Theoretical Study of the Antioxidant Activity of Quercetin Oxidation Products
It was recently shown that, when tested in cellular systems, quercetin oxidized products (Qox) have significantly better antioxidant activity than quercetin (Q) itself. The main Qox identified in the experiments are either 2,5,7,3′,4′-pentahydroxy-3,4-flavandione (Fl) or its tautomer, 2-(3,4-dihydro...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2019-11-01
|
| Series: | Frontiers in Chemistry |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fchem.2019.00818/full |
| _version_ | 1818055673976455168 |
|---|---|
| author | Alejandro Vásquez-Espinal Osvaldo Yañez Edison Osorio Carlos Areche Olimpo García-Beltrán Lina María Ruiz Bruce K. Cassels William Tiznado |
| author_facet | Alejandro Vásquez-Espinal Osvaldo Yañez Edison Osorio Carlos Areche Olimpo García-Beltrán Lina María Ruiz Bruce K. Cassels William Tiznado |
| author_sort | Alejandro Vásquez-Espinal |
| collection | DOAJ |
| description | It was recently shown that, when tested in cellular systems, quercetin oxidized products (Qox) have significantly better antioxidant activity than quercetin (Q) itself. The main Qox identified in the experiments are either 2,5,7,3′,4′-pentahydroxy-3,4-flavandione (Fl) or its tautomer, 2-(3,4-dihydroxybenzoyl)-2,4,6-trihydroxy-3(2H)-benzofuranone (Bf). We have now performed a theoretical evaluation of different physicochemical properties using density functional theory (DFT) calculations on Q and its main Qox species. The most stable structures (for Q and Qox) were identified after a structural search on their potential energy surface. Since proton affinities (PAs) are much lower than the bond dissociation enthalpies (BDEs) of phenolic hydrogens, we consider that direct antioxidant activity in these species is mainly due to the sequential proton loss electron transfer (SPLET) mechanism. Moreover, our kinetic studies, according to transition state theory, show that Q is more favored by this mechanism. However, Qox have lower PAs than Q, suggesting that antioxidant activity by the SPLET mechanism should be a result of a balance between proclivity to transfer protons (which favors Qox) and the reaction kinetics of the conjugated base in the sequential electron transfer mechanism (which favors Q). Therefore, our results support the idea that Q is a better direct antioxidant than its oxidized derivatives due to its kinetically favored SPLET reactions. Moreover, our molecular docking calculations indicate a stabilizing interaction between either Q or Qox and the kelch-like ECH-associated protein-1 (Keap1), in the nuclear factor erythroid 2-related factor 2 (Nrf2)-binding site. This should favor the release of the Nrf2 factor, the master regulator of anti-oxidative responses, promoting the expression of the antioxidant responsive element (ARE)-dependent genes. Interestingly, the computed Keap1-metabolite interaction energy is most favored for the Bf compound, which in turn is the most stable oxidized tautomer, according to their computed energies. These results provide further support for the hypothesis that Qox species may be better indirect antioxidants than Q, reducing reactive oxygen species in animal cells by activating endogenous antioxidants. |
| first_indexed | 2024-12-10T12:16:42Z |
| format | Article |
| id | doaj.art-bb08d4f39aba493588382ad39b80446c |
| institution | Directory Open Access Journal |
| issn | 2296-2646 |
| language | English |
| last_indexed | 2024-12-10T12:16:42Z |
| publishDate | 2019-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Chemistry |
| spelling | doaj.art-bb08d4f39aba493588382ad39b80446c2022-12-22T01:49:12ZengFrontiers Media S.A.Frontiers in Chemistry2296-26462019-11-01710.3389/fchem.2019.00818493231Theoretical Study of the Antioxidant Activity of Quercetin Oxidation ProductsAlejandro Vásquez-Espinal0Osvaldo Yañez1Edison Osorio2Carlos Areche3Olimpo García-Beltrán4Lina María Ruiz5Bruce K. Cassels6William Tiznado7Computational and Theoretical Chemistry Group, Departamento de Ciencias Químicas, Facultad de Ciencias Exactas, Universidad Andres Bello, Santiago, ChileComputational and Theoretical Chemistry Group, Departamento de Ciencias Químicas, Facultad de Ciencias Exactas, Universidad Andres Bello, Santiago, ChileFacultad de Ciencias Naturales y Matemáticas, Universidad de Ibagué, Ibagué, ColombiaDepartamento de Química, Facultad de Ciencias, Universidad de Chile, Santiago, ChileFacultad de Ciencias Naturales y Matemáticas, Universidad de Ibagué, Ibagué, ColombiaFacultad Ciencias de la