In the pursuit of a ‘disappearing’ anhydrous phase of the antipyrine–dipicolinic acid (ANT–DPA) co-crystal: explained through relative stability and charge density analyses

Abstract

The relative stability and growth of the two new cocrystal forms of antipyrine–dipicolinic acid, one of which is the ‘disappearing’ one, were systematically examined. The Cambridge Structural Database was extensively mined to find the hydrogen bonding motifs amenable to crystal engineering. The cocrystallization trials resulted in two cocrystal phases in the same vial. The hydrated phase (ANT–DPA-w) is predominant, stable and easily reproducible, while the anhydrous phase (ANT–DPA) is the ‘disappearing’ one which could only be reproduced under anhydrous conditions. The stability of both the cocrystals was examined within the framework of symmetry-adapted perturbation theory (SAPT), non-covalent interactions (NCIs), detailed topological analysis of the electron density and binding energy analyses which provide useful insight into the role of water molecules in the stability of the structure. A thermogravimetric analysis (TGA) was used to identify the dehydration temperature. In light of the above information, the anhydrous phase (ANT–DPA) was regained via melting and re-crystallization by providing an anhydrous environment to the hydrated phase (ANT–DPA-w).