-alkyl-rac-glycerols are similar to those of the corresponding 1-acyl-rac-glycerols indicating that the change from the ester linkage to the ether linkage does not affect significantly the thermodynamic features. However, pronounced differences in the topological structure are observed. 1-O-hexadecyl-rac-glycerol monolayers form three-armed domains whereby each arm is subdivided into two segments with different molecular orientation. Also fascinating chiral discrimination effects are observable, demonstrated in the case of S-enantiomers by always clockwise curved spirals at the domain periphery. The 1 : 1 racemic mixtures exhibit both clockwise and counterclockwise curved spirals.

Special features of monolayer characteristics of N-alkanoyl substituted threonine amphiphiles.

The monolayers of N-alkanoyl substituted threonine amphiphiles, similar to those of other N-alkanoyl-substituted amino acid amphiphiles, point to substantial differences in the main characteristics compared to usual amphiphilic monolayers. π-A measurements of the enantiomeric and racemic forms of N-alkanoyl-substituted threonine monolayers with C16 and C18 chain lengths reveal that, independent of the alkyl chain length, all compression curves are located above the corresponding decompression curves. A theoretical model developed for the kinetics of two-dimensional condensation of Langmuir monolayers can describe this behavior concluding the attachment of monomers to large aggregates. The linear fit of the entropy changes versus temperature (ΔS = f(T)) at the LE/LC phase transition and extrapolation to zero ΔS specifies the critical temperature Tc, above which the monolayer cannot be compressed into the condensed state. The relatively small ΔTc difference between the enantiomeric and the racemic forms is consistent with the increased strength of van der Waals interactions between the longer alkyl chains reducing the influence of chirality on the thermodynamic parameters. The BAM experiments reveal clearly the absence of inner anisotropy as a specific feature of the domain topology of N-palmitoyl-threonine monolayers. Furthermore, the growth kinetics of the racemic N-palmitoyl-dl-threonine domains reveals a transition from homochiral discrimination and chiral separation within the domain to a state with heterochiral preference. GIXD studies show that at all pressures the enantiomers exhibit three Bragg peaks indicating an oblique lattice structure, whereas the racemates show only two Bragg peaks indicating a NNN tilted orthorhombic structure. Characteristic for the structure of all condensed monolayer phases is the large tilt angle of ∼49°, nearly independent of the lateral pressure. The transition from the oblique lattice structures, as detected for enantiomeric monolayers, to orthorhombic structures of racemic monolayers is clear evidence that the dominant heterochiral interaction in the racemic mixtures leads to the formation of a compound with congruent transition pressure having with ∼20.0 Å2 an essentially smaller alkyl chain cross-sectional area than the enantiomers with ∼20.7 Å2.

The effect of urea and taurine as hydrophilic penetration enhancers on stratum corneum lipid models.

To optimize transdermal application of drugs, the barrier function of the skin, especially the stratum corneum (SC), needs to be reduced reversibly. For this purpose, penetration enhancers like urea or taurine are applied. Until now, it is unclear if this penetration enhancement is caused by an interaction with the SC lipid matrix or related to effects within the corneocytes. Therefore, the effects of both hydrophilic enhancers on SC models with different dimensionality, ranging from monolayers to multilayers, have been investigated in this study. Many sophisticated methods were applied to ascertain the mode of action of both substances on a molecular scale. The experiments reveal that there is no specific interaction when 10% urea or 5% taurine solutions are added to the SC model systems. No additional water uptake in the head group region and no decrease of the lipid chain packing density have been observed. Consequently, we suppose that the penetration enhancing effect of both substances might be based on the introduction of large amounts of water into the corneocytes, caused by the enormous water binding capacity of urea and a resulting osmotic pressure in case of taurine.

Disordering Effects of Digitonin on Phospholipid Monolayers.

