Journal of Computer-Aided Molecular Design

, Volume 23, Issue 2, pp 105–111 | Cite as

Parameterization of an empirical model for the prediction of n-octanol, alkane and cyclohexane/water as well as brain/blood partition coefficients

  • Mohamed Zerara
  • Jürgen BrickmannEmail author
  • Robert Kretschmer
  • Thomas E. Exner


Quantitative information of solvation and transfer free energies is often needed for the understanding of many physicochemical processes, e.g the molecular recognition phenomena, the transport and diffusion processes through biological membranes and the tertiary structure of proteins. Recently, a concept for the localization and quantification of hydrophobicity has been introduced (Jäger et al. J Chem Inf Comput Sci 43:237–247, 2003). This model is based on the assumptions that the overall hydrophobicity can be obtained as a superposition of fragment contributions. To date, all predictive models for the logP have been parameterized for n-octanol/water (logP oct ) solvent while very few models with poor predictive abilities are available for other solvents. In this work, we propose a parameterization of an empirical model for n-octanol/water, alkane/water (logP alk ) and cyclohexane/water (logP cyc ) systems. Comparison of both logP alk and logP cyc with the logarithms of brain/blood ratios (logBB) for a set of structurally diverse compounds revealed a high correlation showing their superiority over the logP oct measure in this context.


Solvation and transfer free energies Hydrophobic effect Hydrophobic interaction LogP Brain/blood barrier Octanol/water Alkane/water Cyclohexane/water 

Supplementary material

10822_2008_9243_MOESM1_ESM.pdf (98 kb)
Supplementary material (99 kb)


  1. 1.
    Leo A, Hansch C, Elkins D (1971) Chem Rev 6:71Google Scholar
  2. 2.
    Caron G, Ermondi G (2005) J Med Chem 48:3269CrossRefGoogle Scholar
  3. 3.
    El Tayar N, Tsai RS, Testa B, Carrupt PA, Leo A (1991) J Pharm Sci 80:590CrossRefGoogle Scholar
  4. 4.
    Abraham MH, Chadha HS, Whiting GS, Mitchell RC (1994) J Pharm Sci 83:1085CrossRefGoogle Scholar
  5. 5.
    Pixner P, Heiden W, Merx H, Möller A, Moeckel G, Brickmann J (1994) J Chem Inf Comput Sci 34:1309–1319Google Scholar
  6. 6.
    Jäger R, Schmidt F, Schilling B, Brickmann J (2000) J Computer-Aided Mol Des 14:631–646CrossRefGoogle Scholar
  7. 7.
    Jäger R, Kast SM, Brickmann J (2003) J Chem Inf Comput Sci 43:237–247Google Scholar
  8. 8.
    Goodford PJ (1996) Chemometrics 10:107CrossRefGoogle Scholar
  9. 9.
    Ghose AK, Crippen GM (1986) J Comp Chem 7:565–577CrossRefGoogle Scholar
  10. 10.
    Viswanadan VN, Ghose AK, Revankar GR, Robins RK (1989) J Chem Inf Comput Sci 29:163–172Google Scholar
  11. 11.
    Ghose AK, Viswanadan VN, Wendoloski JJ (1998) J Phys Chem A 102:3762–3772CrossRefGoogle Scholar
  12. 12.
    No KT, Kim SG, Cho KH, Scheraga HA (1999) Biophys Chem 78:127CrossRefGoogle Scholar
  13. 13.
    Cruciani G (2006) Molecular interaction fields. Wiley-VCHGoogle Scholar
  14. 14.
    Gasteiger J, Rudolph C, Sadowski J (1992) Tetrahedron Comput Meth 3:537CrossRefGoogle Scholar
  15. 15.
    El Tayar N, Tsai RS, Testa B, Carrupt PA, Hansch C, Leo A (1991) J Pharm Sci 80:744CrossRefGoogle Scholar
  16. 16.
    Ganellin CR (1991) Uses of partition coefficients by brain penetration applied to the design of H2-receptor histamine antagonists. ElsevierGoogle Scholar
  17. 17.
    Abraham MH, Chadha HS, Mitchell RC (1994) J Pharm Sci 83:1257CrossRefGoogle Scholar
  18. 18.
    Chadha HS, Abraham MH, Mitchell RC (1994) Bioorg Med Chem Lett 2511:1085Google Scholar
  19. 19.
    Young RC, Mitchell RC, Brown TH, Ganellin CR, Griffiths R, Jones M, Rana KK, Saunders D, Smith IR, Sore NE, Wilks TJ (1988) J Med Chem 31:656CrossRefGoogle Scholar
  20. 20.
    Young RC, Ganellin CR, Griffiths R, Mitchell RC, Parsons ME, Saunders D, Sore NE (1993) J Med Chem 28:201CrossRefGoogle Scholar
  21. 21.
    Wichmann K, Diedenhofen M, Klamt A (2007) J Chem Inf Model 47:228CrossRefGoogle Scholar
  22. 22.
    Platts JA, Abraham MH, Zhao YH, Hersey A, Ijaz L, Butima D (2001) Eur J Med Chem 36:719CrossRefGoogle Scholar
  23. 23.
    Subramanian G, Kitchen DB (2003) J Computer-Aided Mol Des 17:643CrossRefGoogle Scholar
  24. 24.
    Fu X, Song Z, Liang W (2005) Internet Electron J Mol Des 4:737Google Scholar
  25. 25.
    Rishton GM, LaBonte K, Williams AJ, Kassam K, Kolovanov E (2006) Curr Opin Drug Dis Dev 9:303Google Scholar

Copyright information

© Springer Science+Business Media B.V. 2008

Authors and Affiliations

  • Mohamed Zerara
    • 1
    • 2
  • Jürgen Brickmann
    • 1
    • 2
    Email author
  • Robert Kretschmer
    • 3
  • Thomas E. Exner
    • 3
  1. 1.Department of ChemistryDarmstadt University of TechnologyDarmstadtGermany
  2. 2.MOLCAD GmbHDarmstadtGermany
  3. 3.Fachbereich ChemieUniversität KonstanzKonstanzGermany

Personalised recommendations