Mophology of cholesteryl amphiphile-bilayer aggregates

Abstract

To explore the morphology of bilayer aggregates formed by cholesteryl amphiphiles, various cholesterol-containing amphiphiles having different spacer groups were synthesized from cholesterol. The synthesized amphiphiles were as follows: $$CH_2=C(CH_3)CO_2CH_2CH_2\stackrel{+}{N}(CH_3)_2(CH_2)_{10}CO_2CHOL\;Br^-\;(CHODAMA-10),\; CH_2=C(CH_3)CO_2CH_2CH_2 \stackrel{+}{N}(CH_3)_2(CH_2)_5CO_2CHOL\;Br^-\;\; (CHODAMA-5),\; (CH_3)_2CHCO_2CH_2CH_2\stackrel{+}{N} (CH_3)_2 (CH_2)_{10}CO_2CHOL\; Br^-\;\;\; (CHODABU),\; CH_2=CHCO_2(CH_2CH_2O)_2CH_2CH_2\stackrel{+}{N} (CH_3)_2CH_2CO_2CHOL\; Br^-\; (CHODAMA-OXY-3),\; CH_2=CHCO_2CH_2CH_2OCH_2CH_2\stackrel{+}{N} (CH_3)_2CH_2CO_2CHOL\;Br^-\;(CHODAMA-OXY-2),\;\mbox{and}\; HOCH_2CH_2\stackrel{+}{N}(CH_3)_2(CH_2CH_2O)_3CH_2CH_2 CO_2CHOL\;Br^-\;(CH-DDAUN)$$ ring moiety, $C_{27}H_{45}$. These cholesteryl amphiphiles were soluble in water and formed well developed stable bilayer aggregates upon sonication. Morphology of aqueous monomeric or polymeric amphiphilic bilayer aggregates was investigated by optical and electron microscopy, spectroscopic method, differential scanning calorimetry and viscosity measurement. Hydrophobic $C_5$ or $C_{10}$ hydrocarbon spacers of CHODAMA-5, CHODAMA-10 and CHODABU are embeded into the hydrophobic cholesterol ring region. However, the hydrophilic oxyethylene spacers of CHODAMA-OXY-3 and CHODAMA-OXY-2 are fully extended to the outside of the cholesterol rings. Tubular or rodlike aggregates were predominantly formed from these cholesteryl amphiphiles, and initially vesicle formations were not observed in all cases. Tubules formed by CHODABU was very rigid and stacked, and changed to myelin-like multilamellars and finally to the large vesicles according to aging time. Monomeric CHODAMA-5 was observed as random clusters, but poly(CHODAMA-5) formed the large extended ordered aggregates by the entanglement of rods. Monomeric and polymeric CHODAMA-10 formed disklike and spheric folded rodlike aggregates. How...