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Temperature-dependence of radical-trapping activity of phenoxazine, phenothiazine and their aza-analogues clarifies the way forward for new antioxidant design

The prediction and/or rationalization of diarylamine radical-trapping antioxidant (RTA) activity at the elevated temperatures where they are most useful presents a significant challenge, precluding the development of new technology. Whilst structure–activity relationships at ambient temperatures are...

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Detalles Bibliográficos
Autores principales: Poon, Jia-Fei, Farmer, Luke A., Haidasz, Evan A., Pratt, Derek A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Royal Society of Chemistry 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8386644/
https://www.ncbi.nlm.nih.gov/pubmed/34522304
http://dx.doi.org/10.1039/d1sc02976b
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author Poon, Jia-Fei
Farmer, Luke A.
Haidasz, Evan A.
Pratt, Derek A.
author_facet Poon, Jia-Fei
Farmer, Luke A.
Haidasz, Evan A.
Pratt, Derek A.
author_sort Poon, Jia-Fei
collection PubMed
description The prediction and/or rationalization of diarylamine radical-trapping antioxidant (RTA) activity at the elevated temperatures where they are most useful presents a significant challenge, precluding the development of new technology. Whilst structure–activity relationships at ambient temperatures are well established, their predictive capacity at elevated temperatures is poor due to competing reactions. A striking example involves phenoxazine, which is a superior RTA relative to its sulfur analog phenothiazine at ambient temperature (e.g. k = 3.9 × 10(7)vs. 7.6 × 10(6) M(−1) s(−1) at 37 °C, respectively), but is demonstrably inferior at elevated temperatures. Despite being inherently less oxidizable in electrochemical experiments and high-accuracy computations, phenoxazine is more rapidly consumed than phenothiazine in autoxidations at 160 °C – a result which we attribute to a lower reorganization energy barrier to oxidation. Given these observations, we surmised that incorporation of an electronegative N-atom into the phenoxazine ring system would decrease the driving force for oxidation and ‘rescue’ its activity. Indeed, this was found to be the case for nitrogen incorporation at any position, regardless of the impact on the inherent RTA activity. Analogous experiments were carried out on phenothiazines into which nitrogen atoms were incorporated, revealing little benefit at 160 °C. These results suggest that for highly reactive diarylamines (i.e. those with k > 10(6) M(−1) s(−1)), further enhancements in reactivity do not materially improve their ability to inhibit hydrocarbon autoxidation at elevated temperatures. Instead, their stability to one-electron oxidation determines their efficacy.
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spelling pubmed-83866442021-09-13 Temperature-dependence of radical-trapping activity of phenoxazine, phenothiazine and their aza-analogues clarifies the way forward for new antioxidant design Poon, Jia-Fei Farmer, Luke A. Haidasz, Evan A. Pratt, Derek A. Chem Sci Chemistry The prediction and/or rationalization of diarylamine radical-trapping antioxidant (RTA) activity at the elevated temperatures where they are most useful presents a significant challenge, precluding the development of new technology. Whilst structure–activity relationships at ambient temperatures are well established, their predictive capacity at elevated temperatures is poor due to competing reactions. A striking example involves phenoxazine, which is a superior RTA relative to its sulfur analog phenothiazine at ambient temperature (e.g. k = 3.9 × 10(7)vs. 7.6 × 10(6) M(−1) s(−1) at 37 °C, respectively), but is demonstrably inferior at elevated temperatures. Despite being inherently less oxidizable in electrochemical experiments and high-accuracy computations, phenoxazine is more rapidly consumed than phenothiazine in autoxidations at 160 °C – a result which we attribute to a lower reorganization energy barrier to oxidation. Given these observations, we surmised that incorporation of an electronegative N-atom into the phenoxazine ring system would decrease the driving force for oxidation and ‘rescue’ its activity. Indeed, this was found to be the case for nitrogen incorporation at any position, regardless of the impact on the inherent RTA activity. Analogous experiments were carried out on phenothiazines into which nitrogen atoms were incorporated, revealing little benefit at 160 °C. These results suggest that for highly reactive diarylamines (i.e. those with k > 10(6) M(−1) s(−1)), further enhancements in reactivity do not materially improve their ability to inhibit hydrocarbon autoxidation at elevated temperatures. Instead, their stability to one-electron oxidation determines their efficacy. The Royal Society of Chemistry 2021-07-13 /pmc/articles/PMC8386644/ /pubmed/34522304 http://dx.doi.org/10.1039/d1sc02976b Text en This journal is © The Royal Society of Chemistry https://creativecommons.org/licenses/by-nc/3.0/
spellingShingle Chemistry
Poon, Jia-Fei
Farmer, Luke A.
Haidasz, Evan A.
Pratt, Derek A.
Temperature-dependence of radical-trapping activity of phenoxazine, phenothiazine and their aza-analogues clarifies the way forward for new antioxidant design
title Temperature-dependence of radical-trapping activity of phenoxazine, phenothiazine and their aza-analogues clarifies the way forward for new antioxidant design
title_full Temperature-dependence of radical-trapping activity of phenoxazine, phenothiazine and their aza-analogues clarifies the way forward for new antioxidant design
title_fullStr Temperature-dependence of radical-trapping activity of phenoxazine, phenothiazine and their aza-analogues clarifies the way forward for new antioxidant design
title_full_unstemmed Temperature-dependence of radical-trapping activity of phenoxazine, phenothiazine and their aza-analogues clarifies the way forward for new antioxidant design
title_short Temperature-dependence of radical-trapping activity of phenoxazine, phenothiazine and their aza-analogues clarifies the way forward for new antioxidant design
title_sort temperature-dependence of radical-trapping activity of phenoxazine, phenothiazine and their aza-analogues clarifies the way forward for new antioxidant design
topic Chemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8386644/
https://www.ncbi.nlm.nih.gov/pubmed/34522304
http://dx.doi.org/10.1039/d1sc02976b
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