Reactivity of acrylamide as an alkylating agent: a kinetic approach

Acrylamide (AA), an industrially produced reactive molecule, is used worldwide. The US EPA and IARC have classified this molecule as a probable human carcinogen. In this work, the alkylating potential of AA was investigated kinetically. The conclusions drawn are as follows: (i) AA shows alkylating ability on the nucleophile 4-(p-nitrobenzyl)pyridine (NBP), a trap for alkylating agents with nucleophilic characteristics similar to those of DNA bases; (ii) the rate equation for the NBP–AA adduct formation is as follows: ; (ii) the thermoentropic term, TΔ‡Sθ, is the main term responsible for the lower reactivity of AA as an alkylating agent; (iii) the value of the Gibbs energy of activation, Δ‡Gθ, for the NBP alkylation reaction by AA is consistent with the conclusions of epidemiologic studies concerning the carcinogenicity of this substance; (iv) the results obtained here may be useful when working with hydrophilic/lipophilic media, such as in Food Science, since the dielectric constant of the medium, where alkylation occurs, influences the reaction rate, and alkylation can be inhibited by lowering the dielectric constant of the medium. Copyright © 2009 John Wiley & Sons, Ltd.