Weak interactions in cocrystals of isoniazid with glycolic and mandelic acids

ÁLVAREZ-VIDAURRE, RAQUEL; GARCÍA-SANTOS, ISABEL; NICLÓS-GUTIÉRREZ, JUAN; FRONTERA, ANTONIO; GONZÁLEZ-PÉREZ, JOSEFA M.; CASTIÑEIRAS, ALFONSO; GIL, DIEGO M.; TORRES-IGLESIAS, ROCÍO

Crystals

MDPI AG

Año: 2021 vol. 11

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 N0-(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.