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

ABSTRACT

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.

KEYWORDS:

• Minodronic acid
• monohydrate
• polymorphic transformation
• molecular dynamic simulation

Acknowledgements

The authors thank the College of Chemical Engineering and Materials Science for providing instruments and experimental materials. Xuefei Gao participated in study design, research, data collection, analysis and interpretation of data, writing, reviewing and approving the publication. Xuefei Gao and Liang Zhu have no additional conflicts of interest to report. All authors have read and agreed to the published version of the manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

Supporting information. The detailed discussion on the Crystal structure of Form Z and Form E and the Conformation diagram of water molecules in Form D and Form E of the MDA monohydrate and the comparison of the initial and the optimized lattice parameters of MDA.

Accession codes. CCDC 2233027 contains the supplementary crystallographic data of Form E for this paper. CCDC 2269849 contains the supplementary crystallographic data of Form D for this paper. These data can be obtained free of charge via www.ccdc.cam.ac.uk/data_request/cif, by emailing [email protected] or by contacting The Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax: [phone].