Atomic Physicochemical Parameters for Three-Dimensional Structure-Directed Quantitative Structure-Activity Relationships I. Partition Coefficients as a Measure of Hydrophobicity

Earlier we showed (A. K. Ghose and G. M. Crippen, J. Med. Chem. , 28, 333, 1985) the necessity of atomic physicochemical parameters in three-dimensional receptor mapping. Here we derive more refined and widely applicable hydrophobicity parameters. Carbon, hydrogen, oxygen, nitrogen, sulfur, and halogens are classified into 110 atom types. Among these, the hydrophobic contributions of 90 atom types have been evaluated from the log P (water-octanol) values of 494 molecules, using the additive model and leastsquares technique. It gave a standard deviation of 0.347, a correlation coefficient of 0.962, and an explained variance of 0.908. These atomic values were used to predict the log P values of 69 compounds. The predicted values showed a standard deviation of 0.404 and a correlation coefficient of 0.896. This work has been compared with more conventional approaches.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/38274/1/540070419_ftp.pd