The role of solvation in proton transfer reactions: implications for predicting salt/co-crystal formation using the ΔpKa rule

Abstract

The ΔpKa rule is commonly applied by chemists and crystal engineers as a guideline for the rational design of molecular salts and co-crystals. For multi-component crystals containing acid and base constituents, empirical evidence has shown that ΔpKa > 4 almost always leads to salts, ΔpKa