Digitonin, a steroidal saponin obtained from the foxglove plant (Digitalis purpurea), displays a wide spectrum of biological properties and is often used as a model in mechanistic investigations of the biological activity of saponins. In the present study, Langmuir monolayers of zwitterionic (DPPC, DMPE, POPC, POPE, DSPC, DSPE, and DPPE) and ionic (DPPS and DPPG) phospholipids were employed in order to better understand the effect of digitonin on the lipid organization. For this purpose, a combination of surface pressure relaxation, infrared reflection absorption spectroscopy (IRRAS), and fluorescence microscopy measurements was used. The observed increase in surface pressure (Π) suggests that digitonin can adsorb at the air/water interface, both bare and covered with the uncompressed phospholipid monolayers. However, the detailed analysis of IRRAS and fluorescence microscopy data shows that digitonin interacts with the lipid monolayers in a very selective way, and both the headgroup and the lipid tails affect this interaction. Nevertheless, it should be noted that in no case did digitonin cause any disruptive effects on the monolayers. The DPPE and DPPS monolayers get disordered by penetration with digitonin, despite an increase in surface pressure, leading to an unprecedented LC-LE transition. Interestingly, saponin could be easily squeezed out of these monolayers by mechanical compression.

Effect of the Alkanoyl Group Position at the Glycerol Backbone on the Monolayer Characteristics Demonstrated by 2-Monopalmitoyl-rac-glycerol.

The influence of the position of the aliphatic chain at the glycerol backbone has been basically unknown. Solely the results of 2-monopalmitoyl-rac-glycerol obtained at ≥13 °C indicated an essential influence of the position of the palmitoyl group at the glycerol backbone, substantiated by a disordered packing of the alkyl chains. Therefore, the present study extends the comprehensive characterization of 2-monopalmitoyl-rac-glycerol monolayers to the low-temperature range for highlighting the effect of the position of the aliphatic chain at the glycerol backbone of monoalkanoylglycerolester monolayers. Systematic studies of the thermodynamic behavior, the morphological features, and the 2D lattice structures of 2-monopalmitoyl-rac-glycerol monolayers at ≤10 °C allow useful conclusions. Large differences between the π-A isotherms of 1- and 2-monopalmitoyl-rac-glycerol monolayers and their thermodynamic analysis indicate that the change of the substitution from position 1 to position 2 of glycerol backbone is consistent with a shortening of the alkyl chain by roughly two CH2 groups. Quantum chemical calculations of the molecular structure and packing calculations are in reasonable agreement with the thermodynamic results. Considerable diversity in the mesoscopic domain topography exists between the monoalkanoylglycerol esters with the aliphatic chain positioned at the end of the glycerol backbone (1-position) and those with the aliphatic chain in the middle of the glycerol backbone (2-position). The new faceted shape of the 2-monopalmitoyl-rac-glycerol domains, before they develop branched fractal-like structures at the edges, is the essential difference to the round or cardioid-like 1-monoalkanoylglycerol domains. In the low-temperature range, well-defined orthorhombic lattice structures exist at all surface pressures. Comparing all GIXD data from the three racemic compounds (1-monostearoyl-rac-glycerol, 1-monopalmitoyl-rac-glycerol, and 2-monopalmitoyl-rac-glycerol) shows that 2-monopalmitoyl-rac-glycerol behaves as 1-monomyristoyl-rac-glycerol, i.e., the shift from position 1 to position 2 of the glycerol backbone is equivalent to a shortening of the alkyl chain.

Effect of chirality on monoacylglycerol ester monolayer characteristics: 3-monostearoyl-sn-glycerol.

The effect of chirality on the thermodynamic behavior, the morphological features, and the 2D lattice structures of 3-monostearoyl-sn-glycerol monolayers is studied. The present study focusses on the influence of the alkyl chain length on the chiral discrimination. Surface pressure-area (π-A) isotherms, Brewster angle microscopy (BAM), and particularly, grazing incidence X-ray diffraction (GIXD) are the experimental basis of the presented results. The π-A isotherms of the enantiomeric 3-monostearoyl-sn-glycerol monolayers measured between 25 and 38 °C resemble those of the racemic 1-monostearoyl-rac-glycerol monolayers, thus indicating small energetic differences between the enantiomeric and the racemic forms. The absolute ΔS values increase as the temperature decreases and thus, the ordering of the condensed phase increases at lower temperatures. The extrapolation to zero ΔS provides a critical temperature Tc of 42.1 °C (315.3 K), above which the monolayer cannot be compressed into the condensed state. Despite the great tendency of the 3-monostearoyl-sn-glycerol domains to develop irregular deviations in shape and inner texture, regular domains similar to those of the racemic monoacylglycerol esters are also formed. GIXD measurements performed over a large range of lateral pressures at four different temperatures (5, 10, 15 and 20 °C) indicate the dominance of the chiral nature. Contour plots with three clearly separated diffraction signals are observable in a large pressure range which is shifted to higher lateral pressures with increasing temperature. The comparison with the contour plots of the homologous 3-monopalmitoyl-sn-glycerol monolayers reveals the stronger dominance of the chiral nature with increasing alkyl chain length and thus, demonstrates the stronger influence of the lattice symmetry. The lattice data obtained by fitting the contour plots with 3 or 2 peaks demonstrate the resemblance to orthorhombic structures with NN tilted molecules at low pressures and NNN tilted molecules at high pressures. The temperature and alkyl chain length dependence of the distortion at zero tilt angle, d0, of the enantiomeric and racemic monoacylglycerols shows an increased influence of chirality on the lattice distortion for the shorter-chain compound (equivalent to increased temperature). This demonstrates that lattice distortion and lattice symmetry are differently influenced by chirality.

