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Modelling the Repair of Carbon-Centered Protein Radicals by Phenolic Antioxidants Walton-Raaby, Max; Floen, Tyler; Mora-Diez, Nelaine

Abstract

Oxidative stress is a biological process that has been linked to many diseases, hence understanding how to prevent and repair it is essential to medicine. The thermodynamics and kinetics of the repair reactions of radically damaged leucine (a lateral chain in a simplified protein environment) by twenty phenolic antioxidants are studied at the M06-2X(SMD)/6-31++G(d,p) level of theory in water and pentyl ethanoate. The two repair mechanisms modelled are formal-hydrogen atom transfer (f-HAT) and single electron transfer (SET). Although all f-HAT reactions are thermodynamically favourable, only one of the phenols produced rate constants in the diffusion limit, exhibiting biological relevance. SET is not suspected to be an important repair pathway for the phenols studied. We show that the Bell–Evans–Polanyi principle, which relates thermodynamics and kinetics properties for a reaction, breaks down when comparing between the solvents, protein repair sites, and the phenolic antioxidants. While thermodynamic data can be used as valuable screening tools, the kinetic calculation of rate constants in solution is crucial for enhancing the biological relevance of theoretical studies.

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Title
Modelling the Repair of Carbon-Centered Protein Radicals by Phenolic Antioxidants
Creator
Walton-Raaby, Max; Floen, Tyler; Mora-Diez, Nelaine
Publisher
Multidisciplinary Digital Publishing Institute
Date Issued
2024-11-08
Description
Oxidative stress is a biological process that has been linked to many diseases, hence understanding how to prevent and repair it is essential to medicine. The thermodynamics and kinetics of the repair reactions of radically damaged leucine (a lateral chain in a simplified protein environment) by twenty phenolic antioxidants are studied at the M06-2X(SMD)/6-31++G(d,p) level of theory in water and pentyl ethanoate. The two repair mechanisms modelled are formal-hydrogen atom transfer (f-HAT) and single electron transfer (SET). Although all f-HAT reactions are thermodynamically favourable, only one of the phenols produced rate constants in the diffusion limit, exhibiting biological relevance. SET is not suspected to be an important repair pathway for the phenols studied. We show that the Bell–Evans–Polanyi principle, which relates thermodynamics and kinetics properties for a reaction, breaks down when comparing between the solvents, protein repair sites, and the phenolic antioxidants. While thermodynamic data can be used as valuable screening tools, the kinetic calculation of rate constants in solution is crucial for enhancing the biological relevance of theoretical studies.
Subject
DFT; M06-2X; SMD; antioxidants; phenols; leucine; repair; rate constants; HAT; SET; thermodynamics; kinetics
Genre
Article
Type
Text
Language
eng
Date Available
2024-11-29
Provider
Vancouver : University of British Columbia Library
Rights
CC BY 4.0
DOI
10.14288/1.0447374
URI
http://hdl.handle.net/2429/89756
Affiliation
Pharmaceutical Sciences, Faculty of; Non UBC
Citation
Antioxidants 13 (11): 1368 (2024)
Publisher DOI
10.3390/antiox13111368
Peer Review Status
Reviewed
Scholarly Level
Faculty
Rights URI
https://creativecommons.org/licenses/by/4.0/
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CC BY 4.0