Amphipathic compounds

Surface-active compounds are characterised by having two distinct regions in their chemical structure these are termed hydrophilic water-liking ) and hydrophobic ( water-hating ) regions. The existence of two such moieties in a molecule is referred to as amphipathy and the molecules are consequently often referred to as amphipathic molecules. 

The hydrophobic portions are usually saturated or unsaturated hydrocarbon chains or, less commonly, heterocyclic or aromatic ring systems. The hydrophilic regions can be anionic, cationic, zwitterionic, or nonionic. Surfactants are generally classified according to the nature of the hydrophilic group. Typical examples are given in Box 6.1. 

The zwitterionic or ampholytic surfactants shown in Box 6.1 possess both positively and negatively charged groups and can exist as either an anionic or a cationic surfactant depending on the pH of the solution. A typical example is N-dodecyl-N,N-dimethylbetaine (Ci2H25N (CH3)2CH2COO). 

The dual stmcture of amphipathic molecules is the unique feature which is responsible for the characteristic behaviour of this type of compound. Thus their surface activity arises from adsorption at the solution/air interface -the means by which the hydrophobic region of the molecule escapes from the hostile aqueous environment by protmding into the vapour phase above. Similarly, adsorption at the interface between aqueous and non-aqueous solutions occurs in such a way that 

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The amphipathic compounds shown in Scheme 2 can form a disc-like micelle(7). The shape of a molecular aggregate depends on the shape of the constituent molecules(8). For instance, conical molecules with large polar head groups prefer to form spherical micelles while cylindrical molecules tend to give flat aggregates. Trans-azobenzene is a rod-like molecule whereas the cis-form is bent. 

Amphipathic compounds contain regions that are polar (or charged) and regions that are nonpolar (Table 2-2). When an amphipathic compound is mixed with... 

The Alkylglycosides (AGs) and Sucrose esters of fatty acids (SEFAs) are families of nonionic glycosurfactants that have been used for their ability to gently extract membrane proteins with a minimal loss of functionality. These compounds can be synthesized and purified economically, with a worldwide production of thousands of tons per year. Chemically, AGs and SEFAs are a group of uncharged amphipathic compounds that consist of an aliphatic hydrocarbon chain attached to a sugar moiety. Certain AGs and SEFAs such as dodecanoyl sucrose have enjoyed widespread use as food-grade emulsifiers and in cosmetic preparations. 

Surfactants are a class of amphipathic compounds that includes soaps, detergents, and emulsifiers. With the use of surfactants, hydrophobic compounds can be suspended in aqueous solution by forming micelles (see Fig. 2-7). A micelle has a hydrophobic core consisting of the hydrophobic compound and the hydrophobic tails of the surfactant the hydrophilic heads of the surfactant cover the surface of the micelle. A suspension of micelles is called an emulsion. The more hydrophilic the head group of the surfactant, the more powerful it is—that is, the greater its capacity to emulsify hydrophobic material. 

Dietary fat leaves the stomach and enters the small intestine, where it is emulsified (suspended in small particles in the aqueous environment) by bile salts (Fig. 32.2). The bile salts are amphipathic compounds (containing both hydrophobic and hydrophilic components), synthesized in the liver (see Chapter 34 for the pathway) and secreted via the gallbladder into the intestinal lumen. The contraction of the gallbladder and secretion of pancreatic enzymes are stimulated by the gut hormone cholecystokinin, which is secreted by the intestinal cells when stomach contents enter the intestine. Bile salts act as detergents, binding to the globules of dietary fat as they are broken up by the peristaltic action of the intestinal muscle. This emulsified fat, which has an increased surface area as compared with unemulsified fat, is attacked by digestive enzymes from the pancreas (Fig. 32.3). 

A fatty acid has a carboxyl group at the polar end and a hydrocarbon chain at the nonpolar tail. Fatty acids are amphipathic compounds because the carboxyl group is hydrophilic and the hydrocarbon tail is hydrophobic. The carboxyl group can ionize under the proper conditions. 

Phospholipids, or phosphoglycerides, are amphipathic compounds that are used to make cell membranes, generate second messengers, and store fatty acids for use in the generation of prostaglandins. They can be synthesized from phosphatidate, an intermediate in triglyceride synthesis. Two common phospholipids, phosphatidyl choline and phosphatidyl inositol, are shown below (4). 

To further evaluate the potential utility of the Ga-complex as an in vivo marker of Pgp-mediated transport activity, the complexes were injected in wild-type and mdrla/lb (-/-) knoekout mice to study the drug transport across the BBB. As previously mentioned, Pgp is expressed in the luminal surfaces of brain endothelial cells preventing the entry of amphipathic compounds into the central nervous system. Therefore, the mdrla/lb (-/-) knockout mice offer an interesting model to evaluate the applicability of radiotracers for in vivo transport activity of Pgp. At 5 min after injection, the brain uptake of Ga-complex in Pgp-knockout miee was 10-fold higher compared with that in the wild-type mice. As the cerebral blood flow did not differ significantly between the wild-type and the knockout mice, differences on initial brain uptake and retention of Ga-complex were not attributed to changes in cerebral perfusion. 

The word amphiphile is derived from two Greek words amphis meaning both and philia mean love or friendship. Thus, a chemical compound possessing both hydrophilic (water-loving, polar) and lipophilic (fat-loving) or hydrophobic (water-hating) properties is called amphiphilic or an amphipathic compound amphiphilic polymers contain a hydrophilic and lipophilic part in their structure (Figure 2.1) [1,2]. 

Phospholipids are important components of cell membranes and lipoproteins (Chapter 37). They are amphipathic compounds, i.e. they have an affinity for both aqueous and non-aqueous environments. The hydrophobic part of the molecule associates with hydrophobic lipid molecules, while the hydrophilic part of the molecule associates with water. In this way, phospholipids are compounds that form bridges between water and lipids. 

Several other examples may be quoted to illustrate the importance of surface activity of many drugs. Many drugs produce intralysosomal accumulation of phospholipids, which are observable as raultilamellar objects within the cell. Drugs implicated in phospholipidosis induction are often amphipathic compounds [20]. Interaction between the surfactant drug molecules and phospholipid renders the phospholipid resistant to degradation by lysosomal enzymes, resulting in their accumulation in cells. 

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