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

All Science Journal Classification (ASJC) codes

  • Physical and Theoretical Chemistry

Fingerprint Dive into the research topics of 'Electrophilic additions of nitrated fatty acids with biological thiols: comparison with type-2 alkenes'. Together they form a unique fingerprint.

  • Cite this