Molecular orientation of volatile anesthetics at the binding surface: 1H- and 19F-NMR studies of submolecular affinity.

The shift of 1H- and 19F-NMR peaks in the frequency domain was used to resolve the solubilization of volatile anesthetics into sodium dodecylsulfate micelles to submolecular level. Enflurane has protons at both ends of the molecule, and the solubilization parameters (partition coefficients in a broad sense) of each end were estimated by 1H-NMR. The values were: 2130 for the hydrophobic end and 1980 for the hydrophilic end. The hydrophobic end of halothane is CF3, hence 19F-NMR was used: 4330 for the hydrophobic end and 2670 for the hydrophilic end. The ratios of the solubilization parameters between hydrophobic and hydrophilic ends were methoxyflurane 1.9 (Kaneshina et al. (1981) Biochim. Biophys. Acta 647, 223-226), enflurane 1.1, and halothane 1.6. The results indicate that methoxyflurane and halothane adsorb perpendicular to the membrane surface, whereas enflurane molecules stay parallel to the interface. The averaged solubilization parameters of both ends of these anesthetics were in good agreement with their conventional partition coefficients between dipalmitoylphosphatidylcholine (DPPC) membranes and water. The solubilization parameter of chloroform (1H-NMR) was 1580 in agreement with the reported values of DPPC-water partition coefficient.