19F-NMR study on micellar solubilization of a volatile anesthetic halothane: Dose-related biphasic interaction

Abstract

Volatile anesthetics, used clinically at present, contain dipole moments in their molecular structure. Although the hydrocarbon core of lipid membranes is proposed to be the anesthetic action site, it is inconceivable that these dipolar molecules mix with highly structured membrane lipids isotropically. Because of the amphiphilicity, these anesthetics are most likely to associate with the hydrophilic polar surface of macromolecules. The present communication deals with the solvation mode of halothane (CF 3CHClBr) to sodium dodecyl sulfate micelles estimated by 19F-NMR chemical shifts. Depending upon the halothane concentration, two different modes of halothane interacton with the micelles were identified. At low concentrations, halothane solvated onto the micellar surface according to the Langmuir adsorption isotherm. The binding became temporarily saturated when the halothane concentration was about one-half of the surfactant concentration. When halothane was added further, they started to bind the micelle again, without changing the micellar size. The final number of halothane molecules solvated onto the micelles was about equal to the number of surfactant molecules taht forms the micelle. Apparently, half of the hydrophilic parts on the micellar surface are immediately available for the anesthetic binding. When these sites are filled by the anesthetic molecules, the property of the remaining hydrophilic sites must have been changed. Halothane molecules may bind these modified sites. Another possibility is the condensation kinetics where the bound halothane molecules became the novel binding sites.