Layered Crystal Structural Entecavir Monohydrate: Prepared in Pure Water and Calculated by DFT

Abstract 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.