Formation, isomerization, and dissociation of ε- and α-carbon-centered tyrosylglycylglycine radical cations

Abstract

The fragmentation products of the ε-carbon-centered radical cations [Y^ε˙LG]⁺ and [Y^ε˙GL]⁺, made by 266 nm laser photolysis of protonated 3-iodotyrosine-containing peptides, are substantially different from those of their π-centered isomers [Y^π˙LG]⁺ and [Y^π˙GL]⁺, made by dissociative electron transfer from ternary metal–ligand–peptide complexes. For leucine-containing peptides the major pathway for the ε-carbon-centered radical cations is loss of the side chain of the leucine residue forming [YG^α˙G]⁺ and [YGG^α˙]⁺, whereas for the π-radicals it is the side chain of the tyrosine residue that is lost, giving [G^α˙LG]⁺ and [G^α˙GL]⁺. The fragmentations of the product ions [YG^α˙G]⁺ and [YGG^α˙]⁺ are compared with those of the isomeric [Y^ε˙GG]⁺ and [Y^π˙GG]⁺ ions. The collision-induced spectra of ions [Y^ε˙GG]⁺ and [YGG^α˙]⁺ are identical, showing that interconversion occurs prior to dissociation. For ions [Y^ε˙GG]⁺, [Y^π˙GG]⁺ and [YG^α˙G]⁺ the dissociation products are all distinctly different, indicating that dissociation occurs more readily than isomerization. Density functional theory calculations at B3LYP/6-31++G(d,p) gave the relative enthalpies (in kcal mol⁻¹ at 0 K) of the five isomers to be [Y^ε˙GG]⁺ 0, [Y^π˙GG]⁺ −23.7, [YGG^α˙]⁺ −28.7, [YG^α˙G]⁺ −31.0 and [Y^α˙GG]⁺ −38.5. Migration of an α-C–H atom from the terminal glycine residue to the ε-carbon-centered radical in the tyrosine residue, a 1−11 hydrogen atom shift, has a low barrier, 15.5 kcal mol⁻¹ above [Y^ε˙GG]⁺. By comparison, isomerization of [Y^ε˙GG]⁺ to [YG^α˙G]⁺ by a 1–8 hydrogen atom migration from the α-C–H atom of the central glycine residue has a much higher barrier (50.6 kcal mol⁻¹); similarly conversion of [Y^ε˙GG]⁺ into [Y^π˙GG]⁺ has a higher energy (24.4 kcal mol⁻¹).