SURFACE-ORIENTED SATURABLE BINDING OF HALOTHANE WITH MICELLES - PARAMAGNETIC RELAXATION OF F-19 NMR SPIN-LATTICE RELAXATION RATE AND GAS-CHROMATOGRAPHY STUDIES

We proposed that anesthesia is a surface phenomenon characterized by interaction of anesthetic molecules with macro-molecular surfaces (Yoshida et al., Biochim. Biophys. Acta 979, 287 (1989)). In the present study, halothane interaction with anionic sodium dodecylsulfate (SDS) micelles was measured by paramagnetic relaxation of F-19 NMR spin-lattice relaxation rate (R1) and gas chromatography. The F-19 NMR data on halothane interaction with micelles agreed with those obtained by gas chromatography. The halothane concentrations covered sub-clinical to water-saturating range to analyze the total interaction mode. The presence of paramagnetic ions increases the spin-lattice relaxation rates of the nuclei of the nearby molecules. Anionic paramagnetic 3-carboxy-Proxyl stays mainly in the aqueous phase of anionic micellar solutions due to electrostatic repulsion. A change in R1 of halothane by the addition of Proxyl represents the halothane molecules in water. The interaction of halothane with surfactant micelles was bimodal: after saturation was reached at about halothane-SDS mole ratio 0.5, the binding was increased with another saturation when the mole ratio further increased. In each case, the interaction was characterized by the Langmuir adsorption isotherm. The surface adsorption was concluded previously by the lack of halothane effect on the chemical shift of H-1 NMR of the SDS alkyl chain (Yoshida et al., J. Colloid Interface Sci. 124, 177 (1988)). To verify the surface adsorption model, the dodecane-water partition coefficient of halothane was compared with the halothane affinity to the micelles, because the properties of the interior of SDS micelles are similar to those of dodecane. The dodecane-water partition coefficient showed a single value of 135, without concentration dependence. The halothane interaction with SDS micelles was dissimilar to solvation into dodecane. (C) 1994 Academic Press, Inc.