INTERACTIONS OF ANESTHETICS WITH THE WATER-HEXANE INTERFACE - A MOLECULAR-DYNAMICS STUDY

The free energy profiles characterizing the transfer of nine solutes a cross the liquid-vapor interfaces of water and hexane and across the w ater-hexane interface were calculated from molecular dynamics simulati ons. among the solutes were n-butane and three of its halogenated deri vatives, as well as three halogenated cyclobutanes. The two remaining molecules, dichlorodifluoromethane and 1,2-dichloroperfluorethane, bel ong to series of halo-substituted methanes and ethanes. described in p revious studies (J. Chem. Phys. 1996, 104, 3760; Chem. Phys. 1996, 204 , 337). Each series of molecules contains structurally similar compoun ds that differ greatly in anesthetic potency. The accuracy of the simu lations was tested by comparing the calculated and the experimental fo e energies of solvation of all nine compounds in water and in hexane, in addition, the calculated and the measured surface excess concentrat ions of n-butane at the water liquid-vapor interface were compared. In all cases, good agreement with experimental results was found. At the water-hexane interface, the free energy profiles for polar molecules exhibited significant interfacial minima, whereas the profiles for non polar molecules did not. The existence of these minima was interpreted in terms of a balance between the free energy contribution arising fr om solute-solvent interactions and the work to form a cavity that acco mmodates the solute. These two contributions change monotonically, but oppositely, across the interface. The interfacial solubilities of the solutes, obtained from the free energy profiles, correlate very well with their anesthetic potencies. This is the case even when the Meyer- Overton hypothesis, which predicts a correlation between anesthetic po tency and solubility in oil, fails.