Dienoyl lipids

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... 

Fig. 8. Two pairs of a polymerizable zwitterionic dienoyl lipid and a cleavable disulfide amphiphile derived from cysteine. In each pair, one amphiphile has a hydrocarbon tail and the other a fluorocarbon tail.

In contrast to diacetylenes, lipids with alkene-functionalized chains (e.g., acryloyl, dienoyl) can be polymerized in the La phase to a high degree of conversion [74], O Brien and coworkers systematically studied polymerization of acryloyl and dienoyl lipids in bilayer vesicles (see [25,26] for reviews). Subsequently, the Saavedra and O Brien groups prepared and characterized solid supported bilayers composed of dienoyl lipids (Fig. 6) [11, 75-77], Several parameters relating... 

Fig. 6 Structures of some polymerizable dienoyl lipids. Reprinted with permission from [11]. Copyright 2003, American Chemical Society...

Fig. 10. Structures of polymerizable dienoyl ammonium lipid and phospholipids.

Since the fatty acid chains in each lipid were 18 carbons and 16 carbons, respectively, it is reasonable that they could form a mixed lipid phase. Furthermore the bis-dienoyl substitution of 15 favors the formation of crosslinked polymer networks. Ohno et al. showed that the dienoyl group associated with the sn-1 chain could be polymerized by lipid soluble initiators, e.g. AIBN, whereas the dienoyl in the sn-2 chain was unaffected by AIBN generated radicals. Conversely, radicals from a water-soluble initiator, e.g. azo-bis(2-amidinopropane) dihydrochloride (AAPD), caused the polymerization of the sn-2 chain dienoyl group, but not the sn-1 chain. These data provide clear evidence for the hypothesis of Lopez et al. that the same reactive group located in similar positions in the sn-1 and sn-2 chains of polymerizable 1,2-diacyl phospholipids are positionally inequivalent [23]. 

Another enzyme, in addition to the isomerase, is required for the oxidation of polyunsaturated fatty acids which have a double bond at an even-numbered carbon atom. In this case the 2,4-dienoyl intermediate resulting from the action of acyl CoA dehydrogenase is acted on by 2,4-dienoyl CoA reductase to form c/s-A3-enoyl CoA (Fig. 4). This is then converted by the isomerase into the trans form which continues down the pathway. These reactions are important since over half the fatty acids of plant and animal lipids are unsaturated (and often polyunsaturated). 

Willumsen, N., Vaagenes, H., Lie, 0., Rustan, A.C. Berge, R.K. (1996) Lipids, 31, 579-592 Eicos-apentaenoic acid, but not docosahexaenoic acid, increases mitochondrial fatty acid oxidation and upregulates 2,4-dienoyl-CoA reductase gene expression in rats. 

Li, H., Duzgunes, N Ayanoglu, E., and Djerassi, C. (1988) Analogs of unusual sponge phospholipids. Synthesis and thermotropic properties of l,2-di-(6Z,9Z)-6,9-hexacosa-dienoyl phoshatidyl-choline and phos-phatidylethanolamine. Chem. Phys. Lipids, 48,109-117. 

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