Interaction of alcohols and anesthetics with the water-hexane interface: A molecular dynamics study

Abstract

The transfer of eight solutes across the water-hexane interface is studied using molecular dynamics computer simulations. Four of these solutes are model amphiphiles, straight chain alcohols — methanol, ethanol, butanol and hexanol. The remaining four molecules — cyclopropane, nitrous oxide, isoflurane and desflurane — are non-amphiphilec and polar or weakly polar. All of them are clinical anesthetics. All eight molecules exhibit free energy minima at the interface, indicating that they are interfacially active. Whereas interfacial activity of amphiphiles has been well known, it is shown here that a similar, although somewhat weaker behavior is also characteristic of a wide range of polar solutes. This can be explained as a balance between electrostatic and non-electrostatic contributions to the free energy, that change monotonically, but oppositely near the interface. Qualitatively, similar results are expected for solutes at interfaces between water and other non-polar liquids or lipid bilayers. Based on the results showing a very good correlation between anesthetic potencies and interfacial concentrations of 20 anesthetic compounds, it is proposed that the site of anesthetic action is located near the interface between water and the neuronal membrane.