Abstract-Structural investigation of a 2:1 co-crystal between diflunisal and isonicotinamide based on terahertz and Raman spectroscopy

Yaguo Wang, Jiadan Xue, Qiqi Wang, Shunji Jin, Ziming Zhang, Zhi Hong, Yong Du

https://www.x-mol.com/paper/5593201

In order to characterize molecular structure changes of drugs upon co-crystallization by means of spectroscopic techniques, vibrational spectra of solid-state diflunisal (DIF), isonicotinamide (ISO) and their 2:1 co-crystal have been investigated by using terahertz time-domain spectroscopy (THz-TDS) and Raman spectroscopy. A 2:1 DIF-ISO co-crystal between DIF and ISO has been synthesized by slow solution crystallization from ethanol. The experimental THz spectroscopy shows that the co-crystal has a few significantly different absorption peaks compared with raw parent materials within the frequency region from 0.2 to 1.6 THz. Likewise, some differences of vibrational spectra between the co-crystal and starting compounds could also be characterized by Raman spectral results. Density functional theory (DFT) was used to simulate optimized structures and vibrational modes of two kind of possible co-crystal theoretical forms (form I and II) between DIF and ISO. Theoretical co-crystal form I is shown with 2:1 theoretical binary-adduct formed by carboxylic acid-amide and carboxylic acid-pyridine under inter-molecular hydrogen bonding. Theoretical co-crystal form II has a similar structure as form I, meanwhile the only difference is that O63 atom simultaneously forms hydrogen bond with H33 and H64. Also the hydroxyl –OH and carboxyl group –COOH establish molecular heterocycle under intra-molecular hydrogen bonds in both forms. The theoretical results show that both THz and Raman spectra of co-crystal form II between DIF and ISO is more consistent with the experimental observations than those of co-crystal form I. These results provide us with a wealth of information and unique method for characterizing the composition of co-crystal structures and also inter-molecular hydrogen bonding interactions shown within pharmaceutical co-crystallization at the molecular level.

Abstract-Investigation into tautomeric polymorphism of 2-thiobarbituric acid using experimental vibrational spectroscopy combined with DFT theoretical simulation

Qiqi Wang, Jiadan Xue, Yaguo Wang, Shunji Jin, Qi Zhang, Yong Du,

https://www.sciencedirect.com/science/article/pii/S1386142518305687

Vibrational modes of 2-thiobarbituric acid (TBA) tautomeric polymorphs (form I, II and IV) were characterized by terahertz time-domain spectroscopy (THz-TDS) and Raman spectral techniques. The experimental results indicate that both vibrational spectroscopy techniques could be used to recognize the above TBA three tautomeric forms clearly. Experimental THz spectral results show that each of TBA tautomeric polymorphs has distinctive fingerprint peaks in the terahertz region. Raman spectra also show similar results about differences of TBA tautomeric polymorphs, but not significant as that of terahertz spectra since Raman-active vibrational modes are mostly from intra-molecular interaction of various functional groups within the specific molecule while that of terahertz region is more sensitive to inter-molecular interaction within crystalline unit cells. In addition, density functional theory (DFT) was used to simulate the optimized structures and vibrational modes of these three TBA tautomeric forms. The characteristic vibrational modes of TBA polymorphs are assigned comparing the simulated DFT results with experimental vibrational spectra. The results provide fundamental benchmark for the study of pharmaceutical polymorphism based on both Raman and terahertz vibrational spectroscopic techniques combined with theoretical simulations.