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.

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.

[Are there diurnal variations in choroidal thickness?]. / Unterliegt die Aderhautdicke zirkadianen Schwankungen?

PURPOSE: Measurement of diurnal choroidal thickness in healthy eyes to investigate thickness variations. METHODS: A total of 30 healthy eyes in 30 subjects were examined at 6 predefined times within 24 h. Choroidal thickness was visualized using the 7-line scan of spectral domain optical coherence tomography (OCT) with enhanced depth imaging (Spectralis, Heidelberg Engineering) and manually measured by two independent observers. For statistical analyses the mean value was calculated. RESULTS: The mean choroidal thickness was 270 ± 87 µm. Choroidal thickness changes from baseline ranged between - 47 µm and + 41 µm. There was a statistically significant negative correlation between baseline choroidal thickness and the thickness in examinations at 10:30 am, 1:30 pm and 4:30 pm with the Spearman correlation test. Due to the large diversity in the individual diurnal fluctuations, a significant diurnal variation of choroidal thickness was not observed. There was a significant negative correlation between age and choroidal thickness. CONCLUSIONS: In this study a significant diurnal variation of choroidal thickness was not observed. Patient age correlated negatively with choroidal thickness.

Study of the influence of the penetration enhancer isopropyl myristate on the nanostructure of stratum corneum lipid model membranes using neutron diffraction and deuterium labelling.

In order to elucidate the mode of action of the lipophilic penetration enhancer isopropyl myristate (IPM) on a molecular scale, we investigated oriented quaternary stratum corneum (SC) lipid model membranes based on ceramide AP, cholesterol, palmitic acid and cholesterol sulfate containing 10 wt% IPM by means of neutron diffraction. Our results indicate that IPM affects the lamellar lipid assembly in terms of bilayer perturbation and disordering. Phase segregation occurred, indicating that IPM is not likely to mix properly with the other SC lipids due to its branched structure. We used selective deuterium labelling to localize the penetration enhancer, and could successfully prove the presence of IPM in the two coexisting lamellar phases. We conclude that IPM's mode of action as penetration promoter is presumably based on incorporation into the SC lipid matrix, extraction of certain SC lipids into a separate phase and perturbation of the multilamellar lipid assembly.

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.

[Protected mercaptoalkylpyrimidinones: synthesis and test for immunostimulating activity]. / Maskierte Mercaptoalkylpyrimidinone: Synthese und Prüfung auf immunstimulierende Wirkung.

Protected mercaptoalkylpyrimidinones: synthesis and test for immunostimulating activity 3-Hydroxyalkyl-pyrimidine 1 reacts with phosphoroxychloride and thioglycolic acid or thiourea to yield pyrimidin-3-ylalkylthioacetic acids 3 or pyrimidin-3-ylalkylthiouroniumsalts 5 respectively. Some of the pyrimidines 3 and 5 showed immunomodulatory activity.

Biophysical and biochemical properties of a binary lipid mixture for DNA transfection.

The phase and miscibility behavior of a triple-chain phosphatidylcholine (TPHPC) and a single-chain surfactant (CTAB) were investigated in aqueous dispersions and in monolayers at the air/water interface. CTAB can be incorporated in the TPHPC monolayer because of its complementary molecule shape and reduces the tilt angle of TPHPC. The type of phases and the phase sequence (L2 - LS) are the same in the pure TPHPC monolayer and in the TPHPC/CTAB (80:20 mol:mol) mixture. No indication of any ordering of adsorbed DNA was observed. In the aqueous dispersions, TPHPC exhibits an inverted hexagonal phase above the chain melting. The addition of 30 mol% CTAB leads to the appearance of a lamellar Lalpha phase. The binding of DNA to the mixture is obvious but this is accompanied by a separation of the two lipids what is supported by monolayer experiments. The system has no long-term stability. The main reason seems to be not only the stronger interaction of DNA with CTAB, but also especially the unexpected weak interaction between CTAB and TPHPC. The transfection efficiency is lower compared with lipofectamine. The main disadvantage of this system is the cytotoxicity of CTAB, which could not be lowered by incorporation of CTAB in the TPHPC bilayer.

New modified single chained glycolipids. Part 1: synthesis of deoxy and partially O-methylated glycolipids with or without a sulfur containing spacer.

