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Antioxidant properties of phenolic Schiff bases: structure–activity relationship and mechanism of action

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Abstract

Phenolic Schiff bases are known for their diverse biological activities and ability to scavenge free radicals. To elucidate (1) the structure–antioxidant activity relationship of a series of thirty synthetic derivatives of 2-methoxybezohydrazide phenolic Schiff bases and (2) to determine the major mechanism involved in free radical scavenging, we used density functional theory calculations (B3P86/6-31+(d,p)) within polarizable continuum model. The results showed the importance of the bond dissociation enthalpies (BDEs) related to the first and second (BDEd) hydrogen atom transfer (intrinsic parameters) for rationalizing the antioxidant activity. In addition to the number of OH groups, the presence of a bromine substituent plays an interesting role in modulating the antioxidant activity. Theoretical thermodynamic and kinetic studies demonstrated that the free radical scavenging by these Schiff bases mainly proceeds through proton-coupled electron transfer rather than sequential proton loss electron transfer, the latter mechanism being only feasible at relatively high pH.

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Acknowledgments

The authors thank the “Conseil Régional du Limousin” for CALI (CAlcul en LImousin) and Atta-ur-Rahman Institute for Natural Product Discovery, Universiti Teknologi for computing facilities. The authors thank the “Pharmacology and Toxicology Research Laboratory-Faculty of Pharmacy, Universiti Teknologi MARA, Puncak Alam Campus, Malaysia” for antioxidant facilities. P.T. gratefully acknowledges the support by the Operational Program Research and Development for Innovations–European Regional Development Fund (project CZ.1.05/2.1.00/03.0058 of the Ministry of Education, Youth and Sports of the Czech Republic). I.B. and P.T. gratefully thank the ‘Association Djerbienne de France’ (ADF) for the financial support.

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Authors and Affiliations

  1. Atta-ur-Rahman Institute for Natural Product Discovery (RiND), Universiti Teknologi MARA, Kampus Puncak Alam, 42300 Bandar Puncak Alam, Shah Alam, Selangor DE, Malaysia

    El Hassane Anouar, Salwa Raweh, Imene Bayach, Muhammad Taha, Mohd Syukri Baharudin, Nor Hadiani Ismail & Jean-Frédéric F. Weber

  2. Faculty of Pharmacy, Universiti Teknologi MARA, Puncak Alam Campus, Shah Alam, Malaysia

    Salwa Raweh, Mizaton Hazizul Hasan, Aishah Adam & Jean-Frédéric F. Weber

  3. LCSN-Faculté de Pharmacie, Université de Limoges, 2 rue du Dr Marcland, 87000, Limoges, France

    Imene Bayach

  4. INSERM, UMR-S850/Faculté de Pharmacie, Université de Limoges, 2 rue du Dr Marcland, 87000, Limoges, France

    Florent Di Meo & Patrick Trouillas

  5. Faculty of Applied Sciences, Universiti Teknologi MARA, 40450, Shah Alam, Malaysia

    Nor Hadiani Ismail

  6. Laboratoire de Chimie des Matériaux Nouveaux, Université de Mons, Place du Parc, 20, 7000, Mons, Belgium

    Patrick Trouillas

  7. Regional Center of Advanced Technologies and Materials, Department of Physical Chemistry, Faculty of Science, Palacký University, 17. Listopadu 1192/12, 77146, Olomouc, Czech Republic

    Patrick Trouillas

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  1. El Hassane Anouar
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Correspondence to El Hassane Anouar or Patrick Trouillas.

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Anouar, E.H., Raweh, S., Bayach, I. et al. Antioxidant properties of phenolic Schiff bases: structure–activity relationship and mechanism of action. J Comput Aided Mol Des 27, 951–964 (2013). https://doi.org/10.1007/s10822-013-9692-0

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