Characterizing the Energy Surfaces of Competing Pathways in Gas-Phase Charge Inversion Ion/Ion Reactions Involving Cationized Lipids and Anionic Diacids

IF 2.7 2区 化学 Q2 BIOCHEMICAL RESEARCH METHODS
Yingchan Guo, , , Jonathan T. Specker, , , Pratiksha B. Gaikwad, , , Ramón Alain Miranda-Quintana, , and , Boone M. Prentice*, 
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引用次数: 0

Abstract

Accurate structural identification of lipids in mass spectrometry is essential for advancing lipidomics and achieving a holistic understanding of complex cellular systems. Gas-phase charge inversion ion/ion reactions, which allow for alteration of the ion type before dissociation, have been shown to improve lipid identification. The products observed from these reactions arise from competing and consecutive pathways, but limited studies have been performed to characterize the mechanisms of these interactions. Specifically, we have used a charge inversion ion/ion reaction between 1,4-phenylenedipropionic acid (PDPA) and phosphatidylcholines (PCs) to provide structural information on fatty acyl sn-positions and enable separation of isobaric and isomeric lipids. Upon reaction with PDPA, [PC + H]+, [PC + Na]+, and [PC + K]+ analyte ion types each demonstrate differences in partitioning between two major product ion channels: successful lipid charge inversion resulting in a demethylated lipid anion, which can then be subjected to collision induced dissociation (CID) to reveal fatty acyl sn-positions, and single-particle transfer from PC to PDPA resulting in a neutral lipid and charge reduced PDPA, which provides no information on the lipid structure. In this work, density functional theory (DFT) calculations were performed to characterize relevant potential energy barriers for the competing processes, which enables insights into the factors that affect the relative product ion partitioning. These calculations provided detailed insights into the structural dynamics and potential energy barriers associated with proton transfer, methyl group migration, and other competing interactions. Our results revealed that specific transition states differ significantly depending on the ion type and reaction environment, suggesting that the energetic landscape of these processes is influenced by both the size and the coordination state of the cation. Understanding the roles of the energy barriers in these competing reaction processes within the ion–ion reaction complex is crucial to increasing reaction efficiency and designing next-generation reagents to enable improved lipid structural elucidation by gas-phase reactions. This research provides a fundamental perspective of ion/ion reaction mechanisms and illustrates the importance of the ion type and ion structure on product ion partitioning. This deeper mechanistic understanding highlights the nuanced balance between thermodynamics and kinetics in determining product distribution, and these factors can be used to intelligently select new reagents to precisely tune and control desired reaction products.

Abstract Image

表征气相电荷反转离子/离子反应中涉及阳离子脂质和阴离子二酸的竞争途径的能面。
质谱中准确的脂质结构鉴定对于推进脂质组学和实现复杂细胞系统的整体理解至关重要。气相电荷倒置离子/离子反应,允许改变离子类型前解离,已被证明提高脂质鉴定。从这些反应中观察到的产物来自于竞争和连续的途径,但对这些相互作用的机制进行了有限的研究。具体来说,我们使用了1,4-苯二丙酸(PDPA)和磷脂酰胆碱(PCs)之间的电荷倒置离子/离子反应来提供关于脂肪酰基sn位置的结构信息,并使等重脂和异构体脂质的分离成为可能。在与PDPA反应后,[PC + H]+、[PC + Na]+和[PC + K]+分析物离子类型在两个主要产物离子通道之间的分配上各有差异:成功的脂质电荷倒置导致脂质阴离子去甲基化,然后可以进行碰撞诱导解离(CID)以显示脂肪酰基的sn位置,而从PC到PDPA的单粒子转移导致中性脂质和电荷减少的PDPA,这没有提供脂质结构的信息。在这项工作中,进行了密度泛函理论(DFT)计算,以表征竞争过程的相关势能势垒,从而能够深入了解影响相对产物离子分配的因素。这些计算提供了与质子转移、甲基迁移和其他竞争相互作用相关的结构动力学和势能障碍的详细见解。我们的研究结果表明,特定的过渡态取决于离子类型和反应环境,这表明这些过程的能量景观受到阳离子大小和配位态的影响。了解离子-离子反应复合物中这些相互竞争的反应过程中的能量势垒的作用,对于提高反应效率和设计下一代试剂以改进气相反应对脂质结构的解析至关重要。本研究提供了离子/离子反应机理的基本视角,说明了离子类型和离子结构对产物离子分配的重要性。这种更深层次的机制理解强调了在确定产品分布时热力学和动力学之间的微妙平衡,这些因素可以用来智能地选择新的试剂,以精确地调整和控制所需的反应产物。
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来源期刊
CiteScore
5.50
自引率
9.40%
发文量
257
审稿时长
1 months
期刊介绍: The Journal of the American Society for Mass Spectrometry presents research papers covering all aspects of mass spectrometry, incorporating coverage of fields of scientific inquiry in which mass spectrometry can play a role. Comprehensive in scope, the journal publishes papers on both fundamentals and applications of mass spectrometry. Fundamental subjects include instrumentation principles, design, and demonstration, structures and chemical properties of gas-phase ions, studies of thermodynamic properties, ion spectroscopy, chemical kinetics, mechanisms of ionization, theories of ion fragmentation, cluster ions, and potential energy surfaces. In addition to full papers, the journal offers Communications, Application Notes, and Accounts and Perspectives
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