Reactivities of Acrylic and Methacrylic Acids in a Nucleophilic Addition Model of Their Biological Activity (Journal Version)

摘要

The reactivities of derivatives of acrylic and methacrylic acid (AA and MAA) in Michael reactions of nucleophilic addition that have been proposed as the underlying mechanisms for the toxicity of such compounds are evaluated from a study of the mechanism of addition of a nucleophile, fluoride ion, to the activated double bonds. The differences in the molecular properties of AA and MAA that account for the differences in the structure and energy of the resulting carbanions, are calculated with ab-initio methods of quantum chemistry. Based on a detailed analysis of the structural and electronic changes that occur during the interaction with the nucleophile, the greater stabilization of the carbanion from AA is attributed to specific differences in the properties of the isolated molecules. On this basis, it is possible to identify some discriminant reactivity criteria that are based on the properties of the isolated AA and MAA molecules. Analysis of the results can be used to generate parameters for structure-reactivity correlations to predict the reactivity of related compounds. Useful tools for predicting the toxicity of untested compounds in the series are thus obtainable.