Cationic amphiphiles

Shimomura and Kunitake have reported that stable monolayers and LB films were obtained by electrostatic interaction of water soluble anionic polymers with cationic amphiphiles [58]. This polyion-complexation was also a useful method for stabilization of monolayers of unstable [59] or water soluble anionic surfactants [60]. Mixtures of water soluble cationic and anionic surfactants (1 1) also formed stable Langmuir monolayers at the air/ water interface [60]. 

As a cationic polymer and a cationic amphiphile, poly(allyl amine hydrochloride) (PAA) and octadecylamine (ODA) shown in Fig. 6 were used, respectively. The stability of the monolayers of the anionic amphiphiles was increased by polyion-complexation with PAA added in the aqueous subphase in comparison with Ca2+ salt formation. Ion complexation (1 1) of each anionic amphiphile with ODA was also performed at the air-water interface by spreading a chloroform solution of a 1 1 surfactant mixture. 

The sizes of the phase separated HC islands in the mixed monolayers of HC and FC anionic amphiphiles polyion complexed with cationic polymers were increased by addition of a HC cationic amphiphile. The HC islands sat on the FC sea in a structure of on-top in a two story monolayer in the same way as two-component amphiphile systems. By SSPM and conventional and SNOAM fluorescence microscopies, the cationic HC amphiphile was found to dissolve preferentially into the HC islands, although it also dissolved partially in the FC sea phase. 

Dautzenberg et al. reported on an alternative method to produce cationic amphiphilic block copolymers starting from a poly(vinylbenzyl) precursor block, which was then converted into a cationic polyelectrolyte by reaction with tertiary amines [162],... 

Leventis R, Silvius JR. Interactions of mammalian cells with lipid dispersions containing novel metabolizable cationic amphiphiles. Biochim Biophys Acta 1990 1023(1) 124-132. 

Bhattacharya S, Mandal SS. Evidence of interlipidic ion-pairing in anion-induced DNA release from cationic amphiphile-DNA complexes. Mechanistic implications in transfection. Biochemistry 1998 37(21) 7764-7777. 

Massing U, Eichert T. Novel cationic amphiphiles. Patent application WO 01/ 57064 (2000). 

Sofer A, Futerman AH. Cationic amphiphilic drugs inhibit the internalization of cholera toxin to the Golgi apparatus and the subsequent elevation of cyclic AMP. J Biol Chem 1995 270(20) 12117-12122. 

A DNA-lipid complex was prepared by simply mixing two aqueous solutions of DNA and cationic lipids as follows. An aqueous solution of DNA Na" from salmon testes (ca. 30 000 bps or 500 bps) and an aqueous solution of 1.1 eq. mol of cationic amphiphiles were mixed at room temperature and... 

Cationic amphiphiles 2Ci8-glu-N spread on pure water, in the solution of 10 xM DNA containing 10 xM intercalating dyes (proflavine). The dye-intercalated DNA anions were expected to adsorb to the cationic lipid mono-layer due to electrostatic interactions and was transferred to a hydrophobized glass plate at a surface pressure of 35 mN m at 20 °C. From a moving area of a barrier, two layers of the monolayer were confirmed to be transferred in each one cycle (Y-type deposition). When the QCM plate was employed as a transfer plate, the transferred mass could be calculated from frequency decreases (mass increase on the QCM) [29-31]. It was confirmed that 203 10 ng of two lipid monolayers and 74 5 ng of DNA strands were transferred on to the substrate per dipping cycle, which means ca. 95% of the monolayer area was covered by DNA molecules. 

As cationic amphiphilic drugs, p-blockers can exert a membrane-stabilizing effect, as evidenced by the ability of the more lipophilic congeners to inhibit Na+-channel function and impulse conduction in cardiac tissues. At the usual therapeutic dosage, the high concentration required for these effects will not be reached. 

Most local anesthetics exist in part in the cationic amphiphilic form (cf. p. 208). This physicochemical property favors incorporation into membrane interphases, boundary regions between polar and apolar domains. These are found in phospholipid membranes and also in ion-channel proteins. Some evidence suggests that Na+-channel blockade results from binding of local anesthetics to the channel protein. It appears certain that the site of action is reached from the cytosol, implying that the drug must first penetrate the cell membrane (p. 206). 

Depending on the pllipid membrane-permeable form of the local anesthetic (p. 26), which must take on its cationic amphiphilic form in order to exert its action (p.204). 

