Issue 28, 2020

Cyclization step of noradrenaline and adrenaline autoxidation: a quantum chemical study

Abstract

Catecholamine autoxidation has been recognized as one of the potential trigger factors for catecholaminergic neuron loss characteristics of neurodegenerative diseases. The cyclization step with intramolecular Michael addition of catecholamine o-quinones has been shown to be the irreversible and rate limiting step of the autoxidation reaction across a broad pH range and has a complex pH dependence that has not yet been fully understood. Using quantum chemical calculations, we demonstrated that in the case of noradrenaline and adrenaline two catecholamine o-quinone species, one with an unprotonated and one with a protonated quinone group can participate in the cyclization reaction and that the mechanisms of these reactions significantly differ, emphasizing the importance of quinone group protonation states in the reaction mechanism. With a thorough exploration of the reaction kinetics, we further showed that at acidic pH the cyclization reaction rate is pH independent, while at alkaline pH the pH dependence is marked, explaining the experimentally observed complex pH dependence.

Graphical abstract: Cyclization step of noradrenaline and adrenaline autoxidation: a quantum chemical study

Article information

Article type
Paper
Submitted
24 mar 2020
Accepted
17 apr 2020
First published
28 apr 2020
This article is Open Access
Creative Commons BY-NC license

RSC Adv., 2020,10, 16650-16658

Cyclization step of noradrenaline and adrenaline autoxidation: a quantum chemical study

N. Umek, RSC Adv., 2020, 10, 16650 DOI: 10.1039/D0RA02713H

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