CoMFA investigation of Taft Es values

COMP 56

Yvonne C. Martin, yvonnecmartin@comcast.net, 2230 Chestnut St., Waukegan, IL 60087 and Ki H. Kim, pkhkim@gmail.com, Hope Drug Discovery Research Laboratory, 260 Southgate Drive, Vernon Hills, IL 60061.
Es values are the classic linear free energy parameter to describe the steric effect of substituents. With the advent of 3D QSAR, CoMFA in particular, we investigated whether Es is purely steric. We modeled the data on which Es is based, acid-catalyzed hydrolysis of esters, and found that although the majority of the differences between compounds can be explained by steric fields, there is a statistically significant contribution of electrostatic fields. Our work settles the long-standing debate as to whether or this hydrolysis is free of electronic effects Taft originally proposed.