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

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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.

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Notes

  1. Aromatic

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Acknowledgments

The authors gratefully acknowledge the Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran, and the Research and Computational Lab of Theoretical Chemistry and Nano Structures of Razi University, Kermanshah, Iran.

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Authors and Affiliations

  1. Department of Inorganic Chemistry, Faculty of Chemistry, Razi University, Kermanshah, Iran

    Saba Hadidi & Farshad Shiri

  2. Medical Biology Research Center (MBRC), Kermanshah University of Medical Sciences, Kermanshah, Iran

    Saba Hadidi & Farshad Shiri

  3. Nano Science and Technology Research Center, Razi University, Kermanshah, Iran

    Mohammadsaleh Norouzibazaz

  4. Department of Organic Chemistry, Faculty of Chemistry, Razi University, Kermanshah, Iran

    Mohammadsaleh Norouzibazaz

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  1. Saba Hadidi
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  2. Farshad Shiri
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Correspondence to Saba Hadidi.

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Highlights

• The fenoprofen methyl ester photoisomerization is the main process in the photopreparation of anti-inflammatory medicine (S)-fenoprofen

• The rearrangement process of (R)-fenoprofen to its (S)-enantiomer happens in [1,3]-hydrogen shifts

• The excitation of (R)-fenoprofen methyl ester to the first excited singlet state S1 is the rate-limiting step of fenoprofen photoisomerization

• The isomerization process passed through a ~ 84 kcal/mol barrier of transition state

• The incorporation of an explicit water molecule could decrease the barriers to ~ 70 kcal/mol

• The more photostability of (S)-fenoprofen methyl ester than that of its related (R)-enantiomer is attributed to the − 1.34 kcal/mol of thermodynamic stability of the (S)-fenoprofen methyl ester

Electronic supplementary material

ESM 1

The Cartesian coordinates of (R)-fenoprofen methyl ester, (E)-1-methoxy-2-(3-phenoxyphenyl)prop-1-en-1-ol, (S)-fenoprofen methyl ester and the transition states. (DOCX 67 kb)

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Hadidi, S., Shiri, F. & Norouzibazaz, M. Mechanistic study of fenoprofen photoisomerization to pure (S)-fenoprofen: a DFT study. Struct Chem 31, 115–122 (2020). https://doi.org/10.1007/s11224-019-01382-1

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