Phase Characteristics of 1-Monopalmitoyl-rac-glycerol Monolayers at the Air/Water Interface.

1-Monopalmitoyl-rac-glycerol is omnipresent in numerous biological and applied systems. Systematic GIXD measurements of 1-monopalmitoyl-rac-glycerol monolayers are carried out over a large pressure interval at 5, 10, and 15 °C to construct the phase diagram on the basis of reliable 2D lattice structures. These studies are complemented by other monolayer characteristics, such as π-A isotherms and mesoscopic domain topographies. A phase transition is found between the two orthorhombic structures with NN and NNN tilted alkyl chains at low temperatures (5 and 10 °C). It increases linearly with increasing temperature. With a further increase in temperature to 15 °C, only NN-tilted orthorhombic lattices are observed in the whole pressure region. The cross-sectional area, A0, is less affected by surface pressure and temperature and amounts to values of between 19.7 and 19.8 Å(2), as expected for a rotator phase at the lower limit. The tilt angle t with respect to the surface normal decreases with increasing pressure and is only slightly influenced by the temperature. The transition pressure to untilted alkyl chains, as determined by the extrapolation of 1/cos(t) to zero tilt angle, is >50 mN/m for all temperatures. The results of lattice distortion d versus sin 2(t) suggest for 10 and 15 °C the tilt of the aliphatic chains as the reason for the monolayer lattice distortion whereas at 5 °C the nonzero-tilt-angle intercept d0 could be an indication of the prevention of hexagonal packing. The generic π-T phase diagram of racemic monoacylglycerol monolayers is constructed on the basis of the phase diagrams of 1-monopalmitoyl-rac-glycerol and 1-monostearoyl-rac-glycerol, which shows that for 1-monopalmitoyl-rac-glycerol monolayers the oblique phase can occur only close to and below 0 °C. The possible phase behavior of other racemic monoacylglycerol monolayers with alkyl chain lengths of C14 and C20 is discussed on the basis of the generic phase diagram.

A comparative structural study in monolayers of GPI fragments and their binary mixtures.

Glycosylphosphatidylinositols (GPIs), natural complex glycolipids essential for a range of biological functions, are poorly understood with regard to their interactions and arrangements in cellular membranes. To evaluate the role of the head group in the structure formation in 2D model membranes (monolayers formed at the soft air/liquid interface), we employed the highly surface sensitive grazing incidence X-ray diffraction technique to investigate three GPI-fragments bearing the same hydrophobic part but different head groups. Condensed monolayers of simple GPI fragments are defined only by ordered alkyl chains. The monolayers of more complex fragments are additionally characterized by highly ordered head groups. Due to the strong H-bond network formed by the head groups, GPI-fragment both segregates and induces order into a model membrane phospholipid (POPC) that mimics the liquid-disordered phase of cell membranes. Here, we show that the strong van der Waals interactions between hydrophobic chains overcome the head group interactions and dominate the structure formation in mixtures of GPI-fragment with lipids that form liquid-condensed phases. This behaviour can be linked to the GPIs affinity for the lipid rafts.

Monolayers of amino acid-type amphiphiles.

