Electrochemical and Mechanistic Study of Superoxide Elimination by Mesalazine through Proton-Coupled Electron Transfer
The elimination of superoxide radical anions (O<sub>2</sub><sup>•−</sup>) by 5-amino-2-hydroxybenzoic acid (mesalazine, 5-ASA), 4-amino-2-hydroxybenzoic acid (4-ASA), and related compounds used for ulcerative colitis treatment was investigated using cyclic voltammetry and ele...
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| Format: | Article |
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MDPI AG
2021-02-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/14/2/120 |
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| author | Tatsushi Nakayama Ryo Honda |
| author_facet | Tatsushi Nakayama Ryo Honda |
| author_sort | Tatsushi Nakayama |
| collection | DOAJ |
| description | The elimination of superoxide radical anions (O<sub>2</sub><sup>•−</sup>) by 5-amino-2-hydroxybenzoic acid (mesalazine, 5-ASA), 4-amino-2-hydroxybenzoic acid (4-ASA), and related compounds used for ulcerative colitis treatment was investigated using cyclic voltammetry and electron spin resonance (ESR) analyses aided by density functional theory (DFT) calculations. Quasi-reversible O<sub>2</sub>/O<sub>2</sub><sup>•−</sup> redox was found to be modified by the compounds, suggesting that an acid–base reaction in which a hydroperoxyl radical (HO<sub>2</sub><sup>•</sup>) is formed from O<sub>2</sub><sup>•−</sup> occurs. However, the deprotonated 5-ASA anion can eliminate O<sub>2</sub><sup>•−</sup> through proton-coupled electron transfer (PCET), forming a radical product. This electron transfer (ET) was confirmed by ESR analysis. The 4-aminophenol moiety in 5-ASA plays an important role in the PCET, involving two proton transfers and one ET based on π-conjugation. The electrochemical and DFT results indicated that O<sub>2</sub><sup>•−</sup> elimination by 5-ASA proceeds efficiently through the PCET mechanism after deprotonation of the 1-carboxyl group. Thus, 5-ASA may act as an anti-inflammatory agent in the alkali intestine through PCET-based O<sub>2</sub><sup>•−</sup> elimination. |
| first_indexed | 2024-03-09T05:41:43Z |
| format | Article |
| id | doaj.art-ed110ef698584d91a8da0242c111e65c |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-09T05:41:43Z |
| publishDate | 2021-02-01 |
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| series | Pharmaceuticals |
| spelling | doaj.art-ed110ef698584d91a8da0242c111e65c2023-12-03T12:25:02ZengMDPI AGPharmaceuticals1424-82472021-02-0114212010.3390/ph14020120Electrochemical and Mechanistic Study of Superoxide Elimination by Mesalazine through Proton-Coupled Electron TransferTatsushi Nakayama0Ryo Honda1Department of Pharmacy, Gifu Pharmaceutical University, 1-25-4, Daigaku-nishi, Gifu 501-1196, JapanUnited Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, 1-1 Yanagido, Gifu 501-1193, JapanThe elimination of superoxide radical anions (O<sub>2</sub><sup>•−</sup>) by 5-amino-2-hydroxybenzoic acid (mesalazine, 5-ASA), 4-amino-2-hydroxybenzoic acid (4-ASA), and related compounds used for ulcerative colitis treatment was investigated using cyclic voltammetry and electron spin resonance (ESR) analyses aided by density functional theory (DFT) calculations. Quasi-reversible O<sub>2</sub>/O<sub>2</sub><sup>•−</sup> redox was found to be modified by the compounds, suggesting that an acid–base reaction in which a hydroperoxyl radical (HO<sub>2</sub><sup>•</sup>) is formed from O<sub>2</sub><sup>•−</sup> occurs. However, the deprotonated 5-ASA anion can eliminate O<sub>2</sub><sup>•−</sup> through proton-coupled electron transfer (PCET), forming a radical product. This electron transfer (ET) was confirmed by ESR analysis. The 4-aminophenol moiety in 5-ASA plays an important role in the PCET, involving two proton transfers and one ET based on π-conjugation. The electrochemical and DFT results indicated that O<sub>2</sub><sup>•−</sup> elimination by 5-ASA proceeds efficiently through the PCET mechanism after deprotonation of the 1-carboxyl group. Thus, 5-ASA may act as an anti-inflammatory agent in the alkali intestine through PCET-based O<sub>2</sub><sup>•−</sup> elimination.https://www.mdpi.com/1424-8247/14/2/120proton-coupled electron transfersuperoxide radical anionmesalazinecyclic voltammetryelectron spin resonanceulcerative colitis |
| spellingShingle | Tatsushi Nakayama Ryo Honda Electrochemical and Mechanistic Study of Superoxide Elimination by Mesalazine through Proton-Coupled Electron Transfer Pharmaceuticals proton-coupled electron transfer superoxide radical anion mesalazine cyclic voltammetry electron spin resonance ulcerative colitis |
| title | Electrochemical and Mechanistic Study of Superoxide Elimination by Mesalazine through Proton-Coupled Electron Transfer |
| title_full | Electrochemical and Mechanistic Study of Superoxide Elimination by Mesalazine through Proton-Coupled Electron Transfer |
| title_fullStr | Electrochemical and Mechanistic Study of Superoxide Elimination by Mesalazine through Proton-Coupled Electron Transfer |
| title_full_unstemmed | Electrochemical and Mechanistic Study of Superoxide Elimination by Mesalazine through Proton-Coupled Electron Transfer |
| title_short | Electrochemical and Mechanistic Study of Superoxide Elimination by Mesalazine through Proton-Coupled Electron Transfer |
| title_sort | electrochemical and mechanistic study of superoxide elimination by mesalazine through proton coupled electron transfer |
| topic | proton-coupled electron transfer superoxide radical anion mesalazine cyclic voltammetry electron spin resonance ulcerative colitis |
| url | https://www.mdpi.com/1424-8247/14/2/120 |
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