Summary
We have found that Simon's neutral, noncyclic, Li+-selective complexone, which has imide and ether ligands, renders lipid bilayer membranes selectively permeable to certain cations and anions. The present paper characterizes the ability of this molecule to carry monovalent cations; and we show it to be most selective for Li+ among the alkali cations, the first reconstitution of Li+-selective permeation in lipid bilayer membranes. This complexone acts as an “equilibrium-domain” carrier for Ag+> Li+>Tl+>Na+>NH +4 >Rb+>Cs+ over a wide range of experimental conditions. The major type of membrane-permeating species formed is a 2∶1 carrier/cation complex dominant except at the lowest salt and carrier concentrations where a 1∶1 carrier/cation, with a similar selectivity sequence, can be detected. Among the groupIa cations the selectivity sequence in bilayers, Li+>Na+>K+>Rb+>Cs+, is similar to that previously found for this molecule in thick solvent-polymer membrane electrodes. We find this carrier to be more selective to Ag+ than to any other monovalent cation yet studied. This high Ag+ selectivity is used, together with the dependence of the selectivity on the nature of the N-amide substitutents, to argue that the imide oxygens play a major role as ligands.
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References
Amdisen, A., Schou, M. 1978. Lithium.In: Side Effects of Drugs Annual 2, M.N.G. Dukes, editor, pp. 17–29. Excerpta Medica, Amsterdam-Oxford
Ammann, D., Bissig, R., Cimerman, Z., Fiedler, V., Guggi, M., Morf, W.E., Oehme, M., Osswald, H., Pretsch, E., Simon, W. 1976. Synthetic neutral carriers for cations.In: Ion and Enzyme Electrodes in Biology and Medicine. M. Kessler, L.C. Clark, Jr., D.W. Lubbers, I.A. Silver, and W. Simon, editors. pp. 22–37. Urban and Schwarzenberg, Munchen-Berlin-Wien
Ammann, D., Pretsch, E., Simon, W., 1974. A sodium ion-selective electrode based on a neutral carrier.Anal Lett. 7:23–32
Andersen, O.S. 1978. Ion transport across simple lipid membranes.In: Renal Functions. G.E. Giebisch and E.F. Purcell, editors, pp. 71–99. J. Macy, Jr. Foundation, New York
Andersen, O.S., Feldberg, S., Nakadomari, H., Levy, S., McLaughlin, S. 1978. Electrostatic interactions among hydrophobic ions in lipid bilayer membranes.Biophys. J. 21:35–77
Andreoli, T.E., Tieffenberg, M., Tosteson, D.C. 1967. The effects of valinomycin on the ionic permeability of thin lipid membranes.J. Gen. Physiol. 50:2527–2545
Ciani, S. 1976. Influence of molecular variations of ionophore and lipid on the selective ion permeability of membranes: A theoretical model.J. Membrane Biol. 30:45–63
Ciani, S., Eisenman, G., Szabo, G. 1969. A theory for the effects of neutral carriers such as the macrotetralide actin antibiotics on the electrical properties of bilayer membranes.J. Membrane Biol. 1:346–382
Duhm, J., Becker, B.F. 1977. Studies of the lithium transport across the red cell membrane.Pfluegers Arch. Eur. J. Physiol. 367:211–219;370:211–219
Ehrlich, B.E., Diamond, J.M., Clausen, C., Gosenfeld, L., Kaufman-Diamond, S. 1979. The red cell membrane as a model for studying lithium's therapeutic action.In: Lithium: Unresolved Issues and Controversies. Excerpta Medica, Amsterdam (in press)
Eisenman, G. 1961. On the elementary atomic origin of equilibrium ionic specificity.In: Symposium on Membrane Transport. A. Kleinzeller and A. Kotyk, editors, pp. 163–179. Academic press, New York
