The pKa of a compound directly influences its biopharmaceutical profile. This article
describes the development of a method for estimating pKa values for a number of nitrogen
containing chemical structures using semiempirical QM properties derived from frontier
electron theory. Typically, the property giving the best correlation with pKa was the
electrophilic superdelocalisability of the nitrogen atom resulting in regression equations with
r2 values up to 0.94. The advantages of this technique are in the simplicity of the models and …

The electronic properties of small molecules can be calculated quickly and with a
reasonable degree of accuracy using semiempirical QM methods. In this study a set of QM
properties derived from frontier electron theory have been used to produce a predictive
model of the dissociation constants of phenols, benzoic acids and aliphatic carboxylic acids.
The pKa values and structures of nearly 500 compounds were extracted from the Physprop
database for this purpose. Multiple linear regression was used to search for relationships …