Using theoretical descriptors in quantitative structure–activity relationships: gas phase acidity

Abstract

The application of computational techniques to biology, chemistry and physics is growing rapidly. Quantitative structure–activity relationships (QSAR) have been used widely to relate biological activities as well as physicochemical properties to molecular structure features. A difficulty in this approach has been nonuniformity of parameter sets resulting in the inability to examine contributions across properties and data sets. Linear solvation energy relationships (LSER) developed by Kamlet and Taft successfully utilize a single set of parameters to correlate a wide range of biological, chemical and physical properties. We have replaced the empirical LSER solvatochromic parameters with theoretically determined parameters to permit greater ease in a priori property prediction. These TLSER descriptors have given good correlations and interpretations for some biological activities and physicochemical properties. This paper discusses the application of these descriptors to the gas phase acidity of some carboxylic acids, alcohols, silanols, anilines, hydrocarbons, and oximes. Good correlations and physical interpretations result.