Publication Details

Category Text Publication
Reference Category Journals
DOI 10.1021/tx100172x
Title (Primary) Prediction of Michael-type acceptor reactivity toward glutathione
Author Schwöbel, J.A.H.; Wondrousch, D.; Koleva, Y.K.; Madden, J.C.; Cronin, M.T.D.; Schüürmann, G.
Source Titel Chemical Research in Toxicology
Year 2010
Department OEC
Volume 23
Issue 10
Page From 1576
Page To 1585
Language englisch
Abstract A model has been developed to predict the kinetic rate constants (kGSH) of a,ß-unsaturated Michael acceptor compounds for their reaction with glutathione (GSH). The model uses the local charge-limited electrophilicity index ?q [Wondrousch, D., et al. (2010) J. Phys. Chem. Lett. 1, 1605-1610] at the ß-carbon atom as a descriptor of reactivity, a descriptor for resonance stabilization of the transition state, and one for steric hindrance at the reaction sites involved. Overall, the Michael addition model performs well (r2 = 0.91; rms = 0.34). It includes various classes of compounds with double and triple bonds, linear and cyclic systems, and compounds with and without substituents in the a-position. Comparison of experimental and predicted rate constants demonstrates even better performance of the model for individual classes of compounds (e.g., for aldehydes, r2 = 0.97 and rms = 0.15; for ketones, r2 = 0.95 and rms = 0.35). The model also allows for the prediction of the RC50 values from the Schultz chemoassay, the accuracy being close to the interlaboratory experimental error. Furthermore, kGSH and associated RC50 values can be predicted in cases where experimental measurements are not possible or restricted, for example, because of low solubility or high volatility. The model has the potential to provide information to assist in the assessment and categorization of toxicants and in the application of integrated testing strategies.
Persistent UFZ Identifier
Schwöbel, J.A.H., Wondrousch, D., Koleva, Y.K., Madden, J.C., Cronin, M.T.D., Schüürmann, G. (2010):
Prediction of Michael-type acceptor reactivity toward glutathione
Chem. Res. Toxicol. 23 (10), 1576 - 1585 10.1021/tx100172x