Effects of the crystal structure and thermodynamic stability on solubility of bioactive compounds: DFT study of isoniazid cocrystalsстатья
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Дата последнего поиска статьи во внешних источниках: 16 ноября 2017 г.
Аннотация:Intrinsic solubility of the isoniazid-carboxylic acid cocrystals is explored using thermodynamic cycle of transferring from crystal to gas and then to solution. The enthalpy/Gibbs free energy of phase transitions is computed by solid-state DFT (crystal) and DFT methods with/without accounting for polar solvent (aqueous solution/gas). The dissolution process of the isoniazid-dicarboxylic acid 2:1 cocrystals is foundto be enthalpy-determined. The linear correlation between the theoretical sublimation enthalpies andexperimental Gibbs energy of solution is established. According to it, the increase of stability causes the decrease of the considered cocrystals solubility. We conclude that a soluble and relatively stable cocrystal of isoniazid should be characterized by the sublimation enthalpy varying from 185 to 200 kJmol-1. Bader analysis of theoretical periodic electron density enables us to quantify the noncovalent interactions and clarify their role in formation of the isoniazid cocrystals. The sublimation enthalpy of the cocrystals is defined by the structure of the coformer molecule. Its value is less 150 kJmol-1 in the case of aromatic acids and larger than 180 kJmol1 for the aliphatic dicarboxylic acids. The sublimation enthalpy increases with the increase of the dicarboxylic acid hydrocarbon chain.