Full Characterization of Linezolid and Its Synthetic Precursors by Solid-State Nuclear Magnetic Resonance Spectroscopy and Mass Spectrometry.
In this work, for the first time we report complementary structural and spectral studies of linezolid and its synthetic precursors (R)-N-{3-[3-fluoro-4-(morpholin-4-yl)phenyl]-2-oxooxazolidin-5-yl}methanol and (R)-N-{3-[3-fluoro-4-(morpholin-4-yl)phenyl]-2-oxooxazolidin-5-yl}methyl azide employing solid-state nuclear magnetic resonance (SS NMR) spectroscopy and electron ionization mass spectrometry. Each technique provides unique and specific set of information. Through high-resolution SS NMR using (13) C, (15) N, and (19) F as structural probes, we revealed dynamic molecular disorder in the crystal lattice for polymorphs II and III of linezolid, never reported before. Utilizing variable temperature (13) C cross-polarization magic-angle spinning technique, we proved that the disorder has a local character. Only morpholine residue of linezolid is under fast regime exchange at room temperature. This process slows down at a lower temperature and stopped at 213 K. The mass spectrometry revealed that chemical modification at oxazolidinone end of linezolid has a significant influence on fragmentation pathways of studied drug and its synthetic precursors. In particular, the compound that has azide group at the methyl substituent in the position C5 of the oxazolidinone ring is characterized by the most complicated fragmentation pattern, probably caused by thermal decomposition, which was taking place before ionization.
Centre of Molecular and Macromolecular Studies, Polish Academy of Sciences, Lodz 90-363.
Ewelina
E
Wielgus
Centre of Molecular and Macromolecular Studies, Polish Academy of Sciences, Lodz 90-363.
Piotr
P
Paluch
Poland institute of Organic Chemistry, Polish Academy of Sciences, Warsaw 01-224, Poland.
Jadwiga
J
Frelek
Pharmaceutical Research Institute, Warsaw 01-793, Poland.
Wojciech J
WJ
Szczepek
Centre of Molecular and Macromolecular Studies, Polish Academy of Sciences, Lodz 90-363. Electronic address: marekpot@cbmm.lodz.pl.
Marek J
MJ
Potrzebowski
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry*; D003460:Crystallization; D000069349:Linezolid / Q000138:chemical synthesis / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D017550:Spectroscopy, Fourier Transform Infrared
D000900:Anti-Bacterial Agents; D000069349:Linezolid
FTIR; crystal polymorphism; mass spectrometry; molecular dynamics; solid state NMR