Pharmaceutical Research

, Volume 22, Issue 6, pp 875–882 | Cite as

log P Estimation of 1,2-Dithiole-3-thiones and 1,2-Dithiole-3-ones: A Comparison of Experimental and Calculative Approaches

  • Sylvain Gargadennec
  • Gwenola Burgot
  • Jean-Louis Burgot
  • Raimund Mannhold
  • Roelof F. Rekker
Research Paper


To estimate experimental log P values of formerly described 5-formyl- and 5-acyl-dithiole-3-thiones (DTT) and -dithiole-3-ones (DTO) and to check the validity of five log P calculation programs via experimental log P for a database of 68 DTT and DTO.


Experimental log P values were measured by means of octanol/water partitioning; for determining solute concentrations in water, RP-HPLC with spectrophotometric detection was used. For calculating log P, the fragmental methods ACD/log P, CLOGP, and KOWWIN, the atom-based approach XLOGP, and the whole-molecule approach QLOGP were applied.


Quality of calculations significantly differs depending on the subset under consideration. For database compounds 0148, comprising alkyl and aryl substitution in 4- and 5-position, the fragmental methods ACD/log P, CLOGP, and KOWWIN perform significantly better than the atom-based approach XLOGP and the whole-molecule method QLOGP. For database compounds 4968, comprising formyl and acyl substitution in 4- and 5-position, superiority of the whole-molecule method QLOGP over the substructure-based approaches is observed. The strong underestimation of log P for compounds 4968 probably indicates hidden physicochemical phenomena resulting from the juxtaposition of the acyl and dithiole moieties.


All calculation methods included in this study need a thorough refinement to adequately cope with particular solvation behavior suspected to prevail in formyl- or acyl-DTT and DTO, which represent a chemical class of high pharmacological interest.

Key words

1,2-dithiole-3-ones 1,2-dithiole-3-thiones log P calculation octanol/water partitioning 



We thank Dr. Claude Ostermann (Altana Pharma, Konstanz, Germany) for providing us with CLOGP and ACD/log P calculations and Dr. Peter Buchwald (IVAX Research, Miami, FL, USA) for performing QLOGP calculations.


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Copyright information

© Springer Science + Business Media, Inc. 2005

Authors and Affiliations

  • Sylvain Gargadennec
    • 1
  • Gwenola Burgot
    • 1
  • Jean-Louis Burgot
    • 1
  • Raimund Mannhold
    • 2
  • Roelof F. Rekker
    • 3
  1. 1.Laboratoire de Chimie Analytique, Upres EA 2231, Faculté des Sciences Pharmaceutiques et BiologiquesUniversité de Rennes 1Rennes cedexFrance
  2. 2.Department of Laser Medicine, Molecular Drug Research GroupHeinrich-Heine-Universität, Universitätsstr. 1DüsseldorfGermany
  3. 3.1065 BB AmsterdamThe Netherlands

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