Acid–base crystalline complexes and the pKa rule

Differences in the predicted aqueous pKa values (ΔpKa) have been calculated for 6465 crystalline complexes containing ionised and non-ionised acid–base pairs in the Cambridge Structural Database. A linear relationship between ΔpKa and the probability of proton transfer between acid–base pairs has been derived for crystalline complexes with ΔpKa between −1 and 4. The pKa rule is validated and quantitated.