Phospholipids and water

DSC has also been used to determine partition coefficients between phospholipids and water, avoiding radiolabeled solutes and high concentrations. One example is the partitioning of cardiac drugs into DMPC liposomes [48] (Table 3.9). The drug concentration in the liposomes was calculated using the following equation ... 

Table 6.8 shows the average number of hydrogen bonds formed between the phospholipid and water molecules. With an increase in cholesterol content, a slight increase in the total number of H-bonds between DPPC and water can be seen, while the number of H-bond bridges decreased. 

Vanhoutte, B., Dewettinck, K., Foubert, I., Vanlerberghe, B., Huyghebaert, A. 2002a. The effect of phospholipids and water on the isothermal crystallization of milk fat. Eur. J. Lipid Sci. Technol. 104, 490-495. 

The use of partition coefficients between water and lipophilic media is of wide use in pharmaceutical research. As discussed in the last chapters, different lipophilicity scales are used to describe the lipophilicity of a compound and relate it to its absorption behaviour in vivo. Differences between the logPow and partitioning between phospholipids and water (mainly determined using liposomes) for diverse compounds have been described leading to the development of the immobilized artificial membrane chromatography system. However, also the predictivity of the IAM system is limited and only a small number of membrane systems are available. 

Poulin and Theil have developed a mechanistic model for estimating the Vd based on physiologically based pharmacokinetics (PBPK). For this method, the tissue plasma partition coefficient for each organ of the body is calculated by consideration of the volume fraction of neutral and phospholipids and water found in the tissues of a particular organ. For example, the volume fraction of neutral lipids in human adipose tissue is 0.79 whereas the volume fraction of neutral lipids in cardiac tissue is 0.0115. By contrast the volume fraction of water in adipose and heart are 0.18 and 0.76 respectively. Combined with the P, these volume fractions are used to estimate the distribution of a drag molecule into each tissue. Summation of the product of tissue volume and tissue/plasma partition coefficient produces the estimate of Vd. ... 

Liposomes are spherical vesioles formed by the aggregation of amphiphilio phospholipid moleoules in a bilayer struoture. Liposome formation ooours when phospholipids are dispersed into an aqueous medium — usually water — as a result of interaotions between phospholipids and water. Thus, liposomes encapsulate part of the aqueous medium in whioh they are suspended. The amphiphilic charaoter of phospholipids allows them to form olosed struotures where hydrophobic and (or) hydrophilio moleoules oan be entrapped or anohored. 

Pulse field gradient (PFG) NMR spectroscopy is now generally regarded as the method of choice for measuring the translational diffusion coefficients of molecules of virtually any type under many conditions (48). H, H, F, and P variants of this method have been used successfully to study lateral diffusion of cholesterol, phospholipids, and water in model membranes (49,50). This technique introduces two identical gradient pulses of the external magnetic field into the standard spin-echo NMR... 

The saturated aqueous solution of surfactant at 25°C is in equilibrium with a liquid crystalline phase which contains about 25 wt% water. This phase dispersed in solution is the same as the phase formed by water vapor sorption into initially dry surfactant, according to nmr spectroscopy (which virtually eliminates the possibility, mentioned in the Introduction, of a complicating triple point in the two-component system). This hydrated liquid crystal is probably lamellar, to judge by the similarities in texture with lamellar liquid crystals of phospholipids and water (36). It is not uncommon for surfactants for form liquid crystalline phases by absorption of water, or hydrocarbon, or both (37). Moreover the true solubility of many other surfactants (particularly alkyl aryl sulfonates) in water, in salt water, and in hydrocarbon is small, sometimes as small as 0.003 wt% in water, below the Krafft point (38,39). Hence the present finding of liquid crystalline phase in equilibrium with isotropic aqueous solution at surfactant levels above 0.1 wt% may be representative of broad classes of surfactants, including some of interest in connection with... 

