The reaction of protonated methionine with the lowest electronically excited state of molecular oxygen O(2)(a(1)Δ(g)) was studied in a guided ion beam apparatus, including the measurement of reaction cross sections over a center-of-mass collision energy (E(col)) range of 0.1-2.0 eV. A series of electronic structure and RRKM calculations were used to examine the properties of various complexes and transition states that might be important along the reaction coordinate. Only one product channel is observed, corresponding to generation of hydrogen peroxide via transfer of two hydrogen atoms (H2T) from protonated methionine to singlet oxygen. At low collision energies, the reaction approaches the collision limit and may be mediated by intermediate complexes. The reaction shows strong inhibition by collision energy, and becomes negligible at E(col) > 1.25 eV. A large set of quasi-classical direct dynamics trajectory simulations were calculated at the B3LYP/6-21G level of theory. Trajectories reproduced experimental results and provided insight into the mechanistic origin of the H2T reaction, how the reaction probability varies with impact parameter, and the suppressing effect of collision energy. Analysis of the trajectories shows that at E(col) = 1.0 eV the reaction is mediated by a precursor and/or hydroperoxide complex, and is sharply orientation-dependent. Only 20% of collisions have favorable reactant orientations at the collision point, and of those, less than half form precursor and hydroperoxide complexes which eventually lead to reaction. The narrow range of reactive collision orientations, together with physical quenching of (1)O(2) via intersystem crossing between singlet and triplet electronic states, may account for the low reaction efficiency observed at high E(col).

We report a study on the reactions of protonated cysteine (CysH(+)) and tryptophan (TrpH(+)) with the lowest electronically excited state of molecular oxygen (O(2), a(1)Δ(g)), including the measurement of the effects of collision energy (E(col)) on reaction cross sections over the center-of-mass E(col) range of 0.05 to 1.0 eV. Electronic structure calculations were used to examine properties of complexes, transition states and products that might be important along the reaction coordinate. For CysH(+) + (1)O(2), the product channel corresponds to C(α)-C(β) bond rupture of a hydroperoxide intermediate CysOOH(+) accompanied by intramolecular H atom transfer, and subsequent dissociation to H(2)NCHCO(2)H(+), CH(3)SH and ground triplet state O(2). The reaction is driven by the electronic excitation energy of (1)O(2), the so-called dissociative excitation energy transfer. Quasi-classical direct dynamics trajectory simulations were calculated for CysH(+) + (1)O(2) at E(col) = 0.2 and 0.3 eV, using the B3LYP/6-21G method. Most trajectories formed intermediate complexes with significant lifetime, implying the importance of complex formation at the early stage of the reaction. Dissociative excitation energy transfer was also observed in the reaction of TrpH(+) with (1)O(2), leading to dissociation of a TrpOOH(+) intermediate. In contrast to CysOOH(+), TrpOOH(+) dissociates into a glycine molecule and charged indole side chain in addition to ground-state O(2) because this product charge state is energetically favorable. The reactions of CysH(+) + (1)O(2) and TrpH(+) + (1)O(2) present similar E(col) dependence, i.e., strongly suppressed by collision energy and becoming negligible at E(col) > 0.5 eV. This is consistent with a complex-mediated mechanism where a long-lived complex is critical for converting the electronic energy of (1)O(2) to the form of internal energy needed to drive complex dissociation.

Oxidation of histidine by (1)O2 is an important process associated with oxidative damage to proteins during aging, diseases and photodynamic therapy of tumors and jaundice, and photochemical transformations of biological species in the troposphere. However, the oxidation mechanisms and products of histidine differ dramatically in these related environments which range from the gas phase through aerosols to aqueous solution. Herein we report a parallel gas- and solution-phase study on the (1)O2 oxidation of histidine, aimed at evaluating the evolution of histidine oxidation pathways in different media and at different ionization states. We first investigated the oxidation of protonated and deprotonated histidine ions and the same systems hydrated with explicit water molecules in the gas phase, using guided-ion-beam-scattering mass spectrometry. Reaction coordinates and potential energy surfaces for these systems were established on the basis of density functional theory calculations, Rice-Ramsperger-Kassel-Marcus modeling and direct dynamics simulations. Subsequently we tracked the oxidation process of histidine in aqueous solution under different pH conditions, using on-line UV-Vis spectroscopy and electrospray mass spectrometry monitoring systems. The results show that two different routes contribute to the oxidation of histidine depending on its ionization states. In each mechanism hydration is essential to suppressing the otherwise predominant dissociation of reaction intermediates back to reactants. The oxidation of deprotonated histidine in the gas phase involves the formation of 2,4-endoperoxide and 2-hydroperoxide of imidazole. These intermediates evolve to hydrated imidazolone in solution, and the latter either undergoes ring-closure to 6α-hydoxy-2-oxo-octahydro-pyrrolo[2,3-d]imidazole-5-carboxylate or cross-links with another histidine to form a dimeric product. In contrast, the oxidation of protonated histidine is mediated by 2,5-endoperoxide and 5-hydroperoxide, which convert to stable hydrated imidazolone end-product in solution. The contrasting mechanisms and reaction efficiencies of protonated vs. deprotonated histidine, which lead to pH dependence in the photooxidation of histidine, are interpreted in terms of the chemistry of imidazole with (1)O2. The biological implications of the results are also discussed.

The reactions of deprotonated tyrosine ([Tyr-H](-)) and tryptophan ([Trp-H](-)) with the lowest electronically excited state of molecular oxygen O(2)[a(1)Δ(g)] have been studied in the gas phase, including the measurement of the effects of collision energy (E(col)) on reaction cross sections over a center-of-mass E(col) range from 0.05 to 1.0 eV. [Tyr-H](-) and [Trp-H](-) were generated using electrospray ionization, and both have a pure carboxylate anion structure in the gas phase. Density functional theory calculations and RRKM modeling were used to examine properties of various complexes, transition states, and products that might be important along the reaction coordinate. It was found that deprotonation of Tyr and Trp results in a large effect on their (1)O(2)-mediated oxidation. For [Tyr-H](-), the reaction corresponds to the formation of a hydroperoxide intermediate, followed by intramolecular H transfer and subsequent dissociation to product ion 4-(2-aminovinyl)phenolate, and neutral H(2)O(2) and CO(2). Despite that the reaction is 1.83 eV exothermic, the reaction cross section shows a threshold-like behavior at low E(col) and increases with increasing E(col), suggesting that the reaction bears an activation barrier above the reactants. Quasi-classical, direct dynamics trajectory simulations were carried out for [Tyr-H](-) + (1)O(2) at E(col) = 0.75 eV, using B3LYP/4-31G* level of theory. Trajectories demonstrated the intermediacy of complexes at the early stage of the reaction. A similar product channel was observed in the reaction of [Trp-H](-) with (1)O(2), yielding product ion 3-(2-aminovinyl)indol-1-ide, H(2)O(2) and CO(2). However, the reaction cross section of [Trp-H](-) is strongly suppressed by E(col) and becoming negligible at E(col) > 1.0 eV, indicating that this reaction proceeds without energy barriers above the reactants.