Gas-phase chemistry of tryptophan-based radicals
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This work is devoted to the fundamental study of gas-phase tryptophan-based radical cations. It covers: mechanisms of the radical ion formation in the gas-phase; the description and contrast of the two types of tryptophan side chain radicals (pi and N-indolyl) based on their reactivities, infrared spectra, structural energetics and fragmentation patterns; investigation of the N-indolyl tryptophan radical cation fragmentation pathways; formation of the two types of tryptophan radicals (pi and N-indolyl) within short peptides; their characterization and comparison based on the fragmentation patterns and reactivity; and gas-phase study of intramolecular radical migration from tryptophan to cysteine and from tryptophan to tyrosine side chains within short peptides.Two different approaches were followed to regiospecifically form desired radicals on the tryptophan side chain. The tryptophan pi-radical cation was formed via electron transfer during dissociation of ternary metal complex ([CuII(terpy)(Trp)]·2+), while N-indolyl radical was formed by the homolytic cleavage of the NO group from the N-nitrosylated tryptophan during gas-phase fragmentation. Both radicals were exposed to the low-energy collision-induced dissociation in order to elucidate and contrast their fragmentation. To estimate the fragmentation pathway of the N-indolyl tryptophan radical cation, additional experiments (including H/D exchange, dissociation of tryptophan derivatives and DFT calculations) were carried out. The radical reactivity has been tested via gas-phase ion-molecule reactions with benzeneselenol, 1-propanethiol and di-tert-butyl nitroxide. The pi-radical cation was found to be more reactive compared to the N-indolyl radical, which was explained by the charge presence near the radical site. Propanethiol was found to be reactive towards pi-radical cation and showed the lack of reactivity with N-indolyl radical. To investigate the role of amino acid sequence, both types of the radicals were formed within short peptides (AW, WA, GW, WG, GGW). They were also contrasted by their fragmentation and reactivity. The gas-phase radical migration between tryptophan and cysteine (CW, CGW, CGGW model peptides), and tryptophan and tyrosine (GYW, YGW, WGY model peptides) side chains was examined at thermal conditions and with application of additional collision energy. Radical migration between N-indolyl tryptophan radical and tyrosine side chains has been observed. Investigation of the migration between tryptophan pi-radical cation and cysteine side chain remains to be work in progress.