Vibrational spectroscopic detection and analysis of isoniazid-nicotinamide-succinic acid ternary cocrystal

Abstract

In this paper, binary and ternary cocrystals in the ternary cocrystal system of isoniazid-nicotinamide-succinic acid were prepared by solvent evaporation and grinding methods. All of them were characterized by terahertz time-domain spectroscopy (THz-TDS), confirming that the cocrystals could be obtained by the above two methods. In addition, to investigate the formation of hydrogen bonds and their influence in cocrystal, several possible forms of hydrogen bond in cocrystal were simulated by density functional theory (DFT). The simulated result was in good agreement with the experimental result, indicating that the hydrogen bonds in cocrystal were the carboxyl groups on both side of succinic acid forming a pyridine N-carboxylic acid heterosynthon with pyridine N of isoniazid or nicotinamide respectively. Meanwhile, the vibrational modes of the cocrystal were analyzed to investigate the effect of hydrogen bond to the molecules. To further understand the formation process of ternary cocrystal in this system, Raman spectroscopy was used to analyze the cocrystal samples with different time of grinding. Process information of cocrystal formation were obtained by analyzing the changes of the characteristic peaks in the corresponding Raman spectra. These results provide a wealth of information and a unique approach to the analysis of both structures and intermolecular interactions shown within ternary cocrystal.

Keywords: Density functional theory; Hydrogen bond; Raman spectroscopy; Terahertz time-domain spectroscopy; Ternary cocrystal.