Evolution of oxidation dynamics of histidine: non-reactivity in the gas phase, peroxides in hydrated clusters, and pH dependence in solution

Abstract

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.

Mechanistic and Kinetic Study of Singlet O2 Oxidation of Methionine by On-Line Electrospray Ionization Mass Spectrometry

“…This configuration allowed for a high sample transfer rate (11.4 mL/h), and in the meantime delivered only a small fraction of the flow to ESI. We were able to reduce the sample transfer time to less than 30 s [52]. But this method increased the total sample volume needed (by a factor of~200) for each measurement.…”

“…Note that a typical flow rate for ESI is 1 μL/min, which would result in far too long delay for kinetic measurements if this rate is used for sample transfer. In a previous on-line ESI MS experiment [52], we adopted Cooks and coworkers' method [51] by adding a splitter to the sample transfer line, right before ESI. The sample was swept to ESI under N 2 gas pressure.…”

The effects of photodynamic treatment with new methylene blue N on the Candida albicans proteome

“…Even though we did not perform 1-D SDS-PAGE, it is reasonable to assume that some protein aggregation took place during PDT. That is because protein cross-linking mediated by 1 O2 starts with His oxidation and later proceeds to covalent binding of amino groups from other amino acids to oxidized histidine, forming both intra-and intermolecular His-His and His-Lys bonds (SHEN et al 2000, LIU et al 2014. Also, photooxidation of myoglobin leads almost exclusively to the formation of intramolecular cross-linking and results in loss of protein free amino groups (VAN STEVENINCK and DUBBELMAN 1984).…”

Oxidation Dynamics of Methionine with Singlet Oxygen: Effects of Methionine Ionization and Microsolvation

“…33 The reaction of dehydrated protonated HisH + with 1 O 2 leads to no products. The origin of this nonreactivity was revealed on the basis of reaction potential energy surface (PES) calculations, statistical modeling, and dynamics simulations.…”