Hydrogen bonds, phospholipids

Hydrogen bonding and electrostatic interactions between the sample molecules and the phospholipid bilayer membranes are thought to play a key role in the transport of such solute molecules. When dilute 2% phospholipid in alkane is used in the artificial membrane [25,556], the effect of hydrogen bonding and electrostatic effects may be underestimated. We thus explored the effects of higher phospholipid content in alkane solutions. Egg and soy lecithins were selected for this purpose, since multicomponent mixtures such as model 11.0 are very costly, even at levels of 2% wt/vol in dodecane. The costs of components in 74% wt/vol (see below) levels would have been prohibitive. 

Most drug-like molecules dissolved in water form hydrogen bonds with the solvent. When such a molecule transfers from water into a phospholipid bilayer, the solute-water hydrogen bonds are broken (desolvation), as new solute-lipid H bonds form in the lipid phase. The free-energy difference between the two states of solvation has direct impact on the ability of the molecules to cross biological barriers. 

Figure 7.50 Hydrogen bonding/electrostatics scale based on phospholipid-alkane permeability differences A log Pe versus Pe (dodecane).

Hydrogen bonding and electrostatic interactions between the sample molecules and the phospholipid bilayer membranes are thought to play a key role in the transport of such molecules. When dilute 2% wt/vol phospholipid in alkane is used in the artificial membrane [15, 23], the effect of hydrogen bonding and electrostatic effects may be underestimated. 

Kimura M, Fukumoto K, Watanabe J et al (2004) Hydrogen-bonding-driven spontaneous gelation of water-soluble phospholipid polymers in aqueous medium. J Biomater Sci Polym Edn 15 631-644... 

Hauser and Strauss [3.40] assumed the hydrogen bond between sucrose and phospholipid as the cause of the integrity of the unilamellar vesicles and showed, that enclosed ions cannot migrate to the surroundings. 

MD simulations have provided a unique molecular description of cholesterol-phospholipid interactions [31]. Atomistic simulations have succeeded in reproducing the condensing effect of cholesterol on phospholipid bilayers [32-34], With atomistic detail, many properties can be determined, such as the effect of cholesterol on lipid chain ordering or on hydrogen bond formation. Other simulations have focused on the interaction of cholesterol and SM [35-37], Aittoniemi et al. [38] showed that hydrogen bonding alone cannot explain the preferential interaction between cholesterol and SM compared to cholesterol and POPC. 

PAMPA membranes typically consist of phospholipids dissolved in an organic solvent. Both of them affect chemical selectivity. Phospholipids facilitate the permeability of moderately hydrophilic molecules by ionic or hydrogen-bonding interactions (phopholipids are hydrogen bond acceptors). This allows permeation of moderately lipophilic compounds. Recently, it was shown that anionic phospholip-id(s) increases the permeation of basic compounds by ion pair mechanism [54—56]. Many PAMPA variants (and other artificial membrane tools) add anionic phospho-lipid(s) to increase the in vivo predictability. 

As with other multisubunit enzymes (e.g., allosteric enzymes), the structural integrity of a membrane-bound enzyme primarily is maintained by noncovalent interactions such as hydrogen bonding, electrostatics, and hydrophobic interactions. Hydrophobic polypeptides (or hydrophobic portions of polypeptides) apparently are used to anchor the enzymes to the membrane through interactions with phospholipids. Therefore, I would characterize the interaction between the enzyme and membrane as chemical in nature rather than as geometric. ... 

In a very thoughtful investigation of solvent systems to model membrane characteristics, Leahy et al. (1989, 1992) have argued that two receptors sited in different tissues (or membranes) could exist in environments that are very different in hydrogen bonding character one may be surrounded by amphiprotic groups (as in a protein) or by proton donors the other may be surrounded by proton acceptors (as in a phospholipid membrane). 

During the extraction process three types of interactions are usually disrupted, these are van der Waals forces in lipid-lipid, lipid-protein, and liquid-carbohydrate complexes electrostatic and hydrogen bonding interactions between lipids andproteins andcovalent bonding between lipids, carbohydrates, and proteins (Roby t and White, 1987). The solvent of choice depends on the type of lipid and the interactions to be disrupted. Thus, neutral lipids may be extracted with nonpolar solvents, while phospholipids and glycolipids are extracted with more polar solvent mixtures (Shahidi and Wanasundara, 1998). 

Urano, S., Kitahara, M., Kato, Y., Hasegawa, Y., and Matsuo, M. (1990). Membrane stabilizing effect of Vitamin E existence of a hydrogen bond between alpha-tocopherol and phospholipids in bilayer membranesJ. Nutr. Sci. Vitaminol., 36, 513-519. 

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