Modeling Carbon Basicity

This work presents a predictive model of aqueous ionization constants (pKa) of protonatable carbons in certain aromatic rings. The phenomenon of carbon atoms sometimes acting as a stable and reversible base accepting a proton in water solution is surprisingly little recognized in medicinal chemistry, although known to general chemists for the past 70+ years. We present the development and results for two predictive models: 1) identifying the most basic carbon in a ring, and 2) calculating the resulting microscopic pKa value. Both models were incorporated into our global (i.e., taking all ionizable groups into account) S+pKa model.