Eisenman, G. 1969. Theory of membrane electrode potentials: An examination of the parameters determining the selectivity of solid and liquid ion exchangers and of neutral ion-sequestering molecules.In: Ion Selective Electrodes, R.A. Durst, editor. pp. 1–56. Natl. Bureau of Standards Special Publication No. 314
Eisenman, G. 1978.In: Advances in Chemical Physics. R. Lefever and A. Goldbeter, editors, Vol. 39, pp. 316–318. Interscience, New York
Eisenman, G., Ciani, S., Szabo, G. 1968. Some theoretically expected and experimentally observed properties of lipid bilayer membranes containign neutral molecular carriers of ions.Fed. Proc. 27:1289–1304
Eisenman, G., Krasne, S. 1975. The ion selectivity of carrier molecules, membranes and enzymes.In: MTP International Review of Science Biochemistry Series. C.F. Fox, editor. Vol. 2, pp. 27–59. Butterworths, London
Eisenman, G., Krasne, S., Ciani, S. 1975. The kinetic and equilibrium components of selective ionic permeability mediated by nactin and valinomycin-like carriers having systematically varied degrees of methylation.Ann. N.Y. Acad. Sci. 254:34–60
Eisenman, G., Margalit, R. 1978. Amphoteric complexes of a neutral ionophore having tertiary amide ligands—a model for anion binding to the polypeptide backbone.In: Frontiers of Biological Energetics: Electron to Tissue. J.S. Leigh, P.L. Dutton, and A. Scarpa, editors. Vol. II, pp. 1215–1225. Academic Press, New York
Eisenman, G., Sandblom, J., Neher, E. 1977. Ionic selectivity, saturation, binding and block in the gramicidin A channel: A preliminary report.In: Metal-Ligand Interactions in Organic Chemistry and Biochemistry B. Pullman and N. Goldblum, editors. Vol. 2, pp. 1–36. D. Reidel, Dordrecht
Eisenman, G., Sandblom, J., Neher, E. 1978. Interactions in cation permeation through the gramicidin channel: Ca, Rb, K, Na, Li, Tl, H, and effects of anion binding.Biophys. J. 22:307–340
Eisenman, G., Szabo, G., Ciani, S., McLaughlin, S., Krasne, S. 1973. Ion binding and ion transport produced by neutral lipid-soluble molecules.Prog. Surf. Memb. Sci. 6:139–241
Guggi, M. 1977. Ph.D. Thesis. Swiss Federal Institute of Technology. Zürich
Guggi, M., Fiedler, V., Pretsch, E., Simon, W. 1975. A lithium ion-selective electrode based on a neutral carrier.Anal Lett. 8:857–866
Hille, B. 1975. Ionic selectivity of the Na+ and K+ channels of nerve membranes.In: Membranes—A Series of Advances. G. Eisenman, editor, Vol. 3, pp. 255–323. Marcel Dekker, New York
Hladky, S.B., Haydon, D.A. 1973. Membrane conductance and surface potential.Biochim. Biophys. Acta 318:464–468
Kirsh, N.N.L., Funck, R.J.J., Pretsch, E., Simon, W. 1977. Membrane selectivity and synthesis of ionophores for Li+. Stability constants in ethanol.Helv. Chim. Acta 60:2326–2333
Krasne, S., Eisenman, G. 1976. Influence of molecular variations of ionophore and lipid on the selective ion permeability of membranes. I. Tetranactin and the methylation of nonactintype carriers.J. Membrane Biol. 30:1–44
Krasne, S., Eisenman, G., Szabo, G. 1971. Freezing and melting of lipid bilayers and the mode of action of nonactin, vallinomycin and gramicidin A.Science 174:412–415
Kuo, K.H., Eisenman, G. 1977. Na+-selective permeation of lipid bilayers mediated by a neutral ionophore.Biophys. J. 17:212a
Kuo, K.H., Eisenman, G. 1978. Mode of action of Simon's non-cyclic Na+-selective ligand on bilayers.Arzneimittel-Forschung (Drug Research),28(1):707
