Structural Design, H-Bonding Interactions, Vibrational Properties, Periodic-DFT Calculations, and Antibacterial Activity of a Nicotinamide Cocrystal Using Tetradecanoic Acid as a Coformer

Abstract

This paper reports a new nicotinamide cocrystal using tetradecanoic acid as a coformer by a slow solvent evaporation method in acetone. Its structural, thermal, vibrational, and antibacterial properties were characterized and discussed. Single-crystal X-ray diffraction data indicated that the NA–TA cocrystal crystallized in triclinic symmetry and $P\overline{1}\left(C_i\right)$ space group, with two formulas per unit cell (Z = 2). A detailed analysis of the intermolecular interactions was performed based on Hirshfeld surface and noncovalent interactions. Thermoanalyses revealed that the material is stable up to around 128 °C and exhibits endothermic events characteristic of solid–liquid phase transition and decomposition. Additionally, using group theory and periodic calculations based on density functional theory (DFT), all inter- and intramolecular modes of the NA–TA cocrystal were predicted and assigned. The experimental infrared and Raman spectra were well correlated to the spectra calculated via DFT, allowing a suitable assignment of the observed vibration modes. Furthermore, biological experiments demonstrated that the cocrystal exhibits promising antibacterial activity against Escherichia coli (Gram-negative) and Staphylococcus aureus (Gram-positive) bacteria. An in silico study of the pharmacokinetic profile involving absorption, distribution, metabolism, and excretion parameters was performed to support the experimental findings.

A novel antibacterial nicotinamide cocrystal with tetradecanoic acid as the coformer was crystallized using the slow evaporation method. The structural, thermal, and vibrational properties were characterized and analyzed. A detailed study of the noncovalent bonds was conducted using computational methods. Additionally, the inter- and intramolecular modes were assigned through periodic calculations based on density functional theory.