A theoretical investigation of the flurbiprofen methyl ester isomerization as the main step in the photopreparation of anti-inflammatory medicine (S)-flurbiprofen: A DFT study

Current Chemistry Letters

关键词: flurbiprofen;    r/s isomerization;    dft calculation;    conversion mechanism;   

DOI  :  10.5267/j.ccl.2020.02.002

来源: DOAJ

【 摘 要 】

In order to investigate the isomerization and conversion mechanism of the advantageous and widely used nonsteroidal anti-inflammatory medicine flurbiprofen, the hybrid density functional theory was applied. According to the results, the rearrangement reaction of (R)-flurbiprofen to its (S)-enantiomer happens in a [1,3]-hydrogen shifts with inversion of configuration at chiral center C14. From the calculated energies, it can be understood that the rate-limiting step in the flurbiprofen isomerization is the excitation of (R)-flurbiprofen methyl ester in its initial form to the first excited singlet state S1 at λ=243.91 nm. we studied this process by scanning the C14-H17 distance for the excited singlet to get more information about the process of isomerization occurring upon excitation. The results of calculations demonstrated that the isomerization process should pass through a ~71 kcal/mol barrier. The (S)-flurbiprofen methyl ester is more photostable than its related (R)-enantiomer. This issue can be attributed to the -1.50 kcal/mol of thermodynamic stability of the (S)-flurbiprofen methyl ester.

【 授权许可】

Unknown