Drug-biomolecule interactions: mechanisms and kinetics of interactions of biomolecules at interfaces.

At the air-water interface, the area occupied by the molecules of each component of mixed monomolecular layers of cholesterol with hexadecyl alcohol, hexadecylic acid, or hexadecylamine was independent of the presence of the other component. The values of the free energy of mixing of these lipids were within the range of the entropic factor of the free energy even at high surface pressures. Mixed monolayers of cholesterol and bovine serum albumin showed a similar independence of the area per molecule and of the free energy of mixing values when the concentration of the protein was expressed in terms of amino acid residues per molecule of protein forming the mixed monolayer. Higher values of the free energy of mixing were obtained for mixed monolayers of cholesterol with dipalmitoyl lecithin and dipalmitoyl phosphatidylethanolamine than were expected from an entropic factor. The interaction between monomolecular layers of lipidic biomolecules with bulk subphase components, the energy of activation, interaction kinetics, and effects of added electrolytes were also studied. The implications of these data to a mechanism of action are discussed.