Laprade, R., Ciani, S., Eisenman, G., Szabo, G. 1975. The kinetics of carrier-mediated ion permeation in lipid bilayers and its theoretical interpretation.In: Membranes—A Series of Advances. G. Eisenman, editor. Vol. 3, pp. 127–214. Marcel Dekker, New York
Läuger, P. 1972. Carrier-mediated ion transport.Science 178:23–30
Lehn, J.M., Savage, J.R. 1971. Cation and cavity selectivities of alkali and alkaline earth “cryptates.”Chem. Commun. 197:440–441
Margalit, R., Eisenman, G. 1978a. Mode of action of Simon's noncyclic Li+-selective molecule on bilayers including its ability to carry anions selectively.Arzneimittel-Forschung (Drug Research)28(1):707–708
Margalit, R., Eisenman, G. 1978b. Anion selective permeation of lipid bilayers mediated by a neutral carrier with only oxygen ligands.Biophys. J. 21:26a
Margalit, R., Eisenman, G. 1979a. Co-transport of cations and anions across lipid bilayers mediated by a neutral carrier —a model for biological symport systems.Biophys. J. 26:260a
Margalit, R., Eisenman G. 1979b. Some binding properties of the peptide backbone inferred from studies of a neutral non-cyclic carrier having imide ligands.In: Peptides: Structure and Biological Functions. E. Gross and J. Meienhofer, editors. pp. 665–679. Pierce, Rockford (Illinois)
McBride, D., Szabo, G. 1978. Blocking of gramidcin channel conductance by Ag+.Biophys. J. 21:25a
McLaughlin, S.G.A., Szabo, G., Ciani, S., Eisenman, G. 1972. The effects of a cyclic polyether on the electrical properties of phospholipid bilayer membranes.J. Membrane Biol. 9:3–36
Mueller, P., Ruding, D.O. 1967. Development of K+−Na+ discrimination in experimental bimolecular lipid membranes by macrocyclic antibiotics. B.B.R.C.26:398–404
Ovchinnikov, Y.A., Ivanov V.T., Shkrov, A.M. 1974. Membrane Active Complexones. B.B.A. Library, Vol. 12, Elsevier Scientific, New York
Pandey, G.N., Dorus, E., Davis, J.M., Tosteson, D.C. 1979. Lithium transport in red blood cells, genetic and clinical aspects.In: The Li+ Ion Impact on Treatment and Research, F.K. Goodwin, editor.Arch. Gen. Psychiat. Special Issue: 902–908
Szabo, G., Eisenman, G. 1973b. Enhanced cation permeability in glyceryl oleate bilayers.Biophys. J. 13:173a
Szabo, G., Eisenman, G., Ciani, S. 1969. The effects of macrotetralide actin antibiotics on the electrical properties of phospholipid bilayer membranes.J. Membrane. Biol. 1:346–382
Szabo, G., Eisenman, G., Laprade, R., Ciani, S., Krasne, S. 1973a. Experimentally observed effects of carriers on the electrical properties of bilayer membranes-equilibrium domain.In: Membranes—A Series of Advances. G. Eisenman, editor. Vol. 2, pp. 179–328. Marcel Dekker, New York
Szabo, G., McBride, D. 1978. Influence of double-layer and dipolar surface potentials on ionic conductance of gramicidin channels.Biophys. J. 21:25a
Wieland, T., Faulstich, H., Burgermeister, W., Otting, W., Mohle, W., Shemyakin, M.M., Ovchinnikov, Y.A., Ivanov, V.T., Malenkov, G.G. 1970. Affinity of antamanide for sodium ions.FEBS. Lett. 9:89–92
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Margalit, R., Eisenman, G. Ionic permeation of lipid bilayer membranes mediated by a neutral, noncyclic Li+-selective carrier having imide and ether ligands. I. Selectivity among monovalent cations. J. Membrain Biol. 61, 209–219 (1981). https://doi.org/10.1007/BF01870525
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DOI: https://doi.org/10.1007/BF01870525