硫代巴比妥酸多晶型的太赫兹光谱和DFT理论分析

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。

Terahertz Spectroscopy and Density Functional Theory Investigation of 2-Thiobarbituric Acid Polymorphs

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 poly-morphs ,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 simula-ted structure (form a) had absorption peaks at 0.41/0.47 ,0.89 and 1.35 THz ,which agrees with the THz experimental spec-trum .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 .