New cationic surfactants derived from bile acids: Synthesis and thermodynamic and biophysicochemical properties such as membrane perturbation and protein solubilizing abilities

The cationic derivatives, the hydrochloride salts of ethylenediamine monodeoxycholate (EdaDC) and -cholate (EdaC) derived from the respective bile salts, sodium deoxycholate (NaDC) and cholate (NaC), were synthesized and their physicochemical and biological properties together with the possibility of application as crystallizing agents for membrane proteins were studied. The critical micelle concentrations (CMCs) in water were determined to be 4.0 mM for EdaDC and 9.0 mM for EdaC, and the surface tensions were lowered down to 43 and 41 mN m(-1), respectively, in the range above CMCs. When compared with the corresponding natural bile salts, the two cationic bile acid derivatives have the highest surfactant ability, followed by the corresponding taurine-conjugated salts of TDC (taurodeoxycholic acid) and TC (taurocholic acid) and the free bile acid salts of DC and C have the lowest activity. Studies of dye release from pre-encapsulated vesicles, hemolysis and antimicrobial activity indicated that the concentrations leading to a large increase in the membrane permeability and biomembrane perturbation ability are significantly lower than the CMCs of these surfactants. Buffer solution containing EdaC or EdaDC could solubilize a membrane protein, light-harvesting chlorophyll a/b protein complex (LHCII), at concentrations higher than CMCs, but the power was estimated to be one third of that of surfactants such as Triton X-100, n-octyl-beta-D-glucopyranoside and n-nonyl-beta-D-glucopyranoside. Fluroescence depolarization studies showed that some specific molecular interactions between LHCIIs are induced by the cationic bile salts, suggesting that the latter would be valid for the crystallization of LHCII. In fact, LHCII crystals were observed in crystallization media containing 1% EdaC or 0.5% EdaDC.