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Biophys J. Apr 1997; 72(4): 1754–1761.
PMCID: PMC1184369

Contrasting membrane localization and behavior of halogenated cyclobutanes that follow or violate the Meyer-Overton hypothesis of general anesthetic potency.


The membrane localization and properties of two halogenated cyclobutanes were examined using 2H and 19F NMR. The common predictors of potency indicate that these two compounds will have anesthetic activity; however, 1,2-dichlorohexafluorocyclobutane (c(CCIFCCIFCF2CF2)) is not an effective anesthetic, whereas 1-chloro-1,2,2-trifluorocyclobutane (c(CCIFCF2CH2CH2)) is an effective general anesthetic. Using 2H NMR, the effect of these compounds on the acyl chain packing in palmitoyl (d31) oleoylphosphatidylcholine membranes was examined. The addition of the anesthetic c(CCIFCF2CH2CH2) results in small increases in the segmental order near the headgroup, whereas segments deeper in the bilayer show decreases in order. These results are consistent with those obtained previously for halothane, isoflurane, and enflurane. On the addition of the nonanesthetic c(CCIFCCIFCF2CF2), the segmental order in vitually unchanged, except for a slightly changed order near the segents 10-12 of the palmitoyl chains. These results, and the 19F chemical shifts, indicate that the anesthetic c(CCIFCF2CH2CH2) exhibits a preference for the membrane interface, as do the other general anesthetics, whereas the nonanesthetic c(CCIFCIFCF2CF2) resides within the membrane hydrocarbon core. The compound c(CCIFCCIFCF2CF2) and other nonanesthetic halocarbons have lower molecular dipole moments compared to effective anesthetic halocarbons, which may account for their altered distribution within the membrane. These data strongly suggest that preferential localization of a halocarbon within the membrane interface is a predictor of anesthetic potency. Furthermore, the data indicate that the properties and forces in the membrane interface deserve consideration as mediators of anesthetic activity.

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Selected References

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  • Baber J, Ellena JF, Cafiso DS. Distribution of general anesthetics in phospholipid bilayers determined using 2H NMR and 1H-1H NOE spectroscopy. Biochemistry. 1995 May 16;34(19):6533–6539. [PubMed]
  • Baldwin PA, Hubbell WL. Effects of lipid environment on the light-induced conformational changes of rhodopsin. 1. Absence of metarhodopsin II production in dimyristoylphosphatidylcholine recombinant membranes. Biochemistry. 1985 May 21;24(11):2624–2632. [PubMed]
  • Boden N, Jones SA, Sixl F. On the use of deuterium nuclear magnetic resonance as a probe of chain packing in lipid bilayers. Biochemistry. 1991 Feb 26;30(8):2146–2155. [PubMed]
  • Brown MF. Modulation of rhodopsin function by properties of the membrane bilayer. Chem Phys Lipids. 1994 Sep 6;73(1-2):159–180. [PubMed]
  • Eyring H, Woodbury JW, D'Arrigo JS. A molecular mechanism of general anesthesia. Anesthesiology. 1973 May;38(5):415–424. [PubMed]
  • Franks JJ, Sastry BV, Surber MJ, England RE. Halothane and isoflurane alter phospholipid transmethylation in rat brain synaptosomes. Anesthesiology. 1990 Nov;73(5):984–989. [PubMed]
  • Gruner SM, Shyamsunder E. Is the mechanism of general anesthesia related to lipid membrane spontaneous curvature? Ann N Y Acad Sci. 1991;625:685–697. [PubMed]
  • Keller SL, Gruner SM, Gawrisch K. Small concentrations of alamethicin induce a cubic phase in bulk phosphatidylethanolamine mixtures. Biochim Biophys Acta. 1996 Jan 31;1278(2):241–246. [PubMed]
  • Koblin DD, Chortkoff BS, Laster MJ, Eger EI, 2nd, Halsey MJ, Ionescu P. Polyhalogenated and perfluorinated compounds that disobey the Meyer-Overton hypothesis. Anesth Analg. 1994 Dec;79(6):1043–1048. [PubMed]
  • Koehler LS, Cruley W, Koehler KA. Solvent effects on halothane: 19F nuclear magnetic resonance in solvents and artificial membranes. Mol Pharmacol. 1977 Jan;13(1):113–121. [PubMed]
  • Miller KW. The nature of the site of general anesthesia. Int Rev Neurobiol. 1985;27:1–61. [PubMed]
  • Pohorille A, Cieplak P, Wilson MA. Interactions of anesthetics with the membrane-water interface. Chem Phys. 1996 Apr 1;204(2-3):337–345. [PubMed]
  • Qin Z, Szabo G, Cafiso DS. Anesthetics reduce the magnitude of the membrane dipole potential. Measurements in lipid vesicles using voltage-sensitive spin probes. Biochemistry. 1995 Apr 25;34(16):5536–5543. [PubMed]
  • Seelig A, Seelig J. The dynamic structure of fatty acyl chains in a phospholipid bilayer measured by deuterium magnetic resonance. Biochemistry. 1974 Nov 5;13(23):4839–4845. [PubMed]
  • Ueda I, Hirakawa M, Arakawa K, Kamaya H. Do anesthetics fluidize membranes? Anesthesiology. 1986 Jan;64(1):67–71. [PubMed]

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