A model for binding of inhalation anesthetics to membranes: two dose-dependent distinctly different binding modes

Inhalation anesthetics currently in clinical use, such as halothane, methoxyflurane, enflurane, isoflurane, etc., are polar hydrophobic molecules, except nitrous oxide, which is an apolar and weak anesthetic, incapable of inducing surgical stage anesthesia. Experimental data are accumulating that these potent amphipathic inhalation anesthetics preferentially bind membranes and macromolecules on the surface at clinical concentrations. The anesthetic binding to lipid membranes in the low concentration range is characterized by a saturable curve approaching to a limiting value. When the anesthetic concentration s greatly increased above the clinical range, the binding starts to exceed the limiting saturation value. Our model for anesthetic binding to membranes consists of two parts: Langmuir-type adsorption to the membrane surface at the low concentration range and penetration into the hydrophobic core at the high concentration range. The present communication provides a statistical-thermodynamic basis to analyze this twostep interaction. An expression is derived for membrane capacitance as a function of anesthetic concentration, which explains the experimental data well. Binding parameters of anesthetics are estimated according to the theory.This study was supported by NIH grants GM 25716 and GM 26950, and by the Medical Research Service of the Veterans Administration.     

Diffuse double layer interaction between two parallel plates with constant surface charge density in an electrolyte solution

Summary The double layer interaction between two parallel metallic plates with adsorbed surface charge of constant density in a symmetrical electrolyte solution is considered. Numerical calculations using the nonlinearPoisson-Boltzmann equation are made. Analytic expressions for the interaction are also obtained by using theDebye-Hückel approximation. The double layer interaction is found to be influenced by true charges induced on the plate surface due to electrostatic induction. This influence becomes important at small plate separations. It is also shown that the force and potential energy of interaction between metallic plates are small compared with those between insulating plates.

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Zusammenfassung Die Wechselwirkung der Doppelschichten zwischen zwei parallelen metallischen Platten mit der konstanten Dichte der adsorbierten Oberflächenladung in einer symmetrischen Elektrolytlösung wird betrachtet. Numerische Berechnungen werden mittels der nichtlinearenPoisson-Boltzmannschen Gleichung ausgeführt. Durch Benutzung der Debye-Hückel-Näherung werden auch analytische Ausdrücke für die Wechselwirkung gewonnen. Es zeigt sich, daß die Wechselwirkung der Doppelschichten von reellen Ladungen, die an der metallischen Oberfläche durch elektrostatische Induktion induziert werden, beeinflußt wird. Dieser Einfluß wird besonders wichtig für kleine Plattenabstände. Die Kraft und die potentielle Energie der Wechselwirkung zwischen metallischen Platten sind kleiner als die zwischen Isolierplatten.

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With 4 figures and 3 tables     

Catalytic Asymmetric Phase‐Transfer Michael Reaction and Mannich‐Type Reaction of Glycine Schiff Bases with Tartrate‐Derived Diammonium Salts

Catalytic asymmetric Michael and Mannich‐type reactions of glycine Schiff bases with chiral two‐center organocatalysts, tartrate‐derived diammonium salts (TaDiASs), are described. On the basis of conformational studies, optimized TaDiASs with a 2,6‐disubstituted cyclohexane spiroacetal were newly designed. These TaDiASs catalyzed the asymmetric Michael and Mannich‐type reactions of glycine Schiff bases with higher enantioselectivity than previous catalysts. In the Mannich‐type reaction, aromatic N‐Boc‐protected imines (Boc=tert‐butoxycarbonyl) as well as enolizable alkyl imines were applicable. As a synthetic application of the catalytic asymmetric Mannich‐type reaction with the optimized TaDiASs, we developed a catalytic asymmetric total synthesis of (+)‐nemonapride, which is an antipsychotic agent.     

Electrophoretic mobility of a liquid drop in a salt-free medium

A theory is proposed for the electrophoretic mobility mu of dilute spherical liquid drops of radius a in salt-free media containing only counterions (e.g., nonaqueous media). As in the case of the electrophoretic mobility of rigid particle in salt-free media, there is a certain critical value of the drop surface charge separating two cases, that is, the low-surface-charge case and the high-surface-charge case. For the low-surface-charge case, mu coincides with that of a drop in an electrolyte solution in the limit of very low electrolyte concentrations kappaa-->0 (Hückel's limit), where kappa is the Debye-Hückel parameter. For the high-surface-charge case, however, mu becomes constant independent of the drop surface charge, since the counterion condensation takes place near the drop surface.     

Electrophoretic mobility of a charged spherical colloidal particle covered with an uncharged polymer layer

A general expression is derived for the electrophoretic mobility of a spherical charged colloidal particle covered with an uncharged polymer layer in an electrolyte solution in an applied electric field for the case where the particle zeta potential is low. It is assumed that electrolyte ions as well as water molecules can penetrate the polymer layer. Approximate analytic expressions for the electrophoretic mobility of particles carrying low zeta potentials are derived for the two extreme cases in which the particle radius is very large or very small.     

Distribution of local anesthetics in lipid membranes

Absorption of local anesthetics into lipid membranes and adsorption onto their surfaces were studied as a function of the pH of aqueous bulk solutions by measuring lipid vesicle electrophoretic mobility, the partition of the anesthetics between the aqueous and membrane phases by the use of fluorescence and radioactive tracer methods, and the effect of the anesthetics on interfacial tension of lipid monolayers formed at the oil/aqueous interface.

At a pH much lower than the pK_a value of the local anesthetic, the charged form of the local anesthetic was only adsorbed onto the membrane surface, as determined from vesicle electrophoretic mobility, radioisotope tracer and the monolayer surface tension studies. Surface partition coefficients of the charged form of the local anesthetics on phosphatidylcholine and phosphatidylserine membranes were obtained from the data of electrophoretic mobilities for lipid vesicles. The surface partition coefficients of various local anesthetics paralleled those of the bulk partition coefficients.

As the pH of the solutions increased, the adsorbed amount of the charged form of the anesthetic at the membrane interface decreased, while the absorption of the uncharged form of the local anesthetic into the membrane increased. The total amount of local anesthetic adsorbed per unit area of the membrane generally increased as the pH of the solution increased. This was also observed from the measurements of the fluorescence of local anesthetics adsorbed into the membranes. At lower pH than that corresponding to the pK_a value of the local anesthetic, the amount of anesthetic adsorbed depended greatly upon the membrane surface charge. At a higher pH than its pK_a, it did not depend appreciably on the surface charge density of the membrane but did depend on the bulk partition coefficients between the aqueous and oil phases.     

Approximate Expression for the Double-Layer Interaction Energy between Two Parallel Plates with Constant Surface Charge Density

An approximate expression for the potential energy of the double-layer interaction between two parallel similar plates with constant surface charge density is derived via a novel linearization method, in which the Poisson-Boltzmann is linearized with respect to the deviation of the electric potential from the surface potential (which is a function of the interplate separation h). This approximation works quite well for small plate separations h for all values of the surface charge density (or the unperturbed surface potential) and gives a correct limiting form of the interaction energy (or the interaction force) as h --> 0. Copyright 1999 Academic Press.     

Electroosmotic Velocity in Fibrous Porous Media

A theory of electroosmosis in an array of parallel cylindrical fibers of Kozak and Davis (J. Colloid Interface Sci.,112, 403 (1986)), in which the liquid flow is normal to the axes of the cylinders, is developed to derive a simple approximate expression for the electroosmotic velocity for low zeta potentials without involving numerical integration. The relative error is less than 6%.