Predicting the reactivity of nitrile-carrying compounds with cysteine: a combined computational and experimental
Anna Berteotti1, Federica Vacondio2, Alessio Lodola2
1Drug Discovery and Development, Italian Institute of Technology , via Morego 30, 16163 Genova, Italy.
Abstract:
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.
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