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Atomic physicochemical parameters for three dimensional structure directed quantitative structure‐activity relationships III: Modeling hydrophobic interactions
Author(s) -
Ghose Arup K.,
Pritchett Avis,
Crippen Gordon M.
Publication year - 1988
Publication title -
journal of computational chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.907
H-Index - 188
eISSN - 1096-987X
pISSN - 0192-8651
DOI - 10.1002/jcc.540090111
Subject(s) - partition coefficient , chemistry , molecule , octanol , intermolecular force , atom (system on chip) , halogen , cndo/2 , correlation coefficient , heteroatom , computational chemistry , organic chemistry , alkyl , statistics , mathematics , computer science , embedded system
In an earlier article 8 the need was demonstrated for atomic physicochemical properties for three dimensional structure directed quantitative structure‐activity relationships, and it was shown how atomic parameters can be developed for successfully evaluating the molecular octanol‐water partition coefficient, which is a measure of hydrophobicity. In this work we report more refined atomic values of octanol‐water partition coefficients derived from nearly twice the number of compounds. Carbon, hydrogen, oxygen, nitrogen, sulfur and halogens are divided into 110 atom types of which 94 atomic values are evaluated from 830 molecules by least squares. These values gave a standard deviation of 0.470 and a correlation coefficient of 0.931. These parameters predicted the octanol‐water partition coefficient of 125 compounds with a standard deviation of 0.520 and a correlation coefficient of 0.870. There is only a correlation coefficient of 0.432 between the atomic octanol‐water partition coefficients and the atomic contributions to molar refractivity over the 93 atom types used for both the properties. This suggests that both parameters can be used simultaneously to model intermolecular interactions. We evaluated the CNDO/2 gross atomic charge distribution over several molecules to check the validity of our classification. We found that the charge density on the heteroatoms in conjugated systems is strongly affected by the presence of similar atoms in the conjugation which suggests it should be incorporated as a separate parameter in evaluating the partition coefficient.