St. Lin et Si. Sandler, Multipole corrections to account for structure and proximity effects in group contribution methods: Octanol-water partition coefficients, J PHYS CH A, 104(30), 2000, pp. 7099-7105
We propose a new method to correct for structure and proximity effects that
are not generally accounted for in group contribution models. Molecular or
bital calculations for isolated molecules are performed to obtain the net c
harge and dipole moment on each group within the molecule. These group mult
ipoles, which vary as a result of the presence of proximate groups, are use
d as the basis for corrections to simple group contribution methods. We hav
e applied this method to our recently developed GCSKOW model to predict the
octanol-water partition coefficients (K-OW) for complex molecules. We stud
ied this simple, theoretically based method with a total of 450 solutes, in
cluding five pharmaceutical compounds. The root-mean-square (RMS) deviation
in the log(10) K-OW calculated from the GCSKOW model with these multipole
corrections is found to be 0.18 (which leads to a mean error of 52% in K-OW
), compared with a RMS deviation of 0.44 (177%) when no correction is made.
This simpler approach is more accurate than the KOW-UNIFAC model (RMS of 0
.28 or an error of 92% in K-OW for 344 compounds) and is comparable to the
ClogP model (0.18 or 52%), which heretofore had been considered to be the m
ost accurate predictive method for octanol-water partition coefficients.