A 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 Angstrom, and is bound by about 13 kJ mol(-1) (on the basis of 1(.+) + O-2). Direct intramolecular abstraction of an H atom from the C-alpha site is unlikely. It is endothermic by more than 20 kJ mol(-1) and involves a high barrier (DeltaG = 79 kJ mol(-1)). The alpha-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 C-alpha-H BDEs (345-350 kJ mol(-1)). Thus, the peroxy radicals are oxidizing species comparable in strength to thiyl radicals and peptide backbone C-alpha-centered radicals. Each peroxy radical can abstract a hydrogen atom from the backbone C-alpha site of the Met residue to yield the corresponding C-alpha-centered radical/hydroperoxide in a weakly exothermic process with modest barriers in the range of 64-92 kJ mol(-1).