title: 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.
authors.affiliation: Drug Discovery and Development, Italian Institute of Technology , via Morego 30, 16163 Genova, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Berteotti
authors.affiliation: Dipartimento di Farmacia, Università degli Studi di Parma , Parco Area delle Scienze 27/A, 43124 Parma, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Vacondio
authors.affiliation: Dipartimento di Farmacia, Università degli Studi di Parma , Parco Area delle Scienze 27/A, 43124 Parma, Italy.
authors.forename: Alessio
authors.initials: A
authors.lastname: Lodola
authors.affiliation: Dipartimento di Farmacia, Università degli Studi di Parma , Parco Area delle Scienze 27/A, 43124 Parma, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Bassi
authors.affiliation: Dipartimento di Farmacia, Università degli Studi di Parma , Parco Area delle Scienze 27/A, 43124 Parma, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Silva
authors.affiliation: Dipartimento di Farmacia, Università degli Studi di Parma , Parco Area delle Scienze 27/A, 43124 Parma, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Mor
authors.affiliation: Drug Discovery and Development, Italian Institute of Technology , via Morego 30, 16163 Genova, Italy ; Department of Pharmacy and Biotechnology, University of Bologna , via Belmeloro 6, 40126 Bologna, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Cavalli
keywords: Cysteine; DFT; nitrile reactivity; nucleophilic attack