Electrochemical and Mechanistic Study of Superoxide Elimination by Mesalazine through Proton-Coupled Electron Transfer

Abstract

The elimination of superoxide radical anions (O2•−) 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 O2/O2•− redox was found to be modified by the compounds, suggesting that an acid–base reaction in which a hydroperoxyl radical (HO2•) is formed from O2•− occurs. However, the deprotonated 5-ASA anion can eliminate O2•− 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 O2•− 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 O2•− elimination.

Electrochemical and Mechanistic Study of Structure–Activity Relationship of α-, β-, γ-, and δ-Tocopherol on Superoxide Elimination in N,N-Dimethylformamide through Proton-Coupled Electron Transfer

“…In aprotic solvents such as DMF, O2 shows quasi-reversible redox (Equation ( 2)) corresponding to generation of O2 •− in the initial cathodic scan and reoxidation to the starting materials (O2), in the returned anodic scan (1c/1a, solid lines in Figure 2). The reversible CVs investigated here were all modified to irreversible one by the presence of any compounds (a-c, e-h) except (d) δ-TOH with concentration dependency (0 to 5.0, 10.0 × 10 −3 mol dm −3 ), similar to general phenolic compounds [18][19][20][21][25][26][27][28], supporting that CVs of bubbled N2 showed no peak over the potential range. Thus, the loss of reversibility in the CVs of O2/O2 •− is caused by acid-base reaction, the initial PT from the compounds to O2 •− as a Brønsted base forming HO2 • (Equation ( 3)).…”

“…Conversely, in the presence of (a-c, e) TOH, the bielectronic CVs don't appear due to the elimination of HO2 • by the subsequent ET (Equation ( 5)) from the TO − . In our previous study, the ET involved in the PCET mechanism for successful O2 •− elimination required two structural characteristics; 1) the quinone-hydroquinone -conjugated structure characterized by ortho/para-diphenol or aminophenol, and 2) the hydroxyl and amino proton for the second PT [18][19][20][21]27]. Notably, α-, β-, and γ-TOH showed the CV for the successful O2 •− /HO2 • elimination, although the two structural characteristics are not involved in their structures.…”

Electrochemical and Mechanistic Study of Superoxide Scavenging by Pyrogallol in N,N-Dimethylformamide through Proton-Coupled Electron Transfer

“…Conversely, in the presence of (a) PyH3, (b) CatH2, and (d) MoCatH2, the bielectronic CVs don't appear due to the scavenging of HO2 • by the subsequent ET (Equation ( 4)) from the deprotonated anion (PyH2 − , CatH − , and MoCatH − ), where a cathodic prepeak appeared. In our previous study, the ET involved in the PCET mechanism for successful O2 •− scavenging required two structural characteristics; 1) the quinone-hydroquinone -conjugated structure characterized by ortho/para-diphenol, and 2) the OH proton for the second PT [20, [22][23][24]30].…”

Electrochemical and Mechanistic Study of Oxidative Degradation of Favipiravir by Electro-generated Superoxide through Proton-coupled Electron Transfer

“…Considering the possible mechanisms and structure-decomposability relationship of T-705, its T-1105 moiety is thought to play a significant role in the oxidative decomposition mechanism. Our previous studies reported that O2 •− is eliminated by polyphenols, 30 1,4-and 1,2-benzendiols (hydroquinone 29 and catechol 28 ), and mono-phenols including aminophenols 31,34 through the oxidative electron transfer (ET) involved in the PCET. In these studies, the PCET mechanism is based on quinonehydroquinone π-conjugation and involves two PTs and one ET.…”