Reactions of simple and peptidic alpha-carboxylate radical anions with dioxygen in the gas phase

α-Carboxylate radical anions are potential reactive intermediates in the free radical oxidation of biological molecules (e.g., fatty acids, peptides and proteins). We have synthesised well-defined α-carboxylate radical anions in the gas phase by UV laser photolysis of halogenated precursors in an ion-trap mass spectrometer. Reactions of isolated acetate (˙CH₂CO₂−) and 1-carboxylatobutyl (CH₃CH₂CH₂˙CHCO₂−) radical anions with dioxygen yield carbonate (CO₃˙−) radical anions and this chemistry is shown to be a hallmark of oxidation in simple and alkyl-substituted cross-conjugated species. Previous solution phase studies have shown that C_α-radicals in peptides, formed from free radical damage, combine with dioxygen to form peroxyl radicals that subsequently decompose into imine and keto acid products. Here, we demonstrate that a novel alternative pathway exists for two α-carboxylate C_α-radical anions: the acetylglycinate radical anion (CH₃C(O)NH˙CHCO₂−) and the model peptide radical anion, YGGFG˙−. Reaction of these radical anions with dioxygen results in concerted loss of carbon dioxide and hydroxyl radical. The reaction of the acetylglycinate radical anion with dioxygen reveals a two-stage process involving a slow, followed by a fast kinetic regime. Computational modelling suggests the reversible formation of the C_α peroxyl radical facilitates proton transfer from the amide to the carboxylate group, a process reminiscent of, but distinctive from, classical proton-transfer catalysis. Interestingly, inclusion of this isomerization step in the RRKM/ME modelling of a G3SX level potential energy surface enables recapitulation of the experimentally observed two-stage kinetics.