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

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...

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Autor principal: Umek, Nejc
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Royal Society of Chemistry 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9053094/
https://www.ncbi.nlm.nih.gov/pubmed/35498869
http://dx.doi.org/10.1039/d0ra02713h
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author Umek, Nejc
author_facet Umek, Nejc
author_sort Umek, Nejc
collection PubMed
description 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.
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spelling pubmed-90530942022-04-29 Cyclization step of noradrenaline and adrenaline autoxidation: a quantum chemical study Umek, Nejc RSC Adv Chemistry 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. The Royal Society of Chemistry 2020-04-28 /pmc/articles/PMC9053094/ /pubmed/35498869 http://dx.doi.org/10.1039/d0ra02713h Text en This journal is © The Royal Society of Chemistry https://creativecommons.org/licenses/by-nc/3.0/
spellingShingle Chemistry
Umek, Nejc
Cyclization step of noradrenaline and adrenaline autoxidation: a quantum chemical study
title Cyclization step of noradrenaline and adrenaline autoxidation: a quantum chemical study
title_full Cyclization step of noradrenaline and adrenaline autoxidation: a quantum chemical study
title_fullStr Cyclization step of noradrenaline and adrenaline autoxidation: a quantum chemical study
title_full_unstemmed Cyclization step of noradrenaline and adrenaline autoxidation: a quantum chemical study
title_short Cyclization step of noradrenaline and adrenaline autoxidation: a quantum chemical study
title_sort cyclization step of noradrenaline and adrenaline autoxidation: a quantum chemical study
topic Chemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9053094/
https://www.ncbi.nlm.nih.gov/pubmed/35498869
http://dx.doi.org/10.1039/d0ra02713h
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