Hydrophobic interaction between the bile acids and long-chain alkyltrimethylammonium ions: A model for cholesterol-lipid interaction

Abstract

Ion-pair association constants (K) for long-chain alkyltrimethylammonium salts of the bile acids have been measured conductometrically at 25°C in 0.1 mole fraction ethanol-water. The free energy of ion-pair formation (ΔG°_ip = -RT ln K) was separated into its electrostatic and hydrophobic components by examining the effect of alkyl chain length on ΔG°_ip. The electrostatic contribution was the same for each bile acid and agreed with the value previously obtained for long-chain alkyltrimethyl-ammonium carboxylate ion pairs under the same conditions. The hydrophobic contribution depended on the structure of the bile acid and varied linearly with the number of OH groups. (There are no significant attractive forces between non-polar groups in water. Hydrophobic interaction is the tendency of non-polar groups to associate because this minimizes their energetically unfavourable contact with water.) Our results support current theories of hydrophobic interaction and give an indication of the extent of the effect of neighbouring polar groups on hydrophobic interaction. Extrapolation to zero OH groups gave an estimate of the free energy of hydrophobic interaction (ΔG°_HI) between an alkyl chain and a cholesterol analogue (a steroid ring system with a single polar substituent). This value of ΔG°_HI was -2.77 kJ mol^-1 per methylene group compared with -2.24 kJ mol^-1 per methylene group for hydrophobic interaction between two alkyl chains. (The small difference is explained by the greater number of water molecules displaced in an alkyl-steroid contact than in an alkyl-alkyl contact.) This result conflicts with claims made by other workers that the steroid-alkyl interaction is weak, or that cholesterol is less hydrophobic than its structure indicates.