Electrophilic additions of nitrated fatty acids with biological thiols: comparison with type-2 alkenes

Jie Hong Chen, Ching-Han Hu

Research output: Contribution to journalArticle

Abstract

We investigated the adduct formations of cysteine and glutathione with electrophilic substrates. Density functional theory with a continuum model was applied to explore the reactions that serve as models for cell signaling proteins and electrophiles. Biological electrophilic species including nitrated fatty acids (NO 2 -FAs), 15-deoxy-delta12,14-prostaglandin J2 (15d-PGJ2) and neurotoxic type-2 alkenes were included in our investigation. The reaction sequence begins with a thiol proton transfer with the base, followed by nucleophilic attack, and ends with a second proton transfer to accomplish thiol additions to the substrates. It was observed that adduct formations between the thiols and type-2 alkenes are comparatively more exergonic than those with NO 2 -FAs and 15d-PGJ2. The type-2 alkenes that were most exergonic in adduct formations were experimentally identified to be the most toxic. The computational approach presented in this work may serve as a convenient method to predict the degree of neurotoxicity.

Original languageEnglish
Article number68
JournalTheoretical Chemistry Accounts
Volume138
Issue number5
DOIs
Publication statusPublished - 2019 May 1

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Alkenes
fatty acids
Sulfhydryl Compounds
thiols
prostaglandins
adducts
alkenes
Proton transfer
Fatty Acids
Cell signaling
glutathione
protons
Poisons
cysteine
Substrates
attack
Density functional theory
Glutathione
Cysteine
density functional theory

All Science Journal Classification (ASJC) codes

  • Physical and Theoretical Chemistry

Cite this

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Electrophilic additions of nitrated fatty acids with biological thiols : comparison with type-2 alkenes. / Chen, Jie Hong; Hu, Ching-Han.

In: Theoretical Chemistry Accounts, Vol. 138, No. 5, 68, 01.05.2019.

Research output: Contribution to journalArticle

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