Structural Design, H-Bonding Interactions, Vibrational Properties, Periodic-DFT Calculations, and Antibacterial Activity of a Nicotinamide Cocrystal Using Tetradecanoic Acid as a Coformer
João G. de Oliveira Neto, Marinaldo V. Souza, Alejandro Pedro Ayala, C.E.S. Nogueira, Eliana B. Souto, Adenílson O. dos Santos, Francisco F. de Sousa
Abstract
High Resolution Image Download MS PowerPoint Slide 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 1 ¯ ( C i ) 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.