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The investigation on ibuprofen methyl ester isomerization as a fundamental stage in the preparation of antipyretic medicine (R)-ibuprofen: a computational insight

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Abstract

The isomerization of the widely used nonsteroid anti-inflammatory medicine ibuprofen was investigated by employing the hybrid density functional theory. The rearrangement reaction of (R)-(−)-ibuprofen to its (S)-( +)-isomer consists of a [1,3]-hydrogen shifts. This process causes an inversion of configuration at C7. The obtained results revealed that the rate-limiting step of ibuprofen isomerization is the excitation of (R)-(−)-ibuprofen methyl ester in its initial structure to the first excited singlet state S1 at λ = 231 nm. In addition, the C7-H19 distance was investigated and analyzed for the excited singlet to obtain more information about the isomerization reaction occurring upon excitation. Based upon the calculations, passing through a barrier of around 72 kcal/mol is necessary for this isomerization reaction. Furthermore, the -0.944 kcal/mol of thermodynamic stability of the (S)-( +)-ibuprofen methyl ester elucidates the more photostability of (S)-( +)-ibuprofen methyl ester than (R)-(−)-isomer. The overall reactions with the different components belonging to each reaction step have been fully analyzed.

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Notes

  1. Aromatic.

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Acknowledgements

The authors gratefully acknowledge the Research and Computational Lab of Theoretical Chemistry and Nano Structures of Razi University, 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. Department of Nano Chemistry, Faculty of Chemistry, Razi University, Kermanshah, Iran

    Mohammadsaleh Norouzibazaz

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

    Mohammadsaleh Norouzibazaz

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  1. Saba Hadidi
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Supplementary file1 Electronic supplementary information (ESI) available: The Cartesian coordinates of (R)-(-)-ibuprofen methyl ester, (E)-2-(4-isobutylphenyl)-1-methoxyprop-1-en-1-ol, (S)-(+)-ibuprofen methyl ester and the transition states. (DOCX 56 kb)

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Hadidi, S., Shiri, F. & Norouzibazaz, M. The investigation on ibuprofen methyl ester isomerization as a fundamental stage in the preparation of antipyretic medicine (R)-ibuprofen: a computational insight. Theor Chem Acc 139, 101 (2020). https://doi.org/10.1007/s00214-020-02618-8

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