Bilipids

Fig. 4.8. (Below) A diagram of the bilipid layer membrane of a vesicle or a cell with (above) a typical lipid, phosphatidylcholine. Large molecules and ions cannot penetrate the membrane as illustrated by the ions surrounding and inside a cell, but the distribution is reversed in vesicles (see Chapter 7). The ions create chemical and electrical field gradients across the membrane.

Nonpolar compounds, including the majority of xenobiotic chemicals and some metal complexes [249-252], generally diffuse passively through the lipid portions of the membrane by simple diffusion [21,246,253,254]. In this case, internalisation rates are reflected by compound permeability in the bilipid membrane [254,255] and can be predicted by Fick s law [254,256] ... 

Fatty acid molecules can align to form a barrier called a bilipid layer, shown here. In this schematic, the ionic end of the fatty acid is shown as a circle and the nonpolar chain is shown as a squiggly line. Use this diagram for questions 93—94. 

Why do nonpolar molecules have a difficult time passing through the bilipid layer ... 

I Fatty acid molecules can also align to form a bilipid layer that extends in 3 dimensions. Shown here is a cross section of this structure, which is called a liposome. This is similar to the micelle shown in Figure 7.24, though notably different because it contains an inner compartment of water. Add some biomolecules and what does it become (Hint. It forms the basis of all life.)... 

This structure is called a cell, also known as a lysosome. Add a bunch of ions, DNA, organelles, plus many other biomolecules to the cell and you have a living cell. The bilipid barrier is called a plasma membrane, which you will learn all about in your biology classes. 

Free radicals may also be formed by (a) homolysis of covalent bonds, (b) addition of an electron to a neutral atom, or (c) loss of a single electron from a neutral atom. These radicals, especially if they are of low molecular weight, are usually extremely reactive hence, they are short-lived. Since they have an unpaired electron, they are highly electrophilic (i.e., electron loving ) and attack sites of increased electron density, as in compounds with nitrogen atoms (e.g., proteins, amino acids, DNA, RNA) and carbon-carbon double bonds (i.e., polyuunsaturated fatty acids and phospholipids which make up bilipid cell membranes). 

Lipids and sugars, and the combination of both, are popular and successful strategies in drug delivery. This chapter provides details of just a handful of ways these moieties can be incorporated into molecules. There are, of course, many others and the choice of lipidic or carbohydrate group depends very heavily on the functional groups available for manipulation in the drug molecule and the size of that molecule. Drug delivery is always a delicate balance between adequate lipophilicity to cross bilipid layers and water solubility to aid in formulation. 

The use of organic solvents to model complex bilipids is very simplistic. While there have been some successes in modeling the response of compounds, large differences in the activity between molecules of different structures or the activity between enantiomers cannot be easily understood. In these cases, it is very useful to combine physical measurements with molecular modeling, molecular property, and spectroscopic data and use multivariate analysis. For both CNS penetration and gastric absorption, the relationship appears to be parabolic with an optimum log P value of arotmd 2 + 1. Evidence for this comes from a wide variety of experiments tn the literature from brain concentration of radiolabeled compounds to behavioral studies. 

A study of interaction between SQDs and biological structures has shown binding of peptide-functionalized colloidal SQDs to transmembrane proteins in the bilipid membranes of cells [3]. In this work SQDs are bound to CGGGRGDS peptide through the thiol link between the cysteine (C) and SQD. 

The lipid bilayer is a thin polar membrane made of two layers of lipid molecules. These membranes are flat sheets that form a continuous barrier around the cell and thus acts as a good antibacterial agent. Derivatives of neomycin B are examples of bilipids [73, 74]. 

Also shown in Figure 13 are pathways through the bacterial bilipid layer by which protons assist or are transported in conjunction with amino acids, a carbon source (lactose), and other ions such as Na", Mg", Ca", etc. In the case of lactose transport, it has been shown that one proton is transferred per molecule of lactose. Interestingly, this 1 1 ratio remains constant over a pH range of 6-8 in the external medium. Apparently, the bacterium compensates for pH changes by changing its transmembrane potential and/or Na" concentration. 

The electron involved in the donor-acceptor interaction need not originate from the actual surface layer but may well come from the interior of the bilipid membrane, for example, from intramembrane proteins. The electron escape depth in organic materials is comparable to intermolecular distances. 

The role of bacterio-rhodopsin in the proton pumping activity of halobacteria has been further investigated by Bagyinka /a/., while the light transduction via the pigmented bilipid membranes, of the purple membrane of H. halobium, has been studied by Ti Tien. ... 

Free nano continua or discontinua can be defined, also, as surface, line, and point elements, and as their combinations. Free surface elements are ideally composed of two nanolayers placed symmetrically each other (Figure 1.6). Such structures are ideal membranes and can be composed of solid materials, liquids, and even gasses. Ideal membranes exist in nature, e.g., bilipide cell membranes and black surfactant bubbles (Figure 1.7a and b). It is visible that both membranes are composed of only two molecular layers of asymmetric surface-active molecules, with hydrophilic ends placed outward (cell membranes) or inward (surfactant bubbles). Ideal membranes, composed... 

FIGURE 1.7 Black bilipide cell membrane (a) and surfactant bubble (b). 

Interface surface, line, point and overall barriers-symmetries (surface — bilipid membrane cells, free bubbles of surfactants, Langmuir Blodgett films line — genes, liquid crystals, microtubules point — fullerenes, micro-emulsions overall — dry foams, polymer... 

We have shown above that ferrocifens delivery to cells could be improved by CD complexation. However, it is clear that whether ferrocifens are delivered free or encapsulated, they must cross the bilipidic cellular membranes. The purpose of this section is to investigate their interactions with such bilayers. 

On the other hand, considering the 5 x 10 mol/cm coverage of a surface as a reference for a close-packed layer of comparable ferrocene molecules in SAMs [57], the saturation observed at circa 3 x 10 mol/cm for compound 7 shows that the loading of 7 in the bilipid film is considerable, being enough to drastically disorganize the original bilayer... 

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