Here, we report on a mechanistic investigation based on DFT calculations and kinetic measures aimed at determining the energetics related to the cysteine nucleophilic attack on nitrile-carrying compounds. Activation energies were found to correlate well with experimental kinetic measures of reactivity with cysteine in phosphate buffer. The agreement between computations and experiments points to this DFT-based approach as a tool for predicting both nitrile reactivity toward cysteines and the toxicity of nitriles as electrophile agents.
Predicting the reactivity of nitrile-carrying compounds with cysteine: a combined computational and experimental study / Berteotti A; Vacondio F; Lodola A; Bassi M; Silva C; Mor M; Cavalli A.. - In: ACS MEDICINAL CHEMISTRY LETTERS. - ISSN 1948-5875. - 5(2014), pp. 501-505. [10.1021/ml400489b]