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RP-HPLC determination of the lipophilicity of bispyridinium reactivators of acetylcholinesterase bearing a but-2-ene connecting linker

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Abstract

New acetylcholinesterase reactivators with either a (E) or (Z)-but-2-ene connecting linker were recently prepared. The purity of the compounds was checked by HPLC and was found to be sufficient for in-vitro screening. All the discussed bispyridinium reactivators were analyzed by reversed-phase high performance liquid chromatography (RP-HPLC) to measure lipophilicity. The procedure was performed under isocratic conditions with methanol as organic modifier in the mobile phase using an end-capped non-polar C18 stationary phase RP column. Relationships between the lipophilicity (logarithm of the RP-HPLC capacity factor, log k) and chemical structures of the studied compounds are discussed. Lipophilicity was different for the (E) and (Z) compounds and varied among the compounds in each of these groups. The lipophilicity differences also indicated an apparent influence of intramolecular interactions. Lipophilicity calculations (log P/Clog P) by means of commonly used software were not successful due to the presence of quaternary nitrogen atoms in the molecules of the reactivators.

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Acknowledgement

The authors express their appreciation to M. Hrabinova and Petra Hanusova for their technical assistance. The work was supported by Grant Agency of Czech Republic No. 305/07/P162.

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Authors and Affiliations

  1. Department of Pharmaceutical Chemistry and Drug Control, Faculty of Pharmacy in Hradec Kralove, Charles University in Prague, Heyrovskeho 1203, 500 05, Hradec Kralove, Czech Republic

    Kamil Musilek & Martin Dolezal

  2. Department of Toxicology, Faculty of Military Health Sciences, Trebesska 1575, 500 01, Hradec Kralove, Czech Republic

    Kamil Musilek, Daniel Jun & Kamil Kuca

  3. Center of Advanced Studies, Faculty of Military Health Sciences, Trebesska 1575, 500 01, Hradec Kralove, Czech Republic

    Daniel Jun & Kamil Kuca

  4. Zentiva a.s., U kabelovny 130, 102 37, Prague, Czech Republic

    Josef Jampilek & Jiri Dohnal

  5. School of Biology, University of St. Andrews, E6 Bute Building, St. Andrews, KY16 9TS, Fife, UK

    Frank Gunn-Moore

Authors
  1. Kamil Musilek
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  2. Josef Jampilek
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  3. Jiri Dohnal
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  4. Daniel Jun
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  5. Frank Gunn-Moore
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  6. Martin Dolezal
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  7. Kamil Kuca
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Correspondence to Kamil Kuca.

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Musilek, K., Jampilek, J., Dohnal, J. et al. RP-HPLC determination of the lipophilicity of bispyridinium reactivators of acetylcholinesterase bearing a but-2-ene connecting linker. Anal Bioanal Chem 391, 367–372 (2008). https://doi.org/10.1007/s00216-008-2018-8

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  • DOI: https://doi.org/10.1007/s00216-008-2018-8

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