Thermodynamics of cholesterol self-association and its interaction with tripalmitin and L-α-lecithin

Abstract

Apparent molar heat capacities, ϕ_C, have been measured at 25 °C for cholesterol at very low concentrations in CCl₄ and in CCl₄ solutions of tripalmitin (1.0, 2.5 and 3.5 wt%) and L-α-lecithin (2.5 wt%). Plots of ϕ_C against cholesterol concentration show a high maximum which is decreased by the presence of tripalmitin and more strongly by lecithin. Enthalpies (ΔH_M) have been obtained at 25 °C for the mixing of dilute CCl₄ solutions of cholesterol with corresponding solutions of tripalmitin or lecithin. For tripalmitin ΔH_M is positive, becoming negative at very low cholesterol concentrations, while with lecithin ΔH_M is negative. Enthalpies of dilution in CCl₄ have been determined at 25 °C for cholesterol, tripalmitin and a cholesterol + tripalmitin mixture, leading to values of the relative apparent molar enthalpies, ϕ_L, which are consistent with the ΔH_M values. All these results are explained through the Treszczanowicz–Kehiaian model for associated mixtures extended to include the possibility of complex formation between cholesterol and the proton-acceptor compound. Cholesterol in CCl₄ has completely analogous behaviour to that of linear alcohols in hydrocarbon solvents, its self-association through hydrogen bonding constituting the main effect on the thermodynamics and causing the maximum in ϕ_C. Tetramers are the predominant species, dimers being almost absent even at very low cholesterol concentrations. Cholesterol forms hydrogen-bonded dimers with tripalmitin and more strongly with lecithin, their presence being responsible for the decrease of cholesterol self-association and of ϕ_C. At very low concentrations these dimers are the predominant species. The role played in cholesterol self-association by the planarity of the sterol fused-ring structure and by the lateral chain has been assessed through determining ϕ_C for cholestane and 5α- and 5β-androstane in CCl₄. The results indicate that both factors are negligible in cholesterol self-association compared with the formation of hydrogen bonds. However, ϕ_C for the liquid crystal cholesteryl acetate shows evidence of self-association of this solute in CCl₄. The anaesthetic chloroform apparently reduces the self-association of cholesterol in CCl₄.