Weak Interactions in Cocrystals of Isoniazid with Glycolic and Mandelic Acids

Abstract

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.

1-Ethyluracil, a New Scaffold for Preparing Multicomponent Forms: Synthesis, Characterization, and Computational Studies

“…Since we intend to estimate the interactions in the solid state, the crystallographic coordinates have been used. This level of theory and methodology have previously been used to evaluate similar interactions. − In this work the binding energy and interaction energy terms have been used interchangeably. They were computed as the difference between the energies of the isolated monomers and their assembly and were corrected for the basis set superposition error (BSSE) by using the Boys–Bernardi counterpoise method .…”

The Benefits and Challenges of Antibiotics–Non-Steroidal Anti-Inflammatory Drugs Non-Covalent Reaction

“…The multi-component systems comprising isoniazid-acid substituents and natural resources were the following: isoniazid combined with cinnamic acid, fumaric acid [74,82,85,86], mandelic acid [82,91], glutaric acid [84], pimelic acid [84], malonic acid [84], hydroxybenzoic acid [86], adipic acid [84,86], gallic acid [86], gentisic acid [82,86], succinic acid and nicotinamide [88], glycolic acid [91], benzoic acid [90], ferulic acid [98], and oleanolic acid [93], etc., which some of them enhancing stability and solubility, and others decreasing those parameters. It has been hypothesized that the carboxylic acid substitution changes isoniazid's stability and solubility.…”

Structural and Energetic Aspects of Entacapone-Theophylline-Water Cocrystal

“…Hirshfeld surface (HS) analysis has become a valuable tool to elucidate the nature of intermolecular interactions affecting the molecular packing in cocrystals [74,75]. HS analysis can provide useful information about the detailed intermolecular interactions of the whole molecular system through color mapping (red and blue for high and low interaction intensities, respectively).…”