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 language | English |
|---|---|
| Article number | 68 |
| Journal | Theoretical Chemistry Accounts |
| Volume | 138 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - 2019 May 1 |
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All Science Journal Classification (ASJC) codes
- Physical and Theoretical Chemistry
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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 journal › Article
TY - JOUR
T1 - Electrophilic additions of nitrated fatty acids with biological thiols
T2 - comparison with type-2 alkenes
AU - Chen, Jie Hong
AU - Hu, Ching-Han
PY - 2019/5/1
Y1 - 2019/5/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85065475295&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85065475295&partnerID=8YFLogxK
U2 - 10.1007/s00214-019-2455-9
DO - 10.1007/s00214-019-2455-9
M3 - Article
AN - SCOPUS:85065475295
VL - 138
JO - Theoretical Chemistry Accounts
JF - Theoretical Chemistry Accounts
SN - 1432-881X
IS - 5
M1 - 68
ER -