Due to their cationic amphiphilic nature, the TCA exert membrane-stabilizing effects that can lead to disturbances of cardiac impulse conduction with arrhythmias as well as decreases in myocardial contractility. All TCA lower the seizure threshold. Weight gain may result from a stimulant effect on appetite. 

Toxicophore analysis Evaluation of chemical moieties historically associated with safety issues, for example, genotoxidly, cationic amphiphilic drugs and phosphohpidosis, tertiary amines that are charge neutral at physiologic pH and vacuohzation... 

Fatty acid beta-oxidation Inhibition by valproate, tetracyclines, nonsteroidal antiinflammatory drugs, antianginal cationic amphiphilic drugs, female sex hormones, CoA depleters such as valproate and salicylate... 

There are specific fiuorescent dyes for specific pathologies created by specific drug classes, such as phospholipidosis from cationic amphiphilic drugs [18, 19], mitochondrial DNA depletion by nucleoside reverse transcriptase inhibitors that also inhibit mitochondrial DNA polymerase gamma and redox cyclers that produce reactive oxygen species. The complex mechanism of statin-induced toxicity is demonstrated vith early sublethal effects on apoptosis, mitochondrial function and calcium homeostasis [20]. 

Detert H, Seifert R, Schunack W (1996) Cationic amphiphiles with G-protein-stimulatory activity studies on the role of the basic domain in the activation process. Pharmazie 51 67-72 DeVries L, Farquhar MG (1999) RGS proteins more than just GAPs for heterotrimeric G proteins. Trends Cell Biol 9 138-144... 

Ferro, S., Jori, G., Sortino, S., Stancanelli, R., Nikolov, P., Tongon, G., Ricchelli, F., and Mazzaglia, A. (2009). Inclusion of 5-[4-(l-dodecanoylpyridinium)-10,15,20-triphenylpor-phine in supramolecular aggregates of cationic amphiphilic cyclodextrines Physic-chemical characterization of the complexes and strengthening of the antimicrobial photosensitizing activity. Biomacromolecules 10(9), 2592-2600. 

Neutral. A bis(ethylenediamine) structure has been incorporated into the surfactant molecule -Ci6H33C(H)[CON(H)(CH2)2NH2]2 in older to incorporate metal ions in an LB film structure via coordination instead of ionic complexation as occurs for anionic/cationic amphiphiles (14). Also, films of n-octadecylacetoacetate containing Cu2+ have been prepared, and exposure to H2S has resulted in the formation of a copper sulfide (39). Ditetradecyl-A-[4- [6-(A, N, W -trimethyl-ethylenediamino)-hexyl]oxy]benzoyl]-L-glutamate (DTG), which also contains the ethylenediamine unit, was used to make self-assembled films containing Cd2+ (40). 

Drugs that cause phospholipidosis are cationic amphiphiles they contain a hydrophobic ring structure and a hydrophilic side chain with a positively charged amine group. Such chemicals can interact with either the ionic (e.g., chlorophentermine) or hydrophobic (e.g., amiodarone) moieties of phospholipids. 

Haupft, R. and Mohr, K. (1985). In uence of cationic amphiphilic drugs on the phase transition temperature of phospholipids with different polar headgrou ochim. Biophys. Acta, 814, 156-162. 

Bottega, R. and Epand, R.M. (1992) Inhibition of protein kinase C by cationic amphiphiles. Biochemistry, 31, 9025-9030. 

Maslov, M.A., Syicheva, E.V., Morozova, N.G. and Serebrennikova, G.A. (2000) Cationic amphiphiles of both lipid and non lipid nature in gene therapy. Russian Chem. Bull., 49, 385—401. 

Ruysschaert, J.M., El-Ouahabi, A., Willeaume, V., Eluez, G., Fuks, R., Vandenbrandem, M. etal. (1994) A novel cationic amphiphile for transfection of mammalian cells. Biochem. Biophys. Res. Comm., 203,1622-1628. 

Fig. 6 Synthesis of (a) ester-containing SAINT lipids [120] and (b) sunfish cationic amphiphiles [121, 122]...

The linker group that bridges the cationic lipid headgroup with the hydrocarbon moiety controls the biodegradability of a cationic amphiphile. Most of the linker bonds are ether, ester, or amide bonds (Fig. 1). Compounds with ether links generally render better transfection efficiency. However, they are more stable and may cause higher toxicity, while cationic lipids with ester links such as DOTAP are more biodegradable and less cytotoxic in cultured cells [28, 39]. Noteworthy,... 

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