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

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 above. 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.