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Location and orientation of Triclosan in phospholipid model membranes

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Abstract

Triclosan is a hydrophobic antibacterial agent used in dermatological preparations and oral hygiene products. Although the molecular mechanism of action of this molecule has been attributed to inhibition of fatty acid biosynthesis, earlier work in our laboratories strongly suggested that the antibacterial action of Triclosan is mediated at least partly through its membranotropic effects. In order to assess its location in phospholipid membranes, high-resolution magic-angle spinning natural abundance 13C NMR of Triclosan embedded within egg yolk lecithin model membranes has been used to obtain 13C spin–lattice relaxation times for both Triclosan and lecithin carbon atoms in the presence of Gd3+ ions. The results indicate that Triclosan is localized in the upper region of the phospholipid membrane, its hydroxyl group residing in the vicinity of the C=O/C2 carbon atoms of the acyl chain of the phospholipid, and the rest of the Triclosan molecule is probably aligned in a nearly perpendicular orientation with respect to the phospholipid molecule. Intercalation of Triclosan into bacterial cell membranes likely compromises the functional integrity of those membranes, thereby accounting for at least some of this compound’s antibacterial effects.

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Abbreviations

COLOC:

correlation by long-range coupling

EYL:

egg yolk lecithin

HETCOR:

heteronuclear chemical-shift correlation

MAS:

magic-angle spinning

MLV:

multilamellar vesicles

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Acknowledgements

This work was supported partly by grants PM98-0100 and BMC2002-00158 from MCYT, Madrid (to J.V.).

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Authors and Affiliations

  1. Instituto de Biología Molecular y Celular, Universidad “Miguel Hernández”, 03202 , Elche-Alicante, Spain

    Jaime Guillén, Angela Bernabeu & José Villalaín

  2. Basilea Pharmaceutica AG, 4005 , Basel, Switzerland

    Stuart Shapiro

Authors
  1. Jaime Guillén
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  2. Angela Bernabeu
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  3. Stuart Shapiro
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  4. José Villalaín
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Correspondence to José Villalaín.

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Guillén, J., Bernabeu, A., Shapiro, S. et al. Location and orientation of Triclosan in phospholipid model membranes. Eur Biophys J 33, 448–453 (2004). https://doi.org/10.1007/s00249-003-0378-8

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  • DOI: https://doi.org/10.1007/s00249-003-0378-8

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