Towards the systematic crystallisation of molecular ionic cocrystals: insights from computed crystal form landscapesElectronic supplementary information (ESI) available. See DOI: 10.1039/c8fd00036k

The underlying molecular and crystal properties affecting the crystallisation of ionic cocrystals (ICCs) with the general formula A − B + N (A − = anion, B + = cation and N = neutral acid molecule; 1 : 1 : 1 stoichiometry) are reported for a limited set of known crystal structures determined following the cocrystallisation of either 4-aminopyridine (which forms salts) or 4-dimethylaminopyridine (which forms salts and ICCs) with the same set of monoprotic acids with a single hydroxy or halogen substitution at the ortho or para position. Periodic density functional theory calculations (PBE + D2) on the energetic driving force for ICC crystallisation for a set of known crystal structures with well characterised acid, salt and ICC structures show that all but 1 of the 7 experimental ICC structures surveyed were more stable than the sum of their component salt and acid structures with 4 displaying relative stabilities (Δ E ICC ) ranging from 2.47-8.02 kJ mol −1 . The majority of molecular ICCs that are more stable with respect to their component salt and acid structures display the formation of discrete intermolecular O-H acid O anion hydrogen bonds with the D 1 1 (2) graph set between the carboxylic acid OH donor and the carboxylate oxygen acceptor of the anion. Computed crystal form landscapes for model 1 : 1 salts derived from acid-base pairs (involving 4-dimethylaminopyridine) known to form molecular ICCs show that on average the most stable predicted polymorphs of the 1 : 1 salts have efficient packing of the ions with packing coefficients in the range 65-80% and this is comparable to the packing coefficients of the most stable predicted polymorphs of 1 : 1 salts (involving 4-aminopyridine) that have no ICCs reported. This suggests that the cocrystallisation of equimolar amounts of the 1 : 1 salt and the acid to form a 1 : 1 : 1 molecular ICC is a complicated phenomenon that cannot be explained on the basis of inefficiencies in the crystal packing of the salt ions. The underlying molecular and crystal properties affecting the crystallisation of organic molecular ionic cocrystals (ICCs) are investigated.