Liposomes were discovered by Dr. Alec Bangham in 1961. During his studies on phospholipids and blood clotting, he found that if he mixed phospholipids and water, tiny phospholipid bilayer sacs, called liposomes, would form spontaneously. Since that first observation, liposomes have been developed as efficient delivery systems for everything from antitumor and antiviral drugs, to the hair-loss therapy minoxidil ... 

Figure 37.3 Liposomes. Liposomes are small artificial vesicles that are formed when phospholipids and water are subjected to high-shear mixing or to vigorous agitation by an ultrasonic probe. Liposomes can be used to encapsulate hydrophilic drugs and are used for the delivery of some anticancer drugs. They are also used to deliver cosmetics.

Using these methods, it has been demonstrated that apolar lipids associate at the hydrophobic surfaces of amphipathic a-helical regions of specific amino acid sequences of apolipoproteins while phospholipids and water interact at polar surfaces. Interaction of the major apolipoproteins of HDL with lipids stabilizes the a-helical structure and increases its content. In contrast, as the lipid content of LDL increases, the /3-structure of apoB increases. 

Many complex systems have been spread on liquid interfaces for a variety of reasons. We begin this chapter with a discussion of the behavior of synthetic polymers at the liquid-air interface. Most of these systems are linear macromolecules however, rigid-rod polymers and more complex structures are of interest for potential optoelectronic applications. Biological macromolecules are spread at the liquid-vapor interface to fabricate sensors and other biomedical devices. In addition, the study of proteins at the air-water interface yields important information on enzymatic recognition, and membrane protein behavior. We touch on other biological systems, namely, phospholipids and cholesterol monolayers. These systems are so widely and routinely studied these days that they were also mentioned in some detail in Chapter IV. The closely related matter of bilayers and vesicles is also briefly addressed. 

This chapter has given an overview of the structure and dynamics of lipid and water molecules in membrane systems, viewed with atomic resolution by molecular dynamics simulations of fully hydrated phospholipid bilayers. The calculations have permitted a detailed picture of the solvation of the lipid polar groups to be developed, and this picture has been used to elucidate the molecular origins of the dipole potential. The solvation structure has been discussed in terms of a somewhat arbitrary, but useful, definition of bound and bulk water molecules. 

Langmuir-Blodgett films (LB) and self assembled monolayers (SAM) deposited on metal surfaces have been studied by SERS spectroscopy in several investigations. For example, mono- and bilayers of phospholipids and cholesterol deposited on a rutile prism with a silver coating have been analyzed in contact with water. The study showed that in these models of biological membranes the second layer modified the fluidity of the first monolayer, and revealed the conformation of the polar head close to the silver [4.300]. 

Fat absorbed from the diet and lipids synthesized by the liver and adipose tissue must be transported between the various tissues and organs for utilization and storage. Since lipids are insoluble in water, the problem of how to transport them in the aqueous blood plasma is solved by associating nonpolar lipids (triacylglycerol and cholesteryl esters) with amphipathic hpids (phospholipids and cholesterol) and proteins to make water-miscible hpoproteins. 

Like other cells, a neuron has a nucleus with genetic DNA, although nerve cells cannot divide (replicate) after maturity, and a prominent nucleolus for ribosome synthesis. There are also mitochondria for energy supply as well as a smooth and a rough endoplasmic reticulum for lipid and protein synthesis, and a Golgi apparatus. These are all in a fluid cytosol (cytoplasm), containing enzymes for cell metabolism and NT synthesis and which is surrounded by a phospholipid plasma membrane, impermeable to ions and water-soluble substances. In order to cross the membrane, substances either have to be very lipid soluble or transported by special carrier proteins. It is also the site for NT receptors and the various ion channels important in the control of neuronal excitability. 

