H. Hasmonay

Lasalocid and biomimetic membranes: insertion in Langmuir films of lipids

The interfacial properties at the water surface of dipalmitoylphosphatidylcholine (DPPC) in monomolecular films containing various concentrations of lasalocid sodium salt (LAS) have been studied in the range from r = 0.005 to 0.1 (r = molar ratio LAS:DPPC). The data from which the results have been expressed were obtained from the following compression isotherms at constant temperature (22 degrees C): of mixed films, of pure DPPC and of pure LAS. The incorporation of LAS resulted in pressure and concentration dependent molecular area increase, between 0 and 16 mN m-1. The observed effect has been expressed as the area SA* occupied by each antibiotic molecule in the mixed films. The variations of SA* have been discussed at two levels of constant surface pressure, at 8 mN m-1 which is situated in the phase transition region of the DPPC isotherm and at 4 mN m-1 in the liquid expanded state. In both cases, the SA* values decreased as r increased. They have been related to the molar areas SA of LAS, obtained from the compression isotherm of the pure antibiotic and expressed as SA*/SA. This ratio was considerably greater than unity in the phase transition region within the studied concentration range and close to unity in the liquid expanded state. Using the method of Goodrich, the excess free energy of mixing GXS has been calculated. The values were positive above r = 0.01 and they increased with increasing concentrations. The results indicate non miscibility and strong repulsion between the two kinds of molecules in the mixed films. Two different mechanisms of insertion have been suggested.

Lasalocid and Monensin: Aggregation at the Lipid-Water Interface in Mixed Films

Abstract Insertion properties of the antibiotics Lasalocid and Monensin sodium salts (LAS-Na and MON-Na) in Langmuir monolayers of two different lipid molecules, dipalmitoylphosphatidylcholine (DPPC) and octadecanol (C180H), have been investigated. Results from compression isotherms of the films on pure water and on a biologically buffered subphase have been compared. Values of the molecular areas of mixed films of antibiotic/lipid and of the molecular areas of the pure lipids, at a given surface pressure, have been used to calculate the aggregation number k of the solute molecules in a concentration range of ρ (moles of antibiotic/moles of lipid) from 0.005 to 0.1. The k number in the film of DPPC increases when ρ increases, it is enhanced on the buffered subphase compared to the subphase of water and it is more important for MON-Na than for LAS-Na. There is hardly any evidence ofaggregation in the films of C180H. The two lipid systems both have in common that the mixed films with LAS-Na on the buffered ...

Drugs in biomimetic models: a monolayer study of two antibiotics

Abstract We have recently shown that the usual ionic cavity formation in lipid bilayers from the antibiotics lasalocid and monensin is also likely to take place in monolayers. The present study of Langmuir films of the pure antibiotic ionophores indicates that such formation might occur from two ring complexes at the interface.

Monolayers as Membrane Models. A Study of Antibiotic Action on Lipids

Abstract Langmuir films of the lipids dipalmitoylphosphatidylcholine, docosanoic acid and octadecanol, in presence of two antibiotic ionophores, monensin sodium salt and lasalocid sodium salt have been studied. An important area increase as a consequence of antibiotic addition has been observed in the π-A isotherms of the phospholipid. The effect has been considered as a result of ionic cavity formation accompanied by rearrangements in the lipid hydrocarbon chains. A smaller area increase of monolayers from the single chain lipids has been observed only when monensin sodium salt was added. Monolayer studies of monensin sodium salt allowed molecular area estimations of the pure antibiotic in the film.

Equilibrium position of carboxylic acid molecules in monolayers on aqueous subphases

Abstract Langmuir films of the carboxylic acids C22, C20, and C18 disclosed an unusual pressure π i at large molecular areas before compression when spread on subphases containing alkali hydroxydes. The pressure appeared only when the acids were fully ionized and increased with increasing electrolyte concentration in the subphase. π i was ion dependent and varied in the same manner as the sequence Li + + + and it decreased with increasing chain length. We have concluded that π i must be a consequence of carbon chains situated in the plane of the interface. This position is not in equilibrium since π i disappeared with time. We have attributed this to an evolution of the monolayer configuration into a more or less upright chain position. Further spontaneous rearrangements took place in the monolayers. These rearrangements were favored through successive compressions.

Interaction Between Ionophores and Biomimetic Membranes

Abstract Insertion properties of Lasalocid and Monensin as sodium salts (LAS-Na, MON-Na) in model membranes of dipalmitoylphosphatidylcholine (DPPC) have been studied in two biomimetic buffered systems: monolayers (Langmuir Film Balance) and multilamellar bilayers (Differential Scanning Calorimetry). Effects varying with the concentration and with the surface pressure have been observed within the experimental range of molar ratios r = antibiotic/lipid from 0.005 to 0.1. The area occupied by each antibiotic molecule and the relative molecular area increase at a given pressure, are different for the two molecules. The calorimetric measurements result in concentration dependent modifications of the characteristics of the gel-liquid crystal phase transition in the case of LAS-Na. No such modifications are observed in the case of MON-Na.

Some pyramidic liquid crystal Langmuir films at the air-water interface

Two compounds, the hexa-nonanoyloxytribenzocyclononene (I-n9) and the hexa-nonyloxytribenzocyclononene (II-n9), which belong to a new class of thermotropic liquid crystals, called pyramidic, were spread on the water surface. Their ability to form monolayers has been shown. Their surface pressure versus molecular area diagrams show a large plateau and an increase in surface pressure at low molecular areas. A multilayer arrangement of the molecules is discussed.

A monolayer study of the antibiotic ionophore monensin: pH influence and salt effects

Abstract New results from Langmuir films of monensin acid and sodium salt concerning the influence of pH and of the electrolytes NaCl and KCl have been discussed in comparison with previous work. From examination of the surface pressure-molecular area isotherms at the beginning of the compression at large molecular areas, we have considered the molecules as being in ring configurations at the interface down to the area where the pressure started to increase. We have further compared monensin acid and sodium salt in order to study the influence of complexation. Basically, we have observed two types of isotherm, one for protonated forms and another for unprotonated forms, both considered to be in ring configurations. At acidic pH of the subphase, we have assumed that we had empty protonated rings without cations and more or less complexed filled rings when cations were present. At basic pH we had evidence of dissociated carboxylate ions partially out of the interface plane at low electrolyte concentrations and establishment of an unprotonated in-plane ring complex when salt was added. Our results for pure water in the subphase have indicated a mixture of dissociated and undissociated forms which become complexed in presence of the cations. Differences were observed between effects from Na + where the isotherms moved to lower molecular areas and K + where they moved to higher areas, a supposed consequence of the different ionic radii.

A current measurement technique applied to Langmuir films

A charge is produced on an electrode placed a short distance above the air-water interface. This charge is different depending on the presence or the absence of a fatty acid monolayer and the effect is measured as the current produced when the electrode is lifted from the interface. The magnitude and sign of the current, which are highly sensitive to changes in the state of the monolayer, are dependent on the dipoles of the molecules at the water surface.

Electrical state of the water surface determined by the moving electrode set-up

Abstract A new current measurement method has been developed, allowing the determination of electrical characteristics on the water surface in the absence of or in the presence of monolayers. This work is concerned with the study of the surfaces of pure water and of acidic, basic and neutral ionic solutions. From the current versus time curves, i = f ( t ), the dipole density at the water surface has been calculated. On the other hand, the equation of the curve i = f ( t ) has been worked out. The theoretical results is in good agreement with the experimental one. In all cases a considerable decrease of the surface charge is observed for high ionic strength.