Braun,D.E.; Oberacher,H.; Arnhard,K.; Orlova,M.; Griesser,U.J.;
Crystal structure prediction studies indicated the existence of an unknown high density monohydrate structure (Hy1(B)degrees) as the global energy minimum for 4-aminoquinaldine (4-AQ). We thus performed an interdisciplinary experimental and computational study elucidating the crystal structures, solid form interrelationships, and kinetic and thermodynamic stabilities of the stable anhydrate (AH I degrees), the kinetic monohydrate (Hy1(A)) and this novel monohydrate polymorph (Hy1(B)degrees) of 4-AQ. The crystal structure of Hy1(B)degrees was determined by combining laboratory powder X-ray diffraction data and ab initio calculations. Dehydration studies with differential scanning calorimetry and solubility measurements confirmed the result of the lattice energy calculations, which identified Hy1(B)degrees as the thermodynamically most stable hydrate form. At 25 degrees C the equilibrium of the 4-AQ hydrate/anhydrate system was observed at an a(w) (water activity) of 0.14. The finding of Hy1(B)degrees was complicated by the fact that the metastable but kinetically stable Hy1(A) shows a higher nucleation and growth rate. The presence of an impurity in an available 4-AQ sample facilitated the nucleation of Hy1(B)degrees, whose crystallisation is favored under hydrothermal conditions. The value of combining experimental with theoretical studies in hydrate screening and characterisation, as well as the reasons for hydrate formation in 4-AQ, are discussed.
Crystengcomm 2016 18:4053-4067