Acid-base crystalline complexes and the pKa rule

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