ISBN: 978-83-60043-10-3 - eurobic9

Eurobic9, 2-6 September, 2008, Wrocław, Poland
O22. Zinc-thiolate Group: Reactivity and Alkylation Mechanism
D. Picot, G. Ohenessian, G. Frison
Department of Chemistry - Laboratoire des Mécanis, CNRS - Ecole Polytechnique, Route de Saclay, 91128,
Palaiseau Cedex, France
e-mail: frison@dcmr.polytechnique.fr
Alkylation of zinc-bound thiolates occurs in both catalytic and structural zinc sites of enzymes. Recent
biomimetic studies have led to a controversy as to which mechanism is operative in thiolate alkylation.
Furthermore, this alkylation reaction has raised question about the nucleophilicity of thiolates located in the zinccoordination
sphere.[1, 2] Building on one of these biomimetic complexes, we have devised a series of models
that allow for an appraisal of the roles of charge, ligand nature and hydrogen bonding to sulfur on reactivity. The
reactions of these complexes with methyl iodide, leading to thioethers and zinc iodide complexes, have been
examined by density functional theory (DFT) calculations, in the gas phase as well as in aqueous solution. In all
cases, a SN2 reaction is favoured over sigma-bond metathesis. Both the net electronic charge and the H bond
play a significant role on the nucleophilicity of the thiolate. We find that the mechanistic diversity observed
experimentally can be explained by the difference in the net charge of the complexes. Finally, we were able to
determine correlation between the reactivity of these systems and their thermodynamic and structural properties.
This allows us to widen these works to real biological systems.
References:
[1] G. Parkin, Chem. Rev., 2004, 104, 699.
[2] J. Penner-Hahn, Curr. Opin. Chem. Biol., 2007, 11, 166.
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