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

Abstract

<p>Long-range electron transfer in proteins can be rationalized as a sequential short-distance electron-hopping processes <em>via</em> 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 <em>via</em> 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]˙<small>⁺</small> in the gas phase is revealed with its unusual C<small>_α</small>–C<small>_β</small> 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 (–NH<small>₂</small>˙<small>⁺</small>) resulting from an n → π<small>⁺</small> interaction between the nonbonding electron pair of NH<small>₂</small> (n) and the π-electron hole at the Tyr side chain (π<small>⁺</small>). The formation of –NH<small>₂</small>˙<small>⁺</small> is supported by the IRMPD spectrum showing a characteristic NH<small>₂</small> scissor vibration coupled with Tyr side-chain stretches at 1577 cm<small>⁻¹</small>. This n → π<small>⁺</small> interaction facilitates a dissociative electron transfer with NH<small>₂</small> 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<small>⁺</small> interaction.<br></p>