Molecular complexes of alprazolam with carboxylic acids, boric acid, boronic acids, and phenols. Evaluation of supramolecular heterosynthons mediated by a triazole ring

Authors

  • Sunil Varughese,

    1. Solid State and Structural Chemistry Unit, Indian Institute of Science, Bangalore 560 012, India
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  • Yasser Azim,

    1. Solid State and Structural Chemistry Unit, Indian Institute of Science, Bangalore 560 012, India
    2. School of Chemistry, University of Hyderabad, Hyderabad 500 046, India
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  • Gautam R. Desiraju

    Corresponding author
    1. Solid State and Structural Chemistry Unit, Indian Institute of Science, Bangalore 560 012, India
    2. School of Chemistry, University of Hyderabad, Hyderabad 500 046, India
    • Solid State and Structural Chemistry Unit, Indian Institute of Science, Bangalore 560 012, India. Telephone: +91-80-22933311; Fax: +91-80-23602306.
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Abstract

A series of molecular complexes, both co-crystals and salts, of a triazole drug—alprazolam—with carboxylic acids, boric acid, boronic acids, and phenols have been analyzed with respect to heterosynthons present in the crystal structures. In all cases, the triazole ring behaves as an efficient hydrogen bond acceptor with the acidic coformers. The hydrogen bond patterns exhibited with aromatic carboxylic acids were found to depend on the nature and position of the substituents. Being a strong acid, 2,6-dihydroxybenzoic acid forms a salt with alprazolam. With aliphatic dicarboxylic acids alprazolam forms hydrates and the water molecules play a central role in synthon formation and crystal packing. The triazole ring makes two distinct heterosynthons in the molecular complex with boric acid. Boronic acids and phenols form consistent hydrogen bond patterns, and these are seemingly independent of the substitutional effects. Boronic acids form noncentrosymmetric cyclic synthons, while phenols form O[BOND]Hequation imageN hydrogen bonds with the triazole ring. © 2010 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:3743–3753, 2010

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