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

• Published in: Theoretical chemistry accounts Vol. 138; no. 5; pp. 1 - 7
• Main Authors: Chen, Jie-Hong, Hu, Ching-Han
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.05.2019; Springer Nature B.V
• Subjects: Alkenes; Atomic/Molecular Structure and Spectra; Chemistry; Chemistry and Materials Science; Continuum modeling; Density functional theory; Fatty acids; Formations; Glutathione; Inorganic Chemistry; Nitrogen dioxide; Organic Chemistry; Physical Chemistry; Protons; Regular Article; Substrates; Theoretical and Computational Chemistry; Thiols; Type-2 alkene; Electrophilic addition; Nitrated fatty acid
• ISSN: 1432-881X; 1432-2234
• DOI: 10.1007/s00214-019-2455-9

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.