Octanol/water partition coefficients atomic approach

However, the CIMI/bc descriptors are relatively simplistic as they did not recognize differences between some important atom types (e.g., halogens). Based on the results of ARD approach, the octanol-water partition coefficient (log P), the molecular flexibility (number of rotatable bonds), the PSA, and the number of hydrogen bond donors were the most important descriptors in the model. None of the descriptors were significantly correlated with each other except log P and PSA for which the correlation was not high ( 0.5). The molecular weight was found to be the least significant descriptor in the model. 

In most empirical scoring functions, a hydrophobic character is attributed to several atom types, with equivalent weight for all hydrophobic contributions. In a more sophisticated approach, the propensity of particular atom types to be solvent-exposed or embedded in the interior of a protein can be assessed by so-called atomic solvation parameters. These have been derived, for example, from experimental octanol/water partition coefficients (303, 304) or from protein crystal structures (305, 306). Atomic solvation parameters are used in the VALIDATE scoring function (307) and have been tested in DOCK (308). 

Principles of Use. Leo s approach (Hansch and Leo [14]) to the estimation of octanol/water partition coefficients uses empirically derived atomic or group fragment constants (f) and structural factors (F). All calculations are carried out in terms of log Kow ... 

The range of most convenient hydrophobicity of organic compounds for reversed-phase (RP) HPLC separation may be estimated approximately as —1 < log P < + 5 (log P is the logarithm of the partition coefficient of the compound being characterized in the standard solvent system 1-octanol/water). Highly hydrophUic substances with log P < —1 need a special choice of analysis conditions, e.g., introduction of ion-pair additives into the eluents. Another approach is their conversion to more hydrophobic derivatives by the modification of functional groups with active hydrogen atoms. 

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