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Modeling the transition state structure to probe a reaction mechanism on the oxidation of quinoline by quinoline 2-oxidoreductase

BACKGROUND: Quinoline 2-oxidoreductase (Qor) is a member of molybdenum hydroxylase which catalyzes the oxidation of quinoline (2, 3 benzopyridine) to 1-hydro-2-oxoquinoline. Qor has biological and medicinal significances. Qor is known to metabolize drugs produced from quinoline for the treatment of...

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Autor principal: Bayle, Enyew A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer International Publishing 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5123400/
https://www.ncbi.nlm.nih.gov/pubmed/27942266
http://dx.doi.org/10.1186/s13065-016-0219-3
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author Bayle, Enyew A.
author_facet Bayle, Enyew A.
author_sort Bayle, Enyew A.
collection PubMed
description BACKGROUND: Quinoline 2-oxidoreductase (Qor) is a member of molybdenum hydroxylase which catalyzes the oxidation of quinoline (2, 3 benzopyridine) to 1-hydro-2-oxoquinoline. Qor has biological and medicinal significances. Qor is known to metabolize drugs produced from quinoline for the treatment of malaria, arthritis, and lupus for many years. However, the mechanistic action by which Qor oxidizes quinoline has not been investigated either experimentally or theoretically. PURPOSE OF THE STUDY: The present study was intended to determine the interaction site of quinoline, predict the transition state structure, and probe a plausible mechanistic route for the oxidative hydroxylation of quinoline in the reductive half-reaction active site of Qor. RESULTS: Density functional theory calculations have been carried out in order to understand the events taking place during the oxidative hydroxylation of quinoline in the reductive half-reaction active site of Qor. The most electropositivity and the lowest percentage contribution to the HOMO are shown at C(2) of quinoline compared to the other carbon atoms. The transition state structure of quinoline bound to the active site has been confirmed by one imaginary negative frequency of −104.500/s and −1.2365899E+06 transition state energies. The Muliken atomic charges, the bond distances, and the bond order profiles were determined to characterize the transition state structure and the reaction mechanism. CONCLUSION: The results have shown that C(2) is the preferred locus of interaction of quinoline to interact with the active site of Qor. The transition state structure of quinoline bound to the active site has been confirmed by one imaginary negative frequency. Moreover, the presence of partial negative charges on hydrogen at the transitions state suggested hydride transfer. Similarly, results obtained from total energy, iconicity and molecular orbital analyses supported a concerted reaction mechanism.
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spelling pubmed-51234002016-12-09 Modeling the transition state structure to probe a reaction mechanism on the oxidation of quinoline by quinoline 2-oxidoreductase Bayle, Enyew A. Chem Cent J Research Article BACKGROUND: Quinoline 2-oxidoreductase (Qor) is a member of molybdenum hydroxylase which catalyzes the oxidation of quinoline (2, 3 benzopyridine) to 1-hydro-2-oxoquinoline. Qor has biological and medicinal significances. Qor is known to metabolize drugs produced from quinoline for the treatment of malaria, arthritis, and lupus for many years. However, the mechanistic action by which Qor oxidizes quinoline has not been investigated either experimentally or theoretically. PURPOSE OF THE STUDY: The present study was intended to determine the interaction site of quinoline, predict the transition state structure, and probe a plausible mechanistic route for the oxidative hydroxylation of quinoline in the reductive half-reaction active site of Qor. RESULTS: Density functional theory calculations have been carried out in order to understand the events taking place during the oxidative hydroxylation of quinoline in the reductive half-reaction active site of Qor. The most electropositivity and the lowest percentage contribution to the HOMO are shown at C(2) of quinoline compared to the other carbon atoms. The transition state structure of quinoline bound to the active site has been confirmed by one imaginary negative frequency of −104.500/s and −1.2365899E+06 transition state energies. The Muliken atomic charges, the bond distances, and the bond order profiles were determined to characterize the transition state structure and the reaction mechanism. CONCLUSION: The results have shown that C(2) is the preferred locus of interaction of quinoline to interact with the active site of Qor. The transition state structure of quinoline bound to the active site has been confirmed by one imaginary negative frequency. Moreover, the presence of partial negative charges on hydrogen at the transitions state suggested hydride transfer. Similarly, results obtained from total energy, iconicity and molecular orbital analyses supported a concerted reaction mechanism. Springer International Publishing 2016-11-24 /pmc/articles/PMC5123400/ /pubmed/27942266 http://dx.doi.org/10.1186/s13065-016-0219-3 Text en © The Author(s) 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Bayle, Enyew A.
Modeling the transition state structure to probe a reaction mechanism on the oxidation of quinoline by quinoline 2-oxidoreductase
title Modeling the transition state structure to probe a reaction mechanism on the oxidation of quinoline by quinoline 2-oxidoreductase
title_full Modeling the transition state structure to probe a reaction mechanism on the oxidation of quinoline by quinoline 2-oxidoreductase
title_fullStr Modeling the transition state structure to probe a reaction mechanism on the oxidation of quinoline by quinoline 2-oxidoreductase
title_full_unstemmed Modeling the transition state structure to probe a reaction mechanism on the oxidation of quinoline by quinoline 2-oxidoreductase
title_short Modeling the transition state structure to probe a reaction mechanism on the oxidation of quinoline by quinoline 2-oxidoreductase
title_sort modeling the transition state structure to probe a reaction mechanism on the oxidation of quinoline by quinoline 2-oxidoreductase
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5123400/
https://www.ncbi.nlm.nih.gov/pubmed/27942266
http://dx.doi.org/10.1186/s13065-016-0219-3
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