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Article Dans Une Revue ChemPhysChem Année : 2011

Unraveling Gold(I)-Specific Action Towards Peptidic Disulfide Cleavage: A DFT Investigation

Elise Dumont
Carine Michel
Philippe Sautet

Résumé

Ground-state disulfide dissociation is a target of prime importance in structural biochemistry. A main difficulty consists in avoiding competition with carbon–sulfur and backbone scission pathways. In tandem mass spectrometry, such selectivity is afforded using transition elements or coinage-metal ions as catalyst. Yet, the underlying gas-phase mechanistic details remain poorly understood. Gold(I)-assisted disulfide cleavage is investigated by means of DFT calculations, to elucidate the highly selective and specific catalytic action of this transition-metal cation, a most promising one in tandem mass spectrometry. The preferential cleavage of sulfur–sulfur versus carbon–sulfur linkages on dimethyldisulfide, taken as a prototypical aliphatic compound, is rationalized on the basis of molecular orbital arguments. Secondly, it is revealed that the disulfide dissociation profile is dramatically impacted by a peptidic environment. Calculations on l,l-cystine derivatives show two main factors: the topological frustration for an embedded -CH2[BOND]S[BOND]S[BOND]CH2- motif induces a 5 kcal mol−1 penalty, whereas electrophilic assistance via complexation of nitrogen and oxygen atoms lowers activation barriers by a factor of 3. S[BOND]S weakening is both thermodynamically and kinetically driven by the versatile coordination mode of gold(I). The influence of amine-terminus group protonation is finally sketched: it gives rise to an intermediate reactivity. This study sheds lights on the key action of the peptidic environment in tuning the dissociation profile in the presence of this transition-metal monocation.

Dates et versions

hal-01121423 , version 1 (01-03-2015)

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Elise Dumont, Carine Michel, Philippe Sautet. Unraveling Gold(I)-Specific Action Towards Peptidic Disulfide Cleavage: A DFT Investigation. ChemPhysChem, 2011, 12 (14), pp.2596-2603. ⟨10.1002/cphc.201100336⟩. ⟨hal-01121423⟩
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