Flurbiprofen: A Study of the Behavior of the Scalemate by Chromatography, Sublimation, and NMR
| Autor: | Alicja Wzorek, Jianlin Han, Magdalena Kwiatkowska, Vadym Anatolievch Soloshonok, Anna Kolbus, Mariusz Urbaniak, Karel D. Klika |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Electrospray
Physics and Astronomy (miscellaneous) General Mathematics molecular association Flurbiprofen enantiomeric analysis fluorine-containing pharmaceuticals 010402 general chemistry 01 natural sciences chemistry.chemical_compound Column chromatography self-induced diastereomeric anisochronism (SIDA) self-disproportionation of enantiomers (SDE) Computer Science (miscellaneous) medicine molecular chirality Chromatography 010405 organic chemistry Hydrogen bond lcsh:Mathematics diffusion Diastereomer lcsh:QA1-939 Toluene NMR 0104 chemical sciences flurbiprofen Solvent chemistry Chemistry (miscellaneous) Enantiomer medicine.drug |
| Zdroj: | Symmetry Volume 13 Issue 4 Symmetry, Vol 13, Iss 543, p 543 (2021) Addi. Archivo Digital para la Docencia y la Investigación instname Addi: Archivo Digital para la Docencia y la Investigación Universidad del País Vasco |
| ISSN: | 2073-8994 |
| DOI: | 10.3390/sym13040543 |
| Popis: | 2-(2-Fluoro-4-biphenyl) propionic acid (flurbiprofen), from the phenylalkanoic acid family of nonsteroidal anti-inflammatory drugs (NSAID’s), is currently on the pharmaceutical market as a racemate. This racemic compound was tested for its propensity to undergo the self-disproportionation of enantiomers (SDE) phenomenon by various forms of chromatography (SDEvC), such as routine gravity-driven column chromatography, medium-pressure liquid chromatography (MPLC), preparative thin-layer chromatography (PTLC), and size-exclusion chromatography (SEC), as well as by sublimation (SDEvS). Furthermore, examination by nuclear magnetic resonance (NMR) in various solvents found that flurbiprofen exhibited the phenomenon of self-induced diastereomeric anisochronism (SIDA). By measurement of the diffusion coefficient (D), the longitudinal relaxation time (T1), and the transverse relaxation time (T2) using NMR, as well as by electrospray ionization-mass spectrometry (ESI-MS) examinations, the preferred intermolecular association was found to be solvent dependent, e.g., heterochiral association was preferred in toluene, while homochiral association was preferred in more polar solvents. This study also attempted, unsuccessfully, to correlate the NMR measurements of flurbiprofen with chromatographic outcomes for the rationalization and prediction of chromatographic results based on NMR measurements. Because the intermolecular hydrogen bonding of the acid groups in flurbiprofen overwhelmingly predominates over other intermolecular interactions, flurbiprofen seemed to represent a good test case for this idea. The behavior of scalemic samples of flurbiprofen is important, as, although it is currently dispensed as a racemate, clinical applications of the R enantiomer have been investigated. SDEvC and SDEvS both have ramifications for the preparation, handling, and storage of enantioenriched flurbiprofen, and this concern applies to other chiral drugs as well. The authors gratefully acknowledge financial support from the Ministry of Science and Higher Education, Poland (grant no. 668, A.W.; grant no. 659, M.K.; and SMGR.RN.20.264, A.K.) and IKERBASQUE, the Basque Foundation for Science, Spain (V.A.S.). |
| Databáze: | OpenAIRE |
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