Lipid immiscibility

Lipophilicity is a molecular property expressing the relative affinity of solutes for an aqueous phase and an organic, water-immiscible solvent. As such, lipophilicity encodes most of the intermolecular forces that can take place between a solute and a solvent, and represents the affinity of a molecule for a lipophilic environment. This parameter is commonly measured by its distribution behavior in a biphasic system, described by the partition coefficient of the species X, P. Thermodynamically, is defined as a constant relating the activity of a solute in two immiscible phases at equilibrium [111,112]. By convention, P is given with the organic phase as numerator, so that a positive value for log P reflects a preference for the lipid phase ... 

Material barriers Contours of land Immiscible substances (lipids) in membranes Earth s mantle (oxides)... 

The partition of different lipids between two immiscible solvents (countercurrent distribution) is useful for crude fractionation of lipid classes with greatly differing polarities. Repeated extractions in a carefully chosen solvent pair increase the effectiveness of the separation but in practice mixtures of lipids are still found in each fraction. A petroleum ether-ethanol-water system can be used to remove polar contaminants (into the alcoholic phase) when interest lies in the subsequent analysis of neutral glycerides, which may be recovered from the ether phase. Carbon... 

The partition coefficient (P) is a measure of how a drug partitions between a water-immiscible lipid (or an organic phase) and water. It is defined as follows ... 

Various foods (e.g., grains, grain-based foods, fruits, and Ground sampie in water (water-soluble foods or sulfuric acid (water-immiscible foods) and introduce in headspace analyzer GC/MS <0.001 mg/g (wate r-so I u b le foods) 0.01-0.05 mg/g (lipid-containing foods) 90%-100% Entz and Hollifield 1982... 

Moreover, nanoparticles can be prepared by precipitation in oil/water (o/w) emulsions [15]. Lipids dissolved in a water-immiscible organic solvent (e.g., cyclohexane) are... 

Several models have been suggested for the estimation of the distribution ratios of nonionic solutes between water and (practically) immiscible organic solvents. One model takes 1-octanol to represent, in general, lipophilic ( fat-liking ) media, which hydrophobic ( water-fearing ) solutes would prefer over water. Such media may be oils, biological lipid membranes, and, somewhat less suitably, hydrocarbon solvents. 

Emulsions are mixture of two (or more) immiscible substances. Everyday common examples are milk, butter (fats, water, salts), margarine, mayonnaise, skin creams, and others. In butter and margarine, the continuous phase consists of lipids. These lipids surround the water droplets (water-in-oil emulsion). All technical emulsions are prepared by some kind of mechanical agitation or mixing. Remarkably, the natural product, milk, is made by organisms without any agitation inside the mammary glands. 

Figure 2 shows a spin-label-derived phase diagram for binary mixtures of (II) and (IV), dipalmitoylphosphatidylcholine and dielaidoylphosphatidylcholine. It will be seen that the diagram describes miscibility of these two lipids in both the solid and solution phases. (Other binary mixtures of lipids show immiscibility in the solid as well as the fluid phases.45,54)... 

Differentiation between ideal miscibility and complete immiscibility is possible by evaluating surface pressure/area isotherms. According to the phase rule of Defay and Crisp 53-67) in a completely immiscible monolayer the surface pressures observed for phase transitions or collapse points are equal to those of the pure components. This case of a completely immiscible monolayer is schematically illustrated in Fig. 29 (left). In a completely miscible lipid monolayer these surface pressures vary with different molar ratios of the lipid components. 

In contrast, unchanged polymerization rates for all molar ratios of a polymerizable lipid indicate the formation of monomer islands and thus complete immiscibility. 

In contrast to this, the system neutral lipid (2J)/DSPC shows considerably smaller deviations from the additivity rule and the surface pressure/area isotherms indicate two collapse points corresponding to those of the pure components62. Photopolymerization can be carried out down to low monomer concentrations and no rate change is observed. These facts prove that the system (23)/DSPC is immiscible to a great extent. The same holds true for mixed films of diacetylenic lecithin (18, n = 12) with DSPC, as well as for dioleoylphosphatidylcholine (DOPC) as natural component. 

In mixed bilayer vesicles diacetylenic and natural lipids exhibit the same miscibility behavior as in monomolecular films. This can be demonstrated using differential scanning calorimetry (DSC). The neutral lipid (23) is immiscible with DSPC or DOPC as indicated by the two phase transitions of the mixed liposomes which occur at the same temperatures as those of the pure components (Fig. 33 a). 

Besides differential scanning calorimetry, electron microscopy can also serve for characterizing the mixing behavior of multicomponent vesicular systems. The ripple structure of phospholipids with saturated alkyl chains (also referred to as smectic Bca phase, Fig. 35) is taken to indicate patch formation (immiscibility) in mixed phos-close enough (1-2 nm) lipid molecules are able to diffuse from one membrane to the between the pre- and main-transition of the corresponding phospholipid, electron... 