A way to synthesize neoglycolipids with high yields and anomeric purity is described. Starting point of the synthesis strategy is the glycosylation of allyl alcohol with definite steric orientation. Introduction of the hydrophobic moiety was achieved by photoaddition of n-hexadecanethiol and 3-mercaptopropionic acid followed by amidation with n-hexadecylamine, respectively. In order to investigate the influence of different carbohydrate headgroups in the physicochemical behavior of the general glycolipid, especially the orientation of the alkyl chain, a range of neoglycolipids was synthesized. Beside the differences in the configuration between unfunctionalized glycopyranoses like D-glucose, D-galactose and D-mannose, a number of deoxy and partially O-methylated sugar derivatives was prepared. The divergences concerning the different carbohydrate headgroups and the hydrophobic moiety, respectively, can be compared to relatively simple structured glycolipids with hexadecyl residue and without spacer function.

Phase transitions and hydrogen bonding in a bipolar phosphocholine evidenced by calorimetry and vibrational spectroscopy.

As a model for natural archaebacterial bolalipids, we have synthesized omega-hydroxybehenylphosphocholine (HBPC, HO-(CH(2))(22)-OP(O(-)(2))O-(CH(2))(2)-N+(CH(3))(3)) and investigated it, by Fourier-transform infrared and Raman spectroscopy and differential scanning calorimetry, both as fully hydrated dispersions (varying temperature) and as aligned films (varying hydration) in terms of particular structural features predestining such bipolar lipids for their occurrence in extremophilic organisms. The phase behavior of HBPC in dispersions depends on sample pretreatment as it comprises metastabilities in annealed samples. However, main transition proceeds consistently near 81 degrees C. Some (extra) deal of headgroup (phosphate) hydration accompanying a gel-gel phase transition near 66 degrees C appears to precede chain melting. Studies with HBPC films revealed lamellar interdigitated-like solid phases with an extraordinarily strong omega-OH--OPO(-) omega-OH--OPO(-) omega-OH hydrogen-bond pattern formed along both sides of the resulting monolayers. The "clamping" effect inherent to such structures provides a clue to explain the relatively high main-transition temperature of HBPC assemblies.

Synthesis, calorimetry, and X-ray diffraction of lecithins containing branched fatty acid chains.

Lecithins with branched fatty acid chains were synthesized and characterized by differential scanning calorimetry and X-ray diffraction. The influence of three chemical alterations on the phase transition parameters were investigated: length of the branches in 2-position of the acyl chains, position of the branches in the acyl chains, and position of the branched fatty acid chains in the glycerol backbone. The results show that the branched phosphatidylcholines (PCs) have a reduced gel-to-liquid-crystalline phase transition temperature (Tm) compared to the corresponding straight-chain PCs. Depending on both the length of the branches in 2-position of the acyl chains and the position of the branches in the acyl chains, the Tm-values pass through a minimum. The systematic change of the main-transition temperatures Tm is connected with a modified structural polymorphism. If the length of the branches increases three types of polymorphism were observed.

Effect of lysolecithin analogues on plant viruses.

Newly synthesized lysolecithin analogues 2-0-hexadecyl-glycero-3-phosphocholine (1) and its methyl (2), ethyl (3) and benzyl (4) derivatives were tested with regard to the anti- phytoviral effect on potato virus X ( PVX ), red clover mottle virus ( RCMV ) and tobacco mosaic virus (TMV). The first two compounds (1, 2) reduced markedly the content of PVX and RCMV in systemically infected host plants as evidenced by precipitin test and bio-assay. Whereas compounds (1), (2) and (3) did not significantly influence the local lesion formation caused by TMV, compound (4) increased the number of necrotic lesions. In the presence of all four lysolecithin analogues, especially of (1), (2) and (3) the infectivity of virus particles was reduced.

[Synthesis of 2-substituted alkanolphosphoric acid esters with lytic effects]. / Synthese von lysierend wirkenden 2-substituierten Alkanolphosphorsäureestern.

Lysolipid analogues were synthetized and tested for haemolytic activity. Initial substances were long-chain 2-methylalkanols, as well as 2-hexadecylpropane-1,3-diol. The latter compound was prepared starting with hexadecylmalonic acid diester. Among the compounds synthetized, there were also 1-acetoxy-2-hexadecylpropan-3-ol-phosphocholine and acidic-reacting lysolipid analogues.

[Synthesis and biological activity of some lysing and fusogenically active phosphocholine derivatives]. / Syntheses und biologische Aktivität einiger lysierend und fusogen wirkender Phosphocholinderivate.

2-Hexadecylglycerophosphocholine (1) and its 1-O-methyl, 1-O-ethyl and 1-O-benzyl (4) derivatives as well as some n-alkanol phosphocholines were synthetized and tested for haemolytic activity. Most potent (LD50 approximately equal to 5.10(-6) mol/l) were 1 and the hexadecanol and octadecanol phosphocholines (7 and 8). 1, 4 and 7 were tested for fusogenic activity against vegetable protoplasts. When used at sublytic concentrations (0.01 - 0.05 mmol), these compounds were as efficient as polyethylene glycol.