Modeling the octanol-water partition coefficients by an optimized molecular connectivity index.
A procedure that makes it possible to generate a coherent model for prediction of the octanol-water partition coefficient within the molecular connectivity formalism was put forward. The method is based on the optimization of weights for corresponding skeletal atoms and is similar to the method for calculation of a variable connectivity index proposed by Randić. In contrast to Randić's method, we incorporate in the algorithm the possibility that the contribution of a term describing a carbon-heteroatom bond may be negative. When tested on a set of about 300 structurally diverse organic molecules, our procedure proved to be superior to the standard valence connectivity method. External validation on a smaller set of compounds confirmed the superiority of our procedure with respect to the standard one. Intramolecular interactions, which are operative in more complex compounds, are treated in a similar fashion to that in the Hansch-Leo or Rekker methods, by inclusion of empirical correction factors.
Soskić
Milan
M
Department of Chemistry, Faculty of Agronomy, University of Zagreb, HR-10000 Zagreb, The Republic of Croatia. msoskic@agr.hr
Plavsić
Dejan
D
D000465:Algorithms; D008956:Models, Chemical; D000442:Octanols / Q000737:chemistry*; D012995:Solubility; D014867:Water / Q000737:chemistry*
D000442:Octanols; D014867:Water