硫代巴比妥酸是目前多晶型种类较丰富的一类固体药物。 利用太赫兹时域光谱(THz-TDS)技术对硫代巴比妥酸晶型Ⅰ, Ⅱ, Ⅲ, Ⅳ和水合晶型进行表征分析, 得到明显不同的太赫兹光谱, 表明THz光谱技术可以有效鉴别硫代巴比妥酸不同类多晶型。 硫代巴比妥酸晶型Ⅳ为异构多晶型, 它在0.65 THz处的宽峰以及1.02, 1.41 THz处的吸收峰明显区别于晶型Ⅰ和Ⅱ简单的物理混合。 运用密度泛函理论(DFT)对硫代巴比妥酸晶型Ⅳ的两种可能结构进行了分子结构优化和光谱模拟, 模拟结果显示其中的结构a在0.41/0.47, 0.89和1.35 THz处具有吸收峰, 与实验结果较吻合。 由此推断晶型Ⅳ由硫代巴比妥酸异构体A的硫酮键中的S7和异构体B酰胺中的H23构成第一处氢键, 异构体B硫酮键中的S20和异构体A酰胺中的H13形成第二处氢键。 本文还结合理论模拟结果对硫代巴比妥酸晶型Ⅳ的振动模式进行归属。

2-Thiobarbituric acid (TBA) is one of the most polymorphic rich molecular solids currently known. Here, five most common polymorphs of TBA (form Ⅰ, Ⅱ, Ⅲ, Ⅳ and hydrate) were investigated using terahertz time-domain spectroscopy (THz-TDS). All results of the terahertz spectra showed that there were significantly different absorption features for polymorphs, which indicated that THz-TDS technique could effectively identify different types of TBA polymorphs. Form Ⅳ belongs to the tautomeric polymorph, and the absorption features of form Ⅳ at 0.65(broad band), 1.02 and 1.41 THz are significantly different from physical mixture of form Ⅰ and form Ⅱ. Density functional theory (DFT) calculation was performed to optimize two possible molecular structures and simulate the corresponding vibrational spectra. The theoretical result showed that simulated structure (form a) had absorption peaks at 0.41/0.47, 0.89 and 1.35 THz, which agrees with the THz experimental spectrum. Therefore, it is confirmed that, in the TBA form Ⅳ, the first hydrogen bond is formed between thione S7 of isomer A and amide H23 of isomer B in the structure of form Ⅳ, while the second one is constituted by amide H13 of isomer A and thione S20 of isomer B. The characteristic absorption modes of form Ⅳare also assigned based on the simulation results of DFT calculation.