View PDF Version
 
DOI: 10.1039/A806009F (Paper) Reference Section for: J. Chem. Soc., Perkin Trans. 2, 1999, 107-112

Possible interaction mechanism for quaternary ammonium (QA) ions binding to potassium channels: density functional theory and MP2 studies on the interaction between phenol and ammonium cation[hair space]†

(Note: The full text of this document is currently only available in the PDF Version )

Xiao Jian Tan, Hua Liang Jiang, Wei Liang Zhu, Kai Xian Chen and Ru Yun Ji

Abstract

Tetraethylammonium (TEA) and other quaternary ammonium (QA) ions are potent blockers of potassium channels. In order to shed light on the blockade mechanism of QA ions, we have carried out a series of computations on the phenol–ammonium model with density functional theory (DFT) and Möller–Plesset second order perturbation (MP2) methods at levels of 6-31G* and 6-31G** basis sets. NH–aromatic π interaction and NH–OH hydrogen bond interaction, which are important in biological systems, are responsible for the binding of NH4+ to phenol. From analysis of structures, energies, charge populations and transition state features, both the cation–π interaction and hydrogen bond or electrostatic interaction between QAs and the key amino acid residues at the entryways of K+ channels are seen to be significant in the blockade mechanism of QA ions.

References

  1. B. Hill, J. Gen. Physiol., 1967, 50, 1287 Search PubMed.
  2. C. M. Armstrong, J. Gen. Physiol., 1971, 58, 413 Search PubMed.
  3. R. J. French and R. J. Shoukimas, Biophys. J., 1981, 34, 271 CAS.
  4. R. J. French and R. J. Shoukimas, Biophys. J., 1981, 34, 271 CAS.
  5. G. Yellen, M. T. Abramson and R. MacKinnon, Science, 1991, 251, 939 CAS.
  6. D. A. Doyle, J. M. Cabral, R. A. Pfuetzner, A. Kuo, J. M. Gulbis, S. L. Cohen, B. T. Chait and R. MacKinnon, Science, 1998, 280, 69 CrossRef CAS.
  7. R. MacKinnon and G. Yellen, Science, 1990, 250, 276 CAS.
  8. M. P. Kavanaugh, M. D. Varnum, P. B. Osborne, M. J. Christie, A. E. Busch, J. P. Adelman and R. A. North, J. Biol. Chem., 1991, 266, 7583 CAS.
  9. L. Heginbotham and R. MacKinnon, Neuron, 1992, 8, 483 CrossRef.
  10. J. C. Ma and D. A. Dougherty, Chem. Rev., 1997, 97, 1303 CrossRef CAS.
  11. H. Basch and W. J. Stevens, J. Mol. Struct. (THEOCHEM), 1995, 338, 303 CrossRef CAS.
  12. A. D. Becke, J. Chem. Phys., 1993, 93, 5648 CrossRef.
  13. S. Mecozzi, A. P. West, Jr. and D. A. Dougherty, Proc. Natl. Acad. Sci., 1996, 93, 10566 CrossRef CAS.
  14. Hua Liang Jiang, Wei Liang Zhu, Xiao Jian Tan, Jian De Gu, Jian Zhong Chen, Mao Wei Lin, Kai Xian Chen and Ru Yun Ji, Sci. China, Ser. B, 1998, 41, 535 Search PubMed.
  15. L. Choi, C. Mossman, J. Aube and G. Yellen, Neuron, 1993, 10, 533 CrossRef.
Click here to see how this site uses Cookies. View our privacy policy here.