The monolayer characteristics of selected N-alkanoyl substituted α-amino acid are studied with the objective to demonstrate the specific effect of the chemical structure of the polar head group which is highlighted with the D- and L-enantiomers of the following selected examples: R-alanine, R-serine, R-threonine, R-allo-threonine, and R-aspartic acid (R = C16, C18). The thermodynamic effect of the head group variation is studied. Experimental π-A isotherms of the N-tetradecyl-L-alanine monolayers show similar behavior as those of usual amphiphiles. The -CH3-group in R-alanine with the simplest head group structure is substituted by a -CH2-OH group in R-serine and serine methylester and by a -CH- CH3-OH group in R-threonine (or allo-threonine) and threonine methylester. The introduction of the methyl group in 3-position of serine (serine to 3-methyl-serine = threonine) shifts the characteristic temperatures by >20 K to lower values determined for N-C16-Dl-serine. The formation of the corresponding methylester decreases these temperatures by 15 K for serine with the shorter (C16) alkyl chain and only by ∼5 K for threonine with the longer chain (C18). The π-A curves of the enantiomeric and racemic allo-forms show similar features to those of N-stearoyl-threonine. The absolute T0-values (disappearance of the LE/LC-transition) are 4-5 K larger compared with the corresponding N-stearoyl-threonines, but the ΔT0 between the enantiomeric (D) and the racemic (DL) forms is only slightly larger than that of N-stearoyl-threonine. Monolayers of different N-alkanoyl substituted α-amino acid amphiphiles have been mesoscopically characterized. Substantial topological differences are observable at the condensed phase domains of several amino acid amphiphiles, such as, N-palmitoyl aspartic acid, N-palmitoyl- or N-stearoyl serine methyl ester, N-stearoyltyrosine, N-palmitoyl or N-myristoyl alanine. Many fascinating domain shapes are found, but always the curvatures of the two enantiomeric forms are directed in an opposite sense. The domain shape of the 1:1 racemic mixtures is usually different, but very often oppositely curved texture elements are observable. GIXD is used to study the characteristic features of the lattice structure of condensed monolayer phases on the Angstrom scale. Specific for all structures is the large tilt angle with respect to the surface normal, which decreases only marginally by compression. The large size of the head groups and strong interactions between them dominate the monolayer structure. As presented for NC16 and N-C18-threonine, N-C16-DL -serine, N-C16-L -serine, NC16 DL -serine-ME, NC16 L -serine-ME, NC18 DL -threonine-ME, and NC18 L -threonine-ME the enantiomers form an oblique lattice structure (3 diffraction peaks), whereas two peaks are observed for the racemates forming NNN tilted orthorhombic structures. A complete phase diagram of mixed monolayers of the D- and L-enantiomers of N-stearoyl-threonine with two eutectic points at xD ≈ 0.25 and xD ≈ 0.75 is proposed. The quantum chemical semiempirical PM3 method is applied to calculate the thermodynamic and structural parameters of clusterization in finite and infinite clusters for N-alkanoyl-substituted alanine with n = 8-17 carbon atoms in the chain at the air/water interface with the aim to obtain a new theoretical verification of the experimental results.

Monolayer characteristics of a long-chain N,O-diacyl substituted ethanolamine at the air/water interface.

The N- and/or O-acylation of amphiphilic ethanolamine attracts particular attention because of its interesting biological, pharmaceutical, and medicinal properties. Tetradecanoic acid-2-[(1-oxotetradecyl)amino]ethyl ester (TAOAE) as the selected N,O-diacyl derivative of ethanolamine has been synthesized in order to obtain first information about its main interfacial characteristics, such as the surface pressure-area (π-A) isotherms, the morphology of the condensed phase domains, the lattice structure of the condensed phase, and information about the existence of interfacial hydrogen bonds (-NH···O═C-). The π-A isotherms of TAOAE, similar to those of the most usual monolayers of amphiphiles, show a sharp break point (A(c)) indicating the first-order phase transition from the fluid (liquid-expanded (LE), gaseous (G)) to the condensed (liquid-condensed (LC)) phase. On the mesoscopic scale, the dendritic domains homogeneously reflecting suggest an orientation of the alkyl chains perpendicular to the aqueous surface. The grazing incidence X-ray diffraction (GIXD) studies reveal hexagonal packing of the TAOAE molecules oriented perpendicular to the surface in an LS phase. The existence of a hydrogen-bonding network in the monolayer is supported by infrared reflection absorption spectroscopy (IRRAS) experiments.

The influence of steroidal and triterpenoid saponins on monolayer models of the outer leaflets of human erythrocytes, E. coli and S. cerevisiae cell membranes.

