Calculation Methods for the Enhancement of Pharmaceutical Properties in Small Molecules: Estimating the Cationic pKa

Ann R.      Hermone; Rick      Gussio

doi:10.2174/1381612811319230012

Abstract

In this review, a summary of methodologies is covered to enable medicinal chemists to access an overview of pKa estimation devices. In order to stave overutilization of costly synthetic resources, the chemist requires an accurate and computationally tractable solution for estimating a pKa of a candidate molecule. We focus on the cationic moieties, since they are so fundamentally important in the chemistry of drugs, and possess unique requirements to obtain a reasonably reliable pKa estimation.

Keywords: Solvation energy, continuum dielectric, scoring function, training set, pKa calculations, cations, physical chemical properties, computational chemistry, small molecules, pharmaceutics.