Department of Chemistry, University of Hong Kong, Hong Kong, China.
Department of Chemistry, York University, Toronto, ON, Canada.
PLoS One. 2024 Aug 13;19(8):e0308164. doi: 10.1371/journal.pone.0308164. eCollection 2024.
Herein, we explore the generation and characterization of the radical cations of glycylphenylalanylglycine, or [GFG]•+, formed via dissociative electron-transfer reaction from the tripeptide to copper(II) within a ternary complex. A comprehensive investigation employing isotopic labeling, infrared multiple-photon dissociation (IRMPD) spectroscopy, and density functional theory (DFT) calculations elucidated the details and energetics in formation of the peptide radical cations as well as their dissociation products. Unlike conventional aromatic-containing peptide radical cations that primarily form canonical π-radicals, our findings reveal that 75% of the population of the experimentally produced [GFG]•+ precursors are [GFα•G]+, where the radical resides on the middle α-carbon of the phenylalanyl residue. This unexpected isomeric ion has an enthalpy of 6.8 kcal/mol above the global minimum, which has an N-terminal captodative structure, [Gα•FG]+, comprising 25% of the population. The [b₂-H]•+ product ions are also present in a ratio of 75/25 from [GFα•G]+/ [Gα•FG]+, the results of which are obtained from matches between the IRMPD action spectrum and predicted IR absorption spectra of the [b₂-H]•+ candidate structures, as well as from IRMPD isomer population analyses.
在此，我们探索了甘氨酰苯丙氨酰甘氨酸（或[GFG]+）自由基阳离子的生成和特性，该阳离子通过三肽与铜（II）之间的离解电子转移反应形成。采用同位素标记、红外多光子解离（IRMPD）光谱和密度泛函理论（DFT）计算的综合研究阐明了肽自由基阳离子形成及其解离产物的细节和能量学。与主要形成典型π-自由基的传统含芳香族肽自由基阳离子不同，我们的研究结果表明，实验产生的[GFG]+前体中 75%的自由基位于苯丙氨酸残基中间的α-碳原子上，形成[GFα•G]+。这种出人意料的异构离子的焓高于全球最小值 6.8 kcal/mol，其具有 N 端加电子结构[Gα•FG]+，占总离子的 25%。[b₂-H]+产物离子也以 75/25 的比例存在于[GFα•G]+/[Gα•FG]+之间，这是通过将 IRMPD 作用光谱与[b₂-H]+候选结构的预测红外吸收光谱进行匹配以及通过 IRMPD 异构体分析得出的结果。
