Interaction of alkyl ammonium derivatives with red cells: Hemolysis and sodium pump inhibition studies
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Members of four homologous series of tetra-alkyl ammonium bromides (R3N+(CH2)n−1·CH3Br− whereR=H, CH3 or C2H5 andR′N+H3Br− whereR′ represents the isomeric butyl series) have been synthesized and tested as sodium pump inhibitors, measured as ouabain-sensitive K+ influx, and as hemolytic agents on human red cells.
Potency for both effects is presented graphically, plotting the logarithm of the concentration for half maximal effect against alkyl chain length. Both hemolysis and pump inhibition studies yielded a biphasic response consisting of two good straight lines, with effectiveness increasing up to C10–12 and then remaining constant up to C20.
For hemolysis the alkyl ammonium series was most effective. The calculated free-energy change per methylene group was the same for three series of compounds, but the free-energy contribution from the headgroup was lower for the ammonium series.
In contrast, although pump inhibition studies also yielded simple biphasic plots, inhibition occurred at 3- to 50-fold lower concentrations and there were significant differences between the three series, both in the free-energy changes per methylene group and in the headgroup contributions.
We have analyzed these results thermodynamically to take account of hydrophobic interactions and the conformation of the alkyl chains.
KeywordsAlkyl Chain Homologous Series Ammonium Bromide Alkyl Chain Length CH3Br
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- Abe, A., Jernigan, R.L., Flory, P.J. 1966. Conformational energies ofn-alkanes and the random configuration of higher homologs including polymethylene.J. Am. Chem. Soc. 88:631Google Scholar
- Adam, N.K. 1941. The Physics and Chemistry of Surfaces. (3rd ed.) Oxford University Press, OxfordGoogle Scholar
- Davies, J.T., Rideal, E.K. 1961. Interfacial Phenomena. p. 235. Academic Press, New York-LondonGoogle Scholar
- Ellory, J.C., Simonsen, E., Klein, R.A. 1979. Inhibition of the sodium pump in human red cells by tetra alkyl ammonium derivatives.In: The Sodium Pump. P.L. Jørgensen, editor. Academic Press, New York-LondonGoogle Scholar
- Finkelstein, M., Petersen, R.C., Ross, S.D. 1959. The electrochemical decomposition of quaternary ammonium salts.J. Am. Chem. Soc. 81:2361Google Scholar
- Flory, P.J. 1969. Statistical mechanics of chain molecules. John Wiley, New YorkGoogle Scholar
- Glasstone, S. 1960. Textbook of Physical Chemistry. (2nd ed.) pp. 401, 1211. Macmillan, LondonGoogle Scholar
- Grovenstein, E., Blanchard, E.P., Gordon, D.A., Stevenson, R.W. 1959. Carbanions. II. Cleavage of tetraalkylammonium halides by sodium in dioxane.J. Am. Chem. Soc. 81:4842Google Scholar
- Halicioglu, T., Sinanoglu, O. 1969. Solvent effects on cis-trans azobenzene isomerization: A detailed application of a theory of solvent effects on molecular association.Ann. N.Y. Acad. Sci. 158:308Google Scholar
- Hildebrand, J.H. 1979. Is there a “hydrophobic” effect?Proc. Natl. Acad. Sci. USA 76:194Google Scholar
- Horvath, C., Melander, W. 1978. Reversed-phase chromatography and the hydrophobic effect.Int. Lab. Nov Dec: 11Google Scholar
- Horvath, C., Melander, W., Molnar, I. 1977. Liquid chromatography of ionogenic substances with non-polar stationary phases.Anal. Chem. 49:142Google Scholar
- Klein, R.A. 1979. Gas chromatographic resolution of the optical enantiomers of a homologous series of 3-alkyl-serines (2-amino-3-alkyl-3-hydroxy-butanoic acids).J. Chromatogr. 170:468Google Scholar
- Kropp, D.L., Sachs, J.R. 1977. Kinetics of the inhibition of the Na−K pump by tetrapropylammonium chloride.J. Physiol. (London) 264:471Google Scholar
- Littlewood, A.B. 1970. Gas Chromatography. Principles, techniques and applications. p. 467. Academic Press, New York-LondonGoogle Scholar
- Mizushima, S-I., Okasaki, H. 1949. Equilibrium ratio of rotational isomers ofn-pentane: With special reference to its difference from that of 1,2-dichloroethane.J. Am. Chem. Soc. 71:3411Google Scholar
- Moelwyn-Hughes, E.A. 1947. The kinetics of reaction in solution. (2nd ed.) p. 7. Clarendon Press, OxfordGoogle Scholar
- Person, W.B., Pimentel, G.C. 1953. Thermodynamic properties and the characteristic CH2 frequencies ofn-paraffins.J. Am. Chem. Soc. 75:532Google Scholar
- Rojas, E., Rudy, B. 1976. Sodium conductance inactivation induced by quaternary ammonium compounds in squid giant axons in which the inactivation gate has been destroyed.J. Physiol. (London) 256:123Google Scholar
- Sallee, V.L. 1978. Fatty acid and alcohol partitioning with intestinal brush border and erythrocyte membranes.J. Membrane Biol. 43:187Google Scholar
- Sheppard, N., Szasz, G.J. 1949. Spectroscopic studies of rotational isomerism. III. The normal paraffins in the liquid and solid states.J. Chem. Phys. 17:86Google Scholar
- Sinanoglu, O. 1968. Solvent effects on molecular associations.In: Molecular Associations in Biology. B. Pullman, editor. p. 427–445. Academic Press, New York-LondonGoogle Scholar
- Sinanoglu, O., Abdulnur, S. 1965. Effect of water and other solvents on the structure of biopolymers.Fed. Proc. 24:512Google Scholar
- Tanford, C. 1973. The hydrophobic effect: Formation of micelles and biological membranes. John Wiley, New York-LondonGoogle Scholar
- Tanford, C. 1979. Interfacial free energy and the hydrophobic effect.Proc. Nat. Acad. Sci. USA 76:4175Google Scholar
- Vogel, A. 1959. Textbook of Practical Organic Chemistry Including Qualitative Organic Analysis. pp. 281–283. Longmans, LondonGoogle Scholar
- Vogel, A. 1978. Vogel's Practical Organic Chemistry Including Qualitative Organic Analysis. Revised by B.S. Furniss, A.J. Hannaford V. Rogers, P.G.W. Smith, and A.R. Tatchall. pp. 390–392. Longmans, London-New YorkGoogle Scholar