Doxycycline hydrate and doxycycline hydrochloride dihydrate – crystal structure and charge density analysis
| Autor: | Daniel Tchoń, Anna Makal, Matthias J. Gutmann, Krzysztof Woźniak |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
Doxycycline
Materials science Neutron diffraction Charge density Crystal structure 010402 general chemistry 010403 inorganic & nuclear chemistry Condensed Matter Physics 01 natural sciences 0104 chemical sciences Inorganic Chemistry medicine Doxycycline hydrochloride General Materials Science Hydrate medicine.drug Nuclear chemistry |
| Zdroj: | Zeitschrift für Kristallographie - Crystalline Materials. 233:649-661 |
| ISSN: | 2196-7105 2194-4946 |
| Popis: | High-resolution low-temperature X-ray diffraction experiments for doxycycline monohydrate and hydrochloride dihydrate have been performed. Translation-Libration-Screw (TLS) analysis for both crystal forms as well as the data from neutron diffraction experiment for hydrochloride combined with the Hansen-Coppens formalism resulted in precise charge density distribution models for both the zwitterionic monohydrate and a protonated hydrochloride crystal forms. Their detailed topological analysis suggested that the electron structure of doxycycline’s amide moiety undergoes significant changes during protonation due to formation of a very strong resonance-assisted hydrogen bond. A notably increased participation of amide nitrogen atom and hydrogen-accepting oxygen atom in the resonance upon doxycycline protonation was observed. A comparison of TLS- and neutron data-derived hydrogen parameters confirmed the experimental neutron data to be vital for proper description of intra- and inter-molecular interactions in this compound. Finally, calculated lattice and interaction energies quantified repulsive Dox-Dox interactions in the protonated crystal form of the antibiotic, relating with a good solubility of doxycycline hydrochloride relative to its hydrate. |
| Databáze: | OpenAIRE |
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