Entecavir (ETV) is approved by the Food and Drug Administration for the treatment of chronic hepatitis B in 2005. ETV monohydrate (ETV‐H) is used as drug substance in pharmaceutical industry. In this work, ETV‐H is prepared in pure water. The single crystal structure of ETV‐H is originally reported by Jiang and Liu in 2009 and shows a layered structure in ETV‐H crystal. Then ETV‐H is first studied by density functional theory method at B3LYP/6‐311+G(d,p) level. The optimized geometric parameters of ETV‐H agree well with the reported single crystal data and theoretical vibrational frequencies are consistent with experimental spectra. Molecular electronic potential and natural bond orbital results exhibit the molecular connection properties of the layered structure. The theoretical calculated dihedral angles between two ETV molecules are 177.6° and 176.8°, indicating that two ETV molecules are almost in the same plane. The theoretical calculated interlayer space is 16.4 Å, which is similar to the calculated interlayer space 16.7 Å using X‐ray diffraction result according to Bragg's law. These calculated results further illustrate the existence of the layered structure in ETV‐H crystal. This study may provide an idea for the future drug research.

中文翻译：

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恩替卡韦一水合物的层状晶体结构：在纯水中制备并通过DFT计算

恩替卡韦（ETV）在2005年获得了食品药品监督管理局的批准，可用于治疗慢性乙型肝炎。一水合ETV（ETV-H）在制药工业中用作原料药。在这项工作中，ETV‐H是在纯水中制备的。ETV-H的单晶结构最初由Jiang和Liu在2009年报道，并在ETV-H晶体中显示出层状结构。然后首先通过密度泛函理论方法在B3LYP / 6-311 + G（d，p）级别研究ETV-H。ETV-H的优化几何参数与报告的单晶数据非常吻合，理论振动频率与实验光谱一致。分子电子势和自然键轨道结果显示了层状结构的分子连接特性。两个ETV分子之间的理论计算二面角为177。6°和176.8°，表明两个ETV分子几乎在同一平面上。理论上计算出的层间空间为16.4Å，与根据布拉格定律使用X射线衍射结果计算出的层间空间16.7相似。这些计算结果进一步说明了ETV-H晶体中存在分层结构。这项研究可能为将来的药物研究提供一个思路。