Weak Interactions in Cocrystals of Isoniazid with Glycolic and Mandelic Acids
Raquel Álvarez-Vidaurre,
Alfonso Castiñeiras,
Antonio Frontera,
Isabel García-Santos,
Diego M. Gil,
Josefa M. González-Pérez,
Juan Niclós-Gutiérrez,
Rocío Torres-Iglesias
Affiliations
Raquel Álvarez-Vidaurre
Department of Inorganic Chemistry, Faculty of Pharmacy, University of Santiago de Compostela, 15782 Santiago de Compostela, Spain
Alfonso Castiñeiras
Department of Inorganic Chemistry, Faculty of Pharmacy, University of Santiago de Compostela, 15782 Santiago de Compostela, Spain
Antonio Frontera
Department of Química, Universitat de les Illes Balears, Crta. de Valldemossa km 7.5, 07122 Palma de Mallorca, Spain
Isabel García-Santos
Department of Inorganic Chemistry, Faculty of Pharmacy, University of Santiago de Compostela, 15782 Santiago de Compostela, Spain
Diego M. Gil
INBIOFAL (CONICET – UNT), Instituto de Química Orgánica, Facultad de Bioquímica, Química y Farmacia, Universidad Nacional de Tucumán, Ayacucho 471, T4000INI San Miguel de Tucumán, Argentina
Josefa M. González-Pérez
Department of Inorganic Chemistry, Faculty of Pharmacy, University of Granada, 18071 Granada, Spain
Juan Niclós-Gutiérrez
Department of Inorganic Chemistry, Faculty of Pharmacy, University of Granada, 18071 Granada, Spain
Rocío Torres-Iglesias
Department of Inorganic Chemistry, Faculty of Pharmacy, University of Santiago de Compostela, 15782 Santiago de Compostela, Spain
This work deals with the preparation of pyridine-3-carbohydrazide (isoniazid, inh) cocrystals with two α-hydroxycarboxylic acids. The interaction of glycolic acid (H2ga) or d,l-mandelic acid (H2ma) resulted in the formation of cocrystals or salts of composition (inh)·(H2ga) (1) and [Hinh]+[Hma]–·(H2ma) (2) when reacted with isoniazid. An N′-(propan-2-ylidene)isonicotinic hydrazide hemihydrate, (pinh)·1/2(H2O) (3), was also prepared by condensation of isoniazid with acetone in the presence of glycolic acid. These prepared compounds were well characterized by elemental analysis, and spectroscopic methods, and their three-dimensional molecular structure was determined by single crystal X-ray crystallography. Hydrogen bonds involving the carboxylic acid occur consistently with the pyridine ring N atom of the isoniazid and its derivatives. The remaining hydrogen-bonding sites on the isoniazid backbone vary based on the steric influences of the derivative group. These are contrasted in each of the molecular systems. Finally, Hirshfeld surface analysis and Density-functional theory (DFT) calculations (including NCIplot and QTAIM analyses) have been performed to further characterize and rationalize the non-covalent interactions.
