Spirocyclic character of ixazomib citrate revealed by comprehensive XRD, NMR and DFT study

0479130 - FZÚ 2018 RIV NL eng J - Journal Article
Skořepová, E. - Čerňa, I. - Vlasáková, R. - Zvoníček, V. - Tkadlecová, M. - Dušek, Michal
Spirocyclic character of ixazomib citrate revealed by comprehensive XRD, NMR and DFT study.
Journal of Molecular Structure. Roč. 1148, Nov (2017), s. 22-27. ISSN 0022-2860. E-ISSN 1872-8014
R&D Projects: GA MŠMT LO1603
EU Projects: European Commission(XE) CZ.2.16/3.1.00/24510
Institutional support: RVO:68378271
Keywords : ixazomib citrate * molecular structure * stereoisomers * crystal structure * NMR * DFT
OECD category: Condensed matter physics (including formerly solid state physics, supercond.)
Impact factor: 2.011, year: 2017

Ixazomib citrate is a very recently approved anti-cancer drug. Until now, to the best of our knowledge, no one has been able to solve any crystal structures of this compound. In this work, we present the crystal structures of two isostructural solvates of ixazomib citrate. In all currently available literature, the molecule is characterized as containing a single optically active carbon atom and a borate cycle formed when ixazomib is reacted with citric acid to form a stabilized ixazomib citrate that can be administered orally. However, the crystal structures revealed that none of the up-to-date presented structural formulas of ixazomib citrate are fully accurate. In the crystal structures, ixazomib citrate was found to be in forms of two RR and RS stereoisomers. Our results are supported by solid-state and solution NMR and DFT quantum mechanical calculations.

Permanent Link: http://hdl.handle.net/11104/0275203