Emulsifiers. The chemical structures of emulsifiers, or surfactants, enable these materials to reduce the surface tension at the interface of two immiscible surfaces, thus allowing the surfaces to mix and form an emulsion. An emulsifier consists of a polar group, which is attracted to aqueous substances, and a hydrocarbon chain, which is attracted to lipids. Emulsifiers include mono- and diglycerides, lecithin, propylene glycol esters, luctylated esters, sorbttan and sorbitol esters, polysorbate.x, and sucrose esters. 

Reversed-phase chromatography is the term commonly applied to a system where a nonpolar liquid phase is coated on the solid support and elution carried out with an immiscible polar phase. Such systems are often necessary for separations which cannot be carried out by normal partition or adsorption chromatography. For TLC, the stationary phase is normally a liquid of high boiling point which does not readily evaporate from the adsorbent. Paraffin oil, silicone oil or n-tetradecane coated on silica gel or Kieselguhr are frequently used with water-based mobile phases such as acetone—water (3 2) or acetic acid-water (3 1). Reversed-phase chromatography is very useful for the TLC analysis of lipids and related compounds. 

A second physicochemical parameter influencing chemical penetration through membranes is the relative lipid solubility of the potential toxicant that can be ascertained from its known partition coefficient. The partition coefficient is a measure of the ability of a chemical to separate between two immiscible phases. The phases consist of an organic phase (e.g., octanol or heptane) and an aqueous phase (e.g., water). The lipid solvent used for measurement is usually octanol because it best mimics the carbon chain of phospholipids, but many other systems have been reported (chloroform/water, ether/water, olive oil/water). The lipid solubility and the water solubility characteristics of the chemical will allow it to proportionately partition between the organic and water phase. The partition coefficients can be calculated using the following equation ... 

Partition coefficient represents the equilibrium ratio of the molar concentrations of a chemical substance (the solute) in a system containing two immiscible liquids. The octanol / water partition coefficient is expressed as either Kow or P and is a descriptor of a substance s relative affinity for lipids and water. For purposes of simplification, Kow is usually reported as its common logarithm (log Kow or log P). A large log Kow value for a chemical (relative to other substances) indicates that the chemical has a greater affinity for the n-octanol phase and, hence, is more hydrophobic (lipophilic). A negative log Kow value indicates that a chemical has a greater affinity for the water phase and, hence, is more hydrophilic. 

Hansch and Toshio Fujita, a postdoctoral researcher in Hansch s group, designed a parameter, ttr, to estimate the lipophilicity of an R-group.3 Hansch s parameter relies on partition coefficients to measure lipophilicity. Partition coefficients, P, are equilibrium constants describing the degree to which a molecule distributes into a biphasic mixture of two immiscible solvents. Hansch used 1-octanol and water as the model solvents because these were known to simulate the lipid membrane-cytosol interface. The partition coefficient of a molecule is defined as the ratio of a molecule s concentration in an octanol layer to its concentration in an aqueous layer (Equation 12.12). 

If an aqueous sample is shaken with a volume of immiscible organic solvent, uncharged species tend to be extracted into the organic layer. This liquid-liquid extraction procedure has some applications in speciation studies. For example, organically associated copper species have been isolated by extracting water samples with chloroform, carbon tetrachloride (Slowey et al., 1967) or hexane. The lipid-soluble fraction of copper and other metals has been extracted from natural waters using solvent mixtures such as w-hexane, 10% butanol and w-octanol and 20% butanol in hexane (Stiff, 1971 Florence, 1982). The liquid-liquid extraction efficiencies are possibly low, due to... 

Evidence for the validity of the hydrophobicity model of bioconcentration is provided by correlations of it with the octanol-water partition coefficient, Km, using n-octanol as a surrogate for fish lipid tissue. The measurement of Kow consists of determining the concentration of a hydrophobic contaminant in water-immiscible n-oclanol relative to water with which it is in equilibrium. Typical Kow values range from 10 to 107, corresponding to BCF values of 1 to 106. Such Kow/BCF correlations have proven to be reasonably accurate when narrowly defined for a specified class of compounds, most commonly poorly metabolized organohalides. Major inconsistencies appear when attempts are made to extrapolate from one class of contaminants to another. 

Emulsions and suspensions are colloidal dispersions of two or more immiscible phases in which one phase (disperse or internal phase) is dispersed as droplets or particles into another phase (continuous or dispersant phase). Therefore, various types of colloidal systems can be obtained. For example, oil/water and water /oil single emulsions can be prepared, as well as so-called multiple emulsions, which involve the preliminary emulsification of two phases (e.g., w/o or o/w), followed by secondary emulsification into a third phase leading to a three-phase mixture, such as w/o/w or o/w/o. Suspensions where a solid phase is dispersed into a liquid phase can also be obtained. In this case, solid particles can be (i) microspheres, for example, spherical particles composed of various natural and synthetic materials with diameters in the micrometer range solid lipid microspheres, albumin microspheres, polymer microspheres and (ii) capsules, for example, small, coated particles loaded with a solid, a liquid, a solid-liquid dispersion or solid-gas dispersion. Aerosols, where the internal phase is constituted by a solid or a liquid phase dispersed in air as a continuous phase, represent another type of colloidal system. 

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