The present paper discusses the use of monolayers of lipid mixtures mimicking the composition of biological membranes of bacteria, erythrocyte and yeast in the context of the anti-bacterial, hemolytic and anti-fungal activity of saponins. Saponins are plant-produced glycosidic biosurfactants with either steroidal or triterpenoidal aglycone. In the present study we used digitonin as a representative steroidal saponin (extracted from Digitalis purpurea) and a mixture of triterpenoid saponins from Quillaja saponaria Molina. The effect of saponins was studied first on monolayers consisting of single lipids characteristic for the given type of biological membrane, and then - on model mixed lipid monolayers. Finally, the monolayers were formed from total lipid extracts of natural cell membranes (E. coli and S. cerevisiae) to verify the results obtained in the simplified models. The effect of saponins on monolayers was studied by a combination of surface pressure relaxation, infrared reflection - absorption spectroscopy (IRRAS) and fluorescence microscopy. In line with expectations, sterols (cholesterol and ergosterol) play a major role in the saponin-lipid interactions in monolayers, which may explain especially the hemolytic and antifungal properties of saponins. In contrast, bacterial membranes are devoid of sterols, although the presence of similar compounds may be responsible for their affinity to saponins. Nevertheless, the effect of saponins on bacterial models is less pronounced than for the erythrocyte or fungal ones.

Lattice structures and phase behavior of amphiphilic monoglycerol monolayers.

Due to the Angstrom resolution, Grazing incidence X-ray diffraction (GIXD) represents the most important technique for probing the lateral ordering in condensed monolayers at the air/water interface and allows the construction of phase diagrams of amphiphilic monolayers on the basis of two-dimensional lattice structures and tilt directions of the molecules. The high potential of GIXD is demonstrated by the structural characterization of a variety of amphiphilic monoalkanoylglycerol monolayers in Å-scale. The GIXD results have impressively shown that in the racemic 1-monostearoylglycerol monolayer with the appearance of an oblique intermediate phase (Obl) between the nearest neighbor (NN)- and next-nearest neighbor (NNN)-tilted orthorhombic phases symmetry breaking occurs at low temperatures. The generic lateral pressure-temperature phase diagram of racemic monoacylglycerol monolayers constructed on the basis of reliable two-dimensional lattice structures indicates that the new and surprising presence of the oblique phase depends only on the temperature. The significant effect of the substituted polar groups, chemical structure variations at the position of the glycerol backbone and chirality on the lattice structure in Å-scale was highlighted in a systematic overview on the structure and phase behavior of amphiphilic monoglycerol monolayers. The conspicuous effect of the position of the glycerol backbone at which the polar group is substituted is demonstrated. The monolayers of 2-monopalmitoyl-rac-glycerol behave as that of 1-monomyristoyl-rac-glycerol having a two CH2 groups shorter alkyl chain. Further main topics discussed are chiral discrimination and crossover between homo- and heterochiral discrimination supported by quantum chemical calculations.

Monolayer properties of surface-active metalorganic complexes with a tunable headgroup.

Surface-active metalorganic complexes can be used to construct organic thin films with excellent electronic and catalytic properties. We have recently introduced a new versatile surface-active ligand, which can efficiently coordinate a wide range of transition metals. In the present work we report an investigation of Langmuir monolayers of V V, Mo VI and Ti IV complexes of this ligand, using surface pressure-area isotherms, Brewster-angle microscopy, and Grazing incidence X-ray diffraction. The monolayers of these complexes are stable enough over broad temperature ranges to allow efficient transfer to solid substrates.

In-plane miscibility and mixed bilayer microstructure in mixtures of catanionic glycolipids and zwitterionic phospholipids.

SAXS/WAXS studies were performed in combination with freeze fracture electron microscopy using mixtures of a new Gemini catanionic surfactant (Gem16-12, formed by two sugar groups bound by a hydrocarbon spacer with 12 carbons and two 16-carbon chains) and the zwitterionic phospholipid 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) to establish the phase diagram. Gem16-12 in water forms bilayers with the same amount of hydration water as DPPC. A frozen interdigitated phase with a low hydration number is observed below room temperature. The kinetics of the formation of this crystalline phase is very slow. Above the chain melting temperature, multilayered vesicles are formed. Mixing with DPPC produces mixed bilayers above the corresponding chain melting temperature. At room temperature, partially lamellar aggregates with local nematic order are observed. Splitting of infinite lamellae into discs is linked to immiscibility in frozen state. The ordering process is always accompanied by dehydration of the system. As a consequence, an unusual order-disorder phase transition upon cooling is observed.

