Electronic structure analysis of compounds of interest in drug design: mono- and dicarboxylated pyridines

The search for efficacious drug molecules involves, amongst other considerations, identifying compounds that will have activity in the receptor microenvironment through some highly specific microscopic pathway that is governed by molecular interactions. Widespread in the search for compounds with biological activity is the use of quantum pharmacologic structure–activity calculations. In this study, we identify the topological features of ab initio charge densities for a series of carboxylated pyridines. As well, results from conformational and geometric analysis obtained with semi-empirical AM1 and ab initio level geometries are compared. Carboxylated pyridines such as quinolinic and dipicolinic acids, both known to be neuroactive compounds, are logical candidates for a systematic study investigating the suitability of relating topological properties calculated in this manner to biological activity. Future reports will detail the correlation of these properties to biological activity.