Investigation on the structural characteristics and polymorphic transformation mechanism of polymorphic hydrates: a case of minodronic acid monohydrate

The polymorphism of Minodronic acid (MDA) monohydrates (form D and form E) was investigated in this work. The results revealed that the main difference lies in the discrepancy of hydrogen bonds in two polymorphisms. In addition, the atoms-in-molecules (AIM) analysis was conducted to assess the strength of hydrogen bonds. The hydrogen bonds in form D were estimated as electrostatic, while the corresponding hydrogen bonds in form E were partially covalent type. Then the polymorphic transformation mechanism was investigated by experiments coupled with molecular dynamic simulations. As the conformation of the water molecule transforms from Form D to Form E, the hydrogen bond interaction between water and MDA molecules gradually becomes stronger. The observations were consistent with the results obtained from molecular dynamic simulations. The energy barriers of the path I were in line with the simulation results. This indicates the reliability of the polymorphic transformation mechanism of the MDA monohydrates.