Density Functional Theory (DFT) calculations were carried out to evaluate the potential for intramolecular addition of peptide cysteine (Cys) thiyl radicals (CysS(center dot)) to aromatic amino acids (Phe and Tyr) in water. These calculations yielded cyclic conformations, in which pi-complexes were more stable than cyclohexadienyl radicals in water. In these pi-complexes, the C-2-S distances were significantly shorter compared to the C-1-S and C-3-S distances. Comparable results on the relative stabilities were obtained for model calculations for the addition of HS center dot/CH3S center dot to toluene and p-hydroxytoluene. The adduct of thiyl radicals with Phe was more stable than that with Tyr, and the stabilization energies depended on the C-terminal substituents.