| Title: |
Structural Identification and Kinetic Analysis of the in Vitro Products Formed by Reaction of Bisphenol A‑3,4-quinone with N‑Acetylcysteine and Glutathione |
| Authors: |
Stack, Douglas E.; Conrad, John A.; Mahmud, Bejan |
| Source: |
Chemistry Faculty Publications |
| Publisher Information: |
DigitalCommons@UNO |
| Publication Year: |
2018 |
| Collection: |
University of Nebraska Omaha: DigitalCommons@UNO |
| Subject Terms: |
Chemistry |
| Description: |
Bisphenol A (BPA) has received considerable attention as an endocrine disrupting chemical and a possible substrate for genotoxic metabolites. BPA metabolism leads to formation of electrophilic o-quinones cable of binding to DNA and other endogenous nucleophiles. We have structurally identified the products resulting from the reaction of bisphenol A-3,4-quinone (BPAQ) with N-acetylcysteine (NAC) and glutathione (GSH). The major and minor isomers are both the result of 1,6-conjugate addition and are produced almost instantly in high yield. Reactions using 1.3 equiv of GSH showed the presence of a bis-glutathionyl adduct which was not observed using higher GSH concentration relative to BPAQ. NAC reactions with BPAQ showed no bis-N-acetylcysteinyl adducts. Stopped-flow kinetic analysis reveals the 1,6-conjugate additions to be reversible with a forward free energy of activation of 9.2 and 7.8 kcal/mol for the NAC and GSH reactions, respectively. The bimolecular forward rate constant at 19.4 °C was approximately three time faster for GSH compared to NAC, 1547 vs 496 M−1 s−1. The free energy of activation for the reverse reactions were similar, 11.7 and 11.2 kcal/mol for NAC and GSH, respectively. We plan to use this model system to further explore the mechanism of adduct formation between sulfur nucleophiles and o-quinones and the resulting chemical properties of both NAC and GSH adducts. |
| Document Type: |
text |
| File Description: |
application/pdf |
| Language: |
unknown |
| Relation: |
https://digitalcommons.unomaha.edu/chemfacpub/43; https://digitalcommons.unomaha.edu/context/chemfacpub/article/1042/viewcontent/2017_D_Stack_StructuralIdentificationAnd.pdf |
| Availability: |
https://digitalcommons.unomaha.edu/chemfacpub/43; https://digitalcommons.unomaha.edu/context/chemfacpub/article/1042/viewcontent/2017_D_Stack_StructuralIdentificationAnd.pdf |
| Accession Number: |
edsbas.EA164603 |
| Database: |
BASE |