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Reactions of One-Electron-Oxidized Methionine with Oxygen: An ab Initio Study
journal contribution
posted on 2004-07-22, 00:00 authored by Mei Lan Huang, Arvi RaukA one-electron oxidation of a methionine residue is thought to be a key step in the neurotoxicity of the beta
amyloid peptide of Alzheimer's disease. The chemistry of the radical cation of N-formylmethioninamide
(11•+) and two model systems, dimethyl sulfide (1•+) and ethyl methyl sulfide (6•+), in the presence of oxygen
have been studied by B3LYP/6-31G(d) and CBS-RAD calculations. The stable form of 11•+ has a three-electron bond between the sulfur radical cation and the carbonyl oxygen atom of the i − 1 residue. The
radical cation may lose a proton from the methyl or methylene groups flanking the oxidized sulfur. Both 11•+
and the resultant C-centered radicals may add oxygen to form peroxy radicals. The calculations indicate that
unlike C-centered radicals the sulfur radical cation does not form a covalent bond to oxygen but rather forms
a loose ion-induced dipole complex with an S−O separation of about 2.7 Å, and is bound by about 13 kJ
mol-1 (on the basis of 1•+ + O2). Direct intramolecular abstraction of an H atom from the αC site is unlikely.
It is endothermic by more than 20 kJ mol-1 and involves a high barrier (ΔG = 79 kJ mol-1). The α-to-S
C-centered radicals will add oxygen to form peroxy radicals. The OH BDEs of the parent hydroperoxides are
in the range of 352−355 kJ mol-1, similar to SH BDEs (360 kJ mol-1) and αC−H BDEs (345−350 kJ
mol-1). Thus, the peroxy radicals are oxidizing species comparable in strength to thiyl radicals and peptide
backbone αC-centered radicals. Each peroxy radical can abstract a hydrogen atom from the backbone αC site
of the Met residue to yield the corresponding αC-centered radical/hydroperoxide in a weakly exothermic
process with modest barriers in the range of 64−92 kJ mol-1.
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H atommethionine residue79 kJ molcovalent bondethyl methyl sulfideOH BDEsDirect intramolecular abstraction20 kJ mol13 kJ molbackbone α C sitethiyl radicalsoxidizing speciesmethylene groupsα C sitecarbonyl oxygen atomsulfurmodel systemsform peroxy radicalsbeta amyloid peptideparent hydroperoxidesO 2peroxy radicalshydrogen atomSHcationMet residuedimethyl sulfideab Initio StudyB 3LYP
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