Artículos de revistas
Form III-like conformation and Form I-like packing in a chloroform channel solvate of the diuretic drug chlortalidone
Fecha
2012Registro en:
CRYSTENGCOMM, CAMBRIDGE, v. 14, n. 19, pp. 6173-6177, APR, 2012
1466-8033
10.1039/c2ce25766a
Autor
Martins, Felipe T.
Abreu, Polyana J. de
Azarias, Lilian C.
Villis, Paulo C. M.
Campos Melo, Ariane C. de
Ellena, Javier
Doriguetto, Antonio C.
Institución
Resumen
Chlortalidone (CTD) is an antihypertensive drug for which only two solid state phases have been structurally elucidated thus far. Here, we have prepared a chloroform solvate thereof, namely, CTD Form IV, and its structure was compared to those of Form I and Form III. Its two conformers exhibit a dual structural feature in relation to the antecedent polymorphs. Both CTD molecules of Form IV adopt a Form III-like conformation, which is featured, if the conformation of CTD Form I is used as a reference, by a rotation of about 90 degrees on the axis of the C-C bond bridging the substituted benzene and isoindolinyl rings. However, CTD Form IV assembles as in the Form I crystal packing despite the different stacking fashion of their centrosymmetric dimers. In contrast to Form I, there is no offset stacking in Form IV, which forces a bend of ca. 24 degrees between the planes passing through the isoindolinyl moieties of two [100]-stacked dimers. Chloroform molecules at a maximum stoichiometry of 0.25 mol per mol of the drug play a stabilizing role in the assembly of Form IV by filling the channels formed on the crystals.