jp0573036_si_001.pdf (246.21 kB)
Theoretical Study of the Reduction Mechanism of Sulfoxides by Thiols
journal contribution
posted on 2006-06-22, 00:00 authored by B. Balta, G. Monard, M. F. Ruiz-López, M. Antoine, A. Gand, S. Boschi-Muller, G. BranlantTheoretical computations have been carried out to investigate the reaction mechanism of the sulfoxide reduction
by thiols in solution. This reaction is a suitable model for enzymatic processes involving methionine sulfoxide
reductases (Msrs). Recent investigations on the Msr mechanism have clearly shown that a sulfenic acid
intermediate is formed on the catalytic cysteine of the active site concomitantly to the methionine product. In
contrast, experimental studies for the reaction of a number of thiols and sulfoxides in solution did not observe
sulfenic acid formation. Only, a disulfide was identified as the final product of the process. The present study
has been carried out at the MP2/6-311+G(3d2f,2df,2p)//B3LYP/6-311G(d,p) level of theory. The solvent
effect in DMSO has been incorporated using a discrete−continuum model. The calculations provide a basic
mechanistic framework that allows discussion on the apparent discrepancy existing between experimental
data in solution and in the enzymes. They show that, in the early steps of the process in solution, a sulfurane
intermediate is formed the rate of which is limiting. Then, a proton transfer from a second thiol molecule to
the sulfurane leads to the formation of either a sulfenic acid or a disulfide though the latter is much more
stable than the former. If a sulfenic acid is formed in solution, it should react with a thiol molecule making
its experimental detection difficult or even unfeasible.