The Salt−Cocrystal Continuum:  The Influence of Crystal Structure on Ionization State

Salts and cocrystals are multicomponent crystals that can be distinguished by the location of the proton between an acid and a base. At the salt end of the spectrum proton transfer is complete, and on the opposite end proton transfer is absent in cocrystals. However, for acid-base complexes with similar pK(a) values, the extent of proton transfer in the solid state is not predictable and a continuum exists between the two extremes. For these systems, both the DeltapK(a) value (pK(a) of base - pK(a) of acid) and the crystalline environment determine the extent of proton transfer. A total of 20 complexes containing theophylline and guest molecules with DeltapK(a) values less than 3 have been prepared, resulting…