The popular applications of the adsorption potential measurements are those dealing with the surface potential changes at the water/air and water/hydrocarbon interface when a monolayer film is formed by an adsorbed substance. " " " Phospholipid monolayers, for instance, formed at such interfaces have been extensively used to study the surface properties of the monolayers. These are expected to represent, to some extent, the surface properties of bilayers and biological as well as various artificial membranes. An interest in a number of applications of ordered thin organic films (e.g., Langmuir and Blodgett layers) dominated research on the insoluble monolayer during the past decade. 

The intracellular and plasma membranes have a complex structure. The main components of a membrane are lipids (or phospholipids) and different proteins. Lipids are fatlike substances representing the esters of one di- or trivalent alcohol and two aliphatic fatty acid molecules (with 14 to 24 carbon atoms). In phospholipids, phosphoric acid residues, -0-P0(0 )-O-, are located close to the ester links, -C0-0-. The lipid or phospholipid molecules have the form of a compact polar head (the ester and phosphate groups) and two parallel, long nonpolar tails (the hydrocarbon chains of the fatty acids). The polar head is hydrophihc and readily interacts with water the hydrocarbon tails to the... 

FIGURE 12.4 (A) Diagrammatic representation of the separation of major simple lipid classes on silica gel TLC — solvent system hexane diethylether formic acid (80 20 2) (CE = cholesteryl esters, WE = wax esters, HC = hydrocarbon, EEA = free fatty acids, TG = triacylglycerol, CHO = cholesterol, DG = diacylglycerol, PL = phospholipids and other complex lipids). (B) Diagrammatic representation of the separation of major phospholipids on silica gel TLC — solvent sytem chloroform methanol water (70 30 3) (PA = phosphatidic acid, PE = phosphatidylethanolamine, PS = phosphatidylserine, PC = phosphatidylcholine, SPM = sphingomyelin, LPC = Lysophosphatidylcholine). 

It has been proposed that the a-tocopheroxyl radical can be recycled back to tocopherol by ascorbate producing the ascorbyl radical (Packer etal., 1979 Scarpa et al., 1984). The location of a-tocopherol, with its phytyl tail in the membrane parallel to the fatty acyl chains of the phospholipids and its phenolic hydroxyl group at the memisrane-water interface near the polar headgroups of the phospholipid bilayer, enables ascorbate to donate hydrogen atoms to the tocopheroxyl radical. The suitability for ascorbate and tocopherol as chain-breaking antioxidants is exemplified (Buettner,... 

The lag-phase measurement at 234 nm of the development of conjugated dienes on copper-stimulated LDL oxidation is used to define the oxidation resistance of different LDL samples (Esterbauer et al., 1992). During the lag phase, the antioxidants in LDL (vitamin E, carotenoids, ubiquinol-10) are consumed in a distinct sequence with a-tocopherol as the first followed by 7-tocopherol, thereafter the carotenoids cryptoxanthin, lycopene and finally /3-carotene. a-Tocopherol is the most prominent antioxidant of LDL (6.4 1.8 mol/mol LDL), whereas the concentration of the others 7-tocopherol, /3-carotene, lycopene, cryptoxanthin, zea-xanthin, lutein and phytofluene is only 1/10 to 1/300 of a-tocopherol. Since the tocopherols reside in the outer layer of the LDL molecule, protecting the monolayer of phospholipids and the carotenoids are in the inner core protecting the cholesterylesters, and the progression of oxidation is likely to occur from the aqueous interface inwards, it seems reasonable to assign to a-tocopherol the rank of the front-line antioxidant. In vivo, the LDL will also interact with the plasma water-soluble antioxidants in the circulation, not in the artery wall, as mentioned above. 

Dynamic surface tension has also been measured by quasielastic light scattering (QELS) from interfacial capillary waves [30]. It was shown that QELS gives the same result for the surface tension as the traditional Wilhelmy plate method down to the molecular area of 70 A. QELS has recently utilized in the study of adsorption dynamics of phospholipids on water-1,2-DCE, water-nitrobenzene and water-tetrachloromethane interfaces [31]. This technique is still in its infancy in liquid-liquid systems and its true power is to be shown in the near future. 

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