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Evidence for the Prerequisite Formation of Phenoxyl Radicals in Radical‐Mediated Peptide Tyrosine Nitration In Vacuo
Author(s) -
Lai Cheuk Kuen,
Tang Wai Kit,
Siu ChiKit,
Chu Ivan K.
Publication year - 2020
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201904484
Subject(s) - nitration , chemistry , radical , regioselectivity , tautomer , tyrosine , residue (chemistry) , peptide , radical ion , photochemistry , molecule , combinatorial chemistry , stereochemistry , organic chemistry , catalysis , ion , biochemistry
The elementary mechanism of radical‐mediated peptide tyrosine nitration, which is a hallmark of post‐translational modification of proteins under nitrative stress in vivo, has been elucidated in detail by using an integrated approach that combines the gas‐phase synthesis of prototypical molecular tyrosine‐containing peptide radical cations, ion–molecule reactions, and isotopic labeling experiments with DFT calculations. This reaction first involves the radical recombination of . NO 2 towards the prerequisite phenoxyl radical tautomer of a tyrosine residue, followed by proton rearrangements, finally yielding the stable and regioselective 3‐nitrotyrosyl residue product. In contrast, nitration with the π‐phenolic radical cation tautomer is inefficient. This first direct experimental evidence for the elementary steps of the radical‐mediated tyrosine nitration mechanism in the gas phase provides a fundamental insight into the regioselectivity of biological tyrosine ortho ‐nitration.