Form III-like conformation and Form I-like packing in a chloroform channel solvate of the diuretic drug chlortalidone

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 dua...

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Bibliographic Details
Published in:CrystEngComm 2012-01, Vol.14 (19), p.6173-6177
Main Authors: Martins, Felipe T., de abreu, Polyana J., Azarias, Lilian C., Villis, Paulo C. M., de Campos Melo, Ariane C., Ellena, Javier, Doriguetto, Antônio C.
Format: Article
Language:English
Subjects:
Assembly
Channels
Chloroform
Crystals
Dimers
Drugs
Phases
Stacking
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Summary: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 degree 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 degree 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.
ISSN:1466-8033
1466-8033
DOI:10.1039/c2ce25766a