4-Aminoquinaldine monohydrate polymorphism: Prediction and impurity aided discovery of a difficult to access stable form.
CrystEngComm
; 18(22): 4053-4067, 2016 Jun 14.
Article
em En
| MEDLINE
| ID: mdl-28649176
ABSTRACT
Crystal structure prediction studies indicated the existence of an unknown high density monohydrate structure (Hy1B°) as global energy minimum for 4-aminoquinaldine (4-AQ). We thus performed an interdisciplinary experimental and computational study elucidating the crystal structures, solid form inter-relationships, kinetic and thermodynamic stabilities of the stable anhydrate (AH I°), the kinetic monohydrate (Hy1A ) and this novel monohydrate polymorph (Hy1B°) of 4-AQ. The crystal structure of Hy1B° 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 Hy1B° as the thermodynamically most stable hydrate form. At 25 °C the equilibrium of the 4-AQ hydrate/anhydrate system was observed at an aw (water activity) of 0.14. The finding of Hy1B° was complicated by the fact that the metastable but kinetically stable Hy1A shows a higher nucleation and growth rate. The presence of an impurity in an available 4-AQ sample facilitated the nucleation of Hy1B°, 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.
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1
Coleções:
01-internacional
Base de dados:
MEDLINE
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Idioma:
En
Revista:
CrystEngComm
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
Áustria