Cocrystal versus salt, a matter of hydrogen bonds in two benzoic acid crystals

In solid phase, the energetic boundary between the obtainment of salts and cocrystals is often a matter of few kcal. In this work, we compared a salt and a cocrystal arising from the combination of p-chlorobenzoic acid with different crystallization partners. When the melamine was chosen as crystallization partner, we obtained a melaminium chlorobenzoate trihydrate salt (crystal 1) constituted by mono-protonated melaminium cation, coupled with a p-chlorobenzoate anion and three water molecules. Differently, when p-chlorobenzoic acid was coupled with 1,3-bis(4-pyridyl)propane (dpp), we observed a cocrystal with 2:1 acid/dpp ratio (crystal 2). In particular, by taking advantage of SCXRD analysis, we explore the relative spatial distribution of the two partners in the crystal structure with a special focus on understanding the forces involved in the formation of the three-dimensional framework. Finally, we rely on a computational approach to evaluate the different basicity of the crystallization partners in the two analyzed structures and to justify the different behaviors of the acid species in the formation of the two crystals.