Analytical data of synthesized deuterated isopropyl myristate and data about the influence of IPM/IPMdeut on the thermodynamics and morphology of 2D Stratum Corneum models.

The data in this article shows the effect of isopropyl myristate (IPM) on a 2D Stratum Corneum lipid model. In the first part, the analytical characterization of the synthesized deuterated isopropyl myristate is given. Then a BAM image of the pure Stratum Corneum model used is shown and a dataset of surface-pressure - area isotherms considering various ratios of deuterated and non-deuterated IPM and the Stratum Corneum model mixture is provided. Assuming that after the plateau in the isotherm the area per molecule corresponds only to the Stratum Corneum model (squeezing out of IPM), the value of the area will correspond to the percentage of these lipids in the mixture when considering the pure SC model. The comparison of the real and the calculated areas per molecule is also done.

The effect of non-deuterated and deuterated isopropyl myristate on the thermodynamical and structural behavior of a 2D Stratum Corneum model with Ceramide [AP].

Isopropyl myristate (IPM) is a widely used penetration enhancer in pharmaceutical formulations, however, its mechanism of action on a molecular scale is still not completely understood. Previous work using a quaternary Stratum Corneum (SC) lipid model in bulk suggested the incorporation of isopropyl myristate into the SC lipid matrix, phase separation, and perturbation of the multilamellar lipid assembly. Here, we used 2D Langmuir monolayers of a ternary SC lipid model, containing ceramide AP C18:18, stearic acid and cholesterol in a molar ratio of [1:1:0.7], respectively, to shed light on the mechanism of action of this important lipophilic penetration enhancer. To do so, the synthesis of chain deuterated isopropyl myristate was successfully performed in order to study the different coupling possibilities between the hydrogenated and deuterated IPM and the alkyl chains of the SC molecules. Our results indicate that only a small portion of IPM is able to mix with our SC model leading to a limited fluidizing effect (small increase of the wavenumber of CH2 stretching vibration, increase of the SC layer flexibility), but will be squeezed out at higher lateral pressures. Furthermore, the deuteration of IPM enhances the miscibility with this SC model, probably due to a different coupling between the alkyl chains or the alkyl and deuterated chains. Additionally, using the pure D-form of CER[AP] in the SC model amplifies the obtained results.

Convex-concave curvatures in bilayers of dipalmitoylphosphatidylcholine and cholesterol induced by amphotericin B/deoxycholate after prolonged storage.

Freeze-fracture investigations on the influence of amphotericin B/deoxycholate on multilamellar vesicles (MLV) of DPPC containing cholesterol have revealed a new phase structure. Alternating convex and concave curvatures are observed after storage of the vesicles at temperatures below 25 degrees C for at least 4 weeks. Three types of these patterns occur, a small-dimensional (repeat distance approximately 100 nm), an intermediate-dimensional (repeat distance approximately 400 nm) and a large-dimensional (repeat distance approximately 700 nm). The types can be formed on the same bilayer side by side. Additionally, the types differ in the morphology of the tops. In the case of the small-dimensional type the shape of the top can be described as a circular flat plane or opening and in the other cases as a hemispherical cap. The large dimensional type differs from the others by involvement of bilayer stacks. The formation of this new phase after prolonged storage could be confirmed by DSC measurements. The new structure can be explained in the framework of bicontinuous cubic phases and periodically curved bilayer structures. From the electron micrographs a lo (liquid ordered) phase is suggested.

Optical detection of phase transitions in simple and mixed lipid-water phases.

A simple method for the detection of phase transitions in lipid-water systems by recording the intensity of the transmitted light through a sample placed between crossed polarizers as a function of the temperature was developed. A very small amount of lipid material is sufficient for its effective application. Two zwitterionic lipids in water, dipalmitoylphosphatidylcholine (DPPC) and dipalmitoylphosphatidylethanolamine (DPPE) as well as their mixtures were studied by means of this method. The results were compared with differential scanning calorimetry (DSC) data and a good correspondence was established. A phase diagram of the DPPC-DPPE mixture is constructed. This study also throws additional light on the nature of the 'pretransition' of DPPC.