Cm. Du et al., Rapid method for estimating octanol-water partition coefficient (log P-oct) from isocratic RP-HPLC and a hydrogen bond acidity term (A), J LIQ CHR R, 24(5), 2001, pp. 635-649
The linear solvation equation approach has been used to describe the octano
l/water lipophilicity scale (logP(oct)) and the isocratic retention factors
(log k) obtained using;reversed phase HPLC with acetonitrile. Both the oct
anol/water partition coefficients and the RP-HPLC retention data: obtained
from the literature, showed good correlation with the molecular descriptors
such as size, excess molar refractivity, H-bond acidity/basicity, and pola
rity/dipolarity. However, the impact of the H-bond acidity term was very di
fferent on the two lipophilicity scales.
The H-bond acidity term was not significant in describing the octanol/water
lipophilicity, while the H-bond acidity of the molecules decreased signifi
cantly their RP-HPLC retention. As the other terms had very similar impact
on the two lipophilicity scales, it made it possible to convert one scale t
o the other by incorporating only the H-bond acidity of the compounds as is
shown by the equation below, where A is the compound H-bond acidity.
log P-oct = 2.067(+/- 0.04) log k(40) + 1.094(+/- 0.08) A + 0.517(+/- 0.05)
n = 111 r = 0.982 rms = 0.189
Using the simpler hydrogen bond donor counts (HBC) also helped to align the
two lipophilicity scales to each other.
log P-oct = 1.913(+/-0.07) log k(40) + 0.367(+/-0.07) HBC + 0.720(+/-0.08)
n = 111 r = 0.962 rms = 0.272
The validity of the above equations was tested using a test set of 41 drug
compounds with our measured data. The log P-oct values were estimated from
isocratic RP-HPLC retention data with the H-bond acidity term and counts, w
ith an error of 0.284 and 0.325 log unit, respectively.