Lipids, fluorinated

Quazepam (88) has a highly fluorinated sidechain so as to make this tranquilizer resistant to dealkylation. It also incorporates a lipid-solubilizing 2-thione moiety. The synthesis begins with bi aryl ketone derivative by ] -al kylation with 2,2,2-trifluoroethyltriclate to give 86. 

Fig. 17. Fluorous patches direct the pairing of protein segments in lipid micelles. The hydrophobic peptides partition into lipid micelles, forming a-helices. Then, the superhydrophobic hexafluoroleucine residues seek each other, causing self-association into dimers and higher order aggregates. Fluorine is light, while the backbone of the a-helices is dark. From Ref. [81], with permission.

N. Naarmann, B. Bilgiger, H. Meng, K. Kumar, C. Steinem, Fluorinated interfaces drive self-association of transmembrane a helices in lipid bilayers, Angew. Chem. Int. Ed. 45 (2006) 2588-2591. 

The confusion between these two characteristics is common in medicinal chemistry. It comes from the usual empirical measurement of the lipophilicity, which is the logarithm of the partition coefficient between 1-octanol and water (log P). This parameter gives a representative overview of a compound absorbed by a lipidic membrane, an essential datum in medicinal chemistry. It is often considered that the higher the log P value is, the more lipophilic the compound is. Acmally, the log P value is only a measurement of relative solubility. Considering that the solubility of a fluorinated substance decreases more in water than in octanol, this measurement leads one to think that fluorinated compounds are more lipophilic. Actually, this represents the relative lack of affinity of fluorinated compounds for both phases. 

Four highly fluorinated ethers with low boiling points are currently used in anesthesia enflurane, isoflurane, sevoflumne, and desflurane (Figure 8.89). Des-flurane and sevoflurane are now the most used (sevoflurane is especially used in pediatrics). They exhibit the lowest blood-gas partition coefficients, the lowest ratio of toxic metabolites, and the lowest solubilities in lipids. These features limit the retention and, consequently, the metabolism is delayed (Table 8.2). 

The extensive studies of the behavior of mixed monolayers or bilayers of di-acetylenic lipids and other amphiphiles parallel to some degree the studies of dienoyl-substituted amphiphiles. Since the dienoyl lipids do not contain a rigid diacetylenic group in the middle of the hydrophobic chains, they tend to be miscible with other lipids over a wide range of temperatures and compositions. In order to decrease the lipid miscibility of certain dienoyl amphiphiles, Ringsdorf and coworkers utilized the well-known insolubility of hydrocarbons and fluorocarbons. Thus two amphiphiles were prepared, one with hydrocarbon chains and the other with fluorocarbon chains, in order to reduce their ability to mix with one another in the bilayer. Of course it is necessary to demonstrate that the lipids form a mixed lipid bilayer rather than independent structures. Elbert et al. used freeze fracture electron microscopy to demonstrate that a molar mixture of 95% DM PC and 5% of a fluorinated amphiphile formed phase-separated mixed bilayers [39]. Electron micrographs showed extensive regions of the ripple phase (Pb phase) of the DM PC and occasional smooth patches that were attributed to the fluorinated lipid. In some instances it is possible to... 

Burton DJ,Lu L (1997) Fluorinated Organometallic Compounds. 193 45 - 89 Caffrey M (1989) Structural, Mesomorphic and Time-Resolved Studies of Biological Liquid Crystals and Lipid Membranes Using Synchrotron X-Radiation. 151 75 -109 Canceill J, see Collet A (1993) 165 103 -129 Carbd R, see Besalu E (1995) 173 31-62... 

Christie WW, Hamilton JTG, Harper DB (1998) Mass Spectrometry of Fluorinated Fatty Acids in the Seed Oil of Dichapetalum toxicarium. Chem Phys Lipids 97 41... 

Some elements are essential to the composition or function of the body. Since the body is mostly water, hydrogen and oxygen are obviously essential elements. Carbon (C) is a component of all life molecules, including proteins, lipids, and carbohydrates. Nitrogen (N) is in all proteins. The other essential nonmetals are phosphorus (P), sulfur (S), chlorine (Cl), selenium (Se), fluorine (F), and iodine (I). The latter two are among the essential trace elements that are required in only small quantities, particularly as constituents of enzymes or as cofactors (nonprotein species essential for enzyme function). The metals present in macro amounts in the body are sodium (Na), potassium (K), and calcium (Ca). Essential trace elements are chromium (Cr), manganese (Mn), iron (Fe), cobalt (Co), copper (Cu), zinc (Zn), magnesium (Mg), molybdenum (Mo), nickel (Ni), and perhaps more elements that have not yet been established as essential. 

A partially fluorinated lipid (LL-8-8) was found to form stripe-like microdomains at the gas-liquid phase coexistence region, when spread on water as a Langmuir monolayer [28]. 

---