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

Abstract

Long-range electron transfer in proteins can be rationalized as a sequential short-distance electron-hopping processesviaamino 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 intermediatesviaelectron 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 Cα-Cβbond 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 NH2scissor vibration coupled with Tyr side-chain stretches at 1577 cm−1. This n → π+interaction facilitates a dissociative electron transfer with NH2as 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.