Details zur Publikation

Kategorie Textpublikation
Referenztyp Zeitschriften
DOI 10.1021/tx800492x
Titel (primär) Kinetic glutathione chemoassay to quantify thiol reactivity of organic electrophiles - application to α,β-unsaturated ketones, acrylates, and propiolates
Autor Böhme, A.; Thaens, D.; Paschke, A.; Schüürmann, G.
Quelle Chemical Research in Toxicology
Erscheinungsjahr 2009
Department OEC
Band/Volume 22
Heft 4
Seite von 742
Seite bis 750
Sprache englisch
Abstract Glutathione (GSH) is a soft nucleophile and, as such, can be used to sense the reactivity of electrophilic agents toward the thiol group and other electron-rich sites of molecular structures. A new kinetic GSH chemoassay is introduced that employs a photometric method to quantify GSH loss and enables an efficient determination of second-order rate constants, kGSH, of the reaction between electrophilic substances and GSH. Comparison with an existing 2 h static assay shows that the new kinetic variant is superior with respect to the detectable range of electrophilic reactivity and to confounding factors such as additional GSH loss due to oxidation. Analysis of the chemoassay degradation kinetics provides insight into the characteristic reaction times and the contributions of GSH-electrophile Michael addition and GSH oxidation to the overall GSH loss. For 15 a,ß-unsaturated ketones, nine acrylates, and two propiolates acting as Michael acceptors, the measured kGSH values span ca. 5 orders of magnitude. Moreover, log kGSH correlates with the compounds' toxicity toward the ciliates Tetrahymena pyriformis in terms of 48 h log EC50 (50% growth inhibition) values, yielding a squared correlation coefficient (r2) of 0.91 and a root-mean-square error of 0.30 log units. It shows that for these and related compounds, aquatic toxicity is driven by electrophilic reactivity. The findings demonstrate that the kinetic GSH chemoassay can be used as an efficient tool to analyze, interpret, and predict correspondingly reactive toxicity in the context of qualitative and quantitative structure-activity relationship studies and as a nonanimal tool of integrated testing strategies for REACH to screen compounds for excess toxicity.
dauerhafte UFZ-Verlinkung https://www.ufz.de/index.php?en=20939&ufzPublicationIdentifier=89
Böhme, A., Thaens, D., Paschke, A., Schüürmann, G. (2009):
Kinetic glutathione chemoassay to quantify thiol reactivity of organic electrophiles - application to α,β-unsaturated ketones, acrylates, and propiolates
Chem. Res. Toxicol. 22 (4), 742 - 750 10.1021/tx800492x