engleski

Mechanisms of Reactions of Sulfide Radical Cation Complexes with Superoxide and Oxygen

Methionine sulfoxide is a prominent oxidation product of proteins during oxidative stress and biological aging. Such conditions are generally characterized by elevated levels of superoxide. As superoxide does not directly oxidize organic sulfides, we have characterized alternative mechanisms by which superoxide can contribute to sulfoxide formation. One pathway involves the initial formation of sulfide radical cations. Depending on the nature of the sulfide such radical cations associate with neighboring heteroatoms such as sulfur, nitrogen and oxygen. As long as the lifetime of the resulting sulfide radical cation complex is long enough to permit radical cation-superoxide reactions (competitive to other unimolecular or bimolecular pathways) these reactions efficiently lead to two-electron oxidation products of the sulfides, sulfoxide for X=S, and azasulfonium derivates for X=N. Importantly, these reactions are diastereoselective for X=N, with diastereomeric ratios [ƒŃC(S),S(R)]:[ƒŃC(S),S(S)] up to 4:1 for the azasulfonium derivates of Met-Met. Diastereoselectivity appears to be mechanism- and sequence-dependent as it is significantly lower when the C-terminal Met residue is substituted by Leu, i.e. in Met-Leu. Pulse radiolitically, the rate constants for the reaction of superoxide with [S.:S]+ and [S.:NR(H2)]+ have been determined as 2 E10 (1/Ms) and 5 E9 (1/Ms), respectively. In proteins, the formation of [S.:S]+ and [S.:NR(H2)]+ is restricted to spatially close Met residues and N-terminal Met. We will introduce a more general mechanism for the stabilization of methionine sulfide radical cations by complexation either with the oxygen or the nitrogen atom of the C-terminal peptide bond. Thus, the reaction of methionine sulfide radical cations with superoxide can be considered a general possibility for sulfoxide formation in proteins.

pulse radiolysis; radicals; reaction mechanisms

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