Ion/ion Chemistry and Ion Trap Approaches for the Structural Characterization of the Lipidome

在化学系化学测量和成像项目的支持下，普渡大学的Scott McLuckey教授和他的团队正在开发用于脂质分子结构表征的新方法。分子的反应性及其所起的作用与分子的结构密切相关。由相同原子组成但原子之间具有不同键的分子（即异构体）可以具有明显不同的反应性。与所有生命形式相关的化学中充满了同分异构体分子发挥关键和独特作用的例子。作为一类生物分子，脂质正成为生物体生物状态的高信息量标记物。有机体的脂质补体被称为脂质组。在脂质体中已经发现了许多同分异构体的例子，其中许多已经知道具有重要的生物学意义。然而，缺乏表征脂质组结构多样性的工具。麦克卢基教授和他的学生正在发明新的工具和方法来表征脂质组，这将使科学界对生命的化学有更深入的了解。该项目旨在开发新的离子/离子反应和电动力学离子阱方法，用于复杂混合物中脂质衍生离子的结构表征。这项工作的一个基本主题是采用最敏感的电离方法，同时使用气相离子/离子反应将最初形成的离子类型转换为替代离子类型，从而产生单一离子类型无法提供的结构细节。在一系列条件下的碰撞诱导解离将用于探测使用各种试剂产生的离子类型。例如，同分异构体的区分将基于产物离子特性和/或丰度的差异以及解离速率的差异。由电喷雾电离直接产生的偶电子脂质离子将受到导致多种替代离子类型的反应，包括奇电子离子、含金属离子及其组合。这项工作有可能为复杂混合物中存在的各种脂质的结构表征提供一种灵活的方法，因此，可以为脂质组学和脂质生物学的前沿问题研究提供有价值的分析技术。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

With support from the Chemical Measurement and Imaging Program in the Division of Chemistry, Professor Scott McLuckey and his group at Purdue University are developing novel approaches for the structural characterization of lipid molecules. The reactivities of molecules and the roles that they play are intimately tied to their structures. Molecules comprised of the same atoms but with different linkages between atoms (i.e., isomers) can have markedly different reactivities. The chemistries associated with all forms of life are replete with examples in which isomeric molecules play key and unique roles. As a class of biomolecules, lipids are emerging as highly informative markers of the biological state of an organism. The lipid complement of an organism is referred to as its ‘lipidome’. Many examples of isomerism have been identified in lipidomes, many of which are already known to be biologically significant. However, tools to characterize the structural diversity of the lipidome are lacking. Professor McLuckey and his students are inventing new tools and approaches to characterize the lipidome, which will enable the scientific community to generate a deeper understanding of the chemistry of life.This project seeks to develop novel ion/ion reaction and electrodynamic ion trap approaches for the structural characterization of ions derived from lipids present in complex mixtures. An underlying theme of the work is to employ the most sensitive approach to ionization while using gas-phase ion/ion reactions to convert the initially formed ion-type to alternate ion-types that yield structural details that a single ion-type alone cannot provide. Collision-induced dissociation under a range of conditions will be used to probe the ion-types generated using various reagents. Isomer distinction, for example, will be based on differences in product ion identities and/or abundances and differences in dissociation rates. The even-electron lipid ions generated directly by electrospray ionization will be subjected to reactions that will lead multiple alternate ion-types that include odd-electron ions, metal-containing ions, and combinations thereof. This work has the potential to yield a flexible means for the structural characterization of a variety of lipids present in complex mixtures and, as such, could provide valuable enabling analytical technology for the study of frontline questions in lipidomics and lipid biology.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.