GEOMETRIC REQUIREMENTS FOR MEMBRANE PERTURBATION AND ANESTHETIC ACTIVITY - CONFORMATIONAL-ANALYSIS OF ALPHAXALONE AND DELTA-16-ALPHAXALONE AND H-2 NMR-STUDIES ON THEIR INTERACTIONS WITH MODEL MEMBRANES

  • 1 January 1985
    • journal article
    • research article
    • Vol. 27  (6) , 624-629
Abstract
2H NMR spectra were obtained for dimyristoylphosphatidylcholine multilamellar dispersions, perdeuterated in the fatty acid chains, in the presence and absence of 2 steroid analogs. The presence of the active anesthetic steroid alphaxalone results in consistently smaller 2H quadrupolar splittings (.DELTA..nu.Q) for individual C2H2 segments of the fatty acid chains, indicating increased molecular disorder. In contrast, the inactive analog .DELTA.16-alphaxalone causes no significant change in the 2H spectra of the phospholipid. The conformational analysis of alphaxalone and .DELTA.16-alphaxalone in solution was carried out with the help of 1H and 13C high resolution NMR spectroscopy and the results were used to propose a molecular model for the interaction of the 2 steroids with membrane phospholipids. The model correlates the observed differences in the manner in which the 2 steroids interact with model membranes in their respective conformation and provides a molecular basis for anesthetic steroid activity.