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Predicting the reactivity of nitrile-carrying compounds with cysteine: a combined computational and experimental study.

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.

SUBMITTER: Berteotti A

PROVIDER: S-EPMC4027605 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature

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Predicting the reactivity of nitrile-carrying compounds with cysteine: a combined computational and experimental study.

Berteotti Anna A Vacondio Federica F Lodola Alessio A Bassi Michele M Silva Claudia C Mor Marco M Cavalli Andrea A

ACS medicinal chemistry letters 20140224 5

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 tox ...[more]

PMID: 24900869

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