Salud, Instituto de Ciencias Biomédicas, Universidad Autónoma de Chile, Santiago, ChileDepartamento de Química, Facultad de Ciencias, Universidad de Chile, Santiago, ChileComputational and Theoretical Chemistry Group, Departamento de Ciencias Químicas, Facultad de Ciencias Exactas, Universidad Andres Bello, Santiago, ChileIt was recently shown that, when tested in cellular systems, quercetin oxidized products (Qox) have significantly better antioxidant activity than quercetin (Q) itself. The main Qox identified in the experiments are either 2,5,7,3′,4′-pentahydroxy-3,4-flavandione (Fl) or its tautomer, 2-(3,4-dihydroxybenzoyl)-2,4,6-trihydroxy-3(2H)-benzofuranone (Bf). We have now performed a theoretical evaluation of different physicochemical properties using density functional theory (DFT) calculations on Q and its main Qox species. The most stable structures (for Q and Qox) were identified after a structural search on their potential energy surface. Since proton affinities (PAs) are much lower than the bond dissociation enthalpies (BDEs) of phenolic hydrogens, we consider that direct antioxidant activity in these species is mainly due to the sequential proton loss electron transfer (SPLET) mechanism. Moreover, our kinetic studies, according to transition state theory, show that Q is more favored by this mechanism. However, Qox have lower PAs than Q, suggesting that antioxidant activity by the SPLET mechanism should be a result of a balance between proclivity to transfer protons (which favors Qox) and the reaction kinetics of the conjugated base in the sequential electron transfer mechanism (which favors Q). Therefore, our results support the idea that Q is a better direct antioxidant than its oxidized derivatives due to its kinetically favored SPLET reactions. Moreover, our molecular docking calculations indicate a stabilizing interaction between either Q or Qox and the kelch-like ECH-associated protein-1 (Keap1), in the nuclear factor erythroid 2-related factor 2 (Nrf2)-binding site. This should favor the release of the Nrf2 factor, the master regulator of anti-oxidative responses, promoting the expression of the antioxidant responsive element (ARE)-dependent genes. Interestingly, the computed Keap1-metabolite interaction energy is most favored for the Bf compound, which in turn is the most stable oxidized tautomer, according to their computed energies. These results provide further support for the hypothesis that Qox species may be better indirect antioxidants than Q, reducing reactive oxygen species in animal cells by activating endogenous antioxidants.https://www.frontiersin.org/article/10.3389/fchem.2019.00818/fullantioxidantquercetinDFT calculationsoxidized derivatives of quercetinmolecular docking |
| spellingShingle | Alejandro Vásquez-Espinal Osvaldo Yañez Edison Osorio Carlos Areche Olimpo García-Beltrán Lina María Ruiz Bruce K. Cassels William Tiznado Theoretical Study of the Antioxidant Activity of Quercetin Oxidation Products Frontiers in Chemistry antioxidant quercetin DFT calculations oxidized derivatives of quercetin molecular docking |
| title | Theoretical Study of the Antioxidant Activity of Quercetin Oxidation Products |
| title_full | Theoretical Study of the Antioxidant Activity of Quercetin Oxidation Products |
| title_fullStr | Theoretical Study of the Antioxidant Activity of Quercetin Oxidation Products |
| title_full_unstemmed | Theoretical Study of the Antioxidant Activity of Quercetin Oxidation Products |
| title_short | Theoretical Study of the Antioxidant Activity of Quercetin Oxidation Products |
| title_sort | theoretical study of the antioxidant activity of quercetin oxidation products |
| topic | antioxidant quercetin DFT calculations oxidized derivatives of quercetin molecular docking |
| url | https://www.frontiersin.org/article/10.3389/fchem.2019.00818/full |
| work_keys_str_mv | AT alejandrovasquezespinal theoreticalstudyoftheantioxidantactivityofquercetinoxidationproducts AT osvaldoyanez theoreticalstudyoftheantioxidantactivityofquercetinoxidationproducts AT edisonosorio theoreticalstudyoftheantioxidantactivityofquercetinoxidationproducts AT carlosareche theoreticalstudyoftheantioxidantactivityofquercetinoxidationproducts AT olimpogarciabeltran theoreticalstudyoftheantioxidantactivityofquercetinoxidationproducts AT linamariaruiz theoreticalstudyoftheantioxidantactivityofquercetinoxidationproducts AT brucekcassels theoreticalstudyoftheantioxidantactivityofquercetinoxidationproducts AT williamtiznado theoreticalstudyoftheantioxidantactivityofquercetinoxidationproducts |