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

TY - JOUR

T1 - Reactions of simple and peptidic alpha-carboxylate radical anions with dioxygen in the gas phase

AU - Ly, Tony

AU - Kirk, Benjamin B.

AU - Hettiarachchi, Pramesh I.

AU - Poad, Berwyck L. J.

AU - Trevitt, Adam J.

AU - da Silva, Gabriel

AU - Blanksby, Stephen J.

PY - 2011/9/28

Y1 - 2011/9/28

N2 - 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 Cα-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 Cα-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 Cα 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.

AB - 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 Cα-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 Cα-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 Cα 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.

U2 - 10.1039/c1cp20784a

DO - 10.1039/c1cp20784a

M3 - Article

SN - 1463-9076

VL - 13

SP - 16314

EP - 16323

JO - Physical Chemistry Chemical Physics

JF - Physical Chemistry Chemical Physics

IS - 36

ER -