Intramolecular Addition of Cysteine Thiyl Radical to Phenylalanine and Tyrosine in Model Peptides, Phe (CysS^•) and Tyr(CysS^•): A Computational Study

Density Functional Theory (DFT) calculations were carried out to evaluate the potential for intramolecular addition of peptide cysteine (Cys) thiyl radicals (CysS^•) to aromatic amino acids (Phe and Tyr) in water. These calculations yielded cyclic conformations, in which π-complexes were more stable than cyclohexadienyl radicals in water. In these π-complexes, the C₂−S distances were significantly shorter compared to the C₁−S and C₃−S distances. Comparable results on the relative stabilities were obtained for model calculations for the addition of HS^•/CH₃S^• 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.