Terahertz fingerprint spectrum and weak interaction analysis of nicotinamide–sorbic acid cocrystal

Abstract

Sorbic acid (SA) is a naturally occurring food additive that plays an important role in the food industry. The study of nicotinamide–sorbic acid (NIA–SA) cocrystal is significant for improving its dissolution rate, bioavailability, and physical stability. In this study, a liquid-assisted grinding technique was used to prepare the NIA–SA binary cocrystal compound, and powder X-ray diffraction and terahertz time-domain spectroscopy (THz-TDS) confirmed that this method can successfully obtain the cocrystal. Solid-state density functional theory (ss-DFT) calculations were utilized to obtain theoretical spectra, revealing the structural characteristics of the NIA–SA cocrystal and the relationship between terahertz absorption peaks and specific collective vibration modes. Subsequently, the reduced density gradient (RDG) analysis was employed to analyze energy interactions within the molecular system, identifying the characteristic absorption peaks associated with cocrystal formation and explaining their origins. The results demonstrate that combining THz-TDS with ss-DFT can comprehensively and dynamically reveal intermolecular interactions during the formation of cocrystals. The unique sensitivity of THz-TDS to low-frequency vibrations provides robust theoretical and experimental support for the design and development of novel cocrystal materials, highlighting the significant advantages and broad application prospects of this technique in cocrystal characterization.