Mechanistic study of fenoprofen photoisomerization to pure (S)-fenoprofen: a DFT study

Abstract

This work provides a comprehensive DFT study on the conversion mechanism and photoisomerization of the effective and commonly used nonsteroidal anti-inflammatory medicine fenoprofen. The results obtained exhibit that the rearrangement procedure of (R)-fenoprofen to its (S)-enantiomer occurs in [1,3]-hydrogen shifts with inversion of configuration at chiral center C8. According to the computed energies, we can find out that the excitation of (R)-fenoprofen methyl ester in its primary form to the first excited singlet state S1 at λ = 240 nm is the rate-limiting step of photoisomerization of fenoprofen. In order to obtain further insight into the isomerization process occurring upon excitation, this process was studied by scanning the C8-H11 distance for the excited singlet. Our calculations revealed that the isomerization process requires passing a barrier of approximately 84 kcal/mol. Furthermore, the more photostability of (S)-fenoprofen methyl ester than that of its related (R)-enantiomer can be attributed to the − 1.34 kcal/mol of thermodynamic stability of the (S)-fenoprofen methyl ester.