Formation of n → π⁺interaction facilitating dissociative electron transfer in isolated tyrosine-containing molecular peptide radical cations

Long-range electron transfer in proteins can be rationalized as a sequential short-distance electron-hopping processes via amino acid residues having low ionization energy as relay stations. Tyrosine residues can serve as such redox-active intermediates through one-electron oxidation to form a π-radical cation at its phenol side chain. An electron transfer from a vicinal functional group to this π-electron hole completes an elementary step of charge migration. However, transient oxidized/reduced intermediates formed at those relay stations during electron transfer processes have not been observed. In this study, formation of analog reactive intermediates via electron donor-acceptor coupling is observed by using IRMPD action spectroscopy. An elementary charge migration at the molecular level in model tyrosine-containing peptide radical cations [M]^•+ in the gas phase is revealed with its unusual C_α-C_β bond cleavage at the side chain of the N-terminal residue. This reaction is induced by the radical character of the N-terminal amino group (-NH₂^•+) resulting from an n → π⁺ interaction between the nonbonding electron pair of NH₂(n) and the π-electron hole at the Tyr side chain (π⁺). The formation of -NH₂^•+ is supported by the IRMPD spectrum showing a characteristic NH₂ scissor vibration coupled with Tyr side-chain stretches at 1577 cm⁻¹. This n → π⁺ interaction facilitates a dissociative electron transfer with NH₂ as the relay station. The occurrence of this side-chain cleavage may be an indicator of the formation of reactive conformers featuring the n → π⁺ interaction.