Evidence for a Proton‐Coupled Electron Transfer Mechanism in a Biomimetic System for Monoamine Oxidase B Catalysis. Issue 4 (7th January 2020)

• Record Type: Journal Article
• Authors: Nakamura, Akiko; Latif, Marwa Abdel; Deck, Paul A.; Castagnoli, Neal; Tanko, James M.
• Is Part Of: Chemistry. Volume 26:Issue 4(2020)
• Page Start: 823
• Page End: 829
• Publication Date: 2020-01-07
• Subjects: deprotonation -- MAO catalysis -- proton-coupled electron transfer -- radical cations -- single-electron transfer; Chemistry -- Periodicals; 540
• DOI: 10.1002/chem.201904634
• Languages: English
• ISSNs: 0947-6539

Abstract

Abstract: Mechanistic studies with 5‐ethyl‐3‐methyllumiflavinium (Fl + ) perchlorate, a biomimetic model for flavoenzyme monoamine oxidase B (MAO‐B) catalysis, and the tertiary, allyl amine 1‐methyl‐4‐(1‐methyl‐1 H ‐pyrrol‐2‐yl)‐1, 2, 3, 6‐tetrahydropyridine (MMTP) reveal that proton‐coupled electron transfer (PCET) may be an important pathway for MAO catalysis. The first step involves a single‐electron transfer (SET) leading to the free radicals Fl . and MMTP ., the latter produced by deprotonation of the initially formed and highly acidic MMTP .+ . Molecular oxygen (O2 ) is found to play a hitherto unrecognized role in the early steps of the oxidation. MMTP and several structurally similar tertiary amines are the only tertiary amines oxidized by MAO, and their structural/electronic properties provide the key to understanding this behavior. A general hypothesis about the role of SET in MAO catalysis, and the recognition that PCET occurs with appropriately substituted substrates is presented. Abstract : SET is back : Structural features are identified that explain why only certain tertiary amines (e.g., the potent neurotoxin 1‐methyl‐4‐phenyl‐1, 2, 3, 6‐tetrahydropyridine, MPTP) are monoamine oxidase (MAO‐A or ‐B) substrates. Formation of a highly stabilized radical, unique to cyclic, allylic tertiary amines, such as MPTP and derivatives, drives the single‐electron transfer (SET) process.