A Synergistic Approach to a Novel Nicotinamide–Tridecanoic Acid Cocrystal: Crystallization, Properties, Computational Insights, and Antibacterial Activity

Abstract

This study presents the synthesis and comprehensive characterization of a novel nicotinamide–tridecanoic acid (NA–TrA) cocrystal, obtained through slow solvent evaporation in acetone. Single-crystal X-ray diffraction revealed that the NA–TrA cocrystal adopts a triclinic structure with the P1̅ space group, featuring two NA–TrA formulas per unit cell (Z = 2). The cocrystal stability and intermolecular interactions were thoroughly investigated using Hirshfeld surface analysis and noncovalent interaction assessments, highlighting the predominance of hydrogen bonds and van der Waals forces. Vibrational spectroscopy, combined with density functional theory calculations, provided detailed assignments of the infrared and Raman active modes. The NA–TrA cocrystal exhibited enhanced antibacterial activity against Gram-negative (Escherichia coli and Klebsiella pneumoniae) and Gram-positive (Staphylococcus aureus and Streptococcus pneumoniae) strains, outperforming its individual components. In silico pharmacokinetic profiling further supported the cocrystal’s potential as a drug candidate, revealing favorable gastrointestinal absorption and metabolic stability, albeit with moderate solubility. These findings underscore the cocrystal potential for pharmaceutical applications, offering a synergistic approach to improving the physicochemical and